Weight loss, low potassium mark unusual Cushing’s disease case
Woman's case shows patients don't always show classical clinical features
A 75-year-old woman with Cushing’s disease who was first seen with marked weight loss and low blood levels of potassium, or hypokalemia, was described by researchers as an unusual example of the condition, one otherwise resembling ectopic Cushing’s syndrome.
“This case highlights the need to entertain a broad differential in patients presenting with hypokalemia and weight loss and the need to exclude [high cortisol],” the researchers wrote.
The woman’s case was described in “Atypical presentation of Cushing’s disease with weight loss and hypokalemia,” which was published in Endocrinology, Diabetes and Metabolism Case Reports.
Cushing’s syndrome is a group of conditions marked by abnormally high levels of the hormone cortisol. Cushing’s disease is a subtype of the syndrome caused by tumors in the pituitary gland that release large amounts of adrenocorticotropic hormone (ACTH), which cause the adrenal glands atop the kidneys to overproduce cortisol. In some cases, ACTH-producing tumors outside the pituitary gland can trigger cortisol overproduction, which is referred to as ectopic Cushing’s syndrome.
Weight gain is a common sign of Cushing’s disease, whereas weight loss and low potassium levels in the bloodstream, called hypokalemia, are characteristic of ectopic Cushing’s.
Researchers at Dalhousie University in Canada were presented with a 75-year-old woman with Cushing’s disease who had significant hypokalemia and marked weight loss.
Normalizing cortisol reverses weight loss
The woman had a history of type 2 diabetes, high blood pressure, osteoporosis, and coronary artery disease. She arrived at the emergency department with profound weakness in her proximal muscles, that is, those closest to the center of the body, associated with a blood potassium level of 2.4 millimoles per liter (mmol/L), which was below the normal range of 3.6-5.2 mmol/L. She had lost 90 pounds over the previous two years.
Despite taking three medications for high blood pressure, it remained uncontrolled. Her blood sugar levels were also poorly controlled, requiring additional medication.
During her hospitalization, tests showed elevated 24-hour urine-free cortisol that was nearly four times higher than the upper limit of normal (1,904.4 vs. 485.4 nanomoles). Repeated outpatient tests following her referral to endocrinology specialists confirmed elevated cortisol in her urine and blood. Her blood ACTH level was also high at 8.2 picomoles per liter (pmol/L), above the normal 0.5-2.2 pmol/L range.
MRI scans showed no signs of a tumor in the pituitary gland, but bilateral inferior petrosal sinus sampling (BIPSS), during which blood from the veins draining the pituitary gland is gathered for analysis, confirmed elevated ACTH, resulting in the woman being diagnosed with Cushing’s disease.
She was started on ketoconazole and cabergoline to try to control her cortisol. The woman declined a transsphenoidal adenomectomy, a surgical procedure where ACTH-producing tumors in the pituitary gland are removed.
The woman’s medical therapy was adjusted over several weeks until her 24-hour urinary-free cortisol levels normalized. They remained normal over two years of follow-up, recently being 85 nmol. Her potassium and blood pressure normalized, and her blood pressure and blood sugar medicine doses were lowered.
While she regained 15 pounds, the woman again began losing weight, despite taking her medications, and her potassium level dropped to 2.7 mmol/L. Blood and urine tests again showed elevated cortisol.
The researchers learned the woman’s family physician had prescribed the gastric reflux medication omeprazole, which can affect ketoconazole’s efficacy. After it was discontinued, the woman’s cortisol and potassium levels rapidly normalized; she regained 50 pounds and her mobility and strength improved, and she began walking independently with a walker, after initially being bedridden.
“Patients with [Cushing’s disease] do not always present with classical clinical features and may present with symptoms and biochemical findings that would otherwise suggest ectopic ACTH production,” the researchers wrote. “While most patients with [Cushing’s disease] typically lose weight after biochemical remission, some patients gain weight after the normalization of cortisol levels.”
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