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Open access

Clement N Kufe, Lisa K Micklesfield, Maphoko Masemola, Tinashe Chikowore, Andre P Kengne, Fredrik Karpe, Shane A Norris, Nigel J Crowther, Tommy Olsson, and Julia H Goedecke

Aims

Despite a higher prevalence of overweight/obesity in Black South African women compared to men, the prevalence of type 2 diabetes (T2D) does not differ. We explored if this could be due to sex differences in insulin sensitivity, clearance and/or beta-cell function and also sex-specific associations with total and regional adiposity.

Methods

This cross-sectional study included 804 Black South African men (n = 388) and women (n = 416). Dual-energy X-ray absorptiometry was used to measure total and regional adiposity. Insulin sensitivity (Matsuda index), secretion (C-peptide index) and clearance (C-peptide/insulin ratio) were estimated from an oral glucose tolerance test.

Results

After adjusting for sex differences in the fat mass index, men were less insulin sensitive and had lower beta-cell function than women (P  < 0.001), with the strength of the associations with measures of total and central adiposity being greater in men than women (P  < 0.001 for interactions). Further, the association between total adiposity and T2D risk was also greater in men than women (relative risk ratio (95% CI): 2.05 (1.42–2.96), P  < 0.001 vs 1.38 (1.03–1.85), P = 0.031).

Conclusion

With increasing adiposity, particularly increased centralisation of body fat linked to decreased insulin sensitivity and beta-cell function, Black African men are at greater risk for T2D than their female counterparts.

Open access

Connar S J Westgate, Keira Markey, James L Mitchell, Andreas Yiangou, Rishi Singhal, Paul Stewart, Jeremy W Tomlinson, Gareth G Lavery, Susan P Mollan, and Alexandra J Sinclair

Context

Idiopathic intracranial hypertension (IIH) is a disease of raised intracranial pressure (ICP) of unknown aetiology. Reductions in glucocorticoid metabolism are associated with improvements in IIH disease activity. The basal IIH glucocorticoid metabolism yet to be assessed.

Objective

To determine the basal glucocorticoid phenotype in IIH and assess the effects of weight loss on the IIH glucocorticoid phenotype.

Design

A retrospective case-control study and a separate exploratory analysis of a prospective randomised intervention study.

Methods

The case-control study compared female IIH patients to body mass index, age, and sex-matched controls. The randomised intervention study, different IIH patients were randomized to either a community weight management intervention, or bariatric surgery, with patients assessed at baseline and 12 months. Glucocorticoid levels were determined utilising 24-hour urinary steroid profiles alongside the measurement of adipose tissue 11β-HSD1 activity.

Results

Compared to control subjects, patients with active IIH had increased systemic 11β-hydroxysteroid dehydrogenase (11β-HSD1) and 5α-reductase activity. The intervention study demonstrated that weight loss following bariatric surgery reduced systemic 11β-HSD1 and 5α-reductase activity. Reductions in these were associated with reduced ICP. Subcutaneous adipose tissue explants demonstrated elevated 11β-HSD1 activity compared to samples from matched controls.

Conclusion

We demonstrate that in IIH, there is a phenotype of elevated systemic and adipose 11β-HSD1 activity in excess to that mediated by obesity. Bariatric surgery to induce weight loss was associated with reductions in 11β-HSD1 activity and decreased ICP. These data reflect new insights into the IIH phenotype and further point towards metabolic dysregulation as a feature of IIH.

Open access

Christina Wenzek, Anita Boelen, Astrid M Westendorf, Daniel R Engel, Lars C Moeller, and Dagmar Führer

Over the past few years, growing evidence suggests direct crosstalk between thyroid hormones (THs) and the immune system. Components of the immune system were proposed to interfere with the central regulation of systemic TH levels. Conversely, THs regulate innate and adaptive immune responses as immune cells are direct target cells of THs. Accordingly, they express different components of local TH action, such as TH transporters or receptors, but our picture of the interplay between THs and the immune system is still incomplete. This review provides a critical overview of current knowledge regarding the interaction of THs and the immune system with the main focus on local TH action within major innate and adaptive immune cell subsets. Thereby, this review aims to highlight open issues which might help to infer the clinical relevance of THs in host defence in the context of different types of diseases such as infection, ischemic organ injury or cancer.

Open access

Lisa M Shepherd, Kelly Ann Schmidtke, Jonathan M Hazlehurst, Eka Melson, Janine Dretzke, Noel Hawks, Wiebke Arlt, Abd A Tahrani, Amelia Swift, and Debbie M Carrick-Sen

Abstract

Objective: The incidence of adrenal crisis remains high, particularly for people with primary adrenal insufficiency, despite the introduction of behavioural interventions. The present study aimed to identify and evaluate available evidence of interventions aiming to prevent adrenal crisis in primary adrenal insufficiency.

Design: Systematic review of literature and theoretical mapping.

Methods: MEDLINE, MEDLINE in Process, EMBASE, ERIC, Cochrane CENTRAL, CINAHL, PsycINFO, the Health Management Information Consortium (HMIC) and trial registries were searched from inception to November 2021. Three reviewers independently selected studies and extracted data. Two reviewers appraised the studies for risk of bias.

Results: Seven observational or mixed methods studies were identified where interventions were designed to prevent adrenal crisis in adrenal insufficiency. Patient education was the focus of all interventions and utilised the same two behaviour change techniques, instruction on how to perform a behaviour’ and ‘pharmacological support’. Barrier and facilitator themes aiding or hindering the intervention included: knowledge, behaviour, emotions, skills, social influences and environmental context and resources. Most studies did not measure effectiveness and assessment of knowledge was variable across studies. Study quality was moderate.

Conclusion: This is an emerging field with limited studies available. Further research is required in relation to the development and assessment of different behaviour change interventions to prevent adrenal crisis.

Systematic review registration PROSPERO (International prospective register of systematic reviews) CRD 42019137412

Restricted access

Christopher Rohde, Nanna Brix Finnerup, Norbert Schmitz, Troels Staehelin Jensen, Reimar Wernich Thomsen, and Søren Dinesen Østergaard

Objective

It is largely unknown whether individuals with diabetic neuropathy face an increased risk of developing mental illness. Therefore, in a population-based cohort study, we aimed to examine whether individuals with diabetic neuropathy are at elevated risk of being diagnosed with a mental disorder compared to diabetes-duration-matched individuals without diabetic neuropathy.

Methods

We used the nationwide Danish registers to identify all individuals diagnosed with diabetic neuropathy between January 1, 1996, and January 1, 2019. For each of these individuals, we identified up to five individuals with diabetes, matched on the duration of illness, who were not diagnosed with diabetic neuropathy. We then compared incidence rates of mental disorders between individuals with diabetic neuropathy and the diabetes-duration-matched individuals using a Cox proportional-hazards model.

Restults

Individuals with diabetic neuropathy had a substantial and statistically significant increased risk of being diagnosed with any mental disorder (age- and sex-adjusted hazard rate ratio: 1.40, 95% CI: 1.31–1.48) as well as all specific mental disorders (psychotic disorder, bipolar disorder, unipolar depression, and/or anxiety disorder) compared with diabetes-duration-matched individuals without diabetic neuropathy.

Conclusions

Diabetic neuropathy appears to be associated with a substantially increased risk of developing a mental disorder. Knowledge of the potential mechanisms underlying this association could inform prevention and treatment and should therefore be pursued further.

Restricted access

Melek Yildiz, Aysel Bayram, Firdevs Bas, Volkan Karaman, Guven Toksoy, Sukran Poyrazoglu, Feryal Gun Soysal, Semen Onder, Zehra Oya Uyguner, and Feyza Darendeliler

Objective: The aim of this study was to assess the prevalence of ovarian and paraovarian adrenal rest tumors (ARTs) in gonadectomy materials of a subgroup of congenital adrenal hyperplasia (CAH) patients.

Methods: A total of 20 historical cases with clinical/molecular diagnosis of classical CAH were included in the study. All patients had 46,XX karyotype and underwent gonadectomy because of being raised as male.

Results: Median age at diagnosis of CAH was 5.7 years and markedly delayed. All patients revealed severe virilization. Bone age was significantly advanced, and bone age/chronological age ratio was increased with a median ratio of 1.8. Median age at the time of gonadectomy was 9.2 years. Ovarian and paraovarian ARTs were detected on pathological evaluation of gonadectomy materials in 4 patients (20%) (2 with simple virilizing 21-hydroxylase, 2 with 11-beta-hydroxylase deficiency) with previously normal pelvic imaging. In three cases with ARTs, paraovarian area was composed of medium-size polygonal cells, with round or oval monomorphic nuclei and abundant granular eosinophilic cytoplasm which is characteristic of adrenocortical tissue. The fourth case had bilateral ovarian “steroid cell tumors, not otherwise specified” and the tumor was accepted as benign. Except for the ARTs, heterotopic prostate and bilateral paratubal epididymis tissue were detected in a patient.

Conclusions: Ovarian and paraovarian ARTs might be more common than previously described, especially among patients with excessive and prolonged ACTH exposure. These tumors could be detected histopathologically even if not detected by classical imaging methods.

Open access

Catherine Peters and Nadia Schoenmakers

Transient congenital hypothyroidism (TCH) refers to congenital hypothyroidism which spontaneously resolves in the first few months or years of life. Currently, there is a paucity of reliable markers predicting TCH at diagnosis, and the diagnosis is established following withdrawal of levothyroxine therapy around 3 years of age. The incidence of TCH is increasing, and it is a major contributor to the overall increase in incidence of CH in recent studies. Both genetic factors, in particular mutations affecting DUOX2 and DUOXA2, and environmental factors, e.g iodine deficiency and excess, anti- TSHR antibodies and exposure to anti-thyroid or iodine-rich medications may cause TCH. Resolution of TCH in childhood may reflect both normal thyroid physiology (decreased thyroid hormone biosynthesis requirements after the neonatal period) and clearance or cessation of environmental precipitants. The relative contributions and interactions of genetic and environmental factors to TCH, and the extent to which TCH may be prevented, require evaluation in future population-based studies.

Open access

Hanna Nowotny, Uta Neumann, Véronique Tardy-Guidollet, S Faisal Ahmed, Federico Baronio, Tadej Battelino, Jérôme Bertherat, Oliver Blankenstein, Marco Bonomi, Claire Bouvattier, Aude Brac de la Perrière, Sara Brucker, Marco Cappa, Philippe Chanson, Hedi L Claahsen-van der Grinten, Annamaria Colao, Martine Cools, Justin H Davies, Helmut-Günther Dörr, Wiebke K Fenske, Ezio Ghigo, Roberta Giordano, Claus H Gravholt, Angela Huebner, Eystein Sverre Husebye, Rebecca Igbokwe, Anders Juul, Florian W Kiefer, Juliane Léger, Rita Menassa, Gesine Meyer, Vassos Neocleous, Leonidas A Phylactou, Julia Rohayem, Gianni Russo, Carla Scaroni, Philippe Touraine, Nicole Unger, Jarmila Vojtková, Diego Yeste, Svetlana Lajic, and Nicole Reisch

Objective

To assess the current medical practice in Europe regarding prenatal dexamethasone (Pdex) treatment of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency.

Design and methods

A questionnaire was designed and distributed, including 17 questions collecting quantitative and qualitative data. Thirty-six medical centres from 14 European countries responded and 30 out of 36 centres were reference centres of the European Reference Network on Rare Endocrine Conditions, EndoERN.

Results

Pdex treatment is currently provided by 36% of the surveyed centres. The treatment is initiated by different specialties, that is paediatricians, endocrinologists, gynaecologists or geneticists. Regarding the starting point of Pdex, 23% stated to initiate therapy at 4–5 weeks postconception (wpc), 31% at 6 wpc and 46 % as early as pregnancy is confirmed and before 7 wpc at the latest. A dose of 20 µg/kg/day is used. Dose distribution among the centres varies from once to thrice daily. Prenatal diagnostics for treated cases are conducted in 72% of the responding centres. Cases treated per country and year vary between 0.5 and 8.25. Registries for long-term follow-up are only available at 46% of the centres that are using Pdex treatment. National registries are only available in Sweden and France.

Conclusions

This study reveals a high international variability and discrepancy in the use of Pdex treatment across Europe. It highlights the importance of a European cooperation initiative for a joint international prospective trial to establish evidence-based guidelines on prenatal diagnostics, treatment and follow-up of pregnancies at risk for CAH.

Open access

Martin Christa, Stefanie Hahner, Herbert Köstler, Wolfgang Rudolf Bauer, Stefan Störk, and Andreas Max Weng

Background

Sodium homeostasis is disrupted in many cardiovascular diseases, which makes non-invasive sodium storage assessment desirable. In this regard, sodium MRI has shown its potential to reveal differences in sodium content between healthy and diseased tissues as well as treatment-related changes of sodium content. When different tissues are affected disparately, simultaneous assessment of these compartments is expected to provide better information about sodium distribution, reduce examination time, and improve clinical efficiency.

Objectives

The objectives were (1) to investigate sodium storage levels in calf and pectoral muscle in healthy controls and patients and quantify changes following medical treatment and (2) to demonstrate homogeneous disruption in skeletal muscle sodium storage in patients with primary hyperaldosteronism (PHA).

Methods

We assessed sodium storage levels (relative sodium signal intensity, rSSI) in the calf and pectoral muscles of eight patients with PHA prior and after treatment and 12 age- and sex-matched healthy volunteers.

Results

Calf and pectoral muscle compartments exhibited similar sodium content both in healthy subjects (calf vs pectoral rSSI: 0.14 ± 0.01 vs 0.14 ± 0.03) and PHA patients (calf vs pectoral rSSI: 0.19 ± 0.03 vs 0.18 ± 0.03). Further, we observed similar treatment-related changes in pectoral and calf muscles in the patients (proportional rSSI change calf: 26%; pectoral: 28%).

Conclusion

We found that sodium was distributed uniformly and behaved equally in different skeletal muscles in Conn’s syndrome. This allows to measure both heart and skeletal muscle sodium signals simultaneously by a single measurement without repositioning the patient. This increases 23Na-MRI’s clinical feasibility as an innovative technique to monitor sodium storage.

Open access

Feng-Jiao Peng, Paul Palazzi, Sakina Mezzache, Nasrine Bourokba, Jeremie Soeur, and Brice M R Appenzeller

Objective

Endogenous hormones regulate numerous physiological processes in humans. Some of them are routinely measured in blood, saliva and/or urine for the diagnosis of disorders. The analysis of fluids may, however, require multiple samples collected at different time points to avoid the high variability in the concentration of some hormones. In contrast, hair analysis has been proposed as an interesting alternative to reveal average hormone levels over a longer period. In this work, we developed and validated an analytical method for analyzing 36 endogenous steroid and thyroid hormones and one pineal hormone in human hair using ultra-performance liquid chromatography (UPLC)-tandem mass spectrometry (MS/MS).

Methods

Sample preparation involved hair decontamination, pulverization, methanol extraction, and purification with C18-solid phase extraction. Extracts were then divided into two portions, respectively injected into an UPLC-MS/MS system, and analyzed using two different instrumental methods. The method was applied to a healthy female population aged 25–45 years.

Results

The method was validated on supplemented hair samples for the 37 targeted hormones, and its application to the population under study allowed to detect 32 compounds in 2–100% of the samples. Complete reference intervals (2.5–97.5th percentiles) were established for estrone, 17β-estradiol, androstenedione, dehydroepiandrosterone, progesterone, 17α-hydroxyprogesterone, cortisone, cortisol and 3,3’,5-triiodo-L-thyronine. Hair cortisone, cortisol, tetrahydrocortisone and tetrahydrocortisol concentrations were highly correlated with each other, with Kendall’s τ correlation coefficients ranging from 0.52 to 0.68.

Conclusion

Allowing the detection of 32 hormones from different chemical classes, the present method will allow to broaden hormonal profiling for better identifying endocrine disorders.