European Journal of Endocrinology

BACKGROUND AND OBJECTIVE: Apparent mineralocorticoid excess (AME) syndrome is an ultra-rare autosomal-recessive tubulopathy, caused by mutations in HSD11B2, leading to excessive activation of the kidney mineralocorticoid receptor, and characterized by early-onset low-renin hypertension, hypokalemia, and risk of chronic kidney disease (CKD). To date, most reports included few patients, and none described patients from Israel. We aimed to describe AME patients from Israel and to review the relevant literature...

BACKGROUND: Lymph node metastases in papillary thyroid cancer (PTC) increase the risk for persistent and recurrent disease. Data on the predictive value of histopathological features of lymph node metastases, however, are inconsistent. The aim of this study was to evaluate the prognostic significance of known and new histopathological features of lymph node metastases in a well-defined cohort of PTC patients with clinically evident lymph node metastases. METHODS: A total of 1042 lymph node metastases, derived from 129 PTC patients, were re-examined according to a predefined protocol and evaluated for diameter, extranodal extension, cystic changes, necrosis, calcifications and the proportion of the lymph node taken up by tumor cells...

CONTEXT: Reliable estradiol (E2) reference intervals (RIs) are crucial in Pediatric Endocrinology. OBJECTIVES: To develop a sensitive ultra-performance liquid chromatographic tandem mass spectrometry (UPLC-MS/MS) method for E2 in serum, to establish graphically represented RI percentiles and annual RIs for both sexes and to perform a systematic literature comparison. METHODS: First, an UPLC-MS/MS method for E2 was developed. Second, graphically represented RI percentiles and annual RIs covering 0-18 years were computed (cohort of healthy children (1181 girls, 543 boys))...

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We describe herein the European Reference Network on Rare Endocrine Conditions (Endo-ERN)- clinical practice guideline on diagnosis and management of familial forms of hyperaldosteronism. The guideline panel consisted of 10 experts in primary aldosteronism, endocrine hypertension, pediatric endocrinology and cardiology as well as a methodologist. A systematic literature search was conducted, and because of the rarity of the condition, most recommendations were based on expert opinion and small patient series...

BACKGROUND: Various glucocorticoid replacement treatments (GRT) are available for adrenal insufficiency (AI). However, their effectiveness in restoring glucocorticoid rhythm and exposure lacks adequate biochemical markers. We described the diurnal salivary cortisol (SalF) and cortisone (SalE) rhythm among different GRTs and analysed the associations between saliva-derived parameters and life quality questionnaires. METHODS: Control subjects (CS, n=28) and AI patients receiving hydrocortisone (HC, n=9), cortisone acetate (CA, n=23), dual-release hydrocortisone once (DRHC-od, n=10) and twice a day (DRHC-td, n=6) collected 9 saliva samples from 07:00 to 23:00...

OBJECTIVE: Calcium sensing receptor gene (CASR) encodes a G protein-coupled receptor crucial for calcium homeostasis. Gain-of-function CASR variants result in hypocalcemia, while loss-of-function variants lead to hypercalcemia. This study aims to assess the functional consequences of the novel nonsense CASR variant c.2897_2898insCTGA, p.(Gln967*) (Q967*) identified in adolescent patient with chronic hypocalcemia, a phenotype expected for a gain-of-function variants. DESIGN AND METHODS: To functionally characterize the Q967* mutant receptor, both WT and mutant CASR were transiently transfected into HEK293T cells and Calcium sensing receptor (CaSR) protein expression and function were comparatively evaluated using multiple read-outs...

BACKGROUND AND AIMS: Poly- and perfluoroalkyl substances(PFAS) are non-degradable, man-made-chemicals. They accumulate in humans with potential harmful effects, especially in susceptible periods of human development, such as the first months of life. We found that, in our cohort, exclusively breastfed infants(EBF) had 3-times higher PFAS-plasma-levels, compared to exclusively formula-fed infants(EFF) at age 3 months. Thus, PFAS could potentially reduce breastfeeding's health benefits...

OBJECTIVE: Mitotane is an important cornerstone in the treatment of pediatric adrenal cortical tumors (pACC), but experience with the drug in the pediatric age group is still limited and current practice is not guided by robust evidence. Therefore, we have compiled international consensus statements from pACC experts on mitotane indications, therapy, and management of adverse effects. METHODS: A Delphi method with three rounds of questionnaires within the pACC expert consortium of the international network groups ENSAT-PACT and ICPACT was used to create 21 final consensus statements...

OBJECTIVE: Distinguishing arginine vasopressin deficiency (AVP-D; central diabetes insipidus) from primary polydipsia (PP), commonly referred to as psychogenic polydipsia, is challenging. Psychopathologic findings, commonly used for PP diagnosis in clinical practice, are rarely evaluated in AVP-D patients, and no comparative data between the two conditions currently exist. DESIGN: Data from two studies involving 82 participants (39 AVP-D, 28 PP, and 15 healthy controls [HC])...

Cholelithiasis and cholecystitis affect individuals of all ages and are often treated by surgical removal of the gallbladder (cholecystectomy), which is considered a safe, low-risk procedure. Nevertheless, recent findings show that bile and its regulated storage and excretion may have important metabolic effects and that cholecystectomy is associated with several metabolic diseases postoperatively. Bile acids have long been known as emulsifiers essential to the assimilation of lipids and absorption of lipid-soluble vitamins, but more recently, they have also been reported to act as metabolic signaling agents...

OBJECTIVE: Colesevelam, a bile acid sequestrant approved for the treatment of hypercholesterolaemia, improves glycaemic control in type 2 diabetes. We hypothesised that single-dose colesevelam increases postprandial GLP-1 secretion, thus, reducing postprandial glucose excursions in individuals with type 2 diabetes. Further, we explored the effects of single-dose colesevelam on ultrasonography-assessed postprandial gallbladder motility, paracetamol absorption (proxy for gastric emptying) and circulating factors known to affect gallbladder motility...

Directed acyclic graphs (DAGs), or causal diagrams, are graphical representations of causal structures that can be used in medical research to understand and illustrate potential bias, including bias arising from confounding, selection, and misclassification. Further, they provide guidance for researchers about how to address a potential bias.

BACKGROUND: L-[methyl-11C]-methionine-positron emission tomography (Met-PET) is a potentially important imaging adjunct in the diagnostic workup of pituitary adenomas, including somatotroph tumours. Met-PET can identify residual or occult disease and make definitive therapies accessible to a subgroup of patients who would otherwise require lifelong medical therapy. However, existing data on its use are still limited to small case series. Here, we report the largest single centre experience (N=61) in acromegaly...

OBJECTIVE: Childhood cancer survivors are at risk for hypogonadism. Impact of hypogonadism on neurocognitive impairment and emotional distress in the non-cancer population has been shown, however, the relationship among childhood cancer survivor population is unknown. We aimed to evaluate the contribution of hypogonadism to neurocognitive impairment and emotional distress among survivors. DESIGN: Cross-sectional study using retrospective cohort. METHODS: 3628 survivors who completed standard neurocognitive tests (six domains: processing speed, memory, executive function, attention, academics, global cognition) and self-reported emotional distress were included in our study...

BACKGROUND: Homozygous mutations, two identical gene versions (alleles), one from each biological parent, are exceptional. Clinical descriptions of affected families, comprising few carriers only, are scattered throughout the literature, hindering evidence generation. METHODS: Included in this literature analysis were 5 RET families with ≥1 homozygous carrier and ≥3 heterozygous carriers per family. RESULTS: In consanguineous families with first-degree cousins, homozygotes presented with node-positive medullary thyroid cancer and pheochromocytoma in their mid-teens, whereas heterozygotes presented in their end-thirties and early forties...

Adrenocortical carcinoma (ACC) is a rare aggressive cancer with heterogeneous behaviour. Disease surveillance relies on frequent imaging, which comes with significant radiation exposure. The aim of the study was to investigate the role of circulating cell-free DNA (ccfDNA)-related biomarkers (BM) for prognostication and monitoring of ACC. We investigated 34 patients with ACC and 23 healthy subjects (HS) as controls. ccfDNA was extracted by commercial kits and ccfDNA concentrations quantified by fluorimeter (BM1)...

OBJECTIVES: Increased height in patients with acromegaly could be a manifestation of growth hormone (GH) excess before epiphysis closure. The aim of this study was to evaluate the relationship between the height of adult patients with GH excess related to mid-parental height (MPH) and population mean and to find whether taller patients with acromegaly come from tall families. METHODS: This is a single-centre, observational study involving 135 consecutive patients with acromegaly diagnosed as adults and no family history of GH excess...

OBJECTIVE: T-lymphocytes from visceral and subcutaneous white adipose tissue (vWAT and sWAT, respectively) can have opposing roles in the systemic metabolic changes associated with obesity. However, few studies have focused on this subject. Claudin-1 (CLDN1) is a protein involved canonically in Tight Junctions (TJs) and tissue paracellular permeability.We evaluated T lymphocytes gene expression in vWAT and sWAT and in the whole adipose depots in human samples. METHODS: A Clariom D-based transcriptomics analysis was performed on T lymphocytes magnetically separated from vWAT and sWAT from patients with obesity (Cohort 1; N = 11)...

INTRODUCTION: Paradoxical increase of GH following oral glucose load has been described in ∼30% of patients with acromegaly and has been related to the ectopic expression of the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) in somatotropinomas. Recently, we identified germline pathogenic variants and somatic loss of heterozygosity of lysine demethylase 1A (KDM1A) in patients with GIP-dependent primary bilateral macronodular adrenal hyperplasia with Cushing's syndrome...