Overactive adrenal glands (Cushing's syndrome)

Overview

If your child’s adrenal glands produce excessive amounts of certain hormones, they are said to be overactive. The symptoms (and treatment) of overactive adrenal glands depends on which hormone is being overproduced.
Some of the most commonly overproduced hormones are:

• Androgenic steroids (also known as androgen hormones)
  • Testosterone is one of the most well-known androgen hormones. Excessive production of this or other androgen hormones can lead to exaggerated male characteristics in both men and women (like excess hair on the face and body, baldness, acne, a deeper voice and increased muscle mass).
  • If a female fetus is exposed to high levels of androgens early during a mother’s pregnancy, her genitals may develop abnormally. Young boys who experience high levels of androgen levels may grow faster, but their bones may also mature faster and stop growing too soon.
• Aldosterone hormone
  • Overproduction of aldosterone hormone can lead to high blood pressure and to symptoms associated with low levels of potassium (like weakness, muscle aches, spasms and sometimes paralysis).
• Corticosteroids
  • An overproduction of corticosteroids leads to the condition known as Cushing’s syndrome. Rare in children, it’s more commonly seen in adults.
  
  

What causes Cushing’s syndrome?
Cushing’s syndrome—the overproduction of corticosteroids—may be caused by an overproduction of cortisol (the hormone that controls the adrenal gland) by the pituitary gland. Other causes of Cushing’s syndrome include:

• certain lung cancers and other tumors outside the pituitary gland
• benign (non-cancerous) or cancerous tumors on the adrenal gland(s)

What are the symptoms of Cushing’s syndrome?
Children and adolescents with Cushing's syndrome experience weight gain, growth retardation and hypertension (high blood pressure). Other symptoms may include:

• upper body obesity
• round or moon-shaped face
• increased fat around neck
• thinning arms and legs
• fragile and thin skin
• darkened pigmentation of the skin
• acne
• bruising
• stretch marks on abdomen, thighs, buttocks, arms, and breasts
• bone and muscle weakness
• severe fatigue
• high blood sugar
• irritability and anxiety
• excessive hair growth in females
• irregular or stopped menstrual cycles in females
• reduced sex drive and fertility in males

How do doctors diagnose an overactive adrenal glands?
In addition to a complete medical history and physical examination, your child’s doctor will order specific blood and/or urine tests to measure hormone levels.

How can doctors tell if my child has Cushing’s syndrome?
In addition to a complete medical history and physical examination, your child’s doctor may request some or all of the following procedures:

• x-ray - a diagnostic test which uses invisible electromagnetic energy beams to produce images of internal tissues, bones and organs onto film
• 24-hour urinary test (urine is collected over a 24-hour period to measure corticosteroid hormones)
• computerized tomography scan (Also called a CT or CAT scan) - a diagnostic imaging procedure that uses a combination of x-rays and computer technology to produce cross-sectional images (often called slices), both horizontally and vertically, of the body
• magnetic resonance imaging (MRI) - a diagnostic procedure that uses a combination of large magnets, radiofrequencies and a computer to produce detailed images of organs and structures within the body
• dexamethasone suppression test (to differentiate whether the excess production of corticotropins originates from the pituitary gland or tumors elsewhere)
• corticotropin-releasing hormone (CRH) stimulation test (to differentiate whether the cause is a pituitary tumor or an adrenal tumor)

How are overactive adrenal glands/Cushing’s syndrome treated?
Treatment for overactive adrenal glands may include surgical removal of growths on the adrenal gland(s) or the adrenal gland(s) itself. Your doctor may also prescribe medications that block the excessive production of certain hormones.

From https://web1.tch.harvard.edu/az/Site1405/mainpageS1405P0.html

Adrenal venous sampling is crucial before an adrenalectomy whatever the adrenal-nodule size on computed tomography

Journal of Hypertension:

June 2011 - Volume 29 - Issue 6 - p 1196–1202

doi: 10.1097/HJH.0b013e32834666af

Original papers: Aldosterone

Adrenal venous sampling is crucial before an adrenalectomy whatever the adrenal-nodule size on computed tomography

Sarlon-Bartoli, Gabriellea; Michel, Nicolasa; Taieb, Davidb; Mancini, Julienc; Gonthier, Camillea; Silhol, Françoisa; Muller, Cyrild; Bartoli, Jean-Micheld; Sebag, Frédérice; Henry, Jean-Françoise; Deharo, Jean-Claudea; Vaisse, Bernarda

Abstract

Objective: To assess the additional value of adrenal venous sampling (AVS) to diagnose primary aldosteronism sub-types in patients who have a unilateral nodule detected by computed tomography (CT scan) and who should undergo an adrenalectomy.

Methods: A retrospective study to assess consecutive patients with primary aldosteronism undergoing an adrenal CT scan and AVS. Criterion for selective cannulation was an equal or higher cortisol level in the adrenal vein compared to the inferior vena cava. An adrenal-vein aldosterone-to-cortisol ratio of at least two times higher than the other side defined lateralization of aldosterone production.

Results: Sixty-seven patients (mean age 52 years, 39 men) underwent a CT scan accccand AVS. In nine patients (13%), cannulation of the right adrenal vein led to a technical failure. Both procedures led to diagnosis of 29 patients with adenoma-producing aldosterone (APA; 50%), 23 bilateral adrenal hyperplasias (40%), and six unilateral adrenal hyperplasias (10%). Of the 45 patients with a nodule detected by CT, subsequent AVS showed bilateral secretion in 16 patients (36%). Compared to the strategy of coupling CT scans with AVS to diagnosis APA, a CT scan alone had an accuracy of 72.4% (P < 0.001). Among patients with a macronodule detected by CT, 13 (37%) had bilateral secretion as assessed by AVS. The patients with a macronodule detected by CT alone had the same risk of a discrepancy as those with a small nodule (P = 0.99).

Conclusion: AVS is essential to diagnose the unilateral hypersecretion of aldosterone, even in patients in whom a unilateral macronodule is detected by CT, to avoid unnecessary surgery.

From http://journals.lww.com/jhypertension/Abstract/2011/06000/Adrenal_venous_sampling_is_crucial_before_an.24.aspx

NIH Adrenal Clinical Trials Updated 5/5/2011

Rank	Status	Study
1	Completed	Cardiovascular Risk in Patients With Non-Functional Adrenal Incidentaloma Condition: Adrenal Cortex Neoplasms Intervention:
2	Completed Has Results	Changes in Adrenal Hormones During Adrenal Radiofrequency Ablation Condition: Adrenal Gland Neoplasms Intervention: Procedure: Radiofrequency ablation
3	Completed	Adrenal Scans With Radioiodine-Labeled Norcholesterol (NP-59) Conditions: Adrenal Gland Neoplasms;   Adrenal Malignancies;   Abnormal Hormonal Secretions;   Electrolytes Abnormalities Intervention: Other: Imaging, Adrenal acans
4	Recruiting	Trial of Vasopressin and Epinephrine to Epinephrine Only for In-Hospital Pediatric Cardiopulmonary Resuscitation Conditions: Cardiopulmonary Arrest;   Cardiac Arrest Interventions: Drug: Vasopressin;   Drug: Epinephrine
5	Completed	Adrenal Suppression and Adrenal Recovery Induced by Megestrol Acetate Condition: Adrenal Function Intervention: Drug: megestrol acetate
6	Recruiting	Test Predicting Adrenal Insufficiency in Volunteers Under Prednisone Treatment Condition: Adrenal Gland Hypofunction Interventions: Procedure: adrenal insufficiency testing;   Drug: prednisone
7	Recruiting	The Bupivacaine Dose Sparing Effect of Intrathecal Epinephrine Condition: Spinal Anesthesia Interventions: Drug: Placebo;   Drug: epinephrine 25;   Drug: Epinephrine 50;   Drug: epinephrine 100;   Drug: Epi 200
8	Recruiting	SPARTACUS: Subtyping Primary Aldosteronism: a Randomized Trial Comparing Adrenal Vein Sampling and Computed Tomography Scan. Condition: Hyperaldosteronism Intervention: Other: Ct-scan or adrenal vein sampling
9	Completed	Make up for the Epinephrine Autoinjector Condition: Anaphylaxis Intervention: Device: Epinephrine autoinjector
10	Completed	Epinephrine Inhalation Aerosol USP, a HFA-MDI Study for Assessment of Pharmacokinetics Conditions: Asthma;   Bronchospasm;   Wheezing;   Shortness of Breath Interventions: Drug: Epinephrine Inhalation Aerosol, HFA;   Drug: Epinephrine Inhalation Aerosol
11	Completed	Once-Daily Oral Modified-Release Hydrocortisone in Patients With Adrenal Insufficiency Condition: Adrenal Insufficiency Interventions: Drug: hydrocortisone (modified release), oral tablet 20 and 5 mg;   Drug: Hydrocortisone, oral tablet, 10 mg
12	Completed	Pharmacokinetics (PK) Study of Epinephrine Inhalation Aerosol in Healthy Volunteers Condition: Asthma Intervention: Drug: epinephrine inhalation aerosol
13	Completed	ED50 and ED95 of Intrathecal Bupivacaine With or Without Epinephrine for Total Knee Replacement Arthroplasty Conditions: Spinal Anesthesia;   Total Knee Replacement Arthroplasty Interventions: Drug: intrathecal bupivacaine 6 mg with 100 mcg of epinephrine;   Drug: intrathecal bupivacaine 7 mg with 100 mcg of epinephrine;   Drug: intrathecal bupivacaine 8 mg with 100 mcg of epinephrine;   Drug: intrathecal bupivacaine 9 mg with 100 mcg of epinephrine;   Drug: intrathecal bupivacaine 10 mg with 100 mcg of epinephrine;   Drug: intrathecal bupivacaine 11 mg with epinephrine 100 mcg;   Drug: intrathecal bupivacaine 6 mg with 200 mcg of epinephrine;   Drug: intrathecal bupivacaine 7 mg with 200 mcg of epinephrine;   Drug: intrathecal bupivacaine 8 mg with 200 mcg of epinephrine;   Drug: intrathecal bupivacaine 9 mg with 200 mcg of epinephrine;   Drug: intrathecal bupivacaine 10 mg with 200 mcg of epinephrine;   Drug: intrathecal bupivacaine 11 mg with 200 mcg of epinephrine
14	Active, not recruiting	Study of UK Adults With Congenital Adrenal Hyperplasia. Condition: Congenital Adrenal Hyperplasia Intervention:
15	Not yet recruiting	Intranasal Injection Versus Topical Administration of Epinephrin During Endoscopic Sinus Surgery Conditions: Hypertension;   Hypotension;   Tachycardia;   Bradycardia;   Arrhythmia Interventions: Drug: Epinephrin (Intranasal injection);   Drug: Epinephrin (Topical administration)
16	Recruiting	Adrenal Insufficiency in Septic Shock Conditions: Septic Shock;   Acute Adrenal Insufficiency Intervention: Drug: Corticosteroid
17	Recruiting	Performance of 18F-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) in the Diagnosis of Indeterminate Adrenal Tumors on Conventional Imaging: A French Prospective Multicentric Study Condition: Adrenal Gland Neoplasms Intervention: Other: FDG-PET scan
18	Unknown †	Prospective Study on the Incidence of Adrenal Crisis in Patients With Chronic Adrenal Insufficiency Condition: Adrenal Insufficiency Intervention:
19	Completed	Dose Response Relationship for Single Doses of Corticotropin Releasing Hormone (CRH) in Normal Volunteers and in Patients With Adrenal Insufficiency Conditions: Adrenal Gland Hyperfunction;   Adrenal Gland Hypofunction;   Cushing's Syndrome;   Healthy Intervention: Drug: Ovine Corticotropin-Releasing Hormone (oCRH)
20	Recruiting	Adrenal Function in Critical Illness Condition: Adrenal Insufficiency Intervention:

Rank	Status	Study
21	Recruiting	Study of Adrenal Gland Tumors Condition: Adrenal Gland Neoplasm Intervention:
22	Recruiting	The Effects of Epinephrine in Endotoxemia in Normal Volunteers Condition: Immune System Interventions: Biological: Endotoxin, Lipopolysaccharide, LPS;   Biological: Endotoxin, Lipopolysaccharide, LPS /Epinephrine
23	Unknown †	Does Topical Steroid Treatment Impair the Adrenal Function? Conditions: Hypothalamus-Pituitary-Adrenal Axis Assessement;   Topical Steroid Therapy in Chronic Skin Diseases Intervention:
24	Recruiting	Combination Local Anesthetics Condition: Perioperative Pain Interventions: Drug: 1% Lidocaine with Epinephrine;   Drug: 0.25% Bupivacaine with epinephrine;   Drug: 1% Lidocaine + 0.25% Bupivacaine with Epinephrine;   Drug: 2% Lidocaine + 0.5% Bupivacaine with epinephrine
25	Recruiting	Study Comparing Peri-articular Injection of Bupivacaine With and Without Epinephrine Condition: Osteoarthritis Interventions: Procedure: Peri-articular injection of marcaine/epinephrine;   Procedure: Peri-articular injection of marcaine alone
26	Not yet recruiting	Gluing Lacerations Utilizing Epinephrine Condition: Lacerations Intervention: Drug: LET - Lidocaine Epinephrine Tetracaine
27	Recruiting	Use of Local Analgesia With Epinephrine During Total Hip Arthroplasty (THA) Condition: Arthroplasty, Replacement, Hip Intervention: Drug: ropivacaine, physical serum and adrenalin
28	Recruiting	Relative Adrenal Insufficiency in Preterm Very Low Birth Weight Infants With Shock Condition: Adrenal Insufficiency Intervention:
29	Unknown †	Adrenal Insufficiency in Cirrhotics With Ascites. Effects of Hydrocortisone on Renal and Haemodynamic Function Condition: Cirrhosis With Ascites Interventions: Drug: hydrocortisone;   Drug: dextrose solution 5%
30	Recruiting	Bronchiolitis, Optimal Treatment in Infants and Prognosis Condition: Bronchiolitis Interventions: Drug: Racemic adrenaline;   Drug: Isotonic saline
31	Recruiting	RAD001 in Pheochromocytoma or Nonfunctioning Carcinoid Conditions: Pheochromocytoma;   Extra-Adrenal Paraganglioma;   Non-functioning Carcinoid Intervention: Drug: RAD001
32	Not yet recruiting	Hypoglycemia Associated Autonomic Failure in Type 1 DM, Q4 Condition: Type 1 Diabetes Intervention: Drug: epinephrine
33	Recruiting	Effect of Epinephrine/ Phenylephrine for Preventing the Postreperfusion Syndrome During Reperfusion in Liver Transplantation Condition: Hypotension After Reperfusion in Liver Transplantation Interventions: Drug: phenylephrine;   Drug: epinephrine;   Drug: placebo control
34	Recruiting	Safety Study Evaluating the Adrenal Suppression Potential of Product 0405 in Pediatric Subjects With Atopic Dermatitis Condition: Atopic Dermatitis Intervention: Drug: Product 0405
35	Recruiting	Merits of Continuous Paravertebral Block in the Management of Renal/Adrenal Surgery by Laparotomy Condition: Patient Scheduled for Renal and/or Adrenal Surgery Intervention: Procedure: Continuous Paravertebral block
36	Not yet recruiting	Adrenalectomy Versus Follow-up in Patients With Subclinical Cushings Syndrome Condition: Adrenal Tumour With Mild Hypercortisolism Intervention: Procedure: Adrenalectomy
37	Recruiting	Role of the Protein Osteoprotegerin in the Bone Health of Women With Congenital Adrenal Hyperplasia Condition: Adrenal Hyperplasia, Congenital Intervention:
38	Recruiting	Gene Polymorphisms Influencing Steroid Synthesis and Action Conditions: Disorders of Sex Development;   Congenital Adrenal Hyperplasia;   Congenital Adrenal Hypoplasia;   Adrenal Insufficiency;   Mineralocorticoid Deficiency;   Intersex Intervention:
39	Recruiting	Adrenal Function and Use of Intralesional Triamcinolone Acetonide 10 mg/mL (Kenalog-10) in Patients With Alopecia Areata Condition: Alopecia Areata Intervention: Drug: Triamcinolone Acetonide 10 mg/mL (Kenalog-10)
40	Recruiting	Assessment of the Efficacy of Nebulised 3% Hypertonic Saline Among Infants Aged 6 Weeks- 24 Months With Bronchiolitis Condition: Bronchiolitis Interventions: Drug: L-Epinephrine and 0.9% Normal Saline;   Drug: L-Epinephrine and 3% Hypertonic Saline

Congenital adrenal hyperplasia (CAH)

PerkinElmer's Neonatal17 a-OH-Progesterone (17OHP) assay for its DELFIA®, AutoDELFIA® and GSP® platforms platforms provides the highest standards of reliability and safety in screening for congenital adrenal hyperplasia (CAH). It is globally the most widely used assay for 1st tier CAH screening, and in 2008 theproduct was used in 47 countries.

No extraction step needed

The assay is a straightforward dried blood spot assay.  No extraction step is needed, which means savings in both total assay time and materials.

DELFIA®-technology stands for quality

The unique fluorescent properties of lanthanide chelatesare the basis for high sensitivity and low assay variation, and these features, in turn, stand for reliable and accurate 17a-OH-Progesterone measurement with low bias.

Early diagnosis for early disease/Intervention

Congenital adrenal hyperplasia is a genetic disorder affecting 1:10,000 to 1:15,000 newborns worldwide and the most severe form of the disease can lead to a life-threatening condition during the first weeks of life.  The disease is caused by enzyme defects in the steroid biosynthesis, the most frequent types being 21- and 11a-hydroxylase deficiency. In both of these the17a-OH-progesterone, a precursor for cortisol, is increased which makes its determination a useful screening method for 95% of all of the CAH cases.

PerkinElmer's Neonatal 17OHP assay is intended for the quantitative determination of 17a-OH-progesterone indried blood spot specimens as an aid in screening newborns for CAH.

From http://www.perkinelmer.com/Catalog/Category/ID/Congenital%20adrenal%20hyperplasia%20CAH