(CSEMP044) A CHALLENGING CASE OF CUSHING'S SYNDROME

Abstract: Background
Determining the etiology of Cushing’s Syndrome can be challenging.

Case
A 35-year-old female was referred to Endocrinology Clinic for suspected Cushing’s Syndrome. She presented with weight gain and difficult-to-control type 2 diabetes. Past medical history included Celiac disease, hypertension, non-alcoholic fatty liver disease, and a pregnancy 7 months earlier. At her consultation visit, she described unexplained weight gain of 15 pounds, persistent hyperglycemia despite increasing insulin doses, and intermittent episodes of diaphoresis and heat intolerance a few times per week. Her physical exam was remarkable for a dorsocervical fat pad, central obesity and violaceous striae.

Investigations prior to endocrinology assessment: HbA1c 12.8%, TSH 1.03, non-HDL cholesterol 7.02 mmol/L, and triglycerides of 5.36 mmol/L. Free androgen index was slightly elevated at 5.4. AM cortisol was 635, ACTH 8.3, and normal metanephrines. Abdominal ultrasound revealed mild diffuse fatty infiltration of the liver. CT scan of the head showed no acute intracranial abnormality.

Subsequent investigations: 24-hour urine free cortisol elevated at 287.4 nmol/d, 1 mg overnight dexamethasone suppression test: showed non-suppressed cortisol of 302 nmol/L. MR Sella showed mildly heterogeneous enhancement of the pituitary gland with a 6 mm relatively hypoenhancing focus suspicious for a microadenoma. Subsequently, inferior petrosal sinus sampling (IPSS) revealed that ACTH levels, both before and after stimulation, were similar in peripheral blood and in the inferior petrosal sinuses and in the left and right petrosal sinuses. This raised suspicion for a non-pituitary source of ACTH, so an enhanced CT chest/abdomen was completed. It revealed no carcinoid or other abnormalities within the chest or abdomen. To look for other possible sources of ACTH, a Gallium-68 DOTATATE PET was ordered; it showed no somatostatin receptor avid disease.

Comment
Despite these extensive investigations, no clear source of abnormal ACTH secretion has been identified yet. The current presumed diagnosis is cyclical Cushing’s disease of pituitary origin. The patient is now awaiting IPSS to be performed the day after confirmation of an elevated 24-hour urine free cortisol test.