Idiopathic isolated central adrenal insufficiency

From the desk of Lewis S. Blevins, Jr. M.D.  PWN cofounder – Idiopathic isolated central adrenal insufficiency remains a mystery.  I’ve seen several patients with this condition in my career.  I first learned about it when I saw my first patient at Hopkins.

Most patients have come to me already taking steroids.  Some were on doses that were too high causing Cushingoid features.  I have been able to  successfully wean some of them from steroid replacement. Others seem to be unable to recover function and remain on long-term treatment even though they have not been on high doses.  These tend to be patients who also have postural orthostatic hypotension .  Most are also a little overweight.  I often wonder if they have a partial POMC deficiency or some other issue with processing of POMC.  POMC mutations are a recognized cause of obesity so it always comes to mind.  Testing hasn’t been widely available and has mostly been research-related.  Perhaps this syndrome is a form of central adrenal insufficiency and autonomic dysfunction with weight gain related to hypothalamic dysfunction.

When evaluating these patients it’s essential to exclude recent or repeated administration of supraphysiologic doses of steroids that can suppress CRH and ACTH release as a potential cause of secondary insufficiency.  Also, it’s important to review the medication history as narcotics can also suppress the hypothalamic-pituitary-adrenal axis. Most patients have otherwise normal pituitary functions.

The most severe forms of adrenal crisis occur in patients with primary adrenal failure who have both glucocorticoid and mineralocorticoid deficiency states. It’s the mineralocorticoid deficiency that leads to the high risk of crisis.  I’ve seen adrenal crisis in several patients with isolated central adrenal insufficiency and in a few with hypopituitarism.  I’m wondering if it’s more common in those with orthostatic hypotension.  It would make sense that, if these patients have diminished autonomic outflow,  that they might have hyporeninemic hypoaldosteronism leading to mineralocorticoid deficiency thus,  increasing their risk for adrenal crisis.

Treatment involves traditional approaches to glucocorticoid replacement.  I refer patients to neurology, centers specializing in the autonomic nervous system, or to cardiology for evaluation and management of the postural orthostatic hypotension.  Many are treated with compression stockings, alpha-agonists which cause vasoconstriction, and even fludrocortisone which increases salt and water retention by the kidney.

Notes:

Idiopathic isolated central adrenal insufficiency (IIAD) is a rare condition where the pituitary gland fails to produce enough ACTH , leading to secondary adrenal insufficiency, which is characterized by low cortisol levels. Isolated means that only ACTH production is affected, while other pituitary hormones are typically normal.

Postural orthostatic hypotension is when your blood pressure drops when you go from lying down to sitting up, or from sitting to standing.

POMC deficiency is a rare genetic disorder that affects the production of hormones that regulate appetite, metabolism, and pigmentation.  

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