A 75-year-old woman was diagnosed with MRI-negative pituitary Cushing’s disease (CD) after presenting with weight loss and hypokalemia—features that are more commonly associated with ectopic ACTH production, according to a recently published case report.
She had lost 90 lbs over 2 years and presented to the emergency department with profound proximal muscle weakness and a serum potassium level of 2.4 mmol/L. Her hypertension and type 2 diabetes were poorly controlled, despite multiple medications.
Biochemical testing showed elevated 24-hour urinary free cortisol (1904.4 nmol/d; upper limit: 485.4 nmol/d), AM serum cortisol (1749.2 nmol/L; normal: 80–477.3), and ACTH (8.2 pmol/L; normal: 0.5–2.2). Serum cortisol remained high at 1238.8 nmol/L following a 48-hour low-dose dexamethasone suppression test. Imaging via MRI and Ga-68 DOTATATE PET-CT did not reveal a lesion.
Bilateral inferior petrosal sinus sampling with 100 µg ovine CRH confirmed a central ACTH source, with a post-CRH central-to-peripheral ratio of 3, lateralizing to the right (ratio = 2.1). This finding supported a diagnosis of pituitary CD despite negative imaging.
The patient declined surgical treatment and began medical therapy with ketoconazole 200 mg TID and later cabergoline 1 mg twice every week. This regimen normalized cortisol, blood pressure, and potassium levels. However, symptoms recurred when omeprazole, a proton pump inhibitor known to interfere with ketoconazole, was initiated. Discontinuation of omeprazole led to rapid normalization of cortisol and potassium.
At her most recent follow-up, she had regained 50 lbs. Her 24-hour urinary cortisol was 85 nmol/d, AM cortisol was 796 nmol/L, ACTH was 14 pmol/L, and potassium was 4.5 mmol/L.
She is "almost back to her baseline weight, and her mobility and strength have improved from being initially bed-bound to now mobilizing independently using a walker,” wrote Sarah Badawod, of the Division of Endocrinology and Metabolism at Dalhousie University, with colleagues.
CD can present with signs that are usually associated with ectopic ACTH production, the researchers noted. Although weight gain is a hallmark of CD due to cortisol’s orexigenic effects and adenosine monophosphate-activated protein kinase inhibition, older patients may present with catabolic features such as weight loss and muscle wasting. Prior research showed central adiposity in 80% of younger patients with CD, compared with 71.1% of older patients.
Hypokalemia, though more typical in ectopic ACTH syndrome, can occur in CD case, the researchers noted. They added that up to 10% of patients present with low potassium. Excess cortisol may overwhelm 11β-hydroxysteroid dehydrogenase type II (11β-HSD2) and allow cortisol to act on mineralocorticoid receptors and promote potassium excretion.
No ectopic source or alternative pathology were identified. The investigators concluded that hypercortisolemia should remain a diagnostic consideration in patients with unexplained hypokalemia and weight loss, even when imaging is inconclusive.
The authors reported no conflicts of interest.