Insulin sensitivity and obstructive sleep apnea in adolescents with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) in adults is linked with insulin resistance (IR) and obstructive sleep apnea (OSA). However, less is known about these associations in adolescents. METHODS: We studied 3 groups of adolescents: 27 obese PCOS (OPCOS) (ages 13-21)11 normal-weight PCOS (NPCOS) (ages 13-21 years), and 8 healthy controls (ages 18-21 years). A hyperinsulinemic euglycemic clamp study was performed in all groups to determine IR by insulin sensitivity (M/I). Polysomnography was performed to assess for OSA in OPCOS and NPCOS groups. We compared indices of IR among all groups and OSA among OPCOS, and NPCOS. RESULTS: We noted that OPCOS and NPCOS and controls differed significantly in their IR. M/I was significantly lower in OPCOS vs. controls (p=0.0061), and also lower for NPCOS vs control but this approached but did not reach statistical significance (p=0.084). In addition, none of the NPCOS subjects had OSA compared to 42% of OPCOS (p=0.03). CONCLUSIONS: Our study suggests OPCOS adolescents have increased IR compared to controls and NPCOS subjects. Higher IR for NPCOS vs controls approached but did not reach statistical significance. Larger studies are needed. In addition, adolescents with OPCOS are at a high risk for OSA.

The impact of weight change and measures of physical functioning on mortality.

INTRODUCTION: Lower grip strength and measures of physical functioning are associated with all-cause mortality. Relationships among long-term weight loss, physical functioning, and mortality in older women are understudied. METHODS: Participants were 5039 women who were part of the Long Life Study (LLS) ancillary study to the Woman's Health Initiative (WHI). Average age was 78.76 ± 6.92. We defined long-term weight loss or gain as a decrease or increase of 5% or more of baseline body weight. Our primary outcome was all-cause mortality and our secondary outcomes were vascular death, and coronary heart disease (CHD). The mean follow-up time was 5.4 years. Cox regression modeling was performed for each outcome of interest. Variables of interest were weight change, grip strength, and functional status as measured by the Short Physical Performance Battery (SPPB) controlling for multiple potential confounders. RESULTS: Weight loss of 5% or more percent body weight was associated with a hazard ratio of 1.66 (1.37-2.01) for all-cause mortality. Weight gain was not related to mortality or cardiovascular outcomes. Those in the highest grip strength quartile had a hazard ratio of 0.51 (0.39-0.66) for all-cause mortality. For the SPPB the hazard ratio was 0.29 (0.21-0.40), adjusting for changes in weight, race, smoking, history CHD, smoking, and diabetes. Higher grip strength and SPPB were associated with lower risks for vascular death, and CHD, independently of weight change. CONCLUSIONS: Weight loss was associated with increased mortality. Stronger grip strength and higher SPPB scores were associated with lower mortality risk independent of weight change.

Recreational Physical Activity, Sitting, and Androgen Metabolism among Postmenopausal Women in the Women's Health Initiative Observational Study.

BACKGROUND: Prolonged sitting and physical inactivity are associated with higher circulating levels of estrogens. It is unknown whether these risk factors are associated with circulating androgens/androgen metabolites, another set of hormones implicated in the etiology of cancers in postmenopausal women. METHODS: We conducted a cross-sectional analysis of 1,782 postmenopausal women in the Women's Health Initiative Observational Study. Serum concentrations of 12 androgens/androgen metabolites were quantified using liquid chromatography-tandem mass spectrometry. Physical activity and sitting time were self-reported at baseline. We performed linear regression to estimate geometric means (GM) of androgen/androgen metabolite concentrations (pmol/L) according to physical activity and sitting time, adjusting for potential confounders and stratified by menopausal hormone therapy (MHT) use. RESULTS: Physical activity (≥15 vs. 0 MET-h/wk) was inversely associated with estrogen-to-androgen ratios among never/former MHT users (adj-GM = 37.5 vs. 49.6 unconjugated estrone:androstenedione; 20.2 vs. 30.3 unconjugated estradiol:testosterone; all P trend ≤ 0.03) but was not associated among current MHT users. Prolonged sitting (≥10 vs. ≤5 h/d) was positively associated with these ratios among both never/former (adj-GM = 44.2 vs. 38.3, P trend = 0.10; adj-GM = 23.4 vs. 20.2, P trend = 0.17; respectively) and current MHT users (adj-GM = 197 vs. 147; 105 vs. 75.5; respectively; all P trend ≤0.02), but the associations were statistically significant among current MHT users only. The associations persisted after adjustment for BMI. After adjustment for adrenal androgens, physical activity and sitting were not associated with androgen metabolites. CONCLUSIONS: Physical activity and sitting were associated with serum estrogen-to-androgen ratios but not androgen metabolites. IMPACT: This study contributes to our understanding of the link between physical activity, sitting, and cancer risk in postmenopausal women.

Obesity, Height, and Serum Androgen Metabolism among Postmenopausal Women in the Women's Health Initiative Observational Study.

BACKGROUND: Anthropometric measures, including obesity, are important risk factors for breast and endometrial cancers in postmenopausal women. It is unknown whether these risk factors are associated with androgen metabolism, another risk factor for these cancers. METHODS: Using baseline data from 1,765 postmenopausal women in the Women's Health Initiative Observational Study, we conducted a cross-sectional analysis examining associations between anthropometric measures [current body mass index (BMI), waist-to-hip ratio (WHR), height, and recalled BMI at age 18) and serum androgen metabolites. Twelve androgens/androgen metabolites were quantified using LC-MS/MS. Geometric means of androgen/androgen metabolite concentrations were estimated using linear regression, adjusting for potential confounders and stratified by hormone therapy (HT) use. RESULTS: Regardless of HT use, higher current BMI (≥30 vs. <25 kg/m2) was associated with higher serum concentrations of dehydroepiandrosterone sulfate (DHEAS), 5α-reduced glucuronide metabolites [androsterone-glucuronide (ADT-G), 5α-androstane-3α,17ß diol-3-glucuronide (3α-diol-3G), 3α-diol-17-glucuronide (3α-diol-17G)], and DHEAS:DHEA ratio (all P trend ≤ 0.02). BMI was also positively associated with unconjugated estrone:androstenedione and unconjugated estradiol:testosterone ratios among never/former HT users (all P trend < 0.001) but not among current users (P-int < 0.001). WHR was positively associated with adrenal androgens and 5α-reduced glucuronide metabolites in obese women only (BMI ≥ 30 kg/m2; all P-trend ≤ 0.01). BMI at age 18 was inversely associated with adrenal androgens (DHEA, DHEAS, androstenedione, testosterone) and 5α-reduced glucuronide metabolites in never/former HT users (all P trend < 0.06). Height was not associated with androgen metabolites. CONCLUSIONS: Current BMI is associated with androgen metabolism among postmenopausal women. IMPACT: This study contributes to our understanding of the link between obesity and cancer risk in postmenopausal women.

Intrathyroidal Thymic Tissue in an Adolescent with Graves' Disease: Case Report and Review of Current Literature.

Intrathyroidal thymic tissue (ITT) is a benign entity found in children and young adolescents that often mimics a concerning thyroid nodule with microcalcifications on ultrasound. It is challenging for the clinician to distinguish between these two entities, which may lead to unnecessary invasive procedures. We report an adolescent female patient with Graves' disease who underwent total thyroidectomy for a thyroid nodule concerning for malignancy for which the surgical pathology ultimately revealed ITT. As ITT is rarely found beyond childhood, the concurrent Graves' disease may have led to persistence of thymic tissue in this patient. Several sonographic features can help in differentiating ITT from a concerning thyroid nodule. Once identified, ITT should be followed by serial imaging with anticipation of decreasing size or complete resolution over time.

The Impact of Dopamine on Insulin Secretion in Healthy Controls.

OBJECTIVE: Dopamine is very commonly used in the critical care setting and impacts glucose homeostasis. In some studies, it is noted to increase insulin resistance or decrease insulin secretion. The role of insulin secretion in response to dopamine is incompletely understood. METHODS: Eight individuals underwent a hyperglycemic clamp with a dopamine infusion, and eight controls underwent hyperglycemic clamp alone. Insulin, C-peptide, glucagon, cortisol, and norepinephrine (NE) concentrations were measured at various time points. An index of insulin sensitivity (M/I) was calculated. Statistical comparison between the control and treatment arm was done using repeated measures ANOVA. The data is expressed as mean ± standard deviation. Paired t-test was used to compare pre- and post-dopamine infusion time points in the study individuals only. Data was considered to be statistically significant at P < 0.05. RESULTS: On assessing the treatment group before and during dopamine infusion, insulin and C-peptide concentrations were higher at the time of the infusion (P = 0.02 and P = 0.003, respectively). The index of insulin sensitivity was not statistically different. There was a significant decrease in insulin (P = 0.002), C-peptide (P = 0.005), and NE (P < 0.0001) concentrations in the treatment group, compared to the controls. Glucagon concentration was higher in the treatment group (P = 0.02). CONCLUSION: In this study, dopamine infusion did not adversely impact insulin secretion.

Thyroid Function Testing in Neonates With Maternal History of Disease.

Maternal history of thyroid disease can cause congenital hypothyroidism due to thyroid-stimulatng hormone (TSH) blocking antibodies. No guidelines exist regarding testing beyond the newborn screen. TSH and T4 levels exhibit significant fluctuations after birth which complicates testing. A total of 561 newborns with thyroid function testing done for maternal history of thyroid disease in the newborn nursery were identified retrospectively via chart review, and thyroid disease status was assessed in 352. Newborn screening data were also obtained. Of these infants, 7 had hypothyroidism with 3 having negative newborn screens. No cases of neonatal graves were identified. The 3 infants with negative newborn screens had TSH levels ranging from 6.58 to 28.4 prior to treatment with levothyroxine. All required treatment beyond age 3 years, despite trial off levothyroxine. Infants with maternal history of thyroid disease may require additional testing beyond the newborn screen. However, providers can consider delaying test until after thyroid levels are more stable.

Use of Sitagliptin With Closed-Loop Technology to Decrease Postprandial Blood Glucose in Type 1 Diabetes.

BACKGROUND: Postprandial hyperglycemia poses a challenge to closed-loop systems. Dipeptidyl peptidase-4 (DPP-4) inhibitors, like sitagliptin, reduce postprandial glucose concentrations in patients with type 2 diabetes. The objective of this study was to assess sitagliptin's role in type 1 diabetes (T1DM) as an adjunct therapy in reducing postprandial blood glucose with an insulin-only closed-loop system. METHODS: This was a randomized, double-blinded, placebo controlled, crossover design trial. The participants were18-35 years old, had T1DM, and an HbA1c of ≤ 8.5%. A dose determination study included eight subjects with T1DM. There were three study visits. Four hours after receiving study drug (placebo, sitagliptin 50 mg, sitagliptin 100 mg), subjects underwent a mixed meal tolerance test with assessment of hormone concentrations. In a second study, 15 subjects underwent two visits receiving either placebo or 100 mg of sitagliptin plus an insulin only closed-loop system for 25 hours with timed meals. Blood glucose and other hormone concentrations were analyzed using repeated measures ANOVA. RESULTS: For the dose determination study, sitagliptin 100 mg resulted in reduced postprandial blood glucose ( P = .006). For the closed-loop study, glucose concentrations were lower in the treatment group, most prominently during the first two study meals ( P = .03). There was no difference in glucagon concentrations, but insulin concentrations and insulin delivery were lower in the treatment group. CONCLUSIONS: Sitagliptin may be considered as an adjunct therapy in a closed-loop setting. Larger studies are needed to determine the role of oral agents like sitagliptin to lower postprandial hyperglycemia with closed loop.

A Case of Thyroid Storm Associated with Cardiomyopathy and Poststreptococcal Glomerulonephritis.

Thyroid storm has a high mortality rate and is often associated with a precipitating factor such as intercurrent illness or infection. It is rare in pediatric patients. Cardiac disease in hyperthyroidism mostly manifests itself as tachycardia but more serious cardiac findings have also been described. A 5-year-old male with recent strep throat infection presented with dilated cardiomyopathy, hematuria, and symptoms and lab findings consistent with severe hyperthyroidism. He was diagnosed with thyroid storm secondary to concurrent Graves' disease and poststreptococcal glomerulonephritis (PSGN). After starting the treatment with methimazole and a beta-blocker, his cardiac disease gradually improved and the PSGN resolved over time. There are no specific pediatric criteria for thyroid storm. Adult criteria can be difficult to apply to pediatric cases. Criteria for diagnosis of thyroid storm are less clear for pediatric patients. Dilated cardiomyopathy is a rare cardiac manifestation of hyperthyroidism. PSGN is due to glomerular immune complexes and can complicate group A strep infection. Providers should be aware of cardiac disease as a complication of hyperthyroidism. PSGN should not mechanistically be related to hyperthyroidism but can precipitate the signs of thyroid storm such as hypertension. This association has not been previously reported in the literature.