Patient Background: A 75-year-old woman presents with progressive weight loss, generalized weakness, easy bruising, and poorly controlled hypertension. On exam, she has thin skin with ecchymoses, proximal muscle weakness, and hypokalemia (serum potassium 2.9 mmol/L).
Family History: The patient reported no family history of hormonal disorders, malignancy, or pituitary pathology relevant to her presentation.
Assessment and Diagnosis: Evaluation revealed elevated 24-hour urinary free cortisol (UFC), elevated morning (8 am) serum cortisol, and non-suppression on a low-dose dexamethasone suppression test (LDDST), with elevated ACTH. Pituitary MRI was negative, and Ga-68 DOTATATE PET/CT showed no ectopic lesion. Bilateral inferior petrosal sinus sampling (BIPSS) with CRH stimulation confirmed MRI-negative, ACTH-dependent Cushing’s disease, although features such as marked weight loss and hypokalemia initially raised suspicion for ectopic ACTH secretion.
Suggested treatment plan: The patient declined surgery and opted for medical therapy with an adrenal steroidogenesis inhibitor plus a dopamine agonist.
Patient education: The patient was educated on the importance of medication adherence and avoidance of drug–drug interactions. She was specifically advised to avoid concurrent use of gastric acid–reducing agents, which can impair treatment absorption and effectiveness.
Follow-up: Medical therapy led to normalization of UFC, improved potassium levels, blood pressure, and glycemic control, along with a 15-lb weight gain. A relapse occurred after initiation of an acid-suppressing medication, which compromised drug absorption. Discontinuation restored efficacy, with rapid normalization of hormone levels and a 50-lb weight gain, improving mobility and strength.
- What clinical features in this case suggested ectopic ACTH over typical Cushing’s disease? Answer Severe hypokalemia and marked weight loss suggested ectopic ACTH, unlike the usual weight gain in pituitary Cushing’s disease.
- Given the MRI-negative status, what key test confirmed Cushing’s disease and ruled out ectopic ACTH? Answer Bilateral inferior petrosal sinus sampling (BIPSS) showed a post-CRH central-to-peripheral ACTH ratio >3, confirming a pituitary source of ACTH despite negative imaging.
