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.

Remission of hypertension after surgical cure of Cushing's syndrome.

CONTEXT: Hypertension associated with Cushing's syndrome (CS) increases cardiovascular risk. The time-course of improvement after cure is unclear. OBJECTIVE: To describe the time-course and predictors of blood pressure (BP) normalization during one year after surgical cure of CS. DESIGN: Retrospective chart review of 75 hypertensive adults cured of CS (72 with ACTH-dependent CS; 3 with adrenal adenoma). Hypertension was defined as current use of antihypertensives, a systolic BP >130 mm Hg, or diastolic BP >80 mm Hg. MAIN OUTCOME MEASURE(S): Remission of hypertension: BP ≤130/80 mm Hg and no antihypertensive medications. Improvement in hypertension: BP >130/80 mm Hg and decreased number or dose of medications, or blood pressure ≤130/80 with continued use of medications at constant dose. RESULTS: At postoperative discharge, 17 (23%, P < .001), 51 (68%, P < .001) and 7 (9%) patients had remission, improvement in hypertension or no change. Twenty-nine had no follow-up. Others achieved remission at 3 (n = 5), 6 (n = 6), or 12-months (n = 5). At the last evaluation, 33/75 (44%) had remission, 36/75 (48%) had improved hypertension and 6 were unchanged. Patients with improvement discontinued a median of one medication (P < .001). At 12-months, 27/42 (64%) patients had normal BP (P < .002). Longer estimated duration of CS (P = .0106), younger age (P = .0022), and lower baseline body mass index (P = .0413) predicted hypertension remission. CONCLUSIONS: About 80% of CS patients experienced BP normalization or improvement within 10 days of cure, but about half failed to normalize BP by one year. BP should be monitored after cure, and antihypertensive medications adjusted to avoid unwanted cardiovascular effects.