Diurnal rhythms in the white adipose tissue transcriptome are disturbed in obese individuals with type 2 diabetes compared with lean control individuals.

Aims/hypothesis: Animal studies have indicated that disturbed diurnal rhythms of clock gene expression in adipose tissue can induce obesity and type 2 diabetes. The importance of the circadian timing system for energy metabolism is well established, but little is known about the diurnal regulation of (clock) gene expression in obese individuals with type 2 diabetes. In this study we aimed to identify key disturbances in the diurnal rhythms of the white adipose tissue transcriptome in obese individuals with type 2 diabetes.

Early thyroxine treatment in Down syndrome and thyroid function later in life.

Objective: The hypothalamus-pituitary-thyroid (HPT) axis set point develops during the fetal period and first two years of life. We hypothesized that thyroxine treatment during these first two years, in the context of a randomized controlled trial (RCT) in children with Down syndrome, may have influenced the HPT axis set point and may also have influenced the development of Down syndrome-associated autoimmune thyroiditis.

Methods: We included 123 children with Down syndrome 8.

Effects of acute dietary weight loss on postprandial plasma bile acid responses in obese insulin resistant subjects.

Background & Aims: Bile acids (BA) are pleiotropic hormones affecting glucose and lipid metabolism. The physiochemical properties of different BA species affect their enterohepatic dynamics and their affinity for bile acid receptors. The BA pool composition is altered in patients with type 2 diabetes and obesity.

Glucocorticoid receptor haplotypes conferring increased sensitivity (BclI and N363S) are associated with faster progression of multiple sclerosis.

As high cortisol levels are implicated in suppressed disease activity of multiple sclerosis (MS), glucocorticoid receptor (GR) polymorphisms that affect glucocorticoid (GC) sensitivity may impact on this by changing local immunomodulation or regulation of the hypothalamus-pituitary-adrenal (HPA)-axis. In this post-mortem study, we investigated whether GR haplotypes affect MS disease course and production of cortisol and soluble CD163 (sCD163), a molecule induced by GC on microglia/macrophages. We found that GR haplotypes that confer high GC sensitivity are associated with more aggressive MS but do not affect levels of cortisol secreted by the HPA-axis or shedding of CD163.

Inaccurate First-Generation Testosterone Assays Are Influenced by Sex Hormone-Binding Globulin Concentrations.

Background: The quality of testosterone assays has been a matter of debate for several years. Known limitations of testosterone immunoassays are the cross-reactivity with other steroids and a high variation in the low concentration range. We hypothesized that one of the additional limitations of testosterone immunoassays is an ineffective displacement of testosterone from its binding protein.

Determination of urinary aldosterone using a plasma aldosterone 2D ID LC-MS/MS method.

Aim: In the diagnosis for primary aldosteronism, the measurement of urinary aldosterone is part of the confirmation test but diagnostic accuracy may be blunted due to poor immunoassay performance for urinary aldosterone. Nowadays, plasma aldosterone concentrations are measured preferably by LC-MS/MS yet such methods for urinary aldosterone are lacking.

Methods & Results: We show that plasma and urinary aldosterone can be measured with the same 2D isotope dilution LC-MS/MS method.

The Hypercoagulable state in Hyperthyroidism is mediated via the Thyroid Hormone β Receptor pathway.

Objective: Hyperthyroidism is associated with a hypercoagulable state, but the underlying mechanism is unknown. Patients with resistance to thyroid hormone (RTH) due to defective thyroid hormone receptor β (TRβ) exhibit elevated circulating thyroid hormones (TH) with refractoriness to TH action in TRβ-expressing tissues. We tested the hypothesis that the hypercoagulable state in hyperthyroidism is mediated via the TRβ.

Determination of a steroid profile in heel prick blood using LC-MS/MS.

Background: The aim of this study was to improve the sensitivity of the congenital adrenal hyperplasia (CAH) neonatal screening by including second-tier steroid profiling on a DBS using LC-MS.

Results: We developed a method to measure the steroid profile in DBS and established gestational age-specific reference ranges of cortisol, cortisone, 11-deoxycortisol, 21-deoxycortisol, 17-hydroxyprogesterone, testosterone, Δ4-androstenedione, corticosterone and 11-deoxycorticosterone using 450 heel prick samples of neonates, participating in the Dutch Screening Program. Analyzing 92 cards with a positive CAH screening showed that only 21-deoxycortisol was 100% specific for diagnosed CAH patients.

Predicting the Risk of Recurrence Before the Start of Antithyroid Drug Therapy in Patients With Graves' Hyperthyroidism.

Genotyping increases the accuracy of a clinical score (based on pretreatment age, goiter size, FT4, TBII) for predicting recurrence of Graves' hyperthyroidism after a course of antithyroid drugs: a prospective study.

Pituitary Hormone Secretion Profiles in IGSF1 Deficiency Syndrome.

Background: Loss-of-function mutations in immunoglobulin superfamily member 1 (IGSF1) cause an X-linked syndrome of central hypothyroidism, macroorchidism, delayed pubertal testosterone rise, variable prolactin deficiency and variable partial GH deficiency in childhood. The clinical features and gene expression pattern suggest a pivotal role for IGSF1 in the pituitary, but detailed knowledge on pituitary hormone secretion in this syndrome is lacking. We therefore aimed to study the 24-hour pituitary hormone secretion in male patients with IGSF1 deficiency.

Short-Term Effect of Estrogen on Human Bone Marrow Fat.

Bone marrow fat, an unique component of the bone marrow cavity increases with aging and menopause and is inversely related to bone mass. Sex steroids may be involved in the regulation of bone marrow fat, because men have higher bone marrow fat than women and clinical observations have suggested that the variation in bone marrow fat fraction is greater in premenopausal compared to postmenopausal women and men. We hypothesized that the menstrual cycle and/or estrogen affects the bone marrow fat fraction.

Breakfast replacement with a low-glycaemic response liquid formula in patients with type 2 diabetes: a randomised clinical trial.

Low-glycaemic index diets reduce glycated Hb (HbA1c) in patients with type 2 diabetes, but require intensive dietary support. Using a liquid meal replacement with a low glycaemic response (GR) may be an alternative dietary approach. In the present study, we investigated whether breakfast replacement with a low-GR liquid meal would reduce postprandial glycaemia and/or improve long-term glycaemia.

LC-MS/MS in endocrinology: what is the profit of the last 5 years?

Currently, chromatography (GC but more commonly HPLC) is the analytical method of choice for several hormones, either because the immunoassays suffer from extensive crossreactivity or because chromatography permits simultaneous measurements of hormones. However, sometimes the conventional detection systems with HPLC methods do not meet desired specificity. With the increase of robust and affordable LC-MS/MS systems, the next step forward in specificity was taken.

Thyrotropin secretion in healthy subjects is robust and independent of age and gender, and only weakly dependent on body mass index.

Context: Studies of the influence of sex, age, and body weight on TSH secretion are not unanimous. Most reports are based on a single TSH measurement; studies using frequent blood sampling are scarce and include a limited number of selected subjects.

Objective: The goal was to investigate TSH dynamics in 117 healthy adults.

Brain natriuretic peptide is not predictive of dilated cardiomyopathy in Becker and Duchenne muscular dystrophy patients and carriers.

Background: Cardiomyopathy is reported in Duchenne and Becker muscle dystrophy patients and female carriers. Brain Natriuretic peptide (BNP) is a hormone produced mainly by ventricular cardiomyocytes and its production is up regulated in reaction to increased wall stretching. N-terminal-proBNP (NT-proBNP) has been shown to be a robust laboratory parameter to diagnose and monitor cardiac failure, and it may be helpful to screen for asymptomatic left ventricular dysfunction.

Selenite supplementation in euthyroid subjects with thyroid peroxidase antibodies.

Context: Euthyroid thyroid peroxidase (TPO-Ab)-positive subjects are at risk for progression to subclinical and overt autoimmune hypothyroidism. Previous studies have shown a decrease in TPO-Ab and improvement of quality-of-life (QoL) in L-T4-treated hypothyroid patients upon selenium supplementation.

Objectives: To evaluate in euthyroid TPO-Ab-positive women without thyroid medication whether selenite decreases TPO-Ab and improves QoL.

Measuring free thyroxine levels in neonatal heel-prick samples.

The Dutch neonatal screening scheme for Congenital Hypothyroidism (CH) is primarily based on the determination of thyroxine (T4) in filter paper blood spots. In the lowest 5% of T4 values, thyroxine binding globulin (TBG) is measured in order to be able to correct for occasional low TBG levels. However, because the commercial TBG kit has been withdrawn from the market, alternative strategies are needed to be explored including the assessment of free T4.

Deep brain stimulation for obsessive-compulsive disorder is associated with cortisol changes.

Deep brain stimulation (DBS) is an effective treatment for obsessive-compulsive disorder (OCD), but its mechanism of action is largely unknown. Since DBS may induce rapid symptomatic changes and the pathophysiology of OCD has been linked to the hypothalamic-pituitary-adrenal (HPA) axis, we set out to study whether DBS affects the HPA axis in OCD patients. We compared a stimulation ON and OFF condition with a one-week interval in 16 therapy-refractory OCD patients, treated with DBS for at least one year, targeted at the nucleus accumbens (NAc).

Genotypes in relation to phenotypic appearance and exposure to environmental factors in Graves' hyperthyroidism.

Background: Genetic polymorphisms and environmental factors are both involved in the pathogenesis of Graves' disease, but their interaction and effect on Graves' phenotypes have scarcely been investigated.

Objective: To test the hypothesis that subjects with susceptibility genotypes develop more severe Graves' hyperthyroidism at a younger age and after less exposure to environmental factors, with attention to gender differences.

Study Design: A prospective observational multicenter study in 205 adult Caucasian patients with untreated first episode of Graves' hyperthyroidism.

Effects of a hypercaloric diet on β-cell responsivity in lean healthy men.

Objective: Insulin resistance and hyperinsulinaemia precede the onset of obesity-induced DM2. The early adaptation of the β-cell during the initial phase of overfeeding and weight gain has only been partly elucidated. We studied the early changes in insulin clearance and β-cell responsivity during a positive and negative energy balance in lean healthy men.

Treatment of amiodarone-induced thyrotoxicosis type 2: a randomized clinical trial.

Context: Amiodarone-induced thyrotoxicosis (AIT) type 2 is self-limiting in nature, but most physicians are reluctant to continue amiodarone. When prednisone fails to restore euthyroidism, possibly due to mixed cases of AIT type 1 and 2, perchlorate (ClO(4)) might be useful because ClO(4) reduces the cytotoxic effect of amiodarone on thyrocytes.

Objectives: Our objectives were to demonstrate the feasibility of continuation of amiodarone in AIT type 2 and to evaluate the usefulness of ClO(4) (given alone or in combination with prednisone) in AIT type 2.