A Rare Cyclic Cushing Syndrome Mystery Illustrates Diagnostic Principles.

Pheochromocytomas predominantly produce catecholamines, and rarely also produce ACTH, causing Cushing syndrome (CS). Cyclic CS, an uncommon presentation of hypercortisolism, poses a diagnostic challenge. We report a 71-year-old woman who developed cyclic ectopic ACTH secretion from a pheochromocytoma. Previous evaluations showed intermittent elevations in cortisol and ACTH levels, normal pituitary magnetic resonance imaging, and an adrenal nodule. On admission, she was hypertensive and had cushingoid features. Bilateral inferior petrosal sinus sampling with desmopressin stimulation and an 8-mg dexamethasone suppression test suggested ectopic ACTH secretion, but ACTH increased during the peripheral desmopressin stimulation test. Plasma normetanephrines were about 2-fold above the upper reference limit. 18F-fluoro-dopa and 68Gallium-DOTATATE positron emission tomography/computed tomography scans, computed tomography, and magnetic resonance imaging identified an adrenal mass. After doxazosin adrenoceptor blockade, she underwent right adrenalectomy; histopathology and immunohistochemistry confirmed an ACTH-secreting pheochromocytoma. Postoperative blood pressure normalized and serum cortisol and plasma ACTH levels were suppressed, requiring physiologic hydrocortisone replacement. This case underscores the importance of considering pheochromocytoma in ACTH-dependent hypercortisolism with elevated metanephrines and an adrenal mass. Timely diagnosis and treatment can reduce morbidity and improve quality of life.

Longitudinal Evaluation of Reproductive Endocrine Function in Men with ACTH-Dependent Cushing Syndrome.

CONTEXT: Hypogonadism may be caused by Cushing syndrome (CS) and may intensify its adverse consequences. OBJECTIVE: To determine the frequency of male hypogonadism before and after curative surgery for CS, and its cause. DESIGN: Post-hoc analyses of prospective cohort studies. SETTING: Clinical research center. PATIENTS: Men with ACTH-dependent CS. Cohort 1 (C1) (n=8, age 32.5±12 y; studied 1985-1989); Cohort 2 (C2) (n=44, 42.7 ± 15.1 y; studied 1989-2021). INTERVENTIONS: C1: Every 20-minute blood sampling for 24h before and 1-40 months after surgical cure. Three subjects underwent GnRH stimulation tests pre- and post-surgery. C2: Hormone measurements at baseline and 6 and 12 months (M) post-cure. MAIN OUTCOME MEASURES: C1: LH, FSH, LH pulse frequency and LH response to GnRH. C2: LH, FSH, testosterone (T), free T, fT4, T3, TSH and UFC levels and frequency of hypogonadism pre- and post-surgery. RESULTS: C1: mean LH and LH pulse frequency increased after surgery (p < 0.05) without changes in LH pulse amplitude, mean FSH, or peak gonadotropin response to GnRH. C2: 82% had baseline hypogonadism (total T 205 ± 28 ng/dL). Thyroid hormone levels varied inversely with UFC and cortisol. LH, total and free T, and SHBG increased at 6M and 12M post surgery, but hypogonadism persisted in 51% at 6M and in 26% at 12M. CONCLUSION: Hypogonadism in men with CS is widely prevalent but reversible in ∼75% of patients one year after surgical cure and appears to be mediated through suppression of hypothalamic GnRH secretion, and modulated by thyroid hormones.