From the desk of Lewis Blevins, MD – I remember, in the mid-1990s, when a paper was published indicating that food dependent hypercortisolism was due aberrant GIP receptor expression on the adrenal glands.
Eating activates GIP secretion, GIP binds to its receptors. If receptors are expressed abnormally on a cell, such as an adrenal cell, they will be stimulated. In this condition, the GIP produced with eating stimulates adrenal function, causing bilateral macronodular hyperplasia and hypercortisolism.
GIP is an abbreviation for glucose dependent insulinotropic peptide. This hormone leads to the secretion of insulin in response to food in the digestive tract.
The up regulation of GIP receptors on the adrenal cortical cells is related to an inactivating mutation in the KDM1A gene. This gene is for histone demethylase.
This condition is most common in middle-aged women. I saw a patient who I thought had this disorder in the 1990s and my second patient just a few years ago. The second patient provided what I thought was a classic history. She knew that if she didn’t starve herself, she would gain tremendous amounts of weight and look Cushingoid. Patients usually bilateral macronodular adrenal hyperplasia, but I suspect patients in the earlier stages might have less severe hyperplasia. They all have hypercortisolism that is ACTH-independent in nature.
Confirmation, short of genetic studies, involves proving that a mixed meal or an oral glucose tolerance test stimulates cortisol secretion.
Treatment options include somatostatin receptors that might inhibit GIP secretion, adrenal steroidogenesis inhibitors, and bilateral adrenalectomy.
Similar disorders have been reported due to abnormal expression of LH receptors leading to Cushing’s onset during pregnancy and recurrence after menopause.
I tend to put these rare unusual disorders causing adrenal hyperplasia in the category of diseases that you’ll never diagnose if you haven’t heard of them. They prove that it’s an essential that physicians learn as much as is possible because one never knows when that information is going to be useful.
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