From the desk of Lewis Blevins, MD, AWN cofounder – I have a vague recollection of considering the possibility of the coexistence of primary aldosteronism and hypercortisolism in adrenal hyperplasia during my fellowship in Endocrinology 35 years ago. Vague, as I remember wondering if there may be adrenal disorders that could possess the enzymatic machinery to produce aldosterone and cortisol. I had suspected a few patients with adrenocortical carcinoma might produce both aldosterone and cortisol. And, of course I’ve long been aware of the concept of apparent mineralocorticoid excess in patients with hypercortisolism where cortisol acts as a mineralocorticoid and suppresses plasma renin and aldosterone.
My recollections were prompted by a recent patient. After considerable discussion, she proposed she had Connshing syndrome. I told her I didn’t think that was a thing. A week or two later, I looked it up. She was right!
I first saw her when she was a 74-year-old woman who had uncontrolled hypertension and hypercholesterolemia. Her sodium and potassium levels were 142 and 4.0 respectively. Her plasma renin levels were undetectable or low normal and her aldosterone levels were often high normal or elevated. Her aldosterone to renin ratio was always greater than 25 before treatment. She had been on about 17 medication‘s over a 30 year period to treat her hyperaldosteronism and seemed to be in reasonably good control taking eplerenone. She had had an overnight 1 mg dexamethasone suppression test in the recent past. Her serum cortisol was 2.8 mcg/dL with a valid dexamethasone level. This test indicated that she had pathologic cortisol secretion. I arranged for a salivary cortisol profile that showed lack of a diurnal variation. Her urine free cortisol level was slightly elevated at 55 µg. A repeat study revealed a cortisol excretion of 62 µg24. Her ACTH level was low to low normal. A CT scan of her abdomen revealed bilateral adrenal hyperplasia. After discussing the matter with her, I was convinced that she had adrenal modular hyperplasia with Connshing syndrome. When I was in my first year of medical school, one of the professor said “if you allow them, the patient will tell you what’s wrong with them.” What the doctor meant was that if you take a good history, you can probably get about 90% of the way towards the correct diagnosis and make most diagnoses. This patient certainly reinforced that statement. She told me precisely what she had!
This condition has been studied for several decades. The name was first proposed in 2017. It is characterized by aldosterone and cortisol excess due to adrenal disorders. While adrenal adenomas are the most commonly associated abnormality, adrenal hyperplasia, as in my patient, has also been reported.
Hyperaldosteronism accounts for 10% of cases of hypertension. It is most often due to an aldosterone-producing adenoma of the adrenal gland but may be associated with unilateral or bilateral adrenal hyperplasia. The classic clinical features include multi-drug resistant hypertension, hypokalemia and edema in the lower extremities. Most patients have low plasma renin and aldosterone levels. Often, these patients are taking medications that should raise or lower one or both of these in normal persons so it’s essential to interpret results with an eye towards what is expected on therapy along with what is actually observed.
Cortisol production by adrenal disorders ranges from mild autonomous cortisol secretion to absolute hypercortisolism. About one-third of patients with adrenal lesions have disordered cortisol secretion. Patients with this condition often have a history of weight gain, osteopenia or osteoporosis, hypertension and diabetes mellitus. Most do not look Cushingoid. ACTH and DHEA-S levels are typically low or low normal and cortisol levels are normal or slightly elevated. Affected patients do not suppress serum cortisol following ingestion of the test dose of dexamethasone.
Connshing syndrome is, basically, a combination of these conditions. The name is derived from Conn, who described what we know as primary hyperaldosteronism that is referred to as Conn’s syndrome, and from Cushing, who reported a patient who looked like what we refer to as Cushing’s syndrome that is due to overt hypercortisolism.
Interestingly, 20-30% of patients with primary hyperaldosteronism also have disordered cortisol secretion when tests are performed to evaluate for this condition. Thus, Connshing should be considered in all patients with either adrenal hyperaldosteronism or MACS/hypercortisolism. Ask your doctor to do appropriate tests for both of these in the morning including: Plasma Renin, Aldosterone, ACTH, DHEA-S, Cortisol, overnight 1mg Dexamethasone Suppression Test. Further studies may be needed based on the results of these tests.
Often, patients with Connshing syndrome can be suspected based on the presence of multiple cardiometabolic disorders, including diabetes mellitus, hypertension, and hyperlipidemia, that are difficult to treat.
Treatment for unilateral disease usually involves laparoscopic adrenalectomy. Patients with bilateral disease should be treated with medication in attempt to reduce cortisol and aldosterone secretion. Medications to treat hypertension, diabetes, and hyperlipidemia may still be required. My patient was treated with ketoconazole. Therapy normalized aldosterone secretion. Her 24 hour urine aldosterone level was first undetectable and then the drug was adjusted to maintain a normal level of about 7 µg per 24 hours. Her 24 hour urine cortisol has been normal and ranged from 21 to 34 µg with an average of approximately 22 µg.
The other principle that this case affirms is that you have to know about a disease to be able to diagnose it. I can’t under emphasize the importance of doing regular reading and review of the literature to stay appraised of developments. I had missed the article in 2017. There hasn’t been much written about it since but clearly this is a real “thing.” I’m hoping that this article leads some of you to the correct diagnosis and appropriate treatment.
Image by Gerd Altmann from Pixabay
© 2026, AWN. All rights reserved.