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My daughter Lisa Marie Bates died needlessly of Addison's disease

By: Gladys Bates

My daughter Lisa Marie Bates died in 1986 of Addison's disease.  She was misdiagnosed with vitilago a skin disorder, so doctors missed entirely that she had an auto-immune disease that attacks the adrenal gland.  One simple blood test to check her TSH level would have saved her life.  Lisa was only ten years old at the time.

The problem with Addison's disease is that only 1 out of 100,000 people get this.  Lisa's symptoms were classic, vitilago which are white spots, darkened pigment, and flu like symptoms.  Even in this day and age doctors can miss a case of Addison's.

Did you know that President Kennedy had this disease?  I have told hundreds of people about Lisa dying of this disease and hope to send this message out to the whole world for my daughter.

If you do happen to get a rare disease you are at a higher chance of not being diagnosed as doctors tend to look for more common reasons for you being sick.  If I had known about a pigment disorder (darkened pigment) or even vitilago (white spots) being associated with a disease that would have stolen my daughter's life I surely would have demanded that her doctors test her for Addison's.

She kept being diagnosed with flu's and they said don't worry its just a cosmetic problem that would not effect her health.  One of the best children's hospitals in the world missed Lisa's disease.  This should signal to you how easy it is for doctors to miss a case of Addisons.

This disease was diagnosed over one hundred years ago by a Doctor Addison.  Hopefully people reading this article will remember some of these symptoms as anyone, any age, at any time can get this disease.  I would just urge anyone in medical school to pay attention and who knows it could save a life one day.

Lisa's story saved a former co-worker's daughter.  There is a one in a trillion change of that happening.  I call that a miracle.  I hope this story saves more people, maybe yourself or someone you love.

From http://www.articlesbase.com/diseases-and-conditions-articles/my-daughter-lisa-marie-bates-died-needlessly-of-addisons-disease-1067084.html

Joslyn just had adrenal surgery on July 6, 2009. Listen at 7:30PM ET or online for archives. http://ping.fm/zMs7S

Tonight! Cushing's interview with Joslyn. Listen live at 7:30PM ET or online anytime for archives. http://ping.fm/xInn9

Adrenal Glands

Anatomy

The adrenal glands are small, yellowish organs that rest on the upper poles of the kidneys in the Gerota fascia. The right adrenal gland is pyramidal, whereas the left one is more crescentic, extending toward the hilum of the kidney. At age 1 year, each adrenal gland weighs approximately 1 g, and this increases with age to a final weight of 4-5 g. The arterial blood supply comes from 3 sources, with branches arising from the inferior phrenic artery, the renal artery, and the aorta. Venous drainage flows directly into the inferior vena cava on the right side and into the left renal vein on the left side. Lymphatics drain medially to the aortic nodes.

Each adrenal gland is composed of 2 distinct parts: the adrenal cortex and the adrenal medulla. The cortex is divided into 3 zones. From exterior to interior, these are the zona glomerulosa, the zona fasciculata, and the zona reticularis.

Embryology

First detected at 6 weeks’ gestation, the adrenal cortex is derived from the mesoderm of the posterior abdominal wall. Steroid secretion from the fetal cortex begins shortly thereafter. Adult-type zona glomerulosa and fasciculata are detected in fetal life but make up only a small proportion of the gland, and the zona reticularis is not present at all. The fetal cortex predominates throughout fetal life. The adrenal medulla is of ectodermal origin, arising from neural crest cells that migrate to the medial aspect of the developing cortex.

The fetal adrenal gland is relatively large. At 4 months’ gestation, it is 4 times the size of the kidney; however, at birth, it is a third of the size of the kidney. This occurs because of the rapid regression of the fetal cortex at birth. It disappears almost completely by age 1 year; by age 4-5 years, the permanent adult-type adrenal cortex has fully developed.

Anatomic anomalies of the adrenal gland may occur. Because the development of the adrenals is closely associated with that of the kidneys, agenesis of an adrenal gland is usually associated with ipsilateral agenesis of the kidney, and fused adrenal glands (whereby the 2 glands join across the midline posterior to the aorta) are also associated with a fused kidney.

Adrenal hypoplasia occurs in the following 2 forms: (1) hypoplasia or absence of the fetal cortex with a poorly formed medulla and (2) disorganized fetal cortex and medulla with no permanent cortex present. Adrenal heterotopia describes a normal adrenal gland in an abnormal location, such as within the renal or hepatic capsules. Accessory adrenal tissue (adrenal rests), which is usually comprised only of cortex but seen combined with medulla in some cases, is most commonly located in the broad ligament or spermatic cord but can be found anywhere within the abdomen. Even intracranial adrenal rests have been reported.

Physiology

Adrenal Cortex

The adrenal cortex secretes 3 types of hormones: (1) mineralocorticoids (the most important of which is aldosterone), which are secreted by the zona glomerulosa; (2) glucocorticoids (predominantly cortisol), which are secreted by the zona fasciculata and, to a lesser extent, the zona reticularis; and (3) adrenal androgen (mainly dehydroepiandrosterone [DHEA]), which is predominantly secreted by the zona reticularis, with small quantities released from the zona fasciculata.

All adrenocortical hormones are steroid compounds derived from cholesterol (see Media file 3).

Cortisol binds to proteins in the blood, mainly cortisol-binding globulin or transcortin. More than 90% of cortisol is transported in the blood in this bound form. In contrast, only 50% of aldosterone is bound to protein in the blood. All adrenocortical steroids are degraded in the liver and predominantly conjugated to glucuronides, with lesser amounts of sulfates formed. About 75% of these degradation products are excreted in the urine, and the rest is excreted in the stool by means of the bile.

Mineralocorticoids

Aldosterone accounts for 90% of mineralocorticoid activity, with some activity contributed by deoxycorticosterone, corticosterone, and cortisol. The normal concentration of aldosterone in the blood ranges from 2-16 ng/dL supine and 5-41 ng/dL upright, although the concentration exhibits diurnal variation, and the secretory rate is generally 150-250 mcg/d.

Aldosterone promotes sodium reabsorption and potassium excretion by the renal tubular epithelial cells of the collecting and distal tubules. As sodium is reabsorbed, water follows passively, leading to an increase in the extracellular fluid volume with little change in the plasma sodium concentration. Persistently elevated extracellular fluid volumes cause hypertension. This helps minimize further increases in extracellular fluid volume by causing a pressure diuresis in the kidney, a phenomenon known as aldosterone escape. Without aldosterone, the kidney loses excessive amounts of sodium and, consequently, water, leading to severe dehydration.

As sodium is actively reabsorbed, potassium is excreted. Imbalances in aldosterone thus lead to hypokalemia and muscle weakness if levels are increased and to hyperkalemia with cardiac toxicity if levels are decreased. In addition to sodium being exchanged for potassium at the renal tubules, hydrogen is also exchanged, although to a much lesser extent. Therefore, with aldosterone excess, mild metabolic alkalosis may develop.

In addition to the effects of aldosterone on the renal tubules, a smaller but similar effect is noted on the sweat glands and salivary glands. Aldosterone stimulates sodium chloride reabsorption and potassium secretion in the excretory ducts, which helps prevent excessive salivation and conserve body salt in hot climates. Aldosterone also affects sodium absorption in the intestine, especially the colon. Deficiency may cause a watery diarrhea from the unabsorbed sodium and water.

Many factors affect aldosterone secretion, the most important of which involve the renin-angiotensin system and changes in the plasma potassium concentration.
Activation of the renin-angiotensin system: The juxtaglomerular apparatus senses decreased blood flow to the kidney secondary to hypovolemia, hypotension, or renal artery stenosis and releases renin in response. Renin is an enzyme that activates angiotensinogen to release angiotensin I. In the lung, ACE converts angiotensin I to angiotensin II, a potent vasoconstrictor and stimulator of aldosterone release by the adrenal gland.

Concentration of potassium in the extracellular fluid: Increases in the plasma potassium concentration stimulate the release of aldosterone to encourage potassium excretion by the kidney.

Concentration of sodium in the extracellular fluid: Decreases in sodium concentration also stimulate aldosterone release.

Adrenocorticotropic hormone (ACTH) secretion: ACTH secreted by the anterior pituitary primarily affects release of glucocorticoids by the adrenal but, to a lesser extent, also stimulates aldosterone release.

Glucocorticoids

Approximately 95% of glucocorticoid activity comes from cortisol, with corticosterone, a glucocorticoid less potent than cortisol, making up the rest. The normal cortisol concentration in the blood averages 12 mcg/dL, with a secretory rate averaging 15-20 mg/d. Cortisol release is almost entirely controlled by the secretion of ACTH by the anterior pituitary gland, which is controlled by corticotropin-releasing hormone (CRH) secreted by the hypothalamus. In normal situations, CRH, ACTH, and cortisol secretory rates demonstrate a circadian rhythm, with a zenith in the early morning and a nadir in the evening. Various stresses also stimulate increased ACTH and, thus, cortisol secretion. A negative feedback effect of cortisol on the anterior pituitary and the hypothalamus help control these increases and regulate plasma cortisol concentrations.

Cortisol has many effects on the body.
Cortisol stimulates gluconeogenesis in the liver by stimulating the involved enzymes and mobilizing necessary substrates, specifically amino acids from muscle and free fatty acids from adipose tissue. It simultaneously decreases glucose use by extrahepatic cells in the body. The overall result is an increase in serum glucose (ie, adrenal diabetes) and increased glycogen stores in the liver.
Cortisol decreases protein stores in the body, except in the liver, by inhibiting protein synthesis and stimulating catabolism of muscle protein.
Cortisol has clinically significant anti-inflammatory effects, blocking the early stages of inflammation by stabilizing lysosomal membranes, preventing excessive release of proteolytic enzymes, decreasing capillary permeability and, consequently, edema, and decreasing chemotaxis of leukocytes. In addition, it induces rapid resolution of inflammation that is already in progress.
Immunity is adversely affected. Eosinophil and lymphocyte counts in the blood decrease with atrophy of lymphoid tissue.

Adrenal androgens

The adrenal cortex continually secretes several male sex hormones, including DHEA, DHEA sulfate (DHEAS), androstenedione, and 11-hydroxyandrostenedione, with small quantities of the female sex hormones progesterone and estrogen. Most of the effects result from extra-adrenal conversion of the androgens to testosterone. All have weak effects, but they likely play a role in early development of the male sex organs in childhood, and they have an important role in women during pubarche. ACTH has a definite stimulatory effect on androgen release by the adrenal. Therefore, secretion of these hormones parallels that of cortisol.

Adrenal Medulla

The adrenal medulla is a completely different entity. Epinephrine (80%) and norepinephrine (20%), with minimal amounts of dopamine, are secreted into the bloodstream due to direct stimulation by acetylcholine release from sympathetic nerves. Preganglionic sympathetic nerve fibers pass from the intermediolateral horn cells of the spinal cord through the sympathetic chains and splanchnic nerves, without synapsing, into the adrenal medulla. These hormones are responsible for an increase in cardiac output and vascular resistance and for all the physiologic characteristics of the stress response.

Radiology of the Adrenal Gland

CT scanning is the imaging procedure of choice for the evaluation of adrenal lesions, although ultrasonography and, increasingly, MRI have their advantages.

Plain radiography has limited value but may reveal mass effect or calcifications that suggest possible neuroblastoma, previous hemorrhage, or chronic granulomatous disease.

Ultrasonography is often the first imaging study performed in children. It is safe and easy to perform without sedation. It can differentiate cystic from solid adrenal masses and is useful to assess for vascular involvement and liver metastases.

CT scanning most accurately defines the size, location, and appearance of adrenal lesions. In addition, it is useful for assessing local and vascular invasion, involvement of lymph nodes, or distant metastases. For certain lesions (eg, simple cysts, myelolipomas, often hemorrhage), CT scanning enables definitive diagnosis because the image is classic. For solid lesions, unenhanced or delayed–contrast enhanced CT scanning may help in distinguishing benign from malignant lesions by their attenuation. Benign lesions tend to have decreased attenuation because of an increased fat content. However, overlap is substantial; therefore, this finding is not always useful.

MRI is also an excellent study to define the full extent of an adrenal lesion, including its relationship to adjacent organs and major vessels. Its main benefit over CT is its improved ability, with gadolinium enhancement or with chemical shift imaging, to help in differentiating benign from malignant lesions. This is most important in adults with an incidentally discovered adrenal mass.

Radioisotope scanning can be helpful in some situations. Iodocholesterol-labeled analogs (eg, iodine-131 6beta-iodomethyl-19-norcholesterol [NP-59]) are used to detect primary adrenocortical adenomas, carcinomas, or metastases. Dexamethasone administered before the scan enhances sensitivity by suppressing normal ACTH-responsive adrenal tissue. Metaiodobenzylguanidine (MIBG) scans may be used to detect adrenal medullary tumors, pheochromocytomas, and neuroblastomas. This is especially useful in localizing such tumors in extramedullary sites, enabling the entire body to be imaged at once.

More recently positron emission technology (PET) scanning has been introduced in the evaluation of recurrent or metastatic adrenal tumors, especially neuroblastoma. Its role has yet to be fully defined.

Adrenal Pathology

Adrenal pathology can manifest in various ways, including the following:

• Ambiguous genitalia with or without salt wasting in the newborn

• Palpable abdominal mass

• Incidental finding of an adrenal mass on imaging
• Glucocorticoid excess or Cushing syndrome

• Mineralocorticoid excess

• Androgen excess

• Catecholamine excess

• Adrenal insufficiency

• Paraneoplastic process

Ambiguous Genitalia

In the newborn period, ambiguous genitalia, with or without associated salt wasting, is strongly suggestive of congenital adrenal hyperplasia. This is an inherited autosomal recessive disorder caused by deficiency of 1 of the enzymes necessary for adrenal steroid production, especially cortisol. Cortisol deficiency leads to excessive secretion of adrenocorticotropic hormone (ACTH) with resultant bilateral adrenal hyperplasia; thus, a deficiency of the end products of blocked pathways and excess production of steroids in open pathways results.

The most common enzyme deficiency is 21-hydroxylase, which accounts for more than 90% of cases. This is seen in 2 forms: classic (more severe) and nonclassic (less severe).

Classic form

The classic form, which occurs with an incidence of 1 case per 12,000-15,000 population, is characterized by cortisol deficiency and female virilization at birth secondary to excess adrenal androgen production, with salt wasting in 75% of cases secondary to aldosterone deficiency. This is the most common cause of ambiguous genitalia in a newborn girl. The diagnosis must be suspected early on and treatment instituted without delay because congenital adrenal hyperplasia can be life threatening in the newborn period.

The diagnosis is based on elevated baseline and ACTH-stimulated levels of serum 17-hydroxyprogesterone (17-OHP) and adrenal androgens, which are suppressed with the administration of glucocorticoids. When associated salt wasting occurs, the plasma renin-to-aldosterone ratio is also elevated.

Treatment involves replacement glucocorticoids aimed at decreasing ACTH secretion (maintenance hydrocortisone at 10-20 mg/m2/d orally [PO] divided 3 times per day [tid]), and, if salt wasting is prominent, a mineralocorticoid (9-alphafluorohydrocortisone, which is commonly known as fludrocortisone [Florinef], at 0.05-0.3 mg/d PO) and sodium chloride (1-3 g/d PO) are also used. Surgery for clitoral recession and vaginoplasty with correction of the urogenital sinus (usually present) may be performed in early infancy, if the degree of virilization in the newborn girl mandates it.

Nonclassic form

In the nonclassic (relatively mild) form, patients present late with precocious pubarche or problems related to androgen excess, including hirsutism, menstrual irregularities, and infertility. This is said to be the most common autosomal recessive disorder in humans.

The diagnosis is confirmed with elevated ACTH-stimulated levels of serum 17-OHP and adrenal androgens as in the classic form. Baseline levels are usually not as high because they are in the classic form and may even be normal.

Lowered doses of hydrocortisone can be administered as treatment, although some patients never require any therapy. See Congenital Adrenal Hyperplasia for more information.

Palpable Abdominal Mass

A palpable abdominal mass has a large differential diagnosis; adrenal lesions are included.

Neuroblastoma is a malignant tumor derived from neural crest cells in the adrenal medulla or anywhere along the sympathetic chain. About 75% of neuroblastomas arise from within the abdomen or pelvis, with half of these from the adrenal medulla itself, 20% originating from the posterior mediastinum, and 5% coming from the neck. With an overall incidence of 1 case per 10,000 population, it is the most common solid extracranial tumor of childhood. It can manifest in numerous ways, but the most common presentation is as a fixed abdominal mass extending from the flank towards the midline. See Neuroblastoma for more information. Ganglioneuroma, the benign counterpart of neuroblastoma, can also appear as a large palpable abdominal mass.

Another adrenal medullary tumor of neuroendocrine origin that can also be found in extra-adrenal sites is pheochromocytoma. This usually manifests with symptoms attributable to the excess catecholamine secretion by the tumor. In rare cases, an abdominal mass may be noted first.

Adrenal cortical tumors, and especially carcinomas because these tend to be larger than adenomas, can present with a palpable abdominal mass. However, signs and symptoms of excess adrenocortical hormone secretion usually prompt a workup and diagnosis of such tumors. Adrenal cysts are rare in childhood but can be large enough to produce a palpable mass.
Incidental Finding of Adrenal Mass

An adrenal lesion may be incidentally detected during abdominal ultrasonography or CT scanning performed for other reasons. The differential diagnosis of an adrenal mass is extensive.

The differential diagnosis of an adrenal mass is as follows:

• Nonneoplastic conditions

• Hemorrhage

• Cyst

• Abscess

• Chronic granulomatous disease (eg, tuberculosis [TB], histoplasmosis)

• Neoplastic conditions

• Benign conditions

• Myelolipoma

• Ganglioneuroma

• Adrenocortical adenoma

• Hemangioma

• Pheochromocytoma

• Leiomyoma

• Malignant conditions

• Neuroblastoma

• Adrenocortical carcinoma

• Pheochromocytoma

• Non-Hodgkin lymphoma

• Leiomyosarcoma

• Metastases (eg, malignant melanoma, breast carcinoma, hepatocellular carcinoma, squamous cell lung carcinoma)

The differential diagnosis of bilateral adrenal enlargement or mass is as follows:

• Cushing disease

• Adrenal nodular hyperplasia

• Ectopic ACTH or corticotropin-releasing hormone (CRH) production

• Metastases

• Pheochromocytoma

• Lymphoma

• Hemorrhage

In adults, most incidentally discovered adrenal solid masses are adenomas; therefore, such tumors less than 4-5 cm in size, of benign appearance on imaging, and with no extra-adrenal disease are simply observed. In children, the most common adrenal mass is neuroblastoma. In a study of 26 children with an incidentally detected adrenal mass, 30% were found to be malignant; upon review of the imaging, neither size nor appearance could distinguish between benign and malignant.1 Thus, all pediatric adrenal masses found incidentally should be resected.

Glucocorticoid Excess or Cushing Syndrome

The clinical findings associated with excess cortisol secretion in children most commonly include obesity with moonlike facies, growth failure, hirsutism, and acne. Other findings include hypertension, muscle weakness, osteoporosis, glucose intolerance, easy bruising, striae, hyperpigmentation and thin skin, menstrual irregularities, and psychiatric disturbances. Patients with cortisol excess also have impaired wound healing and an increased susceptibility to infection.

The differential diagnosis of Cushing syndrome is as follows:

• Use of exogenous steroids

• ACTH-independent causes

• Adrenal nodular hyperplasia

• Adrenocortical adenoma

• Adrenocortical carcinoma

• ACTH-dependent causes

• Pituitary adenoma (Cushing disease)

• Ectopic ACTH or CRH production from tumors (eg, medullary thyroid cancer, carcinoid tumor, thymoma, Wilms tumor, adrenal rest tumor, pancreatic tumor)

In children younger than 10 years, unlike in older children and adults, primary adrenal pathology (eg, adenoma, adrenal nodular hyperplasia) is the most common cause of Cushing syndrome after use of exogenous corticosteroids and instead of a pituitary adenoma.

In a patient with suspected Cushing syndrome, the first step is to confirm hypercortisolemia (see Media file 1). The best screening test is measurement of free cortisol or 17-hydroxycorticosteroid (17-OHCS) levels in 2-3 consecutive 24-hour urine collections. Normal 24-hour urinary free cortisol values are in the range of 25-75 mcg/m2/d. Plasma levels of cortisol can also be obtained. However, because of the normal diurnal variation, this test is less reliable than urine measurement. The low-dose or overnight dexamethasone suppression test should be used as a confirmatory test when 24-hour urinary levels of 17-OHCS or cortisol are borderline. This involves PO administration of dexamethasone (30 mcg/kg) at 11 pm, with measurement of plasma cortisol at 8 am the next morning. Plasma cortisol levels are normally suppressed to less than 5 mcg/dL. In Cushing syndrome, cortisol secretion is not suppressed.

The next step is to distinguish between ACTH-dependent and ACTH-independent causes, which involve plasma ACTH level measurement. ACTH levels are normally 10-100 pg/mL, with a diurnal variation that parallels that of cortisol but precedes it by 1-2 hours. However, plasma ACTH is low (<5 pg/mL) in patients with adrenocortical neoplasms, intermediate (15-500 pg/mL) in patients with pituitary adenomas and resultant adrenocortical hyperplasia, and highest (usually >1000 pg/mL) in patients with ectopic ACTH-producing tumors.

To further distinguish between the causes of ACTH-dependent Cushing syndrome, the high-dose dexamethasone suppression test is used. It is based on the principle that a high dose of dexamethasone at least partially suppresses adrenal cortisol secretion secondary to an ACTH-secreting pituitary adenoma, whereas secretion secondary to adrenal tumors and ectopic ACTH production is not. Dexamethasone (120 mcg/kg/d given PO divided 4 times a day [qid]) is given for 48 hours. On the second day, a 24-hour urine collection is obtained to measure free cortisol and 17-OHCS levels. In patients with a pituitary adenoma, urinary free cortisol levels are suppressed by 90% to less than 30 mcg/d in 60-70% of patients, and urinary 17-OHCS levels are reduced to less than 3 mg/d.

Another test that can be used to distinguish between Cushing disease and ectopic ACTH production is the metyrapone stimulation test. Because metyrapone blocks the enzyme 11-hydroxylase, which is responsible for conversion of 11-deoxycortisol to cortisol, its administration at 15 mg/kg (or 750 mg for adolescents) PO every 4 hours for 24 hours decreases plasma cortisol and increases ACTH values. The normal response is an increase in plasma 11-deoxycortisol levels to more than 10 mcg/dL and an increase in 24-hour urine 17-OHCS levels to twice the baseline. Patients with pituitary adenomas show this response, whereas those with ectopic ACTH secretion do not. The CRH stimulation test, whereby 1 mcg/kg of CRH is administered and ACTH levels are measured, is also performed to distinguish Cushing disease in most cases. Within 60-180 minutes, patients with Cushing disease had the normal increase in ACTH, and those with other causes of hypercortisolemia do not.

After these distinctions are made, imaging can be used to localize these lesions. Gadolinium-enhanced MRI of the sella turcica is the best imaging modality for assessing pituitary adenomas, with a sensitivity approaching 100%. Sampling of the bilateral inferior petrosal sinuses for ACTH can help identify a pituitary adenoma if imaging does not. Thin-section high-resolution CT scanning or MRI of the adrenals identifies adrenal abnormalities with more than 95% sensitivity. CT or MRI of the chest and abdomen may help in identifying an ectopic ACTH-producing or CRH-producing tumor.

Surgical resection of the offending lesion is the initial treatment of choice for all forms of Cushing syndrome, including bilateral adrenalectomy for bilateral nodular adrenal hyperplasia, transsphenoidal partial hypophysectomy for pituitary adenomas, and unilateral adrenalectomy for adrenal tumors.
Mineralocorticoid Excess

Presenting features of mineralocorticoid excess include hypertension, headache, tachycardia, fatigue, proximal muscle weakness, polyuria, and polydipsia.

The differential diagnosis of hyperaldosteronism is as follows:

• Primary

• Idiopathic adrenal nodular hyperplasia (idiopathic hyperaldosteronism)

• Glucocorticoid-suppressible hyperaldosteronism

• Adrenocortical adenoma

• Adrenocortical carcinoma

Secondary - Elevated renin secretion secondary to renal artery stenosis, a renin-producing tumor, congestive heart failure, and Bartter syndrome (ie, juxtaglomerular hyperplasia)

Primary hyperaldosteronism, characterized by elevated plasma aldosterone, low plasma renin levels, hypokalemia, and hypertension, is rare in children. Unlike in adults, the most common cause is bilateral adrenal hyperplasia, with only a handful of aldosterone-secreting adenomas (ie, Conn syndrome) reported.2 Because adenomas are a curable cause of hypertension, they must be considered in children presenting with hypertension, despite their rarity.

Bilateral adrenal hyperplasia as a cause of hyperaldosteronism occurs in nodular adrenal hyperplasia and in a unique autosomal dominant condition called glucocorticoid-suppressible hyperaldosteronism. This has all of the clinical and biochemical features noted in other causes of primary hyperaldosteronism but demonstrates complete and rapid suppression of aldosterone secretion by administration of dexamethasone.

Adrenocortical carcinoma as a cause of primary hyperaldosteronism is exceptionally rare, with an incidence of 1% in a large series of adults and no reported cases in children.

The first step in the workup of a patient with suspected hyperaldosteronism is to confirm the diagnosis (see Media file 2). Elevated plasma aldosterone levels, hypokalemia (<3.5 mEq/L), and kaliuresis (>30 mEq/d) confirm the diagnosis. A suppressed plasma renin level is compatible with a primary cause. In addition, patients with primary hyperaldosteronism exposed to salt-loading by ingestion of a high-sodium diet for 3-5 days (or by infusion of isotonic sodium chloride solution in a patient who is salt deprived) fail to show suppression of plasma or 24-hour urinary aldosterone. Upright posture and salt depletion also fail to cause a rise in plasma renin activity.

The next step is to distinguish among the various causes of primary hyperaldosteronism. Response to administration of dexamethasone rapidly confirms the diagnosis of glucocorticoid-suppressible hyperaldosteronism. The postural test is most helpful in distinguishing between nodular hyperplasia and adrenal neoplasm. This test is based on the observation that aldosteronomas are sensitive to ACTH and, therefore, exhibit a diurnal variation in aldosterone secretion, whereas adrenal nodular hyperplasia does not.

The patient is kept supine overnight. At 8 am, baseline plasma levels of cortisol, aldosterone, renin, and potassium are measured. The patient stands up and remains upright for 4 hours, at which point all laboratory studies are repeated. An aldosterone-secreting tumor typically results in a drop in aldosterone levels, paralleling the change of cortisol in its natural daytime fall, which the change in posture does not affect. In patients with adrenal hyperplasia, aldosterone responds to the postural change, increasing by more than 33%. Before any of these tests are performed, patients should be potassium replete and not taking any antihypertensive medications for at least 4 weeks.

If an aldosterone-secreting tumor is suspected, imaging is obtained. High-resolution CT scanning can be done to localize approximately 90% of such tumors. Because the lesions are often small, NP-59 scanning can be useful if CT fails to depict the tumor; sensitivity is 70-80% and specificity is 100% in this situation.

As an alternative, selective adrenal venous sampling can be used to definitively identify a tumor. However, it is invasive and technically difficult and, therefore, is used only rarely. Intravenous (IV) ACTH is administered, and adrenal venous blood samples are simultaneously obtained to measure aldosterone and cortisol. An aldosterone-to-cortisol ratio higher than 4:1 is diagnostic of an aldosteronoma and is unilateral as opposed to bilateral.

Aldosterone-secreting tumors are treated by surgical resection. Glucocorticoid-suppressible hyperaldosteronism is treated with glucocorticoids. Bilateral adrenal nodular hyperplasia is treated medically with potassium-sparing diuretics, such as spironolactone or amiloride. Surgery is reserved for cases refractory to medical therapy because less than 20-30% of patients with this disease are cured with adrenalectomy.
Androgen Excess

The predominant clinical feature of hyperandrogenism in the newborn girl is ambiguous genitalia.3 In the older child or adolescent, signs and symptoms include pseudoprecocious puberty in boys and hirsutism, acne, clitoromegaly, deepening of voice, and oligomenorrhea in girls. In both sexes, linear growth and skeletal maturation (ie, bone age) are accelerated.

The differential diagnosis of hyperandrogenism is as follows:

• Use of exogenous anabolic steroids

• Adrenal causes

• Congenital adrenal hyperplasia4

• Adrenocortical adenoma

• Adrenocortical carcinoma

• Exaggerated adrenarche

• Extra-adrenal causes

• Polycystic ovary

• Adrenal rests

• Ovarian tumors- most commonly arrhenoblastoma

• Testicular tumors- most commonly Leydig cell tumors

• Adrenal hyperplasia secondary to a pituitary adenoma or ectopic secretion of ACTH or CRH

• Hyperprolactinemia

• Acromegaly

In infants with failure to thrive, salt wasting and (most obviously in baby girls with clitoromegaly, fused labia, and a persistent urogenital sinus) congenital adrenal hyperplasia must be ruled out. The same is true in boys who present with pseudoprecocious puberty and in older girls with signs and symptoms of hyperandrogenism, although, in teenage girls, polycystic ovary is the most common cause.

Congenital adrenal hyperplasia can be reliably diagnosed with a dexamethasone suppression test. Apart from a few rare causes of hyperandrogenism including exaggerated adrenarche secondary to adrenal hyperresponsiveness to ACTH, hyperprolactinemia, and acromegaly, congenital adrenal hyperplasia is the only virilizing condition in which androgen secretion is suppressed by dexamethasone. ACTH levels can be used to confirm the diagnosis if it is still questionable. An increase in plasma 17-OHP to more than 1200 ng/dL at 60 minutes in response to an IV injection of 250 mcg of cosyntropin is diagnostic of congenital adrenal hyperplasia.

Adrenocortical tumors must always be considered in the differential diagnosis. They are reported to occur from infancy throughout adolescence and well into adulthood. The vast majority of these tumors are virilizing, with 50-80% causing virilization alone and an added 20-40% causing Cushing syndrome in addition to virilization. Rare adrenocortical tumors are predominantly mineralocorticoid secreting or feminizing.

As a group, these tumors are rare, with a childhood incidence of 0.3 per million. Certain children are at increased risk, including those with a family history of p53 mutations, those with Beckwith-Wiedemann syndrome, and those with isolated hemihypertrophy. Distinguishing between benign and malignant adrenocortical lesions is difficult, even pathologically, and the clinical behavior of the tumor is the best determinant of malignancy. Most common sites of metastases are lung and liver, with regional lymph nodes, bone, brain, and pancreatic metastases observed relatively infrequently.

Radical resection, including en bloc resection of locally invaded organs, offers the best chance for cure of adrenocortical tumors. Metastases should also be resected if possible. No survivors after partial resection of tumor have been reported. Adjuvant therapy has shown disappointing results. Mitotane is the most extensively used agent. Although it has not been shown to prolong survival, it can substantially ameliorate the symptoms of hyperandrogenism. It can, however, have significant GI and neurologic side effects. Other, more conventional chemotherapeutic drugs have shown poor results thus far, and radiotherapy has not been proven effective. Pediatric series reveal overall survival rates for adrenocortical tumors of 43-91%. (See Adrenal Carcinoma for more information.)

Distinguishing between ovarian and adrenal virilizing disorders in young girls depends on physical examination, biochemical test, and imaging study findings. Virilizing ovarian tumors are often large, and most are palpable on physical examination. Serum testosterone levels are virtually always elevated. In virilizing adrenocortical tumors, plasma levels of dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), and androstenedione are high, whereas those of testosterone (mainly due to peripheral conversion of androstenedione to testosterone) are elevated much less often and to a lesser extent. Adrenal tumors also result in elevated urinary and plasma 17-ketosteroid levels that are normal or only minimally elevated in ovarian tumors.

In boys, a testicular examination can help determine the source of androgen excess. If both testes are enlarged, they are the most likely source of the androgens in response to gonadotropins (luteinizing hormone [LH], representing central precocious puberty) or a human chorionic gonadotropin (hCG)-secreting tumor. If both testes are prepubertal in size, the most likely source of the androgens is adrenal. Finally, if one testis is enlarged, the likely source is a testicular tumor.

Catecholamine Excess

The clinical manifestations of catecholamine excess include hypertension (either sustained or paroxysmal) orthostatic hypotension, tachycardia or bradycardia, arrhythmias, headache, fatigue, visual blurring, sweating and heat intolerance, weight loss, abdominal pain, and polyuria and polydipsia. These symptoms should prompt biochemical testing to confirm excess catecholamine secretion characteristic of pheochromocytoma.

Measurement of urinary catecholamines, epinephrine and norepinephrine, and their metabolites (ie, metanephrine, homovanillic acid, and vanillylmandelic acid) in a 24-hour urine collection is a sensitive (>90%) test for the diagnosis of pheochromocytoma. Plasma catecholamine levels can also be diagnostic when performed at rest. Levels of more than 2000 pg/mL are diagnostic of a pheochromocytoma. However, the diagnosis can be missed in patients with paroxysmal symptoms.

Various stimulation and suppression tests have been developed to improve diagnostic accuracy. The clonidine suppression test relies on the fact that clonidine suppresses centrally mediated release of catecholamines (to <500 pg/mL) within 2-3 hours of PO administration but does not affect release of catecholamines from a pheochromocytoma. The stimulation tests are dangerous and should only be performed in a monitored setting in situations in which the blood pressure and plasma catecholamine levels are near normal. The glucagon stimulation test demonstrates a more than 3-fold increase in catecholamines or an absolute plasma level of more than 2000 pg/mL after an IV bolus of glucagon in the presence of a pheochromocytoma. Neuroblastoma is also characterized and diagnosed by demonstrating increased catecholamine secretion. However, patients are typically asymptomatic.

Pheochromocytomas are rare tumors that arise from the neural crest–derived chromaffin cells found in the adrenal medulla and sympathetic ganglia. Compared with pheochromocytomas in adults, in children incidences of extra-adrenal tumors (30% vs 10%) and bilateral tumors (30% vs 10%) increase, as does the tendency for a familial occurrence, and the incidence of malignancy is lowered (3.5% vs 10%). Also, pheochromocytomas in children secrete norepinephrine more commonly than they secrete epinephrine; this change may simply reflect the heightened incidence of extra-adrenal tumors. The most common extra-adrenal site is the upper periaortic ganglia, followed by the organs of Zuckerkandl at the base of the inferior mesenteric artery. Other sites include the base of the brain, the chest, and bladder.

Patients at increased risk for pheochromocytomas include those with multiple endocrine neoplasia type II (MEN II) syndrome and neurocutaneous syndromes (eg, Von Recklinghausen disease, tuberous sclerosis, von Hippel–Lindau disease, Sturge-Weber syndrome). In children with a pheochromocytoma, headache is the most common symptom (75%), followed by sweating, nausea, and vomiting. Other frequent symptoms include visual complaints, weight loss, and polyuria and polydipsia.

Hypertension is seen in almost all patients and is sustained in 80-90%, unlike in adults who tend to have paroxysmal hypertension. The hypertension is also more severe in children than in adults, with more than 40% of affected individuals having signs of hypertensive retinopathy, and 40% having signs of cardiomyopathy.

Localization of pheochromocytomas is best accomplished with CT scanning or, particularly, MRI. CT scanning has 94% sensitivity for detection of adrenal tumors and 64% sensitivity for extra-adrenal tumors, with 98% specificity. MRI has 97% sensitivity for detection of adrenal tumors and 88% sensitivity for extra-adrenal tumors, with 100% specificity. Metaiodobenzylguanidine (MIBG) scanning is also highly specific for pheochromocytoma but is less sensitive than MRI. It is most useful to help localize an extra-adrenal pheochromocytoma, which can then be imaged in most detail with CT scanning or MRI.

After the diagnosis is confirmed and the tumor localized, preparations for surgical resection must be started. Patients should be treated with an alpha-adrenergic blocker, such as phenoxybenzamine, with the dose gradually increased to achieve blood pressure and symptom control (0.25-1 mg/kg/d PO in divided doses). Once alpha blockade is accomplished, a beta-adrenergic blocker (eg, propranolol) can be used if arrhythmias occur. Such treatment is begun preferably at least 3 weeks before planned surgery. During surgery, the anesthetist must be prepared for hypertensive episodes, which can be controlled with an agent such as nitroprusside, and for hypotension after the tumor is removed, which responds well to fluids.

The surgical approach of choice is transabdominal. This allows the exploration of both adrenal glands and the sympathetic chain, early ligation of the adrenal vein to prevent excessive catecholamine release with tumor manipulation, and resection of locally invaded organs if necessary. Despite this, extraperitoneal approaches have been used for small tumors. Also, increasingly, a laparoscopic approach is used in adults and children. An attempt should be made to resect the primary tumor in all cases, with resection of metastases if possible, because most of the morbidity and mortality associated with these tumors are the result of the excess catecholamine secretion.

Intensive chemotherapy, principally in the form of cisplatin and doxorubicin, can render some unresectable tumors resectable and should be tried in such cases. Adjuvant chemotherapy is also indicated for residual disease postsurgery and for metastatic disease. It has a response rate of approximately 50% and provides good palliation in a substantial number of patients for years. Radioactive MIBG treatment has also been used and has been shown to provide good palliation in metastatic disease.

As with adrenocortical tumors, the distinction between benign and malignant lesions is not obvious, even pathologically, and only the clinical course of the tumor can define malignancy (either local infiltration or metastases). The most common sites of metastases are the lungs, liver, lymph nodes, and bone. The long-term survival rate of patients with malignant pheochromocytoma is more than 50%.5 Long-term follow-up is essential to detect metastases and metachronous lesions, especially in patients with a familial syndrome. Such lesions have been reported to occur more than 10 years after resection of the initial tumor. Therefore, annual blood pressure and catecholamine measurements should be considered.

Some believe that patients with a familial syndrome should undergo bilateral adrenalectomy at the first operation because the risk of a metachronous tumor is approximately 50%. An important additional issue in children is screening. Children with a familial syndrome and a molecular genetic test that reveals a ret proto-oncogene mutation characteristic of MEN II should undergo annual screening for pheochromocytoma, starting at a young age.

Adrenal insufficiency

This subject is covered extensively in Adrenal Insufficiency. In brief, adrenal insufficiency may be acute or chronic. Chronic adrenal insufficiency may be primary, secondary, or tertiary. Acute adrenal insufficiency results when an acute stress is superimposed on chronic adrenal insufficiency of any type.

Symptoms of chronic adrenal insufficiency may be explained by the lack of adrenal hormones and by the unopposed secretion of ACTH. Hypotension, fatigue, weight loss, anorexia, nausea, vomiting, abdominal pain, salt craving, hypoglycemia, and syncope can occur. Skin and mucous membrane hyperpigmentation result from unopposed secretion of ACTH and melanocyte-stimulating hormone. Hyponatremia, along with hyperkalemia, is sometimes observed and can be explained by the chronic insufficiency of aldosterone. The diagnosis should not be based on the presence or absence of these abnormalities. The loss of secondary sex characteristics is seen only in women with the disease.

Acute adrenal insufficiency is a medical emergency and must be identified and promptly treated. The hallmarks of acute adrenal insufficiency are circulatory collapse with abdominal pain that can simulate an acute abdomen. Profound hypoglycemia, elevated core temperature, and potentially cardiac dysrhythmias are also observed.

Chronic primary adrenal insufficiency results when the adrenal glands themselves are destroyed or infiltrated. Causes include congenital adrenal hyperplasia, bilateral hemorrhage (eg, as in the Waterhouse-Friderichsen syndrome), infection with TB, human immunodeficiency virus (HIV) infection, histoplasmosis, and infiltrative diseases (eg, sarcoidosis). Autoimmune destruction of the adrenal glands is referred to as Addison disease.

Secondary adrenal insufficiency results from diminished release of ACTH from the pituitary. Causes include trauma, pituitary tumors, and pituitary hemorrhage (Sheehan syndrome).

Tertiary adrenal insufficiency results from suppression of the hypothalamic-pituitary-adrenal axis. This is observed with the long-term administration of exogenous steroids. An important distinguishing feature of tertiary adrenal insufficiency is that adrenal medullary and androgen-secreting functions are preserved.

Treatment of chronic adrenal insufficiency is based on the replacement of missing adrenal hormones (hydrocortisone at 15-20 mg/m2/d PO divided tid; fludrocortisone at 0.05-0.1 mg/d). Stress doses of glucocorticoids must be given when any physiologic stress is encountered.

Treatment of acute adrenal insufficiency is life saving and often must be empirically started whenever the entity is suspected. Aggressive fluid resuscitation is the rule and support of the cardiovascular system with the use of exogenous catecholamines may be required in severe cases. Hypoglycemia requires early and often continuous administration of IV dextrose. Hydrocortisone is given as an IV bolus of 50-100 mg/m2 (approximately 50 mg for small children and 100-150 mg for large children and adolescents). Subsequent doses are administered as a continuous IV infusion with 100 mg/m2/d added to the IV fluid infusion or further IV boluses q4-6h until the patient can tolerate PO corticosteroids. Mineralocorticoid replacement is unnecessary in the acute management. Hyperkalemia should be controlled, if present.
Paraneoplastic Process

Approximately 2% of children with neuroblastoma present with opsoclonus-myoclonus. The cause of this manifestation is unclear.

Prenatal Diagnosis of a Suprarenal Mass

With improvements in prenatal ultrasonography, an increasing number of abnormalities are being prenatally detected, including masses in the suprarenal region. These may be cystic, solid or mixed. The differential diagnosis of a suprarenal mass includes:

• Adrenal hemorrhage

• Neuroblastoma

• Extralobar sequestration

• Bronchogenic cyst

• Adrenal or renal cortical cysts

• Adrenocortical carcinoma

Distinguishing between these diagnoses on prenatal imaging alone is difficult and even on postnatal imaging. Adrenal hemorrhage and neuroblastoma are the most common. Unlike neuroblastoma diagnosed later in childhood, neonatal neuroblastoma is usually associated with favorable histology with no N-myc amplification, portending a very good prognosis. It can also spontaneously regress. An adrenocortical tumor is reportable in the newborn. The remaining diagnoses are not urgent. Therefore, babies born with prenatally detected suprarenal masses should undergo postnatal ultrasonography, metaiodobenzylguanidine (MIBG) scanning, and measurement of urinary catecholamine levels, although the latter may be normal even with a diagnosis of neuroblastoma. Small lesions, especially cystic ones that are known to regress more often, should be followed closely.

Monthly follow-up with physical examination and ultrasonography should ensue, with surgery reserved for masses that increase in size or persist. This helps avoid unnecessary surgery for adrenal hemorrhages and spontaneously regressing neuroblastomas. Of course, large masses or any mass that is concerning to family or physician may undergo earlier surgery for definitive diagnosis.

Surgical Approaches to the Adrenal Gland

The 2 main surgical approaches to the adrenal gland are transperitoneal and retroperitoneal, both of which can be used with an open or laparoscopic technique. Advantages of laparoscopic adrenalectomy are early mobilization and oral intake, shortened hospitalization, decreased requirement for narcotics, and similar surgical complication rates. With increasing experience in pediatric laparoscopic adrenalectomy, operative times are comparable with an open approach and the indications are expanding. In the past, larger tumors or suspicion of malignancy were considered contraindications to a laparoscopic approach; currently, absolute size is less important than tumor size in relation to patient size, and successful laparoscopic adrenalectomies for pheochromocytomas, neuroblastomas, and adrenocortical tumors have been reported.

The retroperitoneal laparoscopic approach, compared with a transperitoneal laparoscopic one, is associated with reduced respiratory and hemodynamic effects caused by the pneumoperitoneum and avoids the need to mobilize the abdominal organs to access the adrenal gland. When bilateral adrenal exploration is preferable (eg, for a pheochromocytoma), a transperitoneal approach is preferred. Otherwise, a unilateral lesion can easily be accessed from a retroperitoneal approach with decreased pain and postoperative ileus and with no intraperitoneal adhesion formation. In children, most laparoscopic adrenalectomies have been performed through the transperitoneal route.

The main advantages of a transperitoneal approach include access to the entire abdomen to search for synchronous lesions and metastases and the ability to rapidly identify and resect locally invaded organs en bloc with the primary tumor. In children, an open approach is still most often used mainly because most adrenal tumors in this age group are neuroblastomas that usually present as very large infiltrating lesions.

From http://odlarmed.com/?p=3898

Follow-up of a case of adrenocortical carcinoma

Posted by Thomas Repas, DO, FACP, FACE, CDE  July 24, 2009 03:56 PM

 

Previously, I posted about a young woman who presented with rapid onset Cushing’s syndrome and a 9.0-cm adrenal mass. Her initial 24-hour urine-free cortisol was 1,095 mcg/24 hours (upper limits of normal, 45), one of the highest I have ever seen. She subsequently had surgical resection which confirmed moderately differentiated adrenocortical carcinoma as we had suspected. Fortunately, there was no evidence of extension beyond the adrenal gland or metastatic lymph nodes. Based on size, lack of extension outside the adrenal gland and no known metastasis, she is T2N0MX, stage 2 disease.

 

She is doing amazingly well. She has lost over 20 lbs, looks better and feels better, and her appetite has returned. We placed her on hydrocortisone for glucocorticoid replacement but are weaning her off as the previously suppressed contralateral adrenal recovers.

 

The question we have: Is there any persistent disease?

 

Adrenocortical cancer can be aggressive. Unfortunately, most patients present in stage III or IV. The prognosis for stage IV disease is dismal, with a five-year survival of only 15% to 25%. The only hope for cure is being fortunate enough to completely resect stage I or stage II disease.

 

The next step will be imaging by PET with F-18-fluorodeoxyglucose. Meta-analysis suggests that FDG-PET imaging is reliable in staging and follow-up of disease, with a sensitivity of 96% and specificity of 99%.

 

If persistent disease is detected, unfortunately, her prognosis will be poor. Multiple chemotherapeutic regimens have been tried, with limited results. One study reported that combination of etoposide, doxorubicin and cisplatin with mitotane (Lysodren, Bristol-Myers Squibb) had a response rate of as high as 54%. Most other studies have had much lower success rates.

 

She will be seeing our colleagues in oncology. I hope that we have cured this very pleasant young woman with our initial surgery. We will follow her very closely. If there is evidence of persistent disease, I will also advise her to be seen at a tertiary referral center for additional opinion and the possible option of participation in a clinical trial.

 

From http://www.endocrinetoday.com/blogs.aspx

Tonight! Cushing's interview with Elizabeth. She had pituitary surgery. Listen live at 7:30PM ET or online anytime for archives. Tonight! Cushing's interview with Elizabeth E. She had pituitary surgery. Listen live at 7:30PM ET or go online anytime to listen to archived episodes. http://ping.fm/Z13wM

Cushings Help is almost 9!

It's Our Birthday!

It's unbelievable but the idea for Cushing's Help and Support arrived 9 years ago tonight. I was talking with my dear friend Alice, who runs a wonderful menopause site called Power Surge, wondering why there weren't many support groups online (OR off!) for Cushing's and I wondered if I could start one myself and we decided that I could.

The first website (http://www.cushings-help.com) first went "live" July 21, 2000 and the message boards September 30, 2000. Hopefully, with these sites, I'm going to make some helpful differences in someone else's life!

The message boards are very active and we have weekly online text chats, weekly live interviews, local meetings, email newsletters, a clothing exchange, a Cushing's Awareness Day Forum, podcasts, phone support and much more.

Whenever one of the members of the boards gets into NIH, I try to go to visit them there. Other board members participate in the "Cushie Helper" program where they support others with one-on-one support, doctor/hospital visits, transportation issues and more.

Natural support for your adrenals

Your adrenals are tiny glands that sit atop your kidneys. They are responsible for your "flight" or "fight" instinct. When you are under prolonged stress, your adrenals keep pumping out cortisol and adrenaline. If they continue that process for too long they become depleted and then your immune system, and possibly your thyroid becomes compromised. Hence it is important to take care of these little glands!

 

One of the best ways to care for your adrenals is to get proper rest. Try going to bed at the same time every night, and your adrenals will thank you.

 

Adrenal glands help to regulate blood sugar levels, so reducing the amount of sugar and simple carbs will reduce the amount of stress you put on your glands. Caffeine also compromises your adrenals so it is wise to cut back on that as well.  Try eating organic veggies and fruits, nuts, legumes, complex whole grains, and pasture raised, hormone free meats. Your entire body will benefit from that!

 

How do you know if your adrenals are fatigued? Here are a few symptoms:

Lower back pain and/or knee pain especially on the side
Dark circles under your eyes
Dizziness
A craving for salt or sweets
A feeling of being tired, yet wired
Chronic infections
Low blood sugar

 

You may also want to talk to a healthcare provider about supplementing your diet with B vitamins, Vitamin D, or herbs such as Ashwaganda, or L-Theanine which aid your body in dealing with stress. If you do feel like your suffering from Adrenal Fatigue, definitely talk to your doctor about it as it could adversely affect your thyroid too.

 

From http://www.examiner.com/x-11417-Rochester-Wellness-Examiner~y2009m7d19-Natural-support-for-your-adrenals

Addison's Disease

Medical Codes

---

ICD-9-CM:

255.4 - Disorders of Adrenal Glands, Addisons Disease (Corticoadrenal Insufficiency)

255.5 - Disorders of Adrenal Glands, Other Adrenal Hypofunction; Adrenal Medullary Insufficiency

279.4 - Autoimmune Disease, Not Elsewhere Classified; Autoimmune Disease NOS

 

Definition

Addison's disease (adrenal insufficiency) occurs when the outer layer of the adrenal gland, the cortex, is damaged, causing it to produce insufficient amounts of certain corticosteroid hormones that are essential for life. The three types of corticosteroids are androgens and estrogens, which affect sexual development and reproduction; glucocorticoid hormones such as cortisol, which maintain glucose regulation, suppress immune responses, and provide stress responses; and mineralocorticoid hormones such as aldosterone, which regulate sodium and potassium balance.

Adrenal insufficiency can occur for a variety of reasons. In 70% of cases of primary adrenal insufficiency, the body's immune system attacks and slowly destroys the adrenal glands (autoimmune disease). Tuberculosis, once the most common cause of Addison's disease, is responsible for only about 20% of cases of primary adrenal insufficiency. Since the appearance of acquired immunodeficiency syndrome (AIDS), tuberculosis is once again on the rise and a corresponding increase in Addison's disease caused by tuberculosis is expected. Less common causes of primary adrenal insufficiency include chronic infections, particularly fungal infections and viral infections (cytomegalovirus or CMV) associated with AIDS; amyloidosis; hemorrhage of the adrenal glands; and surgical removal of the adrenal glands. Waterhouse-Friderichsen syndrome is primary adrenal insufficiency that occurs due to adrenal gland hemorrhage during meningococcal infection.

 
In secondary adrenal insufficiency, the adrenal glands are healthy but the body fails to stimulate them to release hormones. This occurs when the pituitary gland, which is located at the base of the brain, fails to secrete adrenocorticotrophic hormone (ACTH), which normally stimulates the adrenal gland to release cortisol. Causes of secondary adrenal insufficiency include long-term use of steroids such as prednisone or surgical removal of pituitary tumors, either cancerous or non-cancerous. Less common causes are loss of blood flow to the pituitary gland, surgical removal of a portion of the pituitary gland, or surgical removal of the area of the brain called the hypothalamus.

 

Risk: Addison's disease tends to run in families. Individuals who take steroids over a long period of time and then develop a severe infection, injury, or undergo a surgical procedure are at increased risk of developing Addison's disease. It is slightly more common among women than men. It can appear at any age but is more often diagnosed in individuals between the ages of 30 and 50 (Odeke). Other conditions that may be associated with adrenal insufficiency include diabetes mellitus, hypoparathyroidism, hypopituitarism, pernicious anemia, testicular dysfunction, Graves' disease, chronic thyroiditis, and myasthenia gravis.

 

Incidence and Prevalence: Addison's syndrome is a rare disorder, with a prevalence of 40 to 60 cases per 1 million people in the US and Europe (Odeke).

 

Diagnosis

History: In most cases of Addison's disease, symptoms appear gradually. Individuals often complain of progressively increasing weakness and fatigue, loss of appetite (anorexia), and unintentional weight loss. Many report dizziness or light-headedness especially when rising from a seated position. Abdominal pain, decreased tolerance to cold, hair loss (alopecia) particularly in women, and cravings for salty foods may also be reported. Nausea, vomiting, and chronic diarrhea occur in about 50% of cases. Women may report that their menstrual cycles have become irregular (dysmenorrhea) or stopped altogether (amenorrhea). Moodiness, irritability, or depression may be evident. In advanced cases, the individual may experience what is known as an Addisonian crisis characterized by abdominal pain; severe vomiting and diarrhea; hypotension; agitation, confusion and loss of consciousness.

 

Physical exam: Findings usually include low blood pressure (hypotension) that may worsen when the individual stands after sitting or lying down (orthostatic hypotension). The individual may be dehydrated. Skin changes are also commonly noted and include freckling and darkening of the skin. The skin darkening may resemble a deep tan but will be present even on parts of the body not exposed to the sun. The skin darkening may also be more visible on scars; pressure points, such as elbows, knees, and toes; lips; mucus membranes; and in skin folds.

 

Tests: The most specific test for Addison's disease is the ACTH stimulation test. In this test, blood is drawn to measure baseline levels of the hormones cortisol and aldosterone. Synthetic ACTH (Cortrosyn, cosyntropin, or Synacthen) is administered intravenously or by intramuscular injection. Blood is drawn again at 30 minutes to measure changes in the cortisol and aldosterone levels. In order to rule out the diagnosis of Addison's disease, there must be an increase in the baseline cortisol value by 7 mcg/dL or more, and the cortisol level must rise to 20 mcg/dL or more in 30 minutes (Odeke). In a healthy individual, the cortisol levels are higher after the injection of synthetic ACTH; in individuals with Addison's disease, there is little or no change in cortisol levels.

If an abnormal result is obtained, a variation of this test in which ACTH is given over a 2 to 3 day period may be conducted. Blood and/or urine samples are collected before and during this 2 to 3 day period. In this longer ACTH stimulation test, the cause of adrenal insufficiency can be determined. Primary adrenal insufficiency results in little or no cortisol production for the entire 72 hour period; secondary adrenal insufficiency, on the other hand, will show an adequate response by the second or third day. Elevated morning ACTH levels confirm a primary adrenal cause.

If the ACTH stimulation test is inconclusive, other tests may be conducted either to help confirm the diagnosis or help rule out other conditions. An insulin-induced hypoglycemia test evaluates the functioning of the pituitary gland and the hypothalamus. In this test, blood sugar (glucose) and cortisol levels are measured and then fast-acting insulin is given. The normal response is for glucose to fall and cortisol to rise, indicating a normal pituitary gland and hypothalamus.

Other blood tests that may prove helpful include a complete metabolic panel (CMP), a complete blood count (CBC) and a thyroid-stimulating hormone level (TSH). Individuals with Addison's disease generally have low sodium and cortisol levels, but high potassium, calcium, blood urea nitrogen (BUN), and creatinine levels. If the individual has not eaten prior to the blood test, there may be low blood sugar (hypoglycemia) and high ACTH levels.

When an autoimmune disease is the cause of adrenal dysfunction, adrenal antibodies may be present in the blood. An abdominal or chest x-ray may help reveal calcium deposits in the adrenal glands—a sign of tuberculosis infection. An abdominal CT may be performed to determine if the adrenal glands are smaller or larger than normal. Small adrenal glands may be a sign of autoimmune adrenal disease and larger than normal adrenal glands may be an indication of hemorrhage or infiltrative disease. Biopsies of the adrenal glands can rule out cancer.

 

Treatment

In the rare instances of Addisonian crisis, potentially life-threatening low blood pressure (hypotension), low blood sugar (hypoglycemia), and high levels of potassium (hyperkalemia) may occur. Individuals experiencing Addisonian crisis require immediate hospitalization. Treatment will include immediate intravenous (IV) or intramuscular (IM) injections of steroids along with saltwater (saline) fluid replacements and sugar (glucose). Oral steroid medications may also be given.

Most cases of Addison's disease, however, do not require inpatient treatment. The goal of therapy is to replace the hormones that the body is not producing. Oral steroid medications are usually a combination of glucocorticoids and mineralocorticoids and are taken for the remainder of the individual's life. The individual is counseled to avoid dehydration by drinking plenty of fluids. An identification and medical instruction bracelet is often advised, and individuals are urged to carry injectable steroid medication for emergency use if medical care is not available.

Individuals with Addison's disease need to recognize the consequences of not closely following their medical regimen. Any stress such as illness, fever, hot and humid weather, profuse sweating, and even emotional stress can precipitate a sudden worsening of the condition and must be met with an increase in replacement hormones. Most individuals with Addison's disease are taught to give themselves an emergency injection of hydrocortisone in times of stress.
If an underlying disease, such as tuberculosis, is responsible, treatment of the underlying disease is important for recovery or resolution of symptoms.

 

Prognosis

With careful management, an individual with Addison's disease can live a full, relatively active life. However, illness, stress, and even general anesthesia for surgery can bring on an adrenal crisis necessitating special care and adjustments in replacement hormone dosages.

Untreated, Addison's disease is a progressive condition that can gradually result in severe abdominal pain, extremely low blood pressure, and kidney failure. Addisonian crisis must be treated immediately or coma and death can occur.

 

Complications

Illness, injury, or any type of stress can result in an Addisonian crisis, a potentially life-threatening condition that is managed with an increase of the hydrocortisone dose.

Other possible complications include extremely high fever (hyperpyrexia), psychotic reactions, accidental overdose of steroid medications and, rarely, a temporary paralysis due to low levels of potassium.

Additional complications related to the individual's underlying disease might also occur and will vary depending upon the particulars of that disease.

 

Return to Work (Restrictions / Accommodations)

In most cases, work accommodations or restrictions are not necessary for individuals with Addison's disease. Taxing physical labor, such as working in hot humid environments or work that carries a great deal of stress, is unsuitable for an individual with Addison's disease. The particulars of the necessary accommodations vary significantly depending on the individual, severity of symptoms, individual's response to treatment, and job requirements.

 

Failure to Recover

If an individual fails to recover within the expected maximum duration period, the reader may wish to consider the following questions to better understand the specifics of an individual's medical case.

 

Regarding diagnosis:

• Was diagnosis of Addison's disease confirmed through an ACTH stimulation test?
• Was the cause of the adrenocortical insufficiency, such as an autoimmune disorder, infection, tumor, or hemorrhage in the adrenal glands identified?
• Were underlying causes also addressed?

Regarding treatment:

• Is individual on oral cortisol with or without fludrocortisone?
• Does current method of treatment appear to be effective?
• Has individual continued to experience any symptoms of adrenal crisis, such as vomiting, diarrhea, fever, confusion, low blood pressure, or dehydration?
• If current treatment is not effective, is individual a candidate for surgery or radiation therapy?
• Is individual on and able to maintain a diet high in fluids, carbohydrates, and protein?
• Would individual benefit from instruction in stress management techniques?
• Does individual wear an identification/medical instruction bracelet?
• Does individual carry injectable steroid medication for use in an emergency if medical care is not available?

Regarding prognosis:

• Were underlying causes, such as autoimmune disorders, infection, tumor, or tuberculosis resolved or brought under control?
• Does individual realize that Addison's disease is a lifelong condition that requires careful management, including avoiding stress and infection?
• Is individual able to adhere to oral therapy and dietary recommendations?
• Does individual attend regular follow-up visits with physician?
• Has individual experienced any complications related to the Addison's disease?
• Does individual have an underlying condition that may impact recovery?

 

Cited References

Odeke, Slyvester, and Steven B. Nagelberg. "Addison Disease." eMedicine. Eds. Daniel Einhorn, et al. 25 Nov. 2003. Medscape. 14 Sep. 2004 http://emedicine.com/med/topic42.htm.

 

From http://www.mdguidelines.com/addisons-disease

Utility of Salivary Cortisol Measurements in Cushing's Syndrome and Adrenal Insufficiency

Hershel Raff PhD*

 

Endocrine Research Laboratory, Aurora St. Luke's Medical Center, Milwaukee, WI 53215; Division of Endocrinology, Metabolism and Clinical Nutrition, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226

 

* To whom correspondence should be addressed. E-mail: hraff@mcw.edu.

 

Context. The measurement of cortisol in saliva is a simple, reproducible, and reliable test to evaluate the normal and disordered control of the hypothalamic-pituitary-adrenal (HPA) axis. There are a variety of simple methods to obtain saliva samples without stress, making this a robust test applicable to many different experimental and clinical situations.

 

Evidence Acquisition. Ovid Medline and PubMed from 1950 to present were searched using the following strategies: [<saliva or salivary>and<cortisol or hydrocortisone>and<Cushing or Cushing's>] and [<saliva or salivary>and<cortisol or hydrocortisone>and<adrenal insufficiency or hypoadrenalism or hypopituitarism or Addison's disease>]. The bibliographies of all relevant citations were evaluated for any additional appropriate citations.

 

Evidence Synthesis. Measurement of an elevated late-night (2300 h – midnight) salivary cortisol has a >90% sensitivity and specificity for the diagnosis of endogenous Cushing's syndrome. Late-night salivary cortisol measurements are also useful to monitor patients for remission and/or recurrence after pituitary surgery for Cushing's disease. Because it is a surrogate for plasma free cortisol, the measurement of salivary cortisol may be useful during an ACTH stimulation test in patients with increased plasma binding protein concentrations due to increased estrogen, or decreased plasma binding protein concentrations during critical illness. Most reference laboratories now offer salivary cortisol testing.

 

Conclusions. It is expected that the use of the measurement of salivary cortisol will become routine in the evaluation of patients with disorders of the HPA axis.

 

From http://jcem.endojournals.org/cgi/content/abstract/jc.2009-1166v1

From 1960...

The Candidates' Health

RECOVERING from his heart attack and his ileitis surgery, President Eisenhower set a precedent in the 1956 election campaign by frankly discussing the state of his health. Last week the Democrats picked up "the health issue" and were playing hard politics with it among themselves. Jack Kennedy began the intramural scrap by declaring that the presidency demands "the strength and health and vigor of ... young men." Supporters of Lyndon Johnson leaped to the conclusion that Kennedy was making a not-so-subtle allusion to L.B.J.'s 1955 heart attack. "Citizens-for-Johnson" Director John B. Connally countercharged that Kennedy secretly suffers from Addison's disease, an incurable but now controllable deficiency of adrenal secretions. And Johnson-lining India Edwards, former vice chairman of the Democratic National Committee, said: "Doctors have told me that [Kennedy] would not be alive were it not for cortisone."

 

The medical facts:

 

Jack Kennedy, 43, says that he did have a "partial adrenal insufficiency." He laid it to a war-born case of malaria, which itself required treatment through 1949. To supplement adrenal output, Kennedy took regular doses of cortisone from 1947 to 1951 and again from 1955 to 1958. He still takes oral doses of corticosteroids (cortisone-type medication) "frequently, when I have worked hard," although a recent test showed his adrenals to be functioning normally. Whether his is an arrested case of Addison's disease or a borderline adrenal insufficiency is unclear. In two years of almost ceaseless campaigning, Kennedy has displayed remarkable energy and none of the classic symptoms of advanced Addison's disease: chronic fatigue, weight loss, low blood pressure, anemia, or a bronzelike darkening of the skin.

 

Kennedy's earlier medical history is complex. Severe and recurring jaundice forced him to leave Princeton during his freshman year (when his health improved, he later went to Harvard). The Army rejected him because of a football injury to his back, but the Navy accepted him. The back was reinjured when a Japanese destroyer knifed through Lieut. Kennedy's PT boat in 1943. He spent most of 1944 in a Navy hospital, underwent a spinal disk operation, which was not fully successful. As a consequence, in October 1954, surgeons performed a delicate fusion of spinal disks. Slow to heal and set back by relapses that were complicated by the adrenal shortage, his condition became so grave that his family was summoned to his bedside. He had a third spinal operation the following February to remove a metal plate. Last rites were administered. But this time, after two weeks abed, recovery was rapid. Total time spent in the hospital or convalescing: seven months. Today, the only vestige of the spinal problem is that he still sleeps on a board, wears a light corset. Last week, at Kennedy's request, his two Manhattan physicians reported: "Your health is excellent."

 

http://www.time.com/time/magazine/article/0,9171,869575,00.html

RT @ePatientDave: What's wrong w this picture? The event "Putting patients first" has no patients on the panels http://ping.fm/lnuyV

NIH Clinical Trials of interest to Cushing's patients updated http://ping.fm/Gmjzd

(Adrenal) UHCG surgeons taught rare surgical procedure

Niamh Mullen

niamh.mullen@imt.ie

 

A world-renowned specialist in minimally invasive surgery visited Ireland last week to perform a procedure that has never been done here before.

 

Prof Martin Walz of the University Hospital of Essen in Germany came to University College Hospital Galway (UCHG) to carry out a laparoscopic retroperitoneal adrenalectomy on three Irish patients.

 

Following the visit, it is hoped the procedure will be performed at UCGH by consultant in general and vascular surgery, Dr Denis Quill. Senior registrar in general and vascular surgery at UCHG, Dr Ilyas Sadiq, said the procedure was so rare it was not done in most countries, but Prof Walz has travelled the world demonstrating it. The laparoscopic procedure is now regarded as the gold standard for resecting most adrenal tumours. It is used to treat pheochromocytoma, Conn’s syndrome and Cushing’s syndrome.

“This is an under-diagnosed problem in the community. It could affect five per cent of people,” said Dr Sadiq.

 

From http://www.imt.ie/news/2009/07/uhcg_surgeons_taught_rare_surg.html

Biopsy of adrenal masses

Posted by Thomas Repas, DO, FACP, FACE, CDE  July 6, 2009 11:52 AM

 

We received an urgent consult request this week to see a young woman with an adrenal mass.

 

She had rapid onset of weight gain, increased hunger, purple striae, increased abdominal girth and mood changes for the last three months. Her primary care provider was concerned but did not know what the explanation was. He ordered extensive testing without finding any obvious abnormality. Echocardiogram, thyroid and other laboratory studies were negative.

 

She had urinary retention and was sent to urology. Renal ultrasound was negative. The patient requested to have a CT which identified a heterogeneous 9.0-cm left adrenal mass. The patient subsequently underwent an adrenal biopsy. She tolerated the procedure well and without hemodynamic instability. However, the results were non-diagnostic. She was then sent to see me.

 

Expert guidelines advise against adrenal biopsy in the routine evaluation of adrenal masses. There are several reasons.

 

First, adrenal biopsy has not been shown to reliably distinguish between benign or malignant adrenocortical masses. If an adrenal mass is large and/or functional, then it should be resected. Adrenal biopsy does not change one’s management in either of those circumstances.

 

Second, there have been reports of adrenal carcinoma seeding along the biopsy needle track.

 

Finally, if a pheochromocytoma were inadvertently biopsied, the consequences could be catastrophic, even fatal.

 

The only situation where adrenal biopsy is useful is a patient with known or highly suspected other primary malignancy which may have metastasized to the adrenal.

 

Despite guidelines to the contrary, I continue to see adrenal masses biopsied prior to coming to see me. Often, as was the case with this woman, the adrenal biopsy occurs before biochemical evaluation has been completed. I have seen two cases with serious complications when the adrenal mass turned out to be pheochromocytoma. If I had been asked prior to the biopsy, I would have advised them not to do it and proceed with biochemical evaluation instead.

 

This woman clearly has Cushing’s syndrome. Her adrenocorticotropic hormone was undetectable, and her 24-hour urine-free cortisol was one of the highest I have ever seen: 1,095 ug/24 hours (upper limits of normal 45). There was no evidence of pheochromocytoma or hyperaldosteronism but dehydroepiandrosterone sulfate was elevated. The rapid onset of symptoms, large tumor size, imaging characteristics and evidence of secretion of more than one adrenal hormone concern me greatly for adrenocortical carcinoma. She will be undergoing surgical resection next week.

 

I know this is a recurring theme in my posts, but I will make this observation yet again: Why is it that the endocrinologist is so often the last subspecialist to see a patient, including the patient with obvious endocrine disease?

For more information:

• Mazzaglia PJ. Arch Surg. 2009;144(5):465-470.
• Mansmann G. Endocr Rev. 2004;25:309-340.
• NIH Statement on management of the clinically inapparent adrenal mass. 2002 Feb 4-6;19(2):1-23. http://consensus.nih.gov/2002/2002AdrenalIncidentalomasos021PDF.pdf

From http://www.endocrinetoday.com/comments.aspx?rid=41362

6 new and updated Cushing's bios added. dx include 3 pituitary, 3 undiagnosed http://ping.fm/mENWm

Cushing's locations page updated, 4 new people added. http://ping.fm/SwH93

Froedtert, medical college open specialty clinic

Froedtert & The Medical College of Wisconsin have opened a new clinic specializing in endocrine and metabolic conditions such as diabetes, obesity and thyroid disorders.

 

The clinic, located in the St. Francis Medical Arts Pavilion, 2025 W. Oklahoma Ave., opened in April.

 

Medical College endocrinologists Dr. Bradley Javorsky and Dr. Ty Carroll practice at the clinic from 1 p.m. to 5 p.m. Wednesdays and 8 a.m. to noon Thursdays.

 

Both physicians treat medical conditions including adrenal and pituitary gland disorders, cholesterol and lipid issues, Cushing’s disease, diabetes, hypoglycemia, osteoporosis, polycystic ovarian syndrome, obesity, thyroid disorders and thyroid cancer.

“Endocrine and metabolic disorders are usually complex, chronic conditions that should be carefully managed,” said Dr. James Findling, a Medical College endocrinologist and professor who heads the college’s community division of endocrinology. “Our new clinic gives residents of Milwaukee’s southern communities easy access to this specialized expertise.”

 

From http://www.bizjournals.com/milwaukee/stories/2009/07/06/daily5.html

Happy Fourth of July!

 

 

 

 

 

Adrenal Testing and Treatment

In the first two newsletters in this series, we discussed the following:
• The endocrine system and how it is composed of glands throughout the body that  release hormones (chemical messengers) into the bloodstream or the fluid surrounding cells. These hormones activate receptors and either alter the cell's existing proteins or instruct the cell in the building of new proteins that create actions in the body.

• The importance of the hypothalamus and the pituitary gland and how these two glands control the two adrenal glands--the HPA axis as it is called, and control the thyroid; 

• Each adrenal gland has two parts, the adrenal cortex and the adrenal medulla and the purpose of each;

• The symptoms of adrenal problems and how many of them are similar to symptoms created by problems in the thyroid and other endocrine glands;

• The primary purpose of the adrenal glands, and the entire endocrine system, is to keep the body in a balanced condition called homeostasis;

• The purpose of cortisol and the problems created when cortisol levels are too high or too low;

• How the adrenals can create hypoglycemia, where blood sugar levels are lower than normal;

• How the adrenals affect fatigue, insomnia and obesity;

• How the adrenals affect proper hydration of the body.

Here are links to the first two articles in the series. (http://media.novusdetox.com/dependence.php?include=139775, http://media.novusdetox.com/dependence.php?include=139840)

   In this newsletter we will look at the tests used to determine adrenal problems and the most common treatments.

TESTS
   If you go to most doctors and say that you are suffering from insomnia, fatigue, hypoglycemia, weight gain and other symptoms of adrenal problems and ask for an adrenal test, most doctors will likely tell you that you need to just take this or that pill and go on a diet.  This is always true of Radio Medicine Doctors because they just want to turn up the volume and drown out the symptoms and not treat the cause.
   If you persist and demand that they test your adrenals, then they likely will do tests to determine if you have Addison's disease or Cushing's syndrome—diseases where you either have the lowest or highest amounts of cortisol. 
   First, we will look at the worst cases of adrenal problems and then the more common adrenal problems that affect the majority of us to a greater or lesser extent.

ADDISON'S DISEASE
   Addison's disease occurs when the adrenal glands do not produce enough cortisol and, in some cases, aldosterone. This disease is also called adrenal insufficiency, hypoadrenia (“hypo”=low and “ism” =condition of) or hypocortisolism.
According to the National Institute of Health:
• Addison's disease affects about 1 in 100,000 people;

• Adrenal insufficiency occurs when at least 90 percent of the adrenal cortex has been destroyed and no cortisol is being produced.

ADDISON'S DISEASE TESTS
   Two of the common tests used to diagnose Addison's disease are:
• ACTH Stimulation Test - where ACTH is released by the pituitary gland to signal the adrenals to produce more cortisol.  The ACTH Test usually measures the levels of  blood cortisol, urine cortisol before and after a synthetic form of ACTH is given by injection.  If the adrenals are functioning properly, there is an increase in blood and urine cortisol levels and the amount of the increase tells doctors about the extent of the adrenal problem.
• CRH Stimulation Test - if the ACTH test is abnormal, a CRH (cortisol releasing hormone from the hypothalamus) stimulation test is used to determine the cause of adrenal insufficiency.  Synthetic CRH is injected intravenously and blood cortisol is measured before and 30, 60, 90, and 120 minutes after the injection. If there is no ACTH response, this indicates the problem may be the pituitary gland.  If there is a delayed ACTH response, the hypothalamus may be the cause.

ADDISON'S DISEASE TREATMENT
   Treatment of Addison's disease requires replacement of the missing cortisol or replacement of the missing aldosterone. 

CUSHING’S SYNDROME
   Cushing’s syndrome or hypercortisolism (“hyper”=high and “ism” =condition of) is diagnosed when there is a high level of cortisol for a long period of time.   According to the National Institute of Health, Cushing’s syndrome is relatively rare and most commonly affects:
• Adults aged 20 to 50;
• People who are obese and have type 2 diabetes.
   Because of the dangerous effects of elevated cortisol levels, this is why people who take prednisone (a synthetic form of cortisone that is used in the treatment of rheumatoid arthritis and other inflammatory diseases) or any other form of cortisol should carefully monitor their cortisol levels. 

CUSHING’S SYNDROME TESTS
   Some of the common tests used to diagnose Cushing’s syndrome are:
• 24-hour urinary free cortisol test where urine is collected over a 24 hour period and tested for cortisol;

• Measurement of midnight plasma cortisol where blood tests to show the level of cortisol at night (when it should be lower at midnight)

• Late-night salivary cortisol where a saliva test is used to determine the level of cortisol at night;

• Giving high or low doses of synthetic cortisol and then checking the urine to see  if there is a drop in blood and urine cortisol levels;

• CRH stimulation test described above.

Cushing’s Syndrome Treatment
   While the treatment will depend on the cause for the high cortisol levels, some of the traditional options are:
• Surgery;
• Radiation
• Chemotherapy;
• Cortisol-inhibiting drugs.

ADRENAL FATIGUE
   As we have learned, your adrenals can be causing problems but you do not have Addison's disease or Cushing's syndrome.  Therefore, if you don't have either disease, most doctors don't really address adrenal fatigue—where your adrenals are just not working properly. What if you are experiencing some or all of these symptoms:
• Fatigue
• Have trouble sleeping
• Anxiety
• Sudden weight gain
• Libido is lessened
• Salt cravings

THE SOLUTION--ALTERNATIVE MEDICINE DOCTORS
   As we have advised in previous newsletters, it is recommended that you find a doctor who will actually spend the time to find out the physiological cause of your symptoms and treat them.  Since the symptoms listed above can be caused by problems with other glands, the doctor will likely have you do a complete set of tests on your most important hormones. 

SALIVA CORTISOL TEST
   This test measures the cortisol levels at least four times during the day, because cortisol levels are supposed to be highest in the morning and start declining until about midnight and then start rising again.  The person uses a small tube to collect the saliva, marks the time and then at set times during the rest of the day and evening the person again spits in a new tube and marks the time.  If the person is feeling more fatigued at certain times of the day, then some doctors will also have the saliva test done when they feel fatigued.  The saliva samples are then sent to a lab and the cortisol levels for the testing period are shown. 
   Using this information, the doctor can then advise you as to whether you have adrenal fatigue.

TREATMENT OF ADRENAL FATIGUE
   While many doctors are quick to prescribe drugs to address any type of adrenal problem, most alternative medicine doctors will try to use a non-pharmaceutical approach.  Here are some of the things that are outlined in Adrenal Fatigue by Dr. James Wilson:
• Do relaxation exercises
• Adjust your sleeping hours
• Physical exercise
• Change your eating times and habits
   ◦ 40% raw or lightly cooked vegetables
   ◦ 30% whole grains
   ◦ 15% beans, seeds and nuts
   ◦ 10% animal foods
   ◦ 5% fruits
• Supplements
   ◦ Vitamin C
   ◦ Magnesium (particularly if you crave chocolate)
   ◦ Vitamin E
   ◦ B vitamins
   ◦ Calcium
   ◦ Fiber
   ◦ Certain herbs

DR. BRENT AGIN'S TREATMENT FOR ADRENAL FATIGUE
   Dr. Agin is  Novus Medical Detox Center's medical director.   In addition to advising on diet changes and on many of the things recommended by Dr. Wilson, Dr. Agin has developed injectable (intra-muscular) vitamins, minerals and herbs that will help provide the support that the adrenals need to recover.  Dr. Agin believes that injecting these supplements directly will ensure that more is actually converted and used by the body.  The following are the supplements that Dr. Agin's research has indicated are needed to help the adrenals recover:
Vitamin C – 2,000-4,000 mg per day (supports the adrenals and improves immune function)
B-Complex - which includes the following:
• B5 - (Pantothenic acid) 1,000-1,500 mg per day
• B6 -  50-100 mg daily
• B3 - 75-125 mg daily
• B12 - 200-400 mcg daily
Minerals:
• Chromium
Herbal support:
• Licorice Root   (not the candy!)- This is well known for supporting the adrenals. It has calming properties along with an ability to increase endurance and energy. It can be taken as a tea, capsule or liquid(in rare cases if large amounts are ingested it can increase the blood pressure).

• Ashwaganda Root- This is considered an adaptogen.  An adaptogen is an herb that  will help normalize cortisol levels. If there is too much cortisol, it will lower the level, if the level is too low, it will help to increase it.

• Siberian Ginseng- This root helps to uphold and revive adrenal function along with increasing the body’s resistance to stress and normalizing the metabolism. It has antidepressant properties and promotes calmness and a sense of well being.  It has  been shown to stimulate antibodies to help fight off viruses and harmful bacteria. It also aids in the absorption of B vitamins.  (This root usually helps to normalize blood pressure, but if someone has very high blood pressure, then it would still be best to avoid it.)

• Ginkgo- When the adrenals are under a lot of stress, there is an increase in the number of free radicals and if not neutralized, then there is increased risk to the immune system. Ginkgo is a powerful antioxidant along with other supplements that are believed to help counteract the free radicals.
   In some cases, Dr. Agin will prescribe additional injectable supplements.  The shots are painless and easy to give to yourself.  If you are interested in more data about Dr. Agin's injectable products, please email us.

CONCLUSION
   At Novus Medical Detox Center, we are very proud that we help people who have become dependent or addicted to substances like OxyContin, methadone, Vicodin, Percocet, heroin, and psychoactive drugs like Xanax and Zoloft and to people who have become addicted to alcohol. 
   Please call us if we can help someone that you know.
NOTE: This information is provided for general educational purposes only and is not intended to constitute (i) medical advice or counseling, (ii) the practice of medicine, health care diagnosis or treatment, or (iii) the creation of a physician patient or clinical relationship.  If you have or suspect that you have a medical problem or that this information may be useful to you or others, please consult with your health care provider before applying any information from our articles to your personal situation or to the personal situation of others.
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From http://media.novusdetox.com/dependence.php?include=139924