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Adrenal Cushing’s Responsive to Food and Other Hormones

Question: I’ve heard that some types of adrenal Cushing’s can be caused by food or other hormones. Is that true?

Answer: The mechanism by which adrenal tumors continue to secrete cortisol in the absence of ACTH (the normal regulator that is suppressed due to excess cortisol) have not been well understood until recently. Recent work by our group and other investigators have suggested that the cause of adrenal Cushing’s syndrome in certain patients could be due to the abnormal presence and/or function of hormone receptors on the adrenal gland (ectopic receptors).

Receptors are proteins on the surface of and in the membranes of individual cells that hormones bind to, causing a response by the cell. For example, ACTH normally stimulates cortisol production by binding to the ACTH receptor present on the adrenal gland cells. The presence of abnormal receptors in the adrenal gland cortex cells, or tumor, can place the production of cortisol under the control of hormones other than ACTH. These other hormones are present in the body, but normally serve a totally different function and do not stimulate cortisol production in normal individuals.

One of the first demonstrations of this concept came from the observation that some patients with adrenal Cushing’s syndrome had increased cortisol production following eating, while cortisol levels remained low during fasting. It was demonstrated that this was secondary to the abnormal presence of receptors for a gastrointestinal hormone, called GIP for gastric inhibitory polypeptide. GIP is normally secreted by intestinal cells every time we eat. GIP normally provides a signal to the pancreas that glucose is entering the circulation and that insulin production should be stimulated to normalize blood glucose levels. GIP receptors are not normally present in large quantity in the adrenal gland and do not normally regulate cortisol production. In certain patients with either a single adrenal tumor or with bilateral macronodular adrenal hyperplasia, the abnormal increased presence of adrenal GIP receptors creates a new mechanism for control of cortisol secretion.

This first demonstration led to an investigation of the potential presence of other abnormal hormone receptors in patients with adrenal Cushing’s syndrome. Since then, it has been demonstrated that other patients have abnormal stimulation of cortisol production by other hormones, mediated by their receptors. The list now includes vasopressin, adrenalin, LH (luteinizing hormone which normally regulates ovarian or testicular function), and serotonin.

The identification of the abnormal receptor can lead to novel approaches in the treatment of these conditions. It has now been shown that the use of drugs to block specific receptors or to block the release of the hormones for those receptors, can bring normalization of the production of cortisol in some individuals without performing surgery. It should be kept in mind that this work is still experimental and preliminary results indicate that this phenomenon may be more frequent in cases of bilateral macronodular adrenal hyperplasia and less frequent in cases of a single adrenal tumor.

By Dr. Andre Lacroix MD (Fall, 1997)

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