Question: I recently had a left adrenalectomy. The tests before my surgery indicated that I should not have Cushing’s Syndrome as well as other adrenal disorders. However, since surgery I have had significant weight loss, a huge improvement in diabetic control, annoying aches and pains and have fluctuated between having improved energy with periods of fatigue. Is it possible for people to undergo surgery on what was thought to be a nonfunctioning tumor but it turned out to be a mild functioning or cyclic tumor? What are the follow-up guidelines if this happens and what signs of adrenal insufficiency should I be alert for?

Answer: There is a wide spectrum of hormone production by tumors of the adrenal gland. There are two main zones of the adrenal glands. The inner portion called the adrenal medulla produces adrenalin or catecholamines; tumors of the adrenal medulla that secrete excess amounts of catecholamines are called pheochromocytomas.

 The outer portion called the adrenal cortex produces steroid hormones including cortisol, aldosterone and the androgen precursor DHEAS. When a tumor of the adrenal cortex produces large amounts of cortisol, patients present with progressive signs and symptoms of Cushing’s syndrome. While extreme excess production of cortisol resulting in adrenal Cushing’s syndrome is rare, a much larger proportion (10-20%) of adrenal cortex tumors found accidentally during the course of abdominal imaging (adrenal incidentalomas) produce slightly increased amounts of cortisol which can cause either no symptoms or only very discrete symptoms of cortisol excess. This condition is often referred to as sub-clinical Cushing’s syndrome. The amount of cortisol production may appear as being in the normal range when cortisol production is measured in a 24-hour urine collection for determination of urinary free cortisol. However cortisol production may not decrease normally when patients are administered a drug called dexamethasone orally. For example when 1 mg of dexametahsone is administered by mouth before bedtime and blood cortisol levels are measured fasting on the following morning, blood cortisol levels should decrease to below 1.8 mcg/dl. Many patients with sub-clinical Cushing’s syndrome may have levels of cortisol between 1.8 and 5 or even up to 10 mcg/dl following overnight dexamethasone and have normal urinary free cortisol levels and no or only very discrete manifestations of cortisone excess. However, even relatively modest cortisol overproduction can progressively cause diabetes, high blood pressure, or osteoporosis. After the tumor is removed and cortisol is normalized, improvements in diabetes, lower blood pressure and weight loss are often observed.

A slight chronic increase of cortisol production by an adrenal tumor may suppress partially the production of ACTH from the pituitary gland, which can result in a mild state of relative rest of the adrenal gland opposite to the adrenal tumor. Mild symptoms of adrenal insufficiency may be present in the weeks following removal of an adrenal tumor that produced sub-clinical Cushing’s syndrome. Mild adrenal insufficiency could be manifested by fatigue, lack of appetite, morning nausea, and muscle aches. Signs of severe adrenal insufficiency very rarely occur with sub-clinical Cushing’s, but the symptoms of severe adrenal insufficiency include vomiting, dizziness and low blood pressure. Should these more severe symptoms occur, consult an endocrinologist immediately.

Patients who were found to have sub-clinical mild overproduction of cortisol and partial ACTH suppression from their adrenal tumor and who undergo adrenalectomy should receive cortisone (hydrocortisone, cortisone acetate or prednisone) supplements during and after surgery to avoid symptoms of adrenal insufficiency. Normal recovery of the remaining adrenal gland can be verified rapidly after surgery or periodically during the recovery period (can take as long as one year) by measuring blood cortisol levels fasting in morning and following injection of synthetic ACTH (ACTH stimulation or cortrosyn test).

In conclusion, all patients with adrenal tumors should have testing for excess production of catecholamines (urinary metanephrines) and of cortisol using overnight 1 mg-overnight dexamethasone test before surgery. If cortisol suppression is not normal, supplementation with hydrocortisone or prednisone may be required for several weeks while awaiting full recovery of ACTH and other adrenal gland.