Addison’s Disease and Congenital Adrenal Hyperplasia (CAH)

Background: The adrenal gland is made up of two distinct parts, the cortex and the medulla. The cortex makes the steroids we need for life, cortisol and aldosterone, as well as others. The medulla makes and stores epinephrine (adrenaline), but is not the only tissue to do so. The synthesis of these steroidal hormones is a process which has a number of steps. Each step has a required catalyst (specific enzyme). In some cases, there is more than one pathway to a particular steroidal hormone. The gonads (ovaries or testes) also make steroidal hormones, which are more specialized if function. The normal adrenal gland also makes androgens, which are male hormones important to both men and women. DHEA is one of these, but the production of testosterone by this pathway is only about 10% that of normal gonad function.

 The pituitary makes a hormone called ACTH that signals the adrenal gland to start making cortisol (HC) from cholesterol, the starting steroid molecule. As the HC concentration in the blood rises, the pituitary begins to decrease the production of ACTH (feedback). This process occurs on a 24 hour cycle with the highest levels of ACTH being made in the early hours of the morning so that HC levels are highest about 8 AM.

The Diseases: In the case of primary adrenal cortical insufficiency (AI, Addison’s Disease), the whole adrenal cortex loses its ability to make any of the steroids necessary for life, as well as DHEA, and others. During the normal development of this disease, which can take several years, the individual becomes weaker and weaker and pigmentation in the skin (sun tan, or extreme freckling), perhaps most prominent in the genitalia, due to the unchecked production of ACTH by the pituitary, becomes greater. Primary AI is diagnosed by the ACTH stimulation test. If the adrenal gland is normal (see below) then there is an increase of at least two times the amount of HC produced. If the test shows an amount less than two times, then primary AI is indicated. With this disorder, the individual cannot make aldosterone. Treatment involves replacement with HC (or prednisone, or less often with dexamethasone, methylprednisone (Medrol), or cortisone acetate) and Florinef (for aldosterone). This disease is rare and has been estimated to affect only 1 in 100,000.

 Another type of Addisons disease, called secondary AI, results from malfunction of the pituitary. This results from the inability of the pituitary to make enough ACTH. The treatment is the same as for primary AI except that florinef may not be needed.

 If the pituitary makes too much ACTH this leads to Cushing’s disease. If the disease cannot be treated at the pituitary level then patients have their adrenal glands removed surgically, and they are treated as those with classical primary AI. The over production of ACTH by the pituitary can result from ACTH secreting benign tumors. Similarly, Cushing’s disease can be produced by malignant or benign tumors which secrete HC.

 If a person is on steroid therapy (typically prednisone) for asthma or another disease where immune suppression or extreme anti-inflammatory is called for, then they can either reversibly, or totally lose adrenal cortical function. This is called steroid induced AI. It is treated like secondary AI, but the prolonged use of prednisone can result in adrenal atrophy and the need for Florinef as well.

 Congenital Adrenal Hyperplasia (CAH) relates to a group of disorders. Regardless of the specific disorder, the individual is lacking or has a severely reduced level of one of those important enzymes that catalyze specific steps in the synthesis of needed steroids. These disorders are much more common than AI and have a genetic basis. They are commonly, but not always, recognized in infants. In the most common form, they cause altered genital development and sexual ambiguity. Other forms of the disease appear later in life. Adults or adolescents diagnosed with CAH have a form of one of the latter less common disorders, which may not involve sexual ambiguity. The severe form, which is diagnosed in infants, leads to death if not diagnosed or treated. In the most common form the ACTH stimulation test is used to detect the disease in infants. This can also be used with older individuals but it must be coupled to tests for altered concentrations of specific molecules such as 17-hydroxyprogesterone and pregnanetriol on stimulation. That is why the testing must be done by an experienced and knowledge endocrinologist. More than one test is required and you must have various aspects of your pituitary function tested as well because this gland is control central for hormone production. For example, increased levels of 17-hydroxyprogesterone and pregnanetriol suggest that the patient has low levels of the enzyme 21-hydroxylase, which is common in CAH. When one enzyme is absent or impaired then the balance of the both the adrenal gland and the gonads can be completely perturbed leading to situations such as increased level of testosterone production. Electrolyte imbalance, which in the case of primary AI results in low sodium and high potassium levels, are sometimes skewed in CAH and can result in low potassium and high sodium. There is a rare form of CAH which shows up in young women. It is called StAR.

 A normal response to the ACTH stimulation test does not definitely rule out CAH. The dexamethasone suppression test is usually given to diagnose Cushing’s disease and the over production of cortisol.

 Please keep in mind that I am not a physician. I am a scientist with primary adrenal cortical insufficiency (Addisons disease), which was diagnosed and treated many years ago.

 Copyright © 2004 by Dick

This page was last updated 03/18/05