Hormonal Contraceptive Use Is Associated With a Decreased Incidence of Hypothyroidism.

OBJECTIVE: Hypothyroidism is one of the most common endocrine disorders affecting 5 to 10 times more women than men. Given this higher incidence in women, it is possible that hormonal differences or medications more commonly used by women may play a role in the risk of developing hypothyroidism. We hypothesized that hormonal contraception affects the risk of developing hypothyroidism. METHODS: Using the TriNetX database, we developed a case-control study and identified women aged 18 to 45 years in 4 distinct groups: (1) estrogen-progestin contraceptive (EPC) use, (2) progestin-only contraceptive (POC) use, (3) progestin-containing intrauterine device (IUD) use, and (4) controls. For each group, we ascertained data including the diagnosis of hypothyroidism, alcohol use, tobacco use, and body mass index. RESULTS: We identified 18 578 patients with sufficient data: EPC use, n = 5849; POC use, n = 5052; IUD use, n = 1000; and controls, n = 6677. A total of 118 individuals (1.8%) in the control group and 165 individuals (1.4%) who received hormonal contraception developed hypothyroidism. After using a logistic model to account for cofounding variables, all forms of hormonal contraception (EPC, POC, and IUD) had a protective effect against the diagnosis of hypothyroidism. POC and IUD uses had the greatest protective effect, with odds ratios of 0.14 and 0.12, respectively. EPC had a less pronounced but still significant effect, with an odds ratio of 0.30 (P < .001). CONCLUSION: This study of >18 000 women and the risk of developing hypothyroidism demonstrates a protective effect of hormonal contraceptive use. Our data, both unadjusted and adjusted using a logistic model to account for cofounding variables, suggest that the use of hormonal contraception, in any form, decreases the risk of developing hypothyroidism.

Alcohol-induced Cushing syndrome: report of eight cases and review of the literature.

Introduction: Alcohol-induced hypercortisolism (AIH) is underrecognized and may masquerade as neoplastic hypercortisolism [Cushing syndrome (CS)] obscuring its diagnosis. Objective and methods: In order to characterize AIH, we performed a chart review of eight patients (4 males and 4 females; 2014-2022) referred for evaluation and treatment of neoplastic hypercortisolism - six for inferior petrosal sinus sampling, one due to persistent CS after unilateral adrenalectomy, and one for pituitary surgery for Cushing disease (CD). Five underwent dDAVP stimulation testing. Results: All eight patients had clinical features of hypercortisolism and plasma ACTH levels within or above the reference interval confirming hypothalamic-pituitary mediation. All had abnormal low-dose dexamethasone suppression test and increased late-night salivary cortisol. Only one had increased urine cortisol excretion. In contrast to CD, the 5 patients tested had blunted or absent ACTH and cortisol responses to desmopressin. Two had adrenal nodules and one had abnormal pituitary imaging. Most patients underreported their alcohol consumption and one denied alcohol use. Elevated blood phosphatidyl ethanol (PEth) was required in one patient to confirm excessive alcohol use. All patients had elevations of liver function tests (LFTs) with AST>ALT. Conclusion: AIH is an under-appreciated, reversible cause of non-neoplastic hypercortisolism that is indistinguishable from neoplastic CS. Incidental pituitary and adrenal imaging abnormalities as well as under-reporting of alcohol consumption further confound the diagnosis. Measurement of PEth helps to confirm an alcohol use disorder. Elevations of LFTs (AST>ALT) and subnormal ACTH and cortisol responses to dDAVP help to distinguish AIH from neoplastic hypercortisolism.

Parathyroidectomy for primary hyperparathyroidism improves sleep quality: A prospective study.

BACKGROUND: This prospective survey study assessed changes in sleep quality in patients with primary hyperparathyroidism after parathyroidectomy. METHODS: Patients undergoing parathyroidectomy for primary hyperparathyroidism (n = 110) or thyroidectomy for benign euthyroid disease (control group; n = 45) were recruited between June 2013 and June 2015 and completed the Pittsburgh Sleep Quality Index preoperatively and at 1- and 6 months postoperatively. "Poor" sleep quality was defined as a score >5; a clinically important and relevant improvement was a ≥3-point decrease. RESULTS: Preoperatively, parathyroid patients had worse sleep quality than thyroid patients (mean 8.1 vs 5.3; P < .001); 76 (69%) parathyroid and 23 (51%) thyroid patients reported poor sleep quality (P = .03). Postoperatively, only parathyroid patients demonstrated improvement in sleep quality; mean scores did not differ between the parathyroid and thyroid groups at 1 month (6.3 vs 5.3; P = .12) or 6 months (5.8 vs 4.6; P = .11). The proportion of patients with a clinically important improvement in sleep quality was greater in the parathyroid group at 1 month (37% vs 10%; P < .001) and 6 months (40% vs 17%; P = .01). Importantly, there was no difference in the proportion of patients with poor sleep quality between the 2 groups at 1 month (50% vs 40%; P = .32) and 6 months (40% vs 29%; P = .22). CONCLUSION: More than two-thirds of patients with primary hyperparathyroidism report poor sleep quality. After parathyroidectomy, over one-third experienced improvement, typically within the first month postoperatively.

POSTSURGICAL RECURRENT CUSHING DISEASE: CLINICAL BENEFIT OF EARLY INTERVENTION IN PATIENTS WITH NORMAL URINARY FREE CORTISOL.

OBJECTIVE: To assess the performance of biochemical markers in the detection of recurrent Cushing disease (CD), as well as the potential benefit of early intervention in recurrent CD patients with elevated late-night salivary cortisol (LNSC) and normal urinary free cortisol (UFC). METHODS: The design was a single-center, retrospective chart review. Patients treated by the authors from 2008-2013 were included. Recurrence was defined by postsurgical remission of CD with subsequent abnormal LNSC, UFC, or dexamethasone suppression test (DST). RESULTS: We identified 15 patients with postsurgical recurrent CD after initial remission; all but one underwent testing with LNSC, DST, and UFC. Although 12 of 15 patients had normal UFC at time of recurrence, DST was abnormal in 11 of 15, and all 14 patients with LNSC results had ≥1 elevated measurement. Nine patients (7 with normal UFC) showed radiologic evidence of a pituitary tumor at time of recurrence. Among the 14 patients with available follow-up data, 12 have demonstrated significant improvement since receiving treatment. Five patients underwent repeat pituitary surgery and 4 achieved clinical and biochemical remission. Eight patients received mifepristone or cabergoline, and 6 showed clinical and/or biochemical improvement. Three patients (2 with prior mifepristone) underwent bilateral adrenalectomy and 2 demonstrated significant clinical improvements. CONCLUSION: LNSC is more sensitive than UFC or DST for detection of CD recurrence. Prompt intervention when LNSC is elevated, despite normal UFC, may yield significant clinical benefit for many patients with CD. Early treatment for patients with recurrent CD should be prospectively evaluated, utilizing LNSC elevation as an early biochemical marker. ABBREVIATIONS: ACTH = adrenocorticotropic hormone CD = Cushing disease CS = Cushing syndrome CV = coefficient of variation DST = dexamethasone suppression test IPSS = inferior petrosal sinus sampling LNSC = late-night salivary cortisol QoL = quality of life TSS = transsphenoidal adenoma resection UFC = urinary free cortisol.

Delayed Calcium Normalization After Presumed Curative Parathyroidectomy is Not Associated with the Development of Persistent or Recurrent Primary Hyperparathyroidism.

BACKGROUND: Following parathyroidectomy for primary hyperparathyroidism (pHPT), serum calcium levels typically normalize relatively quickly. The purpose of this study was to identify potential factors associated with delayed normalization of calcium levels despite meeting intraoperative parathyroid hormone (IOPTH) criteria and to determine whether this phenomenon is associated with higher rates of persistent pHPT. METHODS: This was a retrospective review of 554 patients who underwent parathyroidectomy for sporadic pHPT from January 2009 to July 2013. Patients who underwent presumed curative parathyroidectomy and had elevated POD0 calcium levels (>10.2 mg/dL) were matched 1:2 for age and gender to control patients with normal POD0 calcium levels. RESULTS: Of the 554 patients, 52 (9 %) had an elevated POD0 Ca (median 10.7, range 10.3-12.2). Compared with the control group, these patients had higher preoperative calcium (12 vs. 11.1, p < 0.001) and PTH (144 vs. 110 pg/mL, p = 0.004) levels and lower 25OH vitamin D levels (26 vs. 31 pg/mL; p = 0.024). Calcium normalization occurred in 64, 90, and 96 % of patients by postoperative days (POD) 1, 14, and 30, respectively. There was no difference in rates of single-gland disease or cure rates between the groups. CONCLUSIONS: After presumed curative parathyroidectomy, nearly 10 % of patients had transiently persistent hypercalcemia. Most of these patients had normal serum calcium levels within the first 2 weeks and did not have increased rates of persistent pHPT. Immediate postoperative calcium levels do not predict the presence of persistent pHPT, and these patients may not require more stringent follow-up.

Cosyntropin stimulation testing on postoperative day 1 allows for selective glucocorticoid replacement therapy after adrenalectomy for hypercortisolism: Results of a novel, multidisciplinary institutional protocol.

BACKGROUND: Secondary adrenal insufficiency (AI) can occur after unilateral adrenalectomy for adrenal-dependent hypercortisolism. Postoperative glucocorticoid replacement (GR), although given routinely, may not be necessary. We sought to identify factors that, in combination with postoperative day 1 cosyntropin stimulation testing (POD1-CST), would predict the need for GR. METHODS: We reviewed 31 consecutive patients who underwent unilateral adrenalectomy for hypercortisolism (study patients) or hyperaldosteronism (control patients). A standard POD1-CST protocol was used. Hydrocortisone was started for clinical evidence of AI, basal plasma cortisol ≤ 5 (µg/dL), or a stimulated plasma cortisol <18. RESULTS: A normal POD1-CST was found in all nine control patients and 11 of 22 patients (50%) with Cushing's syndrome; the other 11 study patients (50%) received GR based on the POD1-CST. These patients were younger (51 vs 62 years; P = .017), had a higher body mass index (BMI; 31 vs 29 kg/m(2)), and smaller adrenal neoplasms (16.9 vs 33.0 g; P = .009) than non-GR study patients. CONCLUSION: After unilateral adrenalectomy for hypercortisolism, only 50% of patients received GR. No preoperative biochemical characteristics were associated with postoperative AI, although patients who received GR were younger, and tended to have a higher BMI and smaller adrenal nodules. Use of this novel protocol for postoperative dynamic adrenal function testing prevented unnecessary GR in 50% of patients and allowed for individualized patient care.

Discovery of Cushing's Syndrome After Bariatric Surgery: Multicenter Series of 16 Patients.

PURPOSE: The aim of this study is to demonstrate the importance of considering Cushing's syndrome (CS) as a potential etiology for weight gain and metabolic complications in patients undergoing bariatric surgery (BS). DESIGN AND METHODS: This is a retrospective chart review case series of patients (n = 16) with CS from five tertiary care centers in the USA who had BS. RESULTS: Median age at BS surgery was 35.5 years (median 2.5 years between BS and CS surgery). CS was not identified in 12 patients prior to BS. Four patients had CS surgery prior to BS, without recognition of recurrent or persistent CS until after BS. Median body mass index (BMI) values before BS, nadir after BS, prior to surgery for CS, and after surgery for CS were 47, 31, 38, and 35 kg/m(2), respectively. Prior to BS, 55 % of patients had hypertension and 55 % had diabetes mellitus. Only 17 % had resolution of hypertension or diabetes mellitus after BS. CONCLUSION: CS may be under-recognized in patients undergoing BS. Testing for CS should be performed prior to BS in patients with features of CS and in post-operative BS patients with persistent hypertension, diabetes mellitus, or excessive weight regain. Studies should be conducted to determine the role of prospective testing for CS in subjects considering BS.

Chemotherapy-induced regression of an adrenocorticotropin-secreting pituitary carcinoma accompanied by secondary adrenal insufficiency.

Purpose. Adrenocorticotropin- (ACTH-) secreting pituitary carcinomas are rare and require multimodality treatment. The aim of this study was to report the response to various therapies and discuss the potential development of secondary adrenal insufficiency with cytotoxic chemotherapy. Methods. This report describes a man with a large silent corticotroph adenoma progressing to endogenous hypercortisolism and metastatic ACTH-secreting pituitary carcinoma over a period of 14 years. Results. Seven years after initial presentation, progressive tumor enlargement associated with the development of hypercortisolism mandated multiple pituitary tumor debulking procedures and radiotherapy. Testing of the Ki-67 proliferation index was markedly high and he developed a hepatic metastasis. Combination therapy with cisplatin and etoposide resulted in a substantial reduction in tumor size, near-complete regression of his liver metastasis, and dramatic decrease in ACTH secretion. This unexpectedly resulted in symptomatic secondary adrenal insufficiency. Conclusions. This is the first reported case of secondary adrenal insufficiency after use of cytotoxic chemotherapy for metastatic ACTH-secreting pituitary carcinoma. High proliferative indices may be predictive of dramatic responses to chemotherapy. Given the potential for such responses, the development of secondary adrenal insufficiency may occur and patients should be monitored accordingly.