The influence of GH treatment on glucose homeostasis in girls with Turner Syndrome: a 7 years study.
J Clin Endocrinol Metab. 2016 Dec 02;:jc20163179
Authors: Baronio F, Mazzanti L, Girtler Y, Tamburrino F, Lupi F, Longhi S, Fanolla A, Radetti G
CONTEXT: Growth hormone (GH) influences glucose homeostasis mainly by negatively affecting insulin sensitivity.
OBJECTIVE: to longitudinally study the insulin sensitivity (HOMA-S), insulin secretion (insulinogenic index - IGI) and capacity of beta cells to adapt to changes in insulin sensitivity (oral disposition index-ODI) in girls affected by Turner syndrome (TS) undergoing GH treatment.
DESIGN: a longitudinal retrospective seven years study Setting: a tertiary pediatric endocrine unit and a University pediatric Clinic.
PATIENTS AND METHODS: We studied 104 TS (9.1 ± 3.4 years) for a median period of 7.2 years.
INTERVENTION: every year the children underwent an oral glucose tolerance test (OGTT), which was used to calculate HOMA-S, IGI and ODI.
RESULTS: no significant changes were observed in term of HOMA-S, IGI or ODI.
CONCLUSION: Our results are reassuring, showing no negative influence of GH treatment on insulin sensitivity and on beta cell secretory capacity in girls with TS.
PMID: 27911611 [PubMed - as supplied by publisher]
Type B Insulin Resistance Masquerading As Ovarian Hyperthecosis.
J Clin Endocrinol Metab. 2016 Dec 02;:jc20163674
Authors: Brown RJ, Joseph J, Cochran E, Gewert C, Semple R, Gorden P
CONTEXT: Hyperinsulinemia can lead to pathologic ovarian growth and androgen production.
CASE DESCRIPTION: A 29 year old woman developed an autoantibody to the insulin receptor (Type B insulin resistance), causing extreme insulin resistance and hyperinsulinemia. Testosterone levels were elevated to the adult male range. Treatment with gonadotropin releasing hormone (GnRH) analog led to normalization of testosterone, despite persistent extreme insulin resistance.
CONCLUSIONS: This case demonstrates that gonadotropins are necessary for insulin to cause pathologic ovarian androgen production. Suppression of gonadotropins with GnRH analogs may be a useful therapeutic option in patients with severe hyperandrogenism or ovarian enlargement due to hyperinsulinemia.
PMID: 27911591 [PubMed - as supplied by publisher]
The relationship between thyroid function and the prevalence of type 2 diabetes mellitus in euthyroid subjects.
J Clin Endocrinol Metab. 2016 Dec 1;:jc20162965
Authors: Gu Y, Li H, Bao X, Zhang Q, Liu L, Meng G, Wu H, Du H, Shi H, Xia Y, Su Q, Fang L, Yu F, Yang H, Yu B, Sun S, Wang X, Zhou M, Jia Q, Guo Q, Chang H, Wang G, Huang G, Song K, Niu K
PURPOSE: The thyroid hormones (TH) are primarily responsible for the regulation of energy balance and metabolism, suggesting that TH levels may contribute to the development of type 2 diabetes mellitus (T2DM). However, few studies have investigated the relationship between TH and T2DM in a general population. The aim of this study is to evaluate whether serum TH levels within the reference range are related to T2DM.
METHODS: A cross-sectional study (n=15,296) was performed in Tianjin, China. Serum free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) levels were measured by chemiluminescence immunoassay, and T2DM was defined according to the American Diabetes Association criteria. Multiple logistic regression models were used to assess the gender-specific relationships between FT3, FT4, FT3/FT4 ratios and TSH quintiles and T2DM.
RESULTS: The prevalence of T2DM was 16.2% in males and 7.7% in females, respectively. In males, the multivariable-adjusted odds ratios (95% confidence interval) of T2DM for increasing quintiles of FT3, FT4 and FT3/FT4 ratios were 1.00, 0.75(0.63-0.89), 0.70(0.58-0.84), 0.63(0.52-0.76), 0.56(0.46-0.68) (P for trend<0.0001); 1.00, 1.05(0.87-1.27), 1.16(0.96-1.40), 1.09(0.90-1.31), 1.29(1.07-1.56) (P for trend=0.01); and 1.00, 0.69(0.58-0.83), 0.72(0.60-0.86), 0.59(0.48-0.71), and 0.55(0.46-0.66) (P for trend<0.0001), respectively. Similar results also were observed in females. In contrast, a strong negative correlation between TSH and T2DM was observed in males, but not in females.
CONCLUSIONS: This study demonstrated that decreased FT3, FT3/FT4 ratios and increased FT4 levels are independently related to a higher prevalence of T2DM in both males and females, and TSH is inversely related to T2DM in males only.
PMID: 27906594 [PubMed - as supplied by publisher]
Lower Death Risk for Vascular Dementia than for Alzheimer's Disease with Postmenopausal Hormone Therapy Users.
J Clin Endocrinol Metab. 2016 Dec 1;:jc20163590
Authors: Mikkola TS, Savolainen-Peltonen H, Tuomikoski P, Hoti F, Vattulainen P, Gissler M, Ylikorkala O
CONTEXT: There are conflicting data on postmenopausal hormone therapy (HT) and the risk of vascular dementia (VD) and Alzheimer's disease (AD).
OBJECTIVE: We analyzed the mortality risk attributable to VD or AD in women with a history of HT use. Design, Patients, Interventions and Main Outcome Measures: A total of 489,105 Finnish women using systemic HT in 1994-2009 were identified from the nationwide drug reimbursement register. Of these women, 581 died of VD and 1057 of AD in 1998-2009. The observed deaths in HT users with <5 or ≥5 years of exposure were compared with those having occurred in the age-standardized female population. Furthermore, we compared the VD or AD death risk of women who had started the use of HT at <60 versus ≥60 years of age.
RESULTS: The risk of death caused by VD was reduced by 37-39% (<5 or ≥5 years of exposure) with the use of any systemic HT, and this reduction was not associated with the duration or type (estradiol-only or estradiol-progestin combination) of HT. The risk of death caused by AD was not reduced with systemic HT <5 years of use, but was slightly reduced (15%) if the HT exposure had exceeded 5 years. The age at systemic HT initiation of <60 versus ≥60 years did not affect the death risk reductions.
CONCLUSION: Estradiol-based HT use is associated with a reduced risk of death both from VD and AD, but the risk reduction is larger and appears sooner in VD than AD.
PMID: 27906568 [PubMed - as supplied by publisher]
Short adult stature predicts impaired beta-cell function, insulin resistance, glycemia and type 2 diabetes in Finnish men.
J Clin Endocrinol Metab. 2016 Dec 1;:jc20162933
Authors: Vangipurapu J, Stančáková A, Jauhiainen R, Kuusisto J, Laakso M
CONTEXT: Recent studies have highlighted the role of height in complex diseases but conflicting information has been reported on height as a predictor of changes in glycemia and risk of type 2 diabetes.
OBJECTIVE: Our aim was to investigate the association of height with insulin sensitivity, insulin secretion, glycemia, type 2 diabetes and cardiovascular disease in a large prospective population-based study.
DESIGN: The study included 8,746 Finnish men (mean±SD, age 57.2±7.1 years, BMI 26.8±3.8 kg/m(2)) selected from a population-based METabolic Syndrome In Men (METSIM) study.
SETTING: The study was conducted at Kuopio University Hospital and University of Eastern Finland.
PARTICIPANTS: The participants were non-diabetic at the recruitment, and 5,401 subjects have participated in the follow-up study. During the follow-up, a total of 693 subjects converted to type 2 diabetes and 351 were diagnosed with a new cardiovascular disease event during the follow-up.
MAIN OUTCOME MEASURES: Incidence of type 2 diabetes and cardiovascular disease Results: Height measured at baseline was significantly associated with lower levels of 2 hour glucose in an oral glucose tolerance test, an increase in insulin secretion, a decrease in the risk of type 2 diabetes (Hazard Ratio 0.83[0.77-0.90]) and cardiovascular disease (HR=0.75[0.67-0.83]) during the follow-up.
CONCLUSION: Short stature is associated with unfavorable changes in glucose metabolism and predicts an increase in the risk of type 2 diabetes and cardiovascular events.
PMID: 27906553 [PubMed - as supplied by publisher]
Delayed diagnosis and a lack of information associated with dissatisfaction in women with polycystic ovary syndrome.
J Clin Endocrinol Metab. 2016 Dec 1;:jc20162963
Authors: Gibson-Helm M, Teede H, Dunaif A, Dokras A
CONTEXT: Polycystic ovary syndrome (PCOS) is a complex, chronic and under-recognized disorder. Diagnosis experience may have lasting effects on wellbeing and self-management.
OBJECTIVE: To investigate PCOS diagnosis experiences, information provided and concerns about PCOS.
DESIGN: Cross-sectional study using an online questionnaire.
SETTING: Recruitment via support group websites in 2015-2016.
PARTICIPANTS: 1385 women with a reported diagnosis of PCOS, living in North America (53.0%), Europe (42.2%) or other world regions (4.9%), 64.8% of whom were 18-35 years old.
MAIN OUTCOME MEASURES: Satisfaction with PCOS diagnosis experience, satisfaction with PCOS information received at the time of diagnosis, and current concerns about PCOS.
RESULTS: One third or more of women reported more than two years (33.6%) and three or more health professionals (47.1%) before a diagnosis was established. The minority were satisfied with their diagnosis experience (35.2%) or with the information they received (15.6%). Satisfaction with PCOS information received was positively associated with diagnosis satisfaction (odds ratio (OR): 7.0 95% confidence interval (CI): 4.9 to 9.9); seeing ≥5 health professionals (OR: 0.5 95%CI: 0.3 to 0.8) and longer time to diagnosis (>2 years OR: 0.4 95%CI: 0.3 to 0.6) were negatively associated with diagnosis satisfaction (independent of time since diagnosis, age and world region). Women's most common concerns were difficulty losing weight (53.6%), irregular menstrual cycles (50.8%) and infertility (44.5%).
CONCLUSIONS: In the largest study of PCOS diagnosis experiences, many women reported delayed diagnosis and inadequate information. These major gaps in early diagnosis, education and support are clear opportunities for improving patient experience.
PMID: 27906550 [PubMed - as supplied by publisher]
Anti-inflammatory and ROS Suppressive Effects of the Addition of Fiber to a High Fat High Calorie Meal.
J Clin Endocrinol Metab. 2016 Dec 1;:jc20162669
Authors: Ghanim H, Batra M, Abuaysheh S, Green K, Makdissi A, Kuhadiya N, Chaudhuri A, Dandona P
BACKGROUND: Fiber intake is associated with a reduction in the occurrence of cardiovascular events and diabetes.
OBJECTIVE: To investigate whether the addition of fiber to a high fat-high Calorie (HFHC) meal prevents pro-inflammatory changes induced by HFHC meal.
DESIGN: Ten fasting normal subjects consumed HFHC meal with or without an additional 30g of insoluble dietary fiber on 2 separate visits. Blood samples were collected over 5hr and mononuclear cells (MNC) isolated.
RESULTS: Fiber addition to HFHC meal significantly lowered glucose excursion in the first 90min and increased insulin and C-peptide secretion throughout the 5hr follow-up period compared to meal alone. The HFHC meal induced an increase in LPS concentrations, MNC ROS generation and the expression of IL-1β, TNF-α, TLR-4 and CD14. The addition of fiber prevented the increase in LPS and significantly reduced the increases in ROS generation and the expression of IL-1β, TNF-α, TLR-4 and CD14. Additionally, the meal increased SOCS-3 and PTP-IB mRNA and protein levels which were inhibited when fiber was added.
CONCLUSIONS: The addition of fiber to a pro-inflammatory HFHC meal has beneficial anti-inflammatory and metabolic effects. Thus, the fiber content of the American Heart Association (AHA) meal may contribute to its non-inflammatory nature. If these actions of dietary fiber are sustained following long term intake it may contribute to its known benefits in the prevention of insulin resistance, type 2 diabetes and atherosclerosis.
PMID: 27906549 [PubMed - as supplied by publisher]
Late Diagnosis of POMC Deficiency and in vitro evidence of residual translation from allele with c.-11C>A mutation.
J Clin Endocrinol Metab. 2016 Dec 1;:jc20163318
Authors: Anisimova AS, Rubtsov PM, Akulich KA, Dmitriev SE, Frolova E, Tiulpakov A
CONTEXT: Loss-of-function mutations in the POMC gene are associated with the syndrome of adrenal insufficiency, obesity and red hair. We describe here a case of POMC deficiency, in which adrenal insufficiency was not treated until the fourth year of life. One of the disease-causative POMC mutations was characterized in vitro using a new approach.
CASE DESCRIPTION: A boy presented in the first year of life with red hair, growth acceleration, moderate obesity and recurrent cholestasis, which was followed by two episodes of hypoglycemia at ages of 1.5 and 3 years. The diagnosis was suspected at the age of 3.6 years after documenting undetectable levels of plasma ACTH and serum cortisol, after which replacement with hydrocortisone was initiated. Sequencing of POMC gene revealed compound heterozygocity for c.-11C>A/p.W84X mutations. p.W84X mutation is predicted to result in a significant truncation of preprohormone. Using an mRNA transfection approach followed by in vitro translation assay we could directly demonstrate that the transcript with c.-11C>A substitution is predominantly translated within a new open reading frame, however translation of the POMC main reading frame is preserved, with translation efficiency being ∼17% of the wild-type transcript.
CONCLUSIONS: The current description provides important information on the natural course of POMC deficiency. In vitro translation studies demonstrated residual translation of the main coding region from allele with c.-11C>A mutation, which at least partially explains a relatively late presentation of adrenal insufficiency in the patient.
PMID: 27906547 [PubMed - as supplied by publisher]
Bilateral testicular tumors resulting in recurrent Cushing's syndrome after bilateral adrenalectomy".
J Clin Endocrinol Metab. 2016 Nov 30;:jc20162702
Authors: Puar T, Engels M, van Herwaarden AE, Sweep FC, Hulsbergen-van de Kaa C, Kamphuis-van Ulzen K, Chortis V, Arlt W, Stikkelbroeck N, Claahsen-van der Grinten HL, Hermus AR
CONTEXT: Recurrence of hypercortisolism in patients after bilateral adrenalectomy for Cushing's disease is extremely rare.
PATIENT: We present a rare case of a 27-year-old man who previously underwent bilateral adrenalectomy for Cushing's disease with complete clinical resolution. Cushingoid features recurred 12 years later, along with bilateral testicular enlargement. Hormonal tests confirmed ACTH-dependent Cushing's. Surgical resection of the testicular tumors led to clinical and biochemical remission.
DESIGN AND RESULTS: Gene expression analysis of the tumor tissue by qPCR showed high expression of all key steroidogenic enzymes. Adrenocortical-specific genes were 5.1 x 10(5) (CYP11B1), 1.8 x 10(2) (CYP11B2) and 6.3 x 10(4) (MC2R) times higher than non-steroidogenic fibroblast control. This correlated with urine steroid metabolome profiling showing 2-5 fold increases in the excretion of the metabolites of 11-deoxycortisol, 21-deoxycortisol and total glucocorticoids. Leydig-specific genes were 4.3 x 10(1) (LHCGR) and 9.3 x 10(0) (HSD17B3) times higher than control and urinary steroid profiling showed 2-fold increased excretion of the major androgen metabolites androsterone and etiocholanolone. These distinctly increased steroid metabolites were suppressed by dexamethasone, but unresponsive to hCG stimulation, supporting the role of ACTH, but not LH, in regulating tumor-specific steroid excess.
CONCLUSION: We report bilateral testicular tumors occurring in a patient with recurrent Cushing's disease 12 years after bilateral adrenalectomy. Using mRNA expression analysis and steroid metabolome profiling, the tumors demonstrated both adrenocortical and gonadal steroidogenic properties, similar to testicular adrenal rest tumors found in patients with congenital adrenal hyperplasia. This suggests the presence of pluripotent cells even in patients without CAH.
PMID: 27901643 [PubMed - as supplied by publisher]
ATLANTIC DIP: Insulin Therapy for women with IADPSG-diagnosed Gestational Diabetes Mellitus. Does it work?
J Clin Endocrinol Metab. 2016 Nov 30;:jc20162911
Authors: Bogdanet D, Egan AM, Reddin C, Kgosidialwa O, Kirwan B, Carmody L, Dunne FP
INTRODUCTION: Approximately 40% of women with gestational diabetes mellitus (GDM) diagnosed using IADPSG criteria require insulin therapy.
OBJECTIVE: To assess if the outcomes for women with GDM treated with insulin are comparable to women with normal glucose tolerance (NGT).
MATERIALS AND METHODS: This retrospective cohort study included 752 women with insulin-treated GDM and 2496 women with NGT during pregnancy. Maternal and foetal outcomes were examined.
RESULTS: Infants of insulin-treated GDM women had rates of macrosomia (aOR 1.19, CI 0.87-1.63, p=0.26), large-for-gestational age (LGA) (aOR 1.07, CI 0.77-1.47, p=0.67) and small for gestational age (SGA) (aOR 0.70, CI 0.38-1.38, p=0.26) similar to women with NGT. They were more likely to be hypoglycaemic at birth (aOR 6.85, 95%, CI 2.31-20.28, p<0.01) and require neonatal intensive care unit care (NICU) (aOR 12.09 95%, CI 8.72-16.76, p<0.01), predominantly for non-medical reasons. Maternal rates of hypertensive disorders (pre-eclampsia aOR 0.64, CI 0.34-1.12, p=0.17; pregnancy induced hypertension (aOR 1.11, CI 0.74- 1.66, p=0.60) and haemorrhage (ante partum haemorrhage aOR 0.56, CI 0.19-1.58, p=0.27; post-partum haemorrhage aOR 1,17, CI 0.68-2.03, p=0.55) were similar between groups but the risk of polyhydramnios was increased in GDM cohort (aOR 7.75, 95%, CI 3.96- 15.16, p<0.01).
CONCLUSIONS: Insulin treatment of IADPSG-diagnosed GDM results in similar rates of macrosomia, LGA, SGA and maternal hypertensive disorders to those of women with NGT. Although NICU admissions are greater in the GDM cohort they are primarily for non-medical reasons. Neonatal hypoglycaemia and polyhydramnios remain greater among women with insulin-treated GDM.
PMID: 27901638 [PubMed - as supplied by publisher]
11-oxygenated C19 steroids are the predominant androgens in polycystic ovary syndrome.
J Clin Endocrinol Metab. 2016 Nov 30;:jc20163285
Authors: O'Reilly MW, Kempegowda P, Jenkinson C, Taylor AE, Quanson JL, Storbeck KH, Arlt W
CONTEXT: Androgen excess is a defining feature of polycystic ovary syndrome (PCOS) but the exact origin of hyperandrogenemia remains a matter of debate. Recent studies have highlighted the importance of the 11-oxygenated C19 steroid pathway to androgen metabolism in humans. In this study, we analyzed the contribution of 11-oxygenated androgens to the androgen excess phenotype in women with PCOS.
METHODS: 114 women with PCOS and 49 healthy controls underwent measurement of serum androgens by liquid chromatography-tandem mass spectrometry. 24-h urinary androgen excretion was analyzed by gas chromatography-mass spectrometry. Fasting plasma insulin and glucose were measured for calculation of homeostatic model assessment of insulin resistance (HOMA-IR). Baseline demographic data including body mass index were recorded.
RESULTS: As expected, serum concentrations of the classic androgens testosterone (p<0.001), androstenedione (p<0.001), and DHEA (p<0.01) were significantly increased in PCOS. Mirroring this, serum concentrations of the 11-oxygenated androgens 11β-hydroxyandrostenedione, 11-ketoandrostenedione, 11β-hydroxytestosterone and 11-ketotestosterone were all significantly higher in PCOS women than controls, as was the urinary excretion of the 11-oxygenated androgen metabolite 11β-hydroxyandrosterone. The proportionate contribution of 11-oxygenated to total serum androgens was significantly higher in PCOS compared to controls [53.0% (IQR 48.7-60.3) vs. 44.0% (IQR 32.9-54.9), p<0.0001]. Both obese (n=51) and non-obese (n=63) PCOS patients had significantly increased 11-oxygenated androgens. Serum 11β-hydroxyandrostenedione and 11-ketoandrostenedione correlated significantly with markers of insulin resistance.
CONCLUSIONS: For the first time, we show that 11-oxygenated androgens represent the majority of circulating androgens in women with PCOS, with close correlation to markers of metabolic risk.
PMID: 27901631 [PubMed - as supplied by publisher]