SUN-395 Intermittent Hypogonadotropic Hypogonadism Associated with Cyclic Cushing’s Disease

Abstract

Abstract Introduction: Cyclic Cushing’s syndrome is defined as cortisol excess which fluctuates with periods of normal cortisol secretion, usually associated with Cushing’s disease (CD). Majority of cyclic CD patients exhibit clinical features of hypercortisolism which vary with the “cycle” of disease. We present a case of a patient without overt signs or symptoms of CD and biochemical evidence of intermittent hypogonadism which was associated with the cyclic nature of CD. Case: A 67 year old male with history of mild diabetes mellitus type 2 and hypertension was referred to endocrinology for evaluation of hypercortisolism after a routine screening CT chest revealed a 1.1 cm mass in the right adrenal gland. He had no typical manifestations of hypercortisolism other than mild fullness of bilateral supraclavicular fossae. His screening labs showed 24 hour urine free cortisol level of 243.3 ug (ref. range 4-50) with aldosterone-renin ratio, plasma renin activity and metanephrines within normal limits. After 1 mg dexamethasone suppression, AM serum cortisol was 24 mcg/dL (7-23) with ACTH 42 pg/mL (7-69). AM cortisol remained unsuppressed after 8 mg of dexamethasone as well. MRI brain showed no evidence of pituitary adenoma. Inferior petrosal sinus sampling (IPSS) revealed significantly increased central-peripheral ACTH ratio of 57 at 2 minutes post IV Acthrel 100 ug. Surprisingly, another AM Cortisol was found to be 8 mcg/dL with ACTH of 43 pg/mL. This prompted further 24h-urine cortisol tests with at least 3 elevated and 2 normal results (ranging from 9.1-203 mcg) meeting the consensus-based diagnostic criteria of cyclic Cushing’s disease. He also had intermittent hypogonadotropic hypogonadism with testosterone levels associated with rise and fall of cortisol levels. His free testosterone was 24 and 53 pg/mL (47-244) measured a few months apart which correlated with PM cortisol of 25 ug/dL (3-12) and AM cortisol of 11 ug/mL, respectively. He was also diagnosed with primary hyperparathyroidism. Genetic testing did not detect MEN1 gene mutation. He underwent partial transsphenoidal hypophysectomy and parathyroidectomy, following which he was treated with daily prednisone being gradually tapered off. Up till date he has had clinical improvement in his physical exam and diabetes, along with free testosterone level of 62 pg/mL and normal serum calcium levels. Conclusion: Clinicians should have a high index of suspicion for cyclic CD in patients being screened for hypercortisolism particularly those with mild or no clinical manifestations. Paradoxical responses to dynamic testing are often noted and thus IPSS results may be confounded if not in the active Cushing phase. It is important to remember while interpreting lab results that comorbid disorders like hypogonadism may also show cyclic nature dependent on the cycle of CD the patient may be in.