Thursday, December 30, 2010

Overactive Adrenal Glands

Adrenal glands are small glands located just on top of a person’s kidneys. These glands are just one of the many glands found in the endocrine system. Sometimes, these glands generate excessive amounts of hormones such as androgenic steroids, corticosteroids and aldosterone. They are then referred to as overactive adrenal glands, a condition also called Cushing's syndrome.

Here are some of the most common signs and symptoms of overactive adrenal glands:
1. Weight gain
One of the primary signs of Cushing’s syndrome is weight gain. A common sign of this condition is your face becoming rounder or more moon-shaped. In some cases, there will also be obesity in the upper body, particularly the upper back and the midsection. You may also begin to gain fat around the neck area.

2. Fragility
While you may be generally gaining weight, you will also experience a general thinning in both your arms and legs. Your fragile skin means that you may bruise easily and be more prone to sores and infection. Healing of bites and wounds take longer than usual. Acne breakouts might occur more frequently.

Red or purple stretch marks tend to develop on your buttocks, stomach, breasts, arms and thighs. In response to overactive adrenal glands, you will also probably experience severe fatigue, feeling very weak and tired most of the time. You may also feel muscle and bone weakness.

3. Reproductive system irregularities
Secreting hormones is just one function of the adrenal glands. Cushing’s syndrome can affect the sexual life and reproductive systems of both men and women. There may be a lower sex drive between both genders. Men may feel a drop in libido, as well as a decrease in fertility.  Women, on the other hand, may experience either irregular menstruation periods or may even stop menstruating. Other women may grow excessive amounts of hair on both the legs and face.

4. Psychological signs
Some individuals with overactive adrenal glands display psychological signs and symptoms. Increased irritability, depression and anxiety are common emotions in people with this condition. These emotions may be displayed for no particular reason. This tends to be an effect of a hormonal imbalance that you are probably experiencing.

Treatment for overactive adrenal glands depends on several factors, including the person’s overall health and medical history.

At times, Cushing’s syndrome can be the result of various medical conditions, such as tumors that have grown on the adrenal or pituitary glands. Remember that the symptoms and signs of overactive adrenal glands vary per person, as well as by the extent to which the glands malfunction. Of course, these signs and symptoms may resemble other medical problems and conditions. It would be best to consult with a medical professional immediately.



Friday, December 24, 2010

Happy Holidays!


No matter what your beliefs may be,
we wish the very best holiday season,
full of family, friends and better health.

Wednesday, December 01, 2010

Successful treatment of Lt. Adrenocortical Tumor or Cushing's syndrome

Successful treatment of Lt. Adrenocortical Tumor or Cushing's syndrome (+ Enlarge)

Mohini Nayak the two year old female child was brought to Apollo Hospital with H/O gaining excessive weight and became obese since 1 yr. She was treated by different doctors in multiple hospitals in Bhubaneswar and Cuttack. After investigation in S.C.B. Medical College, Cuttack, it was found that the baby is suffering from Lt. Adrenocortical Tumour. Cushing Syndrome in Pediatric age group, particularly less than 2 years old child is a very rare condition, the incidence being 0.3 – 0.4 in one million child below 15yrs of age. Cushing’s syndrome may occur either due to Pituitary tumor or Adreno cortical tumor, said Dr. B N Mishra, Sr. Pediatric Surgeon, Apollo Hosipitals, Bhubaneswar. The baby had adreno cortical; tumor on left side, informed Dr. Mishra. Adrenal glands are present in our body just above and adjacent (Superiorly) to kidneys on both sides.

She had a very large tumor of left adrenal gland of size 10x6x3 cm size and such type of large tumors is usually malignant and rarely seen. However the biopsy does not show features of malignancy, but needs to be observed for a long time. Dr. Mishra informed that, her obesity will take time to reduce, may be six months to one year. Mohini got admitted on 12th November 2010.

Mohini comes from a very low socio-economic status. The child is the youngest of the three siblings and her parents in spite of their poverty tried their limited resources to provide the best medical treatment. Hopeless slum dwellers finally had a smile. Victory of life over death prevailed. Ashok Naik a low paid sweeper and his wife Jyotsna a domestic help sacrificed what ever little earning they did to save their youngest girl child of 2 years old, Mohini.

The girl became about 20kg within 1 year 2months. Finally parents lost all hope. Some couple of weeks back the heart touching story of the girl and her parents, featured in a local daily. The story dragged few social activists of Lions Club Bhubaneswar met the parent and resolved to take an attempt. After initial checkup, Apollo decided for operation with financial assistance from corporate houses and government of odisha.

It was risky and expensive. A group of expert doctors led by Dr. B.N. Mishra successfully operated the massive tumor after a long operation of three hours. The baby is now free of danger.


Thursday, November 18, 2010

Corticotrophin-releasing factor mediates hypophagia after adrenalectomy, increasing meal-related satiety responses

Ernane Torres Uchoa, Lilian Eslaine Costa Mendes da Silva, Margaret de Castro, Jose Antunes-Rodrigues and Lucila Leico K. Elias

a Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Brazil

b Department of Internal Medicine, School of Medicine of Ribeirao Preto, University of Sao Paulo, Brazil


Adrenalectomy-induced hypophagia is associated with increased satiety-related responses, which involve neuronal activation of the nucleus of the solitary tract (NTS). Besides its effects on the pituitary–adrenal axis, corticotrophin-releasing factor (CRF) has been shown to play an important role in feeding behaviour, as it possesses anorexigenic effects. We evaluated feeding-induced CRF mRNA expression in the paraventricular nucleus (PVN) and the effects of pretreatment with CRF2 receptor antagonist (Antisauvagine-30, AS30) on food intake and activation of NTS neurons in response to feeding in adrenalectomised (ADX) rats.


Compared to the sham group, ADX increased CRF mRNA levels in the PVN of fasted animals, which was further augmented by refeeding. AS30 treatment did not affect food intake in the sham and ADX + corticosterone (B) groups; however, it reversed hypophagia in the ADX group. In vehicle-pretreated animals, refeeding increased the number of Fos and Fos/TH-immunoreactive neurons in the NTS in the sham, ADX and ADX + B groups, with the highest number of neurons in the ADX animals. Similarly to its effect on food intake, pretreatment with AS30 in the ADX group also reversed the increased activation of NTS neurons induced by refeeding while having no effect in the sham and ADX + B animals. The present results show that adrenalectomy induces an increase in CRF mRNA expression in the PVN potentiated by feeding and that CRF2 receptor antagonist abolishes the anorexigenic effect and the increased activation of NTS induced by feeding in the ADX animals. These data indicate that increased activity of PVN CRF neurons modulates brainstem satiety-related responses, contributing to hypophagia after adrenalectomy.

Research Highlights

►Primary adrenal insufficiency increases meal-related satiety responses.

►Adrenalectomy-induced hypophagia is associated with increased CRF mRNA expression in the hypothalamic paraventricular nucleus (PVN) and increased NTS neuron activation in the brainstem. ►The increased activity of PVN CRF neurons modulates brainstem satiety-related responses. ►CRF type 2 receptor mediates CRF suppressing effect on food intake after adrenalectomy.

Keywords: Glucocorticoids; Food intake; Corticotrophin-releasing factor; Paraventricular nucleus of the hypothalamus; Nucleus of the solitary tract

Article Outline
Experimental procedures
Intracerebroventricular (icv) surgery
Perfusion, tissue preparation and immunohistochemistry
Microdissection, total RNA isolation and quantitative real-time PCR
Experimental protocols
Experiment 1: effects of ADX and B replacement on CRF mRNA expression in the PVN in the fasting–refeeding regimen
Experiment 2: effects of pretreatment with CRF2 receptor antagonist on food intake in sham, ADX and ADX + B animals
Experiment 3: effects of pretreatment with CRF2 receptor antagonist on NTS neuron activation in sham, ADX and ADX + B animals in the fasting–refeeding regimen
Statistical analysis
Experiment 1: effects of ADX and B replacement on CRF mRNA expression in the PVN in the fasting–refeeding regimen
Experiment 2: effects of pretreatment with CRF2 receptor antagonist on food intake in sham, ADX and ADX + B animals
Experiment 3: effects of pretreatment with CRF2 receptor antagonist on NTS neuron activation in sham, ADX and ADX + B animals in the fasting–refeeding regimen

Thumbnail image

Fig. 1.

Relative CRF mRNA expression in the PVN of fasted and refed sham, ADX and ADX + B animals (n = 5–8 rats/group). Data are shown as mean ± SEM. *P < 0.05.

View Within Article

Thumbnail image

Fig. 2.

Food intake (g/100 g) after 4 h of refeeding (n = 5–7 rats/group) for sham, ADX and ADX + B animals pretreated with vehicle or d-Phe11,His12-Sauvagine 11–40 (Antisauvagine-30, AS30; 5 μg/5 μL icv). Data are shown as mean ± SEM. *P < 0.05.

View Within Article

Thumbnail image

Fig. 3.

Number of Fos-immunoreactive (A) and Fos/TH-immunoreactive (B) neurons in the NTS (n = 4–8 rats/group) of fasted and refed sham, ADX and ADX + B animals pretreated with vehicle or d-Phe11,His12-Sauvagine 11–40 (Antisauvagine-30, AS30; 5 μg/5 μL icv). Data are shown as mean ± SEM. ND: not detectable. *P < 0.05 vs. respective fasted group. #P < 0.05 vs. refed sham/vehicle, refed ADX + B/vehicle and refed ADX/AS30 groups.

View Within Article

Thumbnail image

Fig. 4.

Representative photomicrographs (40× magnification) of coronal sections showing Fos/TH immunoreactivity in the NTS of refed sham, ADX and ADX + B animals pretreated with vehicle or d-Phe11,His12-Sauvagine 11–40 (Antisauvagine-30, AS30; 5 μg/5 μL icv). Each inset depicts at 20× magnification the area where the photomicrograph was taken. Scale bar, 100 μm.

View Within Article

Table 1. Number (means ± SEM) of TH-immunoreactive neurons and percentage of Fos/TH double labelled neurons in the NTS of fasted and refed sham, ADX, and ADX + B animals, pretreated with vehicle or AS30. View table in article

Data are expressed as means ± SEM (n = 4–8 rats/group). NTS, nucleus of the solitary tract; TH, tyrosine hydroxylase.

a P < 0.05 vs. respective fasted group.
b P < 0.05 vs. refed sham/vehicle, refed ADX + B/vehicle and refed ADX/AS30 groups.

View Within Article

Corresponding Author Contact InformationCorresponding author. Avenida Bandeirantes, 3900, 14049-900 Ribeirao Preto, Sao Paulo, Brazil. Fax: +55 16 3633 0017.

Hormones and Behavior
Volume 58, Issue 5, November 2010, Pages 714-719


Tuesday, November 16, 2010

Unilateral adrenalectomy improves urinary protein excretion but does not abolish its relationship to sodium excretion in patients with aldosterone-producing adenoma

E Pimenta, R D Gordon, A H Ahmed, D Cowley, D Robson, C Kogovsek and M Stowasser



Experimental and human data suggest that adverse cardiovascular (CV) and renal effects of aldosterone excess are dependent on concomitant dietary salt intake.

Increased urinary protein (Uprot) is an early sign of nephropathy independently associated with CV risk. We have previously reported a positive association between Uprot and urinary sodium (UNa) in patients with hyperaldosteronism, but not in patients with normal aldosterone levels.


We aimed to determine whether Uprot is related to UNa in patients with aldosterone-producing adenoma (APA) and whether the degree of Uprot and strength of this relationship is reduced following correction of hyperaldosteronism. Subjects with APA (n=24) underwent measurement of 24 h Uprot and UNa before and after unilateral adrenalectomy (follow-up 15.0±11.9 months).


Following surgery, mean clinic systolic blood pressure fell (150.4±18.2 vs 134.5±14.5 mm Hg, P=0.0008), despite a reduction in number of antihypertensive medications, and Uprot (211.2±101.6 vs 106.0±41.8 mg per day, P<0.0001) decreased. There was a positive correlation between Uprot and UNa both before (r=0.5477, P=0.0056) and after (r=0.5097, P=0.0109) adrenalectomy. Changes in UNa independently predicted Uprot reduction (P=0.0189).


These findings suggest that both aldosterone levels and dietary salt contribute to renal damage, and that once glomerular damage occurs it is not completely resolved following correction of hyperaldosteronism. Our study suggests that treatment strategies based on reduction of aldosterone effects, by adrenalectomy or mineralocorticoid receptor blockade, in conjunction with low-salt diet would provide additional target-organ protection in patients with primary aldosteronism.



Saturday, November 13, 2010

Adrenal Crisis Tips

From Ellen, on the Cushing's Help Message Boards

I have a very good friend who has had more adrenal crises than anyone care to count (more than 20). She has tried hard to teach me some important things for the day I should ever have a crisis. Among them is the reality that (as before surgery) success of your care depends on YOU getting everything prepared for the worst as best you can. We can no more depend on the ER staff than any other doc out there who isn't a specialist in pituitary medicine. You all have already done much of preparing by having your medic alert bracelets on, your injectable Cortef (bring it with you in case they don't have it there) and your letter from Dr. F. But that isn't enough much of the time as you have painfully discovered.

1) Prevention is the key. You, Mary, are SO overdoing it, I don't know what to say. You shouldn't even be leaving your house right now, let alone taking on the care of small children. You need a good talking to, missy. Perhaps you can choose to do ONE easy task a day but overall-you should be bored out of your gourd sitting on your tuckus. The more you do, the more you risk events like this. The hardest part is understanding that recovery is not a linear improvement every day. You are going to have weeks or maybe months where you can do no more than you did the first week after surgery. This recovery takes a long time when surgery works. Each tiny task you accomplish depletes you in an additive way. It might not have seemed much at the time to unload the dishwasher but you better believe it counts when you add in each additional task you want to accomplish.

2) Everything is additive. It isn't just what you did today but also what you did the last three, four or five days. You may have felt good the first day but each successive day my guess is you could feel your body pushing a bit. I find I say things like, "If I could just get this ONE more job done, then I will rest" before I am off to the next job. Before I know it, it is too late. Think hard about the twinges you feel the days before this happened this time around, when you were tired. How do you feel in the evenings after a day of activity? Those are the signs to look for and treat early the next time. You are having to listen to your body in a whole new way. Learn your earliest signs.

3) Take more Cortef when you first get those twinges above--the days before a crisis might strike.

4) Everyone in your household needs to be trained to give you Cortef. Teach them that confusion on your part indicates a crisis coming on-if you aren't making sense they need to understand that YOU are not able to help yourself. In most cases the oral cortef will keep you out of the ER if someone else makes sure you take it. Don't hesitate, don't let yourself talk them out of helping you-just take it-it is better to err high than low with your history of crises right now.

5) Knowing that in spite of all of this you need ER care potentially, consider calling the liason in person and talking real-time about your needs for future visits-explaining how quickly things become life threatening. They need to have something about your history in the computer already-a copy of that letter from Dr. F plus their own notes that it is on the up and up along with the note to please page your doctor. Give them a recipe to follow that they have pre-approved and it will help greatly. Most ER doctors will never see an adrenal crisis patient in their ER. Doctors have limits on their abilities just as everyone else does. I can read English really well but if you handed me a book written by someone in 1610, I would likely take longer to get through it because I am not as familiar with the format...the 'wherefore art thous' are English but they sure slow you down. That is what happens in the ER to Addisonians...doctors eventually get there but it takes longer because it is unfamiliar. Help them out by giving them the Cliff-Notes before you ever get there.

5A) Also insist that for now they order and keep Solu-Cortef on the shelves for you. Many (most?) hospitals do NOT have it stocked, as my friend discovered over and over again when she went to the ER. It took hours for them to track some down and give it to her. In the meantime, she was getting sicker and sicker. She finally asked the liason to help be certain they had it for her, ready to go. Now, they have it ready for her, they know her and they know what to do. She is often out of there in about 3 hours.

6) If you are vomiting/collapsed clearly in serious trouble, by the time you head off to the ER, call 911/ambulance so you get taken in and cared for without waiting. Your life is at risk by that stage and you need immediate care. It is justified and potentially life-saving.

7) Always have a trained advocate with you, have several back ups in your life. My friend has her husband but she also has me ready to go-have the hospital list several people to call ahead of time in case you arrive on your own and they can't reach your primary person. Your advocates need to know what to do independently of you. They need to know what to say and how to push the ER staff to get things done on your behalf. We, as patients struggling with Cushing's, are used to having to push but most people are very intimidated by medical personnel and often hang back, figuring they must know what to do. Make sure they understand this just isn't the case sometimes and that your life may depend on what they say or get the staff to do. It is critical they contact your endocrinologist-have your advocate INSIST they do this. If they won't, have your advocate page the doctor for you. Be sure you go over a plan with your advocate periodically or answer their questions about what may happen. I went over much of my plan with my husband prior to my surgery but discovered that within days of surgery, he had forgotten most of what I said. He really wanted to help but just hadn't taken in the medical stuff because it was overwhelming and scary. Keep going over it until they are comfortable.

I really hope these are the last ER visits for you all. I have agonized each time my friend goes into another crisis. I know that in spite of everything you do (or don't do) to prevent a crisis, they still happen. Hopefully the next time around, everything will be in place for you all to have a smooth experience.

So, sit down, turn on that television and get comfy girls. TAKE IT EASY!!

Monday, November 08, 2010

A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials of DHEA Treatment Effects on Quality of Life in Women with Adrenal Insufficiency

Aziz A. Alkatib, Mihaela Cosma, Mohamed B. Elamin, Dana Erickson, Brian A. Swiglo, Patricia J. Erwin, and Victor M. Montori*

Department of Medicine (A.A.A.), Knowledge and Encounter Research Unit (A.A.A., M.C., M.B.E., D.E., B.A.S., P.J.E., V.M.M.), Mayo Clinic Libraries (P.J.E.), and Division of Endocrinology, Diabetes, Metabolism, and Nutrition (M.C., D.E., B.A.S., V.M.M.), Mayo Clinic, Rochester, Minnesota 55905

* To whom correspondence should be addressed. E-mail:


Context: Women with primary or secondary adrenal insufficiency report a decreased health-related quality of life (HRQOL) despite traditional adrenal replacement therapy. Dehydroepiandrosterone (DHEA) has been studied as an agent to improve HRQOL in these patients.


Objective: We sought to conduct a systematic review and meta-analysis of randomized controlled trials of DHEA effects on HRQOL in women with adrenal insufficiency.

Data Sources: We searched electronic databases (MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science, CINAHL, and PsycInfo) and reference lists of eligible studies through July 2008.


Study Selection: Eligible trials randomly assigned women with primary or secondary adrenal insufficiency to either DHEA or control and measured the effect of treatment on HRQOL.


Data Extraction: Reviewers working independently and in duplicate assessed the methodological quality of trials and collected data on patient characteristics, interventions, and outcomes.


Data Synthesis: We found 10 eligible trials that measured HRQOL and depression, anxiety, and sexual function. Random-effects meta-analysis showed a small improvement in HRQOL in women treated with DHEA compared with placebo [effect size of 0.21; 95% confidence interval, 0.08 to 0.33; inconsistency (I2) = 32%]. There was a small beneficial effect of DHEA on depression; effects on anxiety and sexual well-being were also small and not statistically significant.


Conclusions: DHEA may improve, in a small and perhaps trivial manner, HRQOL and depression in women with adrenal insufficiency. There was no significant effect of DHEA on anxiety and sexual well-being. The evidence appears insufficient to support the routine use of DHEA in women with adrenal insufficiency.



Saturday, November 06, 2010

Adrenal Crisis

A Bhattacharyya, J Macdonald, AA LAkhdar.

The adrenal cortex normally produces three principal steroid hormones: the glucocorticoid cortisol, the mineralocorticoid adosterone, and a small quantity of sex steroids. In primary adrenocortical insufficiency, there is a deficiency of both cortisol and aldosterone with characteristic clinical and laboratory findings.


In contrast, with a pituitary disorder there is isolated hypocortisolism, because its production is dependant on pituitary adrenocortrophic hormone (ACTH), whereas aldosterone production is controlled by extracellular fluid volume, rennin and serum potassium. Acute adrenocortical crisis is an absolute medical emergency and its presentation is not always typical.


We describe three recent cases of acute adrenocortical crisis in our hospital who presented in three different ways in three different wards.


International Journal of clinical Practice 2001;55:141-4.



Tuesday, November 02, 2010

Are Guidelines for Glucocorticoid Coverage in Adrenal Insufficiency Currently Followed?

Coralie Leblicq, MD, Diane Rottembourg, MD, Johnny Deladoëy, MD, PhD, Guy Van Vliet, MD, Cheri Deal, PhD, MD Corresponding Author

Received 11 January 2010; received in revised form 14 July 2010; accepted 17 August 2010. published online 01 November 2010.



To search for evidence of acute adrenal failure linked to inappropriate use of stress management protocols.

Study design

Patients followed up for primary adrenal insufficiency (n = 102) or secondary adrenal insufficiency (n = 34) between 1973 and 2007 were included. All hospitalizations, both urgent (n = 157) and elective (n = 90), were examined. We recorded clinical evidence of acute adrenal failure, parental management before admission, and details of glucocorticoid prescription and administration in the hospital setting.


For urgent hospitalizations, subgroup and time period did not influence the percentage of patients hospitalized (primary adrenal insufficiency 45%; secondary adrenal insufficiency 38%; P = .55). The use of stress glucocorticoid doses by parents increased significantly after 1997 (P < .05), although still only 47% increased glucocorticoids before hospitalization. Stress doses were more frequently administered on arrival in our emergency department after 1990 (P < .05); patients with signs or symptoms of acute adrenal failure decreased to 27% after 1997 (P < .01). Twenty-four percent of all hospitalizations were marked by suboptimal adherence to glucocorticoid stress protocols, with rare but significant clinical consequences.


In spite of an increased use of glucocorticoid stress dose protocols by parents and physicians, patients remain at risk of morbidity and death from acute adrenal failure. This risk may be minimized with conscientious application of stress protocols, but other patient-specific risk factors may also be implicated.



21OH, 21-hydroxylase, 3?HSD, 3-?-hydroxysteroid dehydrogenase, ACTH, Adrenocorticotropic hormone, AI, Adrenal insufficiency, CAH, Congenital adrenal hyperplasia, ED, Emergency department, EH, Elective hospitalization, HPA, Hypothalamic-pituitary-adrenal, PAI, Primary adrenal insufficiency, UH, Urgent hospitalization


Endocrinology Service and Research Center, CHU Sainte-Justine and Department of Pediatrics, University of Montreal, Montreal, Quebec, Canada

Corresponding Author InformationReprint requests: Cheri Deal, PhD, MD, FRCPC, Endocrinology Service, CHU Sainte-Justine Hospital, Research Center, 3175 Côte Sainte-Catherine, Montréal (Québec), Canada, H3T 1C5.

Supported by scholarships from the Belgian Study Group of Pediatric Endocrinology (C.L.), the Fonds de Recherche en Santé du Québec (C.D.), and a donation from Group Cossette Communications (C.D.). The authors declare no conflicts of interest.

PII: S0022-3476(10)00690-6




Monday, October 18, 2010

About the Adrenal Glands

Adapted from and The Merck Manual

Adrenal Gland Disorders

The body has two adrenal glands, one near the top of each kidney. The inner part (medulla) of the adrenal glands secretes hormones such as adrenaline (epinephrine) that affect blood pressure, heart rate, sweating, and other activities also regulated by the sympathetic nervous system. The outer part (cortex) secretes many different hormones, including corticosteroids (cortisone-like hormones), androgens (male hormones), and mineralocorticoids, which control blood pressure and the levels of salt and potassium in the body.

The adrenal glands are part of a complex system that produces interacting hormones. The hypothalamus produces corticotropin-releasing hormone, triggering the pituitary gland to secrete corticotropin, which regulates the production of corticosteroids by the adrenal glands. Adrenal glands may stop functioning when either the pituitary or hypothalamus fails to produce sufficient amounts of the appropriate hormones. Underproduction or overproduction of any adrenal hormones can lead to serious illness.

Underactive Adrenal Glands

Addison's disease (adrenocortical insufficiency) results when underactive adrenal glands produce insufficient amounts of corticosteroids.


Addison's disease affects about 4 out of every 100,000 people. The disease can strike at any age and affects males and females about equally. In 30 percent of people with Addison's disease, the adrenal glands are destroyed by a cancer, amyloidosis, an infection such as tuberculosis, or another identifiable disease. In the other 70 percent, the cause isn't known for certain, but scientists strongly suspect the adrenal glands are destroyed by an autoimmune reaction.


The adrenal glands are also suppressed in people who take corticosteroids such as prednisone. Ordinarily, the dose of corticosteroids is tapered slowly before the drug is stopped completely. When corticosteroids are stopped suddenly after being taken for a month or more, the adrenal glands may be unable to produce corticosteroids in sufficient amounts for several weeks or even months, depending on the dose of corticosteroids and the duration of treatment. Certain other drugs, such as ketoconazole taken to treat fungal infections, can also block the natural production of corticosteroids, resulting in a deficiency.

Corticosteroid deficiency can lead to many problems. For example, when corticosteroids are lacking, the body excretes large amounts of sodium and retains potassium, leading to low levels of sodium and high levels of potassium in the blood. The kidneys aren't able to concentrate urine, so when a person with a corticosteroid deficiency drinks too much water or loses too much sodium, the blood level of sodium falls. Inability to concentrate urine ultimately causes the person to urinate excessively and become dehydrated. Severe dehydration and a low sodium level reduce blood volume and can culminate in shock.

corticosteroid deficiency also leads to an extreme sensitivity to insulin, a hormone normally present in the blood, so that the blood sugar levels may fall dangerously low. The deficiency prevents the body from manufacturing carbohydrates from protein, fighting infections, or healing wounds very well. Muscles weaken, and even the heart can become weak and unable to pump blood adequately.


To compensate for a deficiency of corticosteroids, the pituitary gland produces more corticotropin, the hormone that normally stimulates the adrenal glands. Since corticotropin also affects melanin production, people with Addison's disease often develop a dark pigmentation of the skin and the lining of the mouth. The excessive pigmentation usually occurs in patches. Even people with dark skin can develop excessive pigmentation, although the change may be hard to recognize. Excessive pigmentation doesn't occur when adrenal insufficiency is caused by pituitary or hypothalamus insufficiency, conditions in which the basic problem is a deficiency of corticotropin.


Soon after developing Addison's disease, a person feels weak, tired, and dizzy when standing up after sitting or lying down. The skin becomes dark; this darkness may seem like tanning, but it appears on both sun-exposed and nonexposed areas. Black freckles may develop over the forehead, face, and shoulders; a bluish-black discoloration may develop around the nipples, lips, mouth, rectum, scrotum, or vagina. Most people lose weight, become dehydrated, have no appetite, and develop muscle aches, nausea, vomiting, and diarrhea. Many become unable to tolerate cold. Unless the disease is severe, symptoms tend to become apparent only during times of stress.


If the disease isn't treated, severe abdominal pains, profound weakness, extremely low blood pressure, kidney failure, and shock may occur, especially if the body is subjected to stress such as an injury, surgery, or severe infection. Death may quickly follow.


Because the symptoms may start slowly and be subtle, and because no single laboratory test is definitive, doctors often don't suspect Addison's disease at the outset. Sometimes a major stress, such as an accident, operation, or serious illness, makes the symptoms more obvious and precipitates a crisis.


Blood tests may show a lack of corticosteroids, especially cortisol, as well as low sodium and high potassium levels. Measures of kidney function, such as tests for blood urea nitrogen and creatinine, usually indicate that the kidneys aren't working well. Corticosteroid levels, usually tested after an injection of corticotropin (a challenge test), can help the doctor distinguish adrenal gland insufficiency from pituitary gland insufficiency. When it is the latter, an injection of corticotropin-releasing hormone reveals whether the cause of the problem is hypothalamus insufficiency.


Regardless of the cause, Addison's disease can be life-threatening and must be treated first with corticosteroids. Usually treatment can be started with prednisone taken orally. However, people who are severely ill may be given cortisol intravenously at first and then prednisone tablets. Most people with Addison's disease also need to take 1 or 2 tablets of fludrocortisone every day to help restore the body's normal excretion of sodium and potassium. Fludrocortisone can eventually be reduced or discontinued in some people; however, they will need to take prednisone every day for the rest of their lives. Larger doses of prednisone may be needed when the body is stressed, especially from an illness. Although treatment must be continued for life, the outlook for a normal life span is excellent.

Overactive Adrenal Glands

The adrenal glands can produce too much of one or more hormones. Changes in the adrenal glands themselves or overstimulation by the pituitary gland may be the cause. The symptoms and treatment depend on which hormones--androgenic steroids, corticosteroids, or aldosterone--are being overproduced.

Overproduction of Androgenic Steroids

Overproduction of androgenic steroids (testosterone and similar hormones) is a condition that leads to virilization, the development of exaggerated masculine characteristics in either men or women.


Mild overproduction of androgens is common but may lead only to increased hair growth (hirsutism). True virilizing disease is rare, affecting only about 1 or 2 of every 100,000 women. The incidence of virilizing disease in men is almost impossible to guess.


Signs of virilization include hairiness of the face and body, baldness, acne, deepening of the voice, and increased muscularity. In women, the uterus shrinks, the clitoris enlarges, the breasts become smaller, and normal menstruation stops. Both men and women may experience an increased sex drive.


The combination of body changes makes virilization relatively easy for a doctor to recognize. A test can determine the level of androgenic steroids in the urine. If the level is high, the dexamethasone suppression test can help determine whether the problem is a cancer, a noncancerous tumor (adenoma), or an enlargement of the hormone-producing portions of the adrenal cortex (adrenal hyperplasia). With this test, the corticosteroid dexamethasone is given orally. If the problem is adrenal hyperplasia, dexamethasone prevents the adrenal glands from producing androgenic steroids. If the problem is an adenoma or cancer of the adrenal glands, dexamethasone reduces androgenic steroid production only partially or not at all. The doctor may also order a computed tomography (CT) or magnetic resonance imaging (MRI) scan to obtain a view of the adrenal glands.


Androgen-producing adenomas and adrenal cancers are usually treated by surgically removing the adrenal gland. For adrenal hyperplasia, small amounts of corticosteroids such as dexamethasone generally reduce the production of androgenic steroids, but these drugs may also cause symptoms of Cushing's syndrome if too large a dose is given.

Overproduction of Corticosteroids

Overexposure to corticosteroids, whether from overproduction by the adrenal glands or from administration of excessive amounts by a doctor, results in Cushing's syndrome.

An abnormality in the pituitary gland, such as a tumor, can cause the pituitary to produce large amounts of corticotropin, the hormone that controls the adrenal glands. Pituitary tumors that overproduce corticotropin occur in about 6 in every 1 million people. Small-cell carcinoma in the lung and some other tumors outside the pituitary gland can produce corticotropin as well (a condition called ectopic corticotropin syndrome). This is the most common cause of excessive adrenal cortical function, found in at least 10 percent of people with small-cell carcinoma in the lung, a common type of tumor.

Sometimes the adrenal gland produces excessive corticosteroids even when corticotropin levels are low, usually when a benign tumor (adenoma) has developed in the adrenal gland. Benign tumors of the adrenal cortex are extremely common; half of all people have them by the age of 70. Only a small fraction of these benign tumors are active; the incidence of adenomas causing disease is about 2 in every 1 million people. Cancerous tumors of the adrenal cortex are equally common, but cancers causing endocrine disease are quite rare.


Because corticosteroids alter the amount and distribution of body fat, a person with Cushing's syndrome usually has a large, round face (moon face). Excessive fat develops throughout the torso and may be particularly noticeable at the top of the back (buffalo hump). Fingers, hands, and feet are usually slender in proportion to the thickened trunk. Muscles lose their bulk, leading to weakness. The skin becomes thin, bruises easily, and heals poorly when bruised or cut. Purple streaks that look like stretch marks may develop over the abdomen.


High corticosteroid levels over time raise the blood pressure, weaken bones (osteoporosis), and diminish resistance to infections. The risk of developing kidney stones and diabetes is increased, and mental disturbances, including depression and hallucinations, may occur. Women with Cushing's syndrome usually have an irregular menstrual cycle. Children who have the condition grow slowly and remain short. In some people, the adrenal glands also produce large amounts of androgenic steroids, leading to increased facial and body hair, balding, and an increased sex drive.


Doctors who suspect Cushing's syndrome after observing the symptoms measure the blood level of cortisol, the main corticosteroid hormone. Normally, cortisol levels are high in the morning and decrease during the day. In people who have Cushing's syndrome, cortisol levels are very high in the morning and don't decrease late in the day as would be expected. Measuring cortisol in the urine can be useful because tests performed a few hours apart can indicate how much cortisol has been produced in that time.


If the cortisol levels are high, the doctor may recommend a dexamethasone suppression test. The test is based on the ability of dexamethasone to suppress the pituitary gland, thereby reducing adrenal gland stimulation. First a urine sample is tested for cortisol. Then dexamethasone is given, and cortisol levels are measured in another sample of urine. If the Cushing's syndrome is caused by pituitary stimulation, the level of cortisol will fall; if the Cushing's syndrome is caused by stimulation from a nonpituitary source of corticotropin or an adrenal tumor, the urinary cortisol level will remain high.


Results of a dexamethasone suppression test may not be clear-cut. Other laboratory tests may be needed to help determine the precise cause of the syndrome. These tests may be followed by a computed tomography (CT) or magnetic resonance imaging (MRI) scan of the pituitary or adrenal glands and by a chest x-ray or CT scan of the lungs.


Treatment is directed at the pituitary or adrenal gland depending on the source of the problem. Surgery or radiation therapy may be needed to remove or destroy a pituitary tumor. Adenomas of the adrenal gland can often be removed surgically. Both adrenal glands may have to be removed if these treatments aren't effective or if no tumor is present. Any person who has had both adrenal glands removed, and many people who have had part of their adrenal glands removed, must take corticosteroids for life.


Some 5 to 10 percent of the people who have both adrenal adrenal glands removed develop Nelson's syndrome. In this condition, the pituitary gland enlarges, producing large amounts of corticotropin and other hormones such as beta-melanocyte-stimulating hormone, which darkens the skin. If necessary, Nelson's syndrome can be treated with radiation or surgical removal of the pituitary gland.

Overproduction of Aldosterone

Overproduction of aldosterone (hyperaldosteronism) by the adrenal glands is a condition that affects the blood levels of sodium, potassium, bicarbonate, and chloride, leading to high blood pressure, weakness, and, rarely, periods of paralysis.


Aldosterone, a hormone produced and secreted by the adrenal glands, signals the kidney to excrete less sodium and more potassium. Aldosterone production is regulated partly by corticotropin in the pituitary and partly by a control mechanism in the kidneys (the renin-angiotensin-aldosterone system).  Renin, an enzyme produced in the kidneys, controls the activation of the hormone angiotensin, which stimulates the adrenal glands to produce aldosterone.


Hyperaldosteronism can be caused by a tumor (usually noncancerous) in the adrenal gland (a condition called Conn's syndrome). Sometimes hyperaldosteronism is a response to certain diseases. For example, the adrenal glands secrete large amounts of aldosterone if the blood pressure is very high or if the artery that carries blood to the kidneys is narrowed.


High levels of aldosterone can lead to low levels of potassium, causing weakness, tingling, muscle spasms, and paralysis. The nervous system may not function properly. Some people become extremely thirsty and urinate frequently, and some experience personality changes.

Symptoms of hyperaldosteronism are also associated with eating licorice, which contains a chemical very similar to aldosterone. In rare cases, people who eat a great deal of candy with real licorice flavoring may develop all the symptoms of hyperaldosteronism.

Diagnosis and Treatment

A doctor who suspects that high blood pressure or related symptoms are caused by hyperaldosteronism may measure the sodium and potassium levels in the blood. The doctor may also measure aldosterone levels and, if they're high, may prescribe spironolactone, a drug that blocks the action of aldosterone, to see if the levels return to normal. Other tests generally aren't needed.


When too much aldosterone is being produced, doctors examine the adrenal glands for an adenoma or cancer. While a computed tomography (CT) or magnetic resonance imaging (MRI) scan can be helpful, exploratory surgery is often necessary. If a growth is found, it can usually be removed. When a simple adenoma is removed, blood pressure returns to normal and other symptoms disappear about 70 percent of the time. If no tumor is found and the entire gland is overactive, partial removal of the adrenal glands may not control high blood pressure and complete removal will produce adrenal insufficiency, requiring treatment for the rest of the person's life. However, spironolactone can usually control the symptoms, and drugs for high blood pressure are readily available. Rarely do both adrenal glands have to be removed.



Addison’s Disease Knol at

Addison's Disease (Adrenal insufficiency): Caused by low levels of cortisonelike hormones produced by the adrenal glands. The cause is usually unknown, but may be a complications of tuberculosis, cancer, pituitary disease of cortisone drugs.

Addison's Disease
This Topic on the Message Boards.


Adrenal: Pertaining to one or both of these endocrine glands located on top of the kidneys. These glands secrete many hormones, including epinephrine (adrenaline), norepinephrine, and the corticosteroid, and play an important part in the body's endocrine system.

The adrenal is made up of an outer wall (the cortex) and an inner portion (the medulla).

A closer look at the adrenal glands, including an illustration.

Adrenal cortex: Outer layer of the adrenal gland, it secretes various hormones including cortisone, estrogen, testosterone, cortisol, androgen, aldosterone and progesterone.


Adrenalectomy: Surgical removal of the adrenal glands is a final measure for halting excess cortisol production This is used only when all other measures fail in individuals with pituitary tumors.


Adrenal gland tumor: A benign tumor, or adenoma, that usually results in the excess production of adrenal gland hormones.


Sometimes, an abnormality of the adrenal glands, most often an adrenal tumor, causes Cushing's syndrome. The average age of onset is about 40 years. Most of these cases involve non-cancerous tumors of adrenal tissue, called adrenal adenomas, which release excess cortisol into the blood. adrenal glands. In Primary Pigmented Micronodular Adrenal Disease and the familial Carney's complex, surgical removal of the adrenal glands is required.


Adrenal insufficiency: See Addison's Disease. Adrenal insufficiency is a life threatening chronic illness. An active and vigorous lifestyle with normal life expectancy is possible as long as the prescribed medications are taken regularly and adjusted when indicated. As with most chronic diseases, adrenal insufficiency demands that the patients take responsibility and develop self-management skills and techniques.

Read an article on Adrenal insufficiency

Adrenal medulla: Middle part of the adrenal gland, it secretes epinephrine (adrenalin) and norepinephrine.


Adrenocortical carcinomas, or adrenal cancers: These are the least common cause of Cushing's syndrome. Cancer cells secrete excess levels of several adrenal cortical hormones, including cortisol and adrenal androgens. Adrenocortical carcinomas usually cause very high hormone levels and rapid development of symptoms.


Adrenocortical hyperplasia: Increase in the number of cells of the adrenal cortex. It secretes cortisol, androgens and aldosterone. Increased production of any or all of these hormones may result in a variety of disorders, such as Cushing's syndrome and hypertension.


Adrenocorticotropic-hormone deficiency: Not enough ACTH is produced by the pituitary gland.


Adrenoleukodystrophy: Disturbance in brain substance caused by abnormal function of the adrenal gland.


Aldosterone: Adrenal hormone that affects the body's handling of sodium, chloride, and potassium.

Read an article on Aldosterone testing

Tuesday, October 05, 2010

Addison's Disease – Will Your Insurance Cover the Price of Therapy?

Addison's disease was first described by Dr. Thomas Addison, whom the disease is called after, in 1849. Also known as adrenal insufficiency, Addison's is a malfunction of the adrenal glands which causes the glands for fail to supply sufficient of the hormones cortisol, aldosterone, or both. It's an uncommon condition that is typically brought on by harm to the gland by an autoimmune dysfunction or an infection. It is a considerably silent disease in that the signs progress so slowly that the particular person does not realize they've the disease till they expertise a very stressful scenario and the adrenal gland fails to supply sufficient hormones to help the physique deal with it.


The primary remedy of Addison's disease is through medication. Patients are prescribed hormone replacements resembling hydrocortisone or prednisone for cortisol insufficiency and a mineralocorticoid for aldosterone insufficiency. Depending on the underlying explanation for the disease, secondary remedy may be necessary. For example, autoimmune issues are the principle explanation for Addison's. Therefore, your doctor could prescribe additional medications and treatments to handle that downside as well. Cancer of the adrenal gland is also a explanation for this disease and you may need surgery and chemotherapy to do away with the cancer.


Insurance firms will probably cowl the cost of your medical care since remedy typically entails doctor's visits and medication. You will most likely be scheduling common appointments along with your doctor, so when you find yourself searching for health care insurance coverage be sure to evaluate the cost of copays for office visits. Additionally, you will want to find a plan that may pay some or the entire cost of your prescription drugs since there is no cure for Addison's disease and you will be on treatment for the rest of your life. Having your insurance coverage firm decide up the tab will save you money over the lengthy term.


Addison's disease is classed as a preexisting condition. Therefore, if you change insurance policy you may be subject to a ready period or end up paying increased premiums to your plan. To help you discover one of the best deal within the shortest amount of time, use a medical health insurance quote web site to get insurance coverage quotes from a number of providers. You will be able to do a facet by facet comparability of the completely different plans supplied which is able to make it simple to see how a lot you will be paying out of pocket to deal with your illness.


Untreated Addison's is potentially fatal but, with the correct medical care, you may reside a protracted and healthy life.



Thursday, September 30, 2010

HPA Axis: Accuracy of several parameters of hypothalamic–pituitary–adrenal axis activity in predicting before surgery the metabolic effects of the rem

European Journal of Endocrinology (2010) In press
DOI: 10.1530 / EJE-10-0602
Copyright © 2010 by European Society of Endocrinology

Cristina Eller-Vainicher, Valentina Morelli, Antonio Stefano Salcuni, Claudia Battista, Massimo Torlontano, Francesca Coletti, Laura Iorio, Elisa Cairoli, Paolo Beck-Peccoz, Maura Arosio, Bruno Ambrosi, Alfredo Scillitani and Iacopo Chiodini

C Eller-Vainicher, Department of Medical Sciences, Endocrinology and Diabetology Unit, Fondazione Ospedale Maggiore Policlinico, I.R.C.C.S., Milan, Italy
V Morelli, Milan, 20122, Italy
A Salcuni, Endocrinology Unit, Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
C Battista, Endocrinology Unit, Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
M Torlontano, Endocrinology Unit, Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
F Coletti, Endocrinology Unit, Ospedale San Giuseppe Multimedica, Milan, Italy
L Iorio, Policlinico San Donato Institute, I.R.C.C.S.Depertment of Medical and Surgical Sciences, University of Milan, san Donato Milanese, Milan, Italy
E Cairoli, Department of Medical Sciences, Endocrinology and Diabetology Unit, Fondazione Ospedale Maggiore Policlinico, I.R.C.C.S., Milan, Italy
P Beck-Peccoz, Department of Medical Sciences, Endocrinology and Diabetology Unit, Fondazione Ospedale Maggiore Policlinico, I.R.C.C.S., Milan, Italy
M Arosio, University of Milan, Milan, Italy
B Ambrosi, Policlinico San Donato Institute, I.R.C.C.S.Depertment of Medical and Surgical Sciences, University of Milan, san Donato Milanese, Milan, Italy
A Scillitani, Endocrinology Unit, Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
I Chiodini, Department of Medical Sciences, Endocrinology and Diabetology Unit, Fondazione Ospedale Maggiore Policlinico, I.R.C.C.S., Milano, 20123, Italy

Correspondence: Iacopo Chiodini, Email:

Context: It is unknown if the metabolic effects of the removal of an adrenal incidentalomas (AI) can be predicted by the assessment of cortisol hypersecretion before surgery.

Objective: To evaluate the accuracy of several criteria of hypothalamic-pituitary-adrenal axis activity in predicting the metabolic outcome after adrenalectomy.

Design: Retrospective longitudinal study.

Patients: In 55 surgically-treated AI patients (Group 1) before surgery and in 53 non-treated AI patients (Group 2) at baseline, urinary free cortisol (UFC), cortisol after 1mg-overnight dexamethasone-suppression test (1mg-DST), ACTH and midnight serum cortisol (MSC) were measured. In Group 1 and 2, metabolic parameters were evaluated before and 29.6±13.8 months after surgery and at baseline and after 35.2±10.9 months, respectively.

Main Outcome Measures: The improvement/worsening of weight, blood pressure, glucose and cholesterol levels (endpoints) was defined in the presence of a >5% weight decrease/increase and following the European Society of Cardiology or the ATPIII criteria, respectively. The accuracy of UFC, 1mg-DST, ACTH and MSC, singularly taken or in combination, in predicting the improvement/worsening of ≥2 endpoints was calculated.

Results: The presence of ≥2 among UFC>70 µg/24h (193 nmol/L), ACTH<10>3.0 µg/dL (83 nmol/L) (UFC-ACTH-DST criterion) had the best accuracy in predicting the endpoints’ improvement (sensitivity 65.2%, specificity 68.8%) after surgery. In the non-treated AI patients, this criterion predicted the worsening of ≥2 endpoints (sensitivity 55.6%, specificity 82.9%).

Conclusions: The UFC-ACTH-DST criterion seems the best for predicting the metabolic outcome in surgically-treated AI patients.


Friday, July 30, 2010

Nelson’s Syndrome

Thomas M Barber, Emily Adams, Olaf Ansorge, James V Byrne, Niki Karavitaki and John Wass
T Barber, Department of Endocrinology, OCDEM, University of Oxford, Oxford, United Kingdom
E Adams, Department of Endocrinology, OCDEM, University of Oxford, Oxford, United Kingdom
O Ansorge, Department of Pathology, University of Oxford, Oxford, United Kingdom
J Byrne, Department of Radiology, University of Oxford, Oxford, United Kingdom
N Karavitaki, Department of Endocrinology, OCDEM, University of Oxford, Oxford, United Kingdom
J Wass, Endocrinology, Oxford University, Oxford, OX3 7LJ, United Kingdom
Correspondence: John Wass, Email:

Nelson’s Syndrome is a potentially life-threatening condition that not infrequently develops following total bilateral adrenalectomy (TBA) for the treatment of Cushing’s Disease. In this review article, we discuss some controversial aspects of Nelson’s Syndrome including diagnosis, predicitve factors, aetiology, pathology and management based on data from the existing literature and the experience of our own tertiary centre.

Definitive diagnostic criteria for Nelsons’s Syndrome are lacking. We argue in favour of a new set of criteria. We propose that Nelson’s Syndrome should be diagnosed in any patient with prior TBA for Cushing’s Disease and at least one of the following criteria: i) an expanding pituitary mass lesion compared with pre-TBA images; ii) an elevated 0800hrs plasma level of ACTH (>500ng/l) in addition to progressive elevations of ACTH (a rise of >30%) on at least three consecutive occasions. Regarding predictive factors for the development of Nelson’s Syndrome post-TBA, current evidence favours: the presence of residual pituitary tumour on MRI post-TSA; an aggressive subtype of corticotrophinoma (based on MRI growth rapidity and histology of TSA samples); lack of prophylactic neo-adjuvant pituitary radiotherapy at the time of TBA, and; a rapid rise of ACTH levels in year one post-TBA. Finally, more studies are needed to assess the efficacy of therapeutic strategies in Nelson’s Syndrome, including the alkylating agent, temozolomide which holds promise as a novel and effective therapeutic agent in the treatment of associated aggresive corticotroph tumours. It is timely to review these controversies and to suggest guidelines for future audit.



Monday, July 12, 2010

Sexuality and Fertility in Women with Addison's Disease

Sexuality and Fertility in Women with Addison's Disease
Journal of Clinical Endocrinology and Metabolism, 07/12/10


Erichsen MM et al. – The aim was to determine peripheral androgen status, sexual functioning, and birth rates in Addison's disease females. Despite androgen depletion, females with Addison's disease do not report impaired sexuality. The fertility is reduced after the diagnosis is made; the reasons for this remain unknown.


Read the abstract at

Monday, June 28, 2010

Adrenal incidentaloma: Does an adequate workup rule out surprises?

Raymon H. Grogan, MD, Elliot Mitmaker, MD, Menno R. Vriens, MD, PhD, Avital Harari, MD, Jessica E. Gosnell, MD, Wen T. Shen, MD, Orlo H. Clark, MD, Quan-Yang Duh, MDCorresponding Author Informationemail address

Accepted 14 May 2010. published online 24 June 2010.
Corrected Proof


Adrenal incidentaloma remains a diagnostic challenge. Despite well-established management guidelines, the long-term results of following these guidelines are unknown. We sought to determine how accurately these guidelines identify functioning incidentalomas and how often these guidelines result in adrenalectomy for benign tumors.


We catalogued adrenal incidentalomas from a retrospective review of 500 consecutive adrenalectomies at a single institution. The outcome measures studied were patient demographics, preoperative biochemical analysis, imaging characteristics, tumor size, type of operation performed, and postoperative histologic diagnosis.


Eighty-one of the 500 adrenalectomies performed were for incidentalomas. Size was the only significant characteristic that distinguished cortical cancers from benign adenomas. Only 1 out of 26 functioning tumors was incorrectly identified on preoperative workup. We also found that 25% of cortisol-secreting incidentalomas were cystic, and that benign adenomas accounted for 42% of all tumors resected.


Current guidelines accurately predict the functional status of adrenal incidentalomas. Some cystic lesions may be functioning and should therefore be screened for hormonal hypersecretion. However, even with the most up-to-date diagnostic tools available, most adrenal incidentalomas resected are benign tumors.


Department of Endocrine Surgery, University of California San Francisco, San Francisco, CA

Corresponding Author InformationReprint requests: Quan-Yang Duh, MD, UCSF Department of Endocrine Surgery, 1600 Divisadero Street C-347, Box 1674, San Francisco, CA 94143.

PII: S0039-6060(10)00261-8


© 2010 Mosby, Inc. All rights reserved.



Saturday, June 26, 2010

Adrenal Disorders: Cushing's Disease & Cushing's Syndrome

The production of cortisol by the adrenal glands is stimulated by ACTH (Adrenal Cortical Tropic Hormone), which is produced by the pituitary gland in the brain. Thus, overproduction of cortisol can be caused by either a tumor in the pituitary gland (Cushing's disease), or in the adrenal glands (Cushing's syndrome). Less commonly, a tumor producing too much ACTH may be found outside of the pituitary gland. In patients with Cushing's disease, the blood levels of both ACTH and cortisol are elevated. In patients with Cushing's syndrome, the blood level of cortisol is increased in the setting of a low level of ACTH. Rarely, adrenocortical cancers may cause Cushing's syndrome.


There is a great deal of variability throughout the day in the amounts of cortisol produced by the adrenal glands. For this reason, the most sensitive test measures the amount of cortisol excreted in the urine over a 24-hour period. A 24 hour free cortisol level greater than 100 µg is diagnostic of Cushing's syndrome. Patients suspected of having Cushing's syndrome will also undergo a dexamethasone suppression test which helps to determine the cause of the increased cortisol production. A CT or MRI scan is used to determine the location of the tumor.


Patients with Cushing's disease typically have benign tumors of the pituitary gland in the brain. These patients are referred to a neurosurgeon for removal of the tumors. If removal of the pituitary tumor and medications fail to control Cushing's disease, removing both adrenal glands may be indicated. In patients with Cushing's syndrome, an adrenalectomy—surgical removal of the adrenal gland—is curative. This operation is usually performed laparoscopically, through several very small incisions.


Friday, June 25, 2010

Adrenal Alerts ~ June 25, 2010

Day 175 in the life of a (former) Cushing's patient - 365 days ...
My adrenal glands were "generous", for sure, especially after being on keto for so long. Of course, no one was surprised. The left, after fat removal, was 13.5 grams. The right was 11.6 grams. The fat removed around it is removed before ...
365 days with Cushing's Disease -


Crazy Happy Thyroid Dance | Dear Thyroid™
By Dear Thyroid
Another key aspect of interdependence is the dance between PCOS, your adrenals and your thyroid. While the cause isn't well-delineated, I believe most of PCOS begins with the stress cascade of overtaxed adrenals and too much cortisol in ...
Dear Thyroid™ -


Journal of Clinical Investigation -- Adrenal glucocorticoids have ...
Manipulation of the adrenal circadian clock, in particular phase-shifting of adrenal glucocorticoid rhythms, regulated the speed of behavioral reentrainment ...


What Are the Causes of Secondary Adrenal Insufficiency
What Are the Causes of Secondary Adrenal Insufficiency news, info, articles, and resources shared by health experts on OrganizedWisdom Health.


Adrenal cortical insufficiency medications -
Performance of 1 Adrenal cortical insufficiency drug in real world: hydrocortisone, and more. Long term effects of Adrenal cortical insufficiency drug are ...

Thursday, June 24, 2010

CAH (congenital adrenal hyperplasia) and Prenatal Dexamethasone

MountainQueen posted this on the Cushing's Help Boards.  She said:

I came across this article about the clinical use of Dex for CAH carriers. After reading this article I remembered that NO ONE asked me if I was pregnant before I took the Dex test. What would have happened if I had been?
Very interesting article for CAH gene carriers: From Time Magazine on line

Medical Ethics: Prenatal Dexamethasone Use Questioned

By CATHERINE ELTON Catherine Elton Mon Jun 21, 11:45 pm ET

When Marisa Langford found out she was pregnant again, she called Dr. Maria New, a total stranger, before calling her own mother. New, a prominent pediatric endocrinologist and researcher at Mount Sinai Medical Center in New York City, is one of the world's foremost experts in congenital adrenal hyperplasia, or CAH, a group of inherited disorders of the adrenal gland.

Langford and her husband learned they were silent carriers of the genetic variation that causes CAH when their son was diagnosed with the condition after birth. Their son - like the 1 in 16,000 babies born with CAH each year in the U.S. - faces a lifetime of taking powerful steroid medications to compensate for his faulty adrenal glands. When Langford contacted New about her second pregnancy, New, who was not Langford's regular doctor, called a local pediatric endocrinologist. That doctor prescribed Langford a commonly used medication for CAH. "Dr. New told me I had to start taking dexamethasone immediately," says Langford, 30, who lives in Tampa. "We felt very confident in someone of her stature and that what she was telling us was the right thing to do."(See the most common hospital mishaps.)

The early prenatal use of dexamethasone, or dex, has been shown to prevent some of the symptoms of CAH in girls, namely ambiguous genitalia. Because the condition causes overproduction of male hormones in the womb, girls who are affected tend to have genitals that look more male than female, though internal sex organs are normal. (In boys, in contrast, the condition leads to early signs of puberty, such as deep voice, body hair and enlarged penis by age 2 or 3.) But while the prenatal treatment may address girls' physical symptoms, it does not prevent the underlying, medical condition, which in some severe cases can be life-threatening, nor does it preclude the need for medication throughout life.

Langford says also that neither New nor her prescribing physician mentioned that prenatal dexamethasone treatment is an off-label use of the drug (an application for which it was not specifically approved by the government) or that the medical community is sharply divided over whether dexamethasone should be used during pregnancy at all.

Is It Safe - or Even Necessary?

To date, there has been just one controlled, prospective, long-term trial of prenatal dexamethasone for the prevention of ambiguous genitalia, conducted in Sweden. The results, published in 2007 in the Journal of Clinical Endocrinology & Metabolism - more than two decades after doctors began using the medication in pregnant patients - found some mild behavioral and cognitive deficits in children whose mothers had been treated. But the study, with just 26 participants, was too small to be definitive. "We just don't know what we are doing to these kids," says Dr. Walter Miller, the chief of endocrinology at University of California, San Francisco. "It's not sufficient to say, The baby was born and had all fingers and toes, so it's fine."(See the top 10 medical breakthroughs of 2009.)

In animal studies, dexamethasone has been shown to cause birth defects, but proponents of the treatment note that no human birth defects have ever been associated with the treatment, and that it is uncertain whether findings in lab animals translate to humans. Meanwhile, the possible benefits are clear: the treatment can spare young girls the potential psychosocial problems associated with having ambiguous genitalia as well as the ordeal of surgery to correct deformities later. "I see potential for benefits and I don't see evidence there's any negatives to this. There are lots of risks associated with surgery, and if this can prevent surgery, then it's a good thing," says Dr. Ingrid Holm, a pediatric endocrinologist at Children's Hospital in Boston.

Research has also suggested that affected women who were treated with dex in the womb show more typical gender behavior than other women with CAH; the latter group tends to behave more tomboyishly and express little interest in having children. New told the Wall Street Journal in 2009 that the treatment further spares parents the "terrifying prospect" of not knowing whether their newborn is a boy or a girl. (Comment on this story.)

It is these very benefits, however, that lead some researchers to question what, exactly, doctors are treating - and whether it needs to be treated at all. Miller believes that prenatal dex is being used to alleviate "parental anxiety," rather than the child's condition. Other doctors and researchers have criticized New for introducing gender behavior into the medical prognosis - in two recent presentations on CAH at medical conferences, New offered medical outcome data on prenatal dex alongside data on typical gender behavior. "Maybe this gives clinicians the idea that the treatment goal is normalizing behavior. To say you want a girl to be less masculine is not a reasonable goal of clinical care," says David E. Sandberg, a University of Michigan pediatric psychologist who treats and conducts research on children with CAH.(Read how postpartum depression can strike fathers.)

Perhaps most controversially, prenatal dex must be given as soon as a woman learns she is pregnant, which is usually several weeks before genetic tests can determine if the fetus is in fact a female affected with CAH - the chance of which is 1 in 8 for parents who already have an affected child or know they are carriers of the genetic disorder. If the baby is healthy, treatment is stopped, but at that point, the fetus has been exposed to the steroid drug for weeks. There is no data on how many mothers receive prenatal dex, but according to the odds, 7 of 8 may be taking medication unnecessarily.

Concerns over Patient Consent

Some critics strongly oppose prenatal dex in large part because of the way it is presented to patients. Guidelines issued by pediatric endocrine societies in Europe and North America recommend that doctors obtain written informed consent from the patient as well as ethics-committee oversight for the treatment, but it is not known how many physicians adhere to these guidelines. Langford says she was not made aware of them. In addition, 2010 practice guidelines from the international Endocrine Society suggest that prenatal dex be administered as part of clinical research, which requires informed consent and ethics-committee oversight.

However, prenatal dex is routinely given outside the research setting, as an off-label treatment. It is common - and perfectly legal - for doctors to use their own discretion when prescribing drugs off-label. Antiseizure drugs like topiramate are commonly prescribed to treat migraine headache pain, for example. The practice allows patients to receive valuable treatment for which the drug may not have been expressly approved and may never be - it takes money and drug-company interest, which are hard to come by, to conduct the large randomized controlled trials required for a new-use the Food and Drug Administration (FDA) approval of a drug that is already on the market.

But as doctors share information about a drug's perceived off-label benefits and lack of harm, it gets even harder to take a step back and launch a formal randomized controlled trial - considered the gold standard in medical research - because patients demand the treatment, and doctors say it would be unethical to withhold it from them or from control groups in clinical trials. "It's a risky and dangerous way to innovate," says prominent University of Pennsylvania bioethicist Arthur Caplan. "There's no systematic collection of information. So, yes, things do get proven this way, and it is a way to innovate, but it also can come at a cost of unnecessary expense and, sometimes, bad side effects."

It also enables doctors to do human research without gaining proper approval. All participants in human medical research are, by law, entitled to the protective oversight of an institutional review board (IRB), a committee that safeguards the interests of research volunteers and ensures they have been fully informed about the potential risks and benefits of an experimental treatment. If doctors are simply treating a patient with an off-label drug, they are not required to obtain written informed consent from patients. But if doctors give treatment with the intent to gain knowledge, they are technically doing research, which must receive IRB approval.

Ethicists say physicians may sometimes treat patients off-label, then decide later to launch a follow-up study; or, they do follow-up research on patients who have been treated by other doctors. In the process, they have converted these patients into unwitting research volunteers. Some doctors game the system this way, Caplan says, to avoid battles with IRBs.

Critics suspect that Mount Sinai's New, who has long championed prenatal dex and bills it as safe on her foundation website, has gamed the system. In a letter dated Feb. 2, 2010, a group of 36 bioethicists, including Alice Dreger, a professor of bioethics at Northwestern University, asked the FDA and the federal Office for Human Research Protections to investigate New's practices; the authors contend that the doctor has conducted follow-up studies on prenatal dex patients without receiving IRB approval for treatment trials. Dreger says she has also asked Weill Cornell Medical College, where New previously worked, and Mount Sinai Medical Center to investigate the matter.

New, who declined to be interviewed for this article, does not administer the treatment in her current practice - according to Mount Sinai Medical Center, she has prescribed it only once since joining the hospital in 2004 - but ethical concerns remain, Dreger says, if the doctor consults with patients, resulting in their being prescribed dex elsewhere, then follows up with them for research purposes. At a medical conference in January, where New presented data from her research on prenatal dex, the doctor refused to answer a fellow researcher's questions regarding her process of informed consent.

Clinical Trials vs. Legal Trials

For Langford's part, she says she is grateful to New for her help, even though her daughter, now 4 and healthy, was found not to have CAH.

But Jenny Westphal, 24, who took dexamethasone throughout her pregnancy at the recommendation of another doctor, says she feels misled. Like Langford she was not asked to give informed consent. Unlike Langford, however, her daughter, now 3, who has CAH, has also had serious and mysterious health problems since birth, including feeding disorders, that are not commonly associated with her adrenal-gland disorder.

In April, Westphal, who lives in Wisconsin, started doing research online and discovered there was some controversy over the treatment. "I was outraged, frustrated and confused. Confused, because no one had ever warned me about this. I wasn't given the chance to decide for myself, based on the risks and benefits, if I wanted the treatment or not," she says.

Westphal may never know whether her daughter's problems were caused by dexamethasone, though she will likely always believe they were. That is why so many similar situations, in which experimental drugs are prescribed off-label without informed consent rather than in clinical trials, wind up becoming case studies - not in scientific journals, but exactly where Westphal and her husband are considering taking theirs: to court.

Originally from