Adrenal Gland Disorders

The adrenal glands. Source: National Institute of Child Health and Development

Adrenal gland disorders occur when the adrenal glands don’t work properly. The adrenal glands are organs situated on top of the kidneys. The adrenal glands have several important functions. These include:

• Maintenance of metabolic processes, such as managing blood sugar levels and regulating inflammation
• Regulation of salt and water balance
• Control of the "fight or flight" response to stress
• Maintenance of pregnancy
• Initiation and control of sexual maturation during childhood and puberty

The adrenal glands are also an important source of sex steroids, such as estrogen and testosterone.

Adrenal gland disorders may result from diseases of the adrenal glands or from a problem in another gland that helps to regulate the adrenal gland.

Types

Cushing Syndrome

Cushing Syndrome results from high levels of the hormone cortisol. In this syndrome, the adrenal glands make more cortisol than the body needs. This syndrome can result from adrenal tumors (which can be inherited) or some medications that cause the glands to make too much cortisol.

Congenital Adrenal Hyperplasia

Congenital Adrenal Hyperplasia is a genetic disorder that causes mutations in the genes responsible for adrenal hormone synthesis. In this disorder, the adrenal glands don’t make enough cortisol. Often this condition occurs in conjunction with other hormonal imbalances, such as deficiencies in aldosterone, (which regulate salt balance), or excessive androgen (a male sex hormone)

Pituitary tumors

The pituitary gland is located in the brain and helps regulate the activity of many other glands, including the adrenal glands. In rare cases, benign (non-cancerous) tumors may grow on the pituitary gland. The tumor(s) may reduce hormone secretion and in some cases can lead to Cushing syndrome.

Addison disease

Addison disease occurs when the adrenal glands do not secrete adequate amounts of cortisol and aldosterone. These hormones have many functions. Cortisol's most important function is to help the body respond to stress.

Signs and Symptoms

Below are some symptoms of adrenal gland insufficiency:

• Fatigue
• Low blood sugar
• Low blood pressure
• Sensitive to allergies
• Depression
• Anxiety
• Craving for sweets
• Headaches

Overproduction of adrenal hormones can cause the following effects:

• Weight gain, especially in the torso and face (“moon face”)
• Constipation
• Increased appetite
• Acne
• Hair growth
• High blood pressure
• Stomach ulcers

Causes

The causes of adrenal gland disorders vary depending on the type of disorder.

• Cushing syndrome occurs when the body's tissues are exposed to excessive levels of cortisol for long periods of time. Many people suffer the symptoms of Cushing's syndrome because they take glucocorticoid hormones such as prednisone for asthma, rheumatoid arthritis, lupus and other inflammatory diseases, or for immunosuppression after transplantation. Others develop Cushing's syndrome because of overproduction of cortisol by the body. If something goes wrong with the adrenal glands or their regulating switches in the pituitary gland or the hypothalamus, cortisol production can be affected.

• Congenital adrenal hyperplasia results from the lack of an enzyme needed by the adrenal gland to make the hormones cortisol and aldosterone (21-hydroxylase or 11-ß hydroxylase.).

• A pituitary tumor is an abnormal growth of cells within the pituitary gland. Most pituitary tumors are benign, which means they are non-cancerous, grow slowly and do not spread to other parts of the body, however they can make the pituitary gland produce too many hormones, which can cause problems in the body. Tumors that make hormones are called functioning tumors, and they can cause a wide array of symptoms depending upon the hormone affected. Tumors that don’t make hormones are called non-functioning tumors.

• Addison disease may be caused by an autoimmune reaction, cancer, an infection, or some other disease.

Diagnosis

Cushing syndrome

Tests used to diagnose Cushing syndrome include:

• 24-Hour urinary free cortisol level is the most specific test used to diagnose Cushing syndrome. Once the diagnosis is made, more tests are usually done. These may include:

• A dexamethasone suppression test which helps to distinguish patients with excess production of ACTH due to pituitary adenomas from those with ectopic ACTH-producing tumors. In this test, patients are given dexamethasone, a synthetic glucocorticoid, by mouth every 6 hours for 4 days. For the first 2 days, low doses of dexamethasone are given, and for the last 2 days, higher doses are given. Twenty-four hour urine collections are made before dexamethasone is administered and on each day of the test. Since cortisol and other glucocorticoids signal the pituitary to lower secretion of ACTH, the normal response after taking dexamethasone is a drop in blood and urine cortisol levels. Different responses of cortisol to dexamethasone are obtained depending on whether the cause of Cushing's syndrome is a pituitary adenoma or an ectopic ACTH-producing tumor.

• The CRH Stimulation test helps to distinguish between patients with pituitary adenomas and those with ectopic ACTH syndrome or cortisol-secreting adrenal tumors. Patients are given an injection of CRH, (corticotropin-releasing hormone} which causes the pituitary to secrete ACTH. Patients with pituitary adenomas usually experience a rise in blood levels of ACTH and cortisol. This response is rarely seen in patients with ectopic ACTH syndrome and practically never in patients with cortisol-secreting adrenal tumors.

• In petrosal sinus sampling, samples of blood are drawn from the petrosal sinuses, veins which drain the pituitary, by introducing catheters through a vein in the upper thigh/groin region. ACTH levels higher in the petrosal sinuses than in the forearm vein indicate the presence of a pituitary adenoma; similar levels suggest ectopic ACTH syndrome.

• The dexamethasone-CRH test was developed to distinguish between Cushing syndrome and pseudo-Cushing syndrome (high cortisol levels without the side effects of Cushing syndrome) so that Cushing's patients can receive prompt treatment. This test combines the dexamethasone suppression and the CRH stimulation tests. Elevations of cortisol during this test suggest Cushing's syndrome.

Congenital adrenal hyperplasia

Tests which may be helpful in diagnosing congenital adrenal hyperplasia include:

• Sodium levels in blood (serum electrolytes) and urine
• Level of 17-OH progesterone in the blood (high in CAH)
• Level of serum DHEA sulfate (high in CAH)
• Levels of urinary 17-ketosteroids (high)
• Blood levels of aldosterone and cortisol (low)
• Urinary 17-hydroxycorticosteroid levels (normal or low)
• X-ray for bone age (shows older bones than normal for the person's age)

Genetic tests can help diagnose, confirm, and manage the disease.

This disease may also affect the results of the serum or urine estriol and pregnanediol tests.

Pituitary tumors

Tests for pituitary tumors include: A thorough physical examination to note any problems with double vision and visual fields, such as loss of peripheral vision or the ability to see in certain areas.

Endocrine function tests include:

• Cortisol levels:
  • Dexamethasone suppression test
  • Urine cortisol test
• Follicle-stimulating hormone (FSH) levels
• Insulin growth factor-1 (IGF-1) levels
• Luteinizing hormone (LH) levels
• Serum prolactin levels
• Testosterone/estradiol levels
• Thyroid hormone levels:
  • Free T4 test
  • TSH test

Magnetic resonance imaging (MRI) of the head can confirm the diagnosis.

Addison disease

A diagnosis of Addison disease is made by laboratory tests. The aim of these tests is first to determine whether levels of cortisol are insufficient and then to establish the cause. X-ray exams of the adrenal and pituitary glands also are useful in helping to establish the cause.

• The ACTH stimulation test, described above, is the most specific test for the dianosis of Addison disease.
• When the response to the short ACTH test is abnormal, a long CRH stimulation test is required to determine the cause of adrenal insufficiency. In this test, synthetic CRH is injected intravenously and blood cortisol is measured before and 30, 60, 90, and 120 minutes after the injection. Patients with primary adrenal insufficiency have high ACTHs but do not produce cortisol. Patients with secondary adrenal insufficiency have deficient cortisol responses but absent or delayed ACTH responses. Absent ACTH response points to the pituitary as the cause; a delayed ACTH response points to the hypothalamus as the cause.

Treatment

The treatment for adrenal gland disorders depends on the specific disorder or specific cause.

• The treatment for Cushing syndrome depends on the cause. If the excess cortisol is caused by medication, the dosages can be changed a different medication used to correct the problem. If the Cushing’s syndrome is caused by the body making too much cortisol, treatments may include oral medication, surgery, radiation, or a combination of these treatments.
• Congenital adrenal hyperplasia can’t be cured, but it can be treated and controlled. People with congenital adrenal hyperplasia can take medication to help replace the hormones their bodies are not making. Some people with congenital adrenal hyperplasia only need these medications when they are sick, but others may need to take them every day.
• Doctors can successfully treat most pituitary tumors with microsurgery, radiation therapy, surgery, drugs, or a combination of these treatments. Surgery is currently the treatment of choice for tumors that grow rapidly, especially if they threaten or affect vision. The treatment plan for other pituitary tumors differs according to the type and size of the tumor.
• Treatment approaches to Addison disease include supplementation of the missing hormones with steroids, such as hydrocortisone.

Chances of Developing Adrenal Gland Disorders

The incidence of each condition varies.

• The incidence of Cushing syndrome has been estimated at 10 to 15 of every million people each year. ^[1]

• About 1 in 10,000 to 18,000 children are born with congenital adrenal hyperplasia. ^[2]

• Autopsy reports and radiologic and MRI evidence from around the globe indicate that one out of every five people worldwide has a pituitary tumor. ^[3]

• According to the Pituitary Network Association, ^[4], Addison disease affects about 1 in 100,000 people.

Clinical Trials

A list of U.S. government-sponsored clinical trials related to adrenal gland disorders is available here

Research

Recent discoveries

• CT, MRI, PET and PET/CT have all been shown to be clinically useful in differentiating benign from malignant adrenal involvement. Image-guided adrenal biopsy should be considered if needed for treatment planning and for the now relatively uncommon lesions that remain indeterminate by imaging. ^[5]
• A study was done to determine whether postoperative histologic evaluation using the previously proposed Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and cell cycle/apoptosis markers can predict patients at risk for recurrence. A PASS score of <4 predicted benign pheochromocytomas and all malignant pheochromocytomas had a PASS score >/=6, which was significantly higher compared with the benign lesions. The study concluded that patients with a PASS score >/=4 should be followed closely for recurrence. ^[6]

Current research

• An ongoing study is evaluating whether or not certain MRI sequences can accurately diagnose adrenal masses of unknown origin. ^[7]
• A study to determine if a combination of four drugs (flutamide, testolactone, reduced hydrocortisone dose, and fludrocortisone) can normalize growth in children with congenital adrenal hyperplasia. ^[8]
• The effects of intense exercise on the release of catecholamines in patients with congenital adrenal hyperplasia (CAH) and in healthy persons are being evaluated. Catecholamines are hormones (adrenaline and noradrenaline) that are produced by the adrenal glands and released into the blood stream during stress, such as trauma, illness, intense exercise, or low blood sugar. The study will also assess exercise tolerance in patients with CAH, compared with healthy persons. ^[9]
• * The Dutch ARR (aldosterone-to-renin ratio) AT Study has been initiated. This is a multicentre, prospective trial aiming to evaluate the test characteristics of the ARR within a Dutch population of therapy-resistant hypertensive patients. The effect of antihypertensive medication on the ARR will be studied. ^[10]

References

1. ↑ National Endocrine and Metabolic Diseases Information Service. Cushing's Syndrome
2. ↑ Medline Plus. Congenital adrenal hyperplasia
3. ↑ Pituitary Network Association. pituitary FAQ's
4. ↑ Pituitary Network Association. Adrenal Insufficiency
5. ↑ Blake MA, Calra MK. Current status of imaging for adrenal malignant involvement. Cancer Treat Res. 2008;143:319-29. Abstract
6. ↑ Strong VE, Kennedy T, Al-Ahmadie H, et al. Prognostic indicators of malignancy in adrenal pheochromocytomas: clinical, histopathologic, and cell cycle/apoptosis gene expression analysis. Surgery. 2008 Jun;143(6):759-68. Epub 2008 Apr 14. Abstract
7. ↑ ClinicalTrials.gov. Lipid-Poor Adrenal Masses: Evaluation With Chemical Shift MRI
8. ↑ ClinicalTrials.gov. Three Drug Combination Therapy Versus Conventional Treatment of Children With Congenital Adrenal Hyperplasia
9. ↑ ClinicalTrials.gov. Catecholamine Reserve and Exercise Tolerance in Healthy Volunteers and Patients With Congenital Adrenal Hyperplasia
10. ↑ Jansen PM, Boomsma F, van den Meiracker AH, Dutch ARRAT Investigators. Aldosterone-to-renin ratio as a screening test for primary aldosteronism--the Dutch ARRAT Study. Neth J Med. 2008 May;66(5):220-8. Abstract

External Links

Congenital Adrenal Hyperplasia.org

Pituitary Network Association

The Magic Foundation

American Academy of Clinical Endocrinologists