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Open access

Heike Hoyer-Kuhn, Angela Huebner, Anette Richter-Unruh, Markus Bettendorf, Tilman Rohrer, Klaus Kapelari, Stefan Riedl, Klaus Mohnike, Helmuth-Günther Dörr, Friedrich-Wilhelm Roehl, Katharina Fink, Reinhard W Holl, and Joachim Woelfle

Objective

Treatment of classic congenital adrenal hyperplasia (CAH) is necessary to compensate for glucocorticoid/mineralocorticoid deficiencies and to suppress androgen excess. Hydrocortisone (HC) is preferred in growing children with classic CAH but recommendations regarding dosage/administration are inconsistent. The aim of this study was to evaluate HC dosing in children with CAH in relation to chronological age, sex, and phenotype based on a multicenter CAH registry.

Design

The CAH registry was initiated in 1997 by the AQUAPE in Germany. On December 31st 2018, data from 1571 patients were included.

Methods

A custom-made electronic health record software is used at the participating centers. Pseudonymized data are transferred for central analysis. Parameters were selected based on current guidelines. Descriptive analyses and linear regression models were implemented with SAS 9.4.

Results

We identified 1288 patients on exclusive treatment with hydrocortisone three times daily (604 boys; median age 7.2 years; 817 salt-wasting phenotype, 471 simple-virilizing phenotype). The mean (lower-upper quartiles) daily HC dose (mg/m² body surface area) was 19.4 (18.9–19.8) for patients <3 months (n = 329), 15.0 (14.6–15.3) for age ≥3–12 months (n = 463), 14.0 (13.7–14.3) for age 1–5.9 years (n = 745), 14.2 (14.0–14.5) for age 6 years to puberty entry (n = 669), and 14.9 (14.6–15.2) during puberty to 18 years (n = 801). Fludrocortisone was administered in 74.1% of patients with a median daily dosage of 88.8 µg.

Conclusion

Our analyses showed that still a high proportion of children are treated with HC doses higher than recommended. This evaluation provides comprehensive information on nationwide hydrocortisone substitution dosages in children with CAH underlining the benefit of systematic data within a registry to assess daily practice.

Open access

Alice Costantini, Mari H Muurinen, and Outi Mäkitie

In the last decade, the widespread use of massively parallel sequencing has considerably boosted the number of novel gene discoveries in monogenic skeletal diseases with short stature. Defects in genes playing a role in the maintenance and function of the growth plate, the site of longitudinal bone growth, are a well-known cause of skeletal diseases with short stature. However, several genes involved in extracellular matrix composition or maintenance as well as genes partaking in various biological processes have also been characterized. This review aims to describe the latest genetic findings in spondyloepiphyseal dysplasias, spondyloepimetaphyseal dysplasias, and some monogenic forms of isolated short stature. Some examples of novel genetic mechanisms leading to skeletal conditions with short stature will be described. Strategies on how to successfully characterize novel skeletal phenotypes with short stature and genetic approaches to detect and validate novel gene-disease correlations will be discussed in detail. In summary, we review the latest gene discoveries underlying skeletal diseases with short stature and emphasize the importance of characterizing novel molecular mechanisms for genetic counseling, for an optimal management of the disease, and for therapeutic innovations.

Open access

Qingrong Pan, Shuxin Gao, Xia Gao, Ning Yang, Zhi Yao, Yanjin Hu, Li Miao, Zhe Chen, and Guang Wang

Objective

It has been found that both serum homocysteine (Hcy) and serum creatinine levels were increased in hypothyroidism patients. The aim of this study was to investigate the correlation between serum Hcy and kidney function in patients with subclinical hypothyroidism or hypothyroidism.

Methods

A total of 448 subjects were enrolled and divided into three groups: hypothyroidism (n = 129), subclinical hypothyroidism (n = 141), and control group (n = 168). Anthropometric information, metabolic parameters, serum Hcy and creatinine levels, and estimated glomerular filtration rate (eGFR) were analyzed.

Results

Compared with healthy subjects, patients with subclinical hypothyroidism or hypothyroidism had significantly higher serum Hcy and creatinine levels and lower eGFR level (all P < 0.001). Serum Hcy was negatively correlated with eGFR in subclinical hypothyroidism patients (r = −0.220, P = 0.009), and in hypothyroidism patients (r = −0.422, P < 0.001). After adjusting for age, sex and BMI, eGFR was still significantly correlated with serum Hcy in subclinical hypothyroidism or hypothyroidism patients (both P < 0.05). Levothyroxine treatment resulted in significantly decreased Hcy and increased eGFR in hypothyroidism patients (both P < 0.001). The decrease in Hcy was correlated with the increased eGFR after treatment (P = 0.001).

Conclusion

Serum Hcy was negatively correlated with eGFR in subclinical hypothyroidism or hypothyroidism patients. After levothyroxine treatment, a correlation was found between the decrease in serum Hcy and the increase in eGFR in hypothyroidism patients.

Open access

Athanasios Zervas, George Chrousos, and Sarantis Livadas

‘Snow White and the Seven Dwarfs’, a fairytale that is widely known across the Western world, was originally written by the Brothers Grimm, and published in 1812 as ‘Snow White’. Though each dwarf was first given an individual name in the 1912 Broadway play, in Walt Disney’s 1937 film ‘Snow White and the Seven Dwarfs’, they were renamed, and the dwarfs have become household names. It is well known that myths, fables, and fairytales, though appearing to be merely children’s tales about fictional magical beings and places, have, more often than not, originated from real facts. Therefore, the presence of the seven brothers with short stature in the story is, from an endocrinological point of view, highly intriguing, in fact, thrilling. The diversity of the phenotypes among the seven dwarfs is also stimulating, although puzzling. We undertook a differential diagnosis of their common underlying disorder based on the original Disney production’s drawings and the unique characteristics of these little gentlemen, while we additionally evaluated several causes of short stature and, focusing on endocrine disorders that could lead to these clinical features among siblings, we have, we believe, been able to reveal the underlying disease depicted in this archetypal tale.

Open access

Melony C Fortuin-de Smidt, Amy E Mendham, Jon Hauksson, Ali Alhamud, Darko Stefanovski, Olah Hakim, Jeroen Swart, Louise M Goff, Steven E Kahn, Tommy Olsson, and Julia H Goedecke

The role of ectopic fat, insulin secretion and clearance in the preservation ofβ-cell function in black African women with obesity who typically present with hyperinsulinaemia is not clear. We aim to examine the associations between disposition index (DI, an estimate of β-cell function), insulin secretion and clearance and ectopic fat deposition. This is a cross-sectional study of 43 black South African women (age 20–35 years) with obesity (BMI 30–40 kg/m2) and without type 2 diabetes that measured the following: DI, insulin sensitivity (SI), acute insulin response (AIRg), insulin secretion rate (ISR), hepatic insulin extraction and peripheral insulin clearance (frequently sampled i.v. glucose tolerance test); pancreatic and hepatic fat, visceral adipose tissue (VAT) and abdominal s.c. adipose tissue (aSAT) volume (MRI), intra-myocellular (IMCL) and extra-myocellular fat content (EMCL) (magnetic resonance spectroscopy). DI correlated positively with peripheral insulin clearance (β 55.80, P = 0.002). Higher DI was associated with lower VAT, pancreatic fat and soleus fat, but VAT explained most of the variance in DI (32%). Additionally, higher first phase ISR (P = 0.033) and lower hepatic insulin extraction (P = 0.022) were associated with lower VAT, independent from SI, rather than with ectopic fat. In conclusion, peripheral insulin clearance emerged as an important correlate of DI. However, VAT was the main determinant of a lower DI above ectopic fat depots. Importantly, VAT, but not ectopic fat, is associated with both lower insulin secretion and higher hepatic insulin extraction. Prevention of VAT accumulation in young black African women should, therefore, be an important target for beta cell preservation.

Open access

David C Llewellyn, Rajaventhan Srirajaskanthan, Royce P Vincent, Catherine Guy, Eftychia E Drakou, Simon J B Aylwin, Ashley B Grossman, John K Ramage, and Georgios K Dimitriadis

Calcitonin-secreting neuroendocrine neoplasms of the lung are rare, with few cases reported in the literature. Differentiating between medullary thyroid carcinoma and an ectopic source of calcitonin secretion can represent a complex diagnostic conundrum for managing physicians, with cases of unnecessary thyroidectomy reported in the literature. This manuscript reports a case of ectopic hypercalcitonaemia from a metastatic neuroendocrine neoplasm of the lung with concurrent thyroid pathology and summarises the results of a systematic review of the literature. Medical Literature Analysis and Retrieval System Online, Excerpta Medica, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and SCOPUS databases were systematically and critically appraised for all peer reviewed manuscripts that suitably fulfilled the inclusion criteria established a priori. The protocol for this systematic review was developed according to the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols, and followed methods outlined in The Cochrane Handbook for Systematic Reviews of Interventions. This systematic review is registered with PROSPERO. It is vital to consider diagnoses other than medullary thyroid carcinoma when presented with a patient with raised calcitonin, as it is not pathognomonic of medullary thyroid carcinoma. Lung neuroendocrine neoplasms can appear similar to medullary thyroid carcinoma histologically, they can secrete calcitonin and metastasize to the thyroid. Patients with medullary thyroid carcinoma may show stimulated calcitonin values over two or more times above the basal values, whereas calcitonin-secreting neuroendocrine neoplasms may or may not show response to stimulation tests. The present review summarises existing evidence from cases of ectopic hypercalcitonaemia to lung neuroendocrine neoplasms.

Open access

Jia Liu, Lin Zhang, Jing Fu, Qiu Wang, and Guang Wang

Objective

Prolactin (PRL) has been demonstrated as a metabolic hormone to regulate energy metabolism recently. The present study aims to investigate the association between PRL and metabolic alterations in different obesity phenotypes.

Methods

A total of 451 drug-naive participants were recruited, comprising 351 obese patients and 100 age- and sex-matched healthy participants with normal weight. PRL, anthropometric, and clinical parameters were measured.

Results

In the obesity group, 15.1% (53/351) were categorized as 'metabolically healthy obesity (MHO)'. Besides favorable blood pressure, glucose, and lipids profiles, the MHO group exhibited increased PRL, and lower levels of high-sensitivity C-reactive protein (hsCRP), homeostasis model assessment of insulin resistance (HOMA-IR), and adipose tissue insulin resistance (adipo-IR) than the metabolically unhealthy obesity (MUHO) group (PRL, HOMA-IR, and adipo-IR: P < 0.01; hsCRP: P < 0.05). The severe MUHO group showed significantly decreased PRL levels than the mild MUHO group (P < 0.05). Multivariate linear regression analysis indicated that fasting plasma glucose (FBG) and adipo-IR were significantly associated with PRL (FBG: β = −0.263, P < 0.05; adipo-IR: β = −0.464, P < 0.01). Multivariable logistic regression analysis showed that hsCRP (OR = 0.824) and PRL (OR = 1.211) were independent predictors of MHO (all P < 0.01).

Conclusion

The MHO group had significantly increased circulating PRL levels when compared with the control and MUHO groups, and multivariable logistic regression analysis showed that PRL was independent predictors of MHO. Our findings suggested that increased circulating PRL might be a compensatory response for favoring energy metabolism during obesity.

Open access

Punith Kempegowda, Eka Melson, Agnes Johnson, Lucy Wallett, Lucretia Thomas, Dengyi Zhou, Catherine Holmes, Agata Juszczak, Mohammed Ali Karamat, Sandip Ghosh, Wasim Hanif, Parth Narendran, and Srikanth Bellary

Objective

COVID-19 in people with diabetes is associated with a disproportionately worse prognosis. DKA is an acute complication of diabetes with a mortality rate of approximately 0.67%. Little is known about the natural history of DKA in the presence of COVID-19. This study aimed to explore the effects of COVID-19 on presentation, clinical course and outcome in patients presenting with DKA.

Design

Retrospective cohort study.

Methods

All patients treated for DKA between 1 March 2020 and 30 May 2020 were included. Patients were categorised as COVID-positive or COVID-negative based on the swab test. A pre-COVID group was established using data from 01 March 2019 to 30 May 2019 as external control. Data regarding demographics, diabetes type, pH, bicarbonate, lactate, glucose, DKA duration, complications and outcome were collected.

Results

A total of 88 DKA episodes were included in this study. There was no significant difference in the severity or duration of DKA between the three groups. COVID-positive T1DM were more hyperglycaemic on admission compared to COVID-negative and pre-COVID patients. There was an over representation of T2DM in COVID-positive patients with DKA than in pre-COVID or COVID-negative groups.

Conclusion

COVID-19 appears to influence the natural history of DKA differently in T1DM and T2DM. Patients with T1DM and COVID-19 presented with more hyperglycaemia (60 mmol/L (35.9–60.0) vs 31.4 mmol/L (28.0–39.1) vs 24 mmol/L (20.2–33.75), respectively). Patients with T2DM were unusually presenting in DKA when infected with COVID-19 with greater ICU need and higher mortality rates. A collaborative, multi-centre study is needed to provide more definitive results.

Open access

Nadia Sawicka-Gutaj, Ariadna Zybek-Kocik, Michał Kloska, Paulina Ziółkowska, Agata Czarnywojtek, Jerzy Sowiński, Dorota Mańkowska-Wierzbicka, and Marek Ruchała

Dysregulation of thyroid function has known impact on body metabolism, however, data regarding metabolic outcome after restoration of thyroid function is limited. Therefore, the aim of the study was to investigate the effect of restoration of euthyroidism on serum visfatin, and its associations with insulin resistance and body composition. This is an observational study with consecutive enrollment. Forty-nine hyperthyroid (median age of 34 years) and 44 hypothyroid women (median age of 46 years) completed the study. Laboratory parameters and body composition analysis were assessed before and after the therapy. In the hyperthyroid group, visfatin concentrations increased (P < 0.0001), while glucose concentrations decreased (P < 0.0001). Total body mass and fat mass in the trunk and limbs significantly increased during the treatment. In the hypothyroid group, significant weight loss resulted from decrease of fat and muscle masses in trunk and limbs. Visfatin serum concentrations positively correlated with total fat mass (r = 0.19, P = 0.01) and insulin concentrations (r = 0.17, P = 0.018). In conclusion, restoration of thyroid function is not associated with beneficial changes in body composition, especially among hyperthyroid females.

Open access

Laura Potasso, Julie Refardt, Irina Chifu, Martin Fassnacht, Wiebke Kristin Fenske, and Mirjam Christ-Crain

Objective

Hyperkalemia has been reported upon different hypertonic saline infusion protocols. Since hypertonic saline test has recently been validated for the differential diagnosis of diabetes insipidus (DI), we aimed to investigate the course of plasma potassium during the test.

Design

We analyzed data of 90 healthy volunteers and 141 patients with polyuria–polydipsia syndrome (PPS) from two prospective studies evaluating the hypertonic saline test. Our primary outcome was the incidence rate of hypertonic saline-induced hyperkalemia > 5 mmol/L.

Methods

Participants received a 250 mL bolus of 3% NaCl solution, followed by 0.15 mL/min/kg body weight continuously infused targeting a plasma sodium level of 150 mmol/L. Blood samples and clinical data were collected every 30 min.

Results

Of the 231 participants, 16% (n = 37/231) developed hyperkalemia. The incidence of hyperkalemia was higher in healthy volunteers and in patients with primary polydipsia (25.6% (n = 23/90) and 9.9% (n = 14/141), respectively), and only occurred in 3.4% (n = 2/59) of patients with diabetes insipidus. Hyperkalemia developed mostly at or after 90-min test duration (81.1%, n => 30/37). Predictors of hyperkalemia (OR (95% CI)) were male sex (2.9 (1.2–7.4), P => 0.02), a plasma potassium at baseline > 3.9 mmol/L (5.2 (1.8–17.3), P => 0.004), normonatremia at 30-min test duration (3.2 (1.2–9.5), P => 0.03), and an increase in potassium levels already at 30-min test duration as compared to baseline (4.5 (1.7–12.3), P => 0.003). Hyperkalemia was transient and resolved spontaneously in all cases.

Conclusion

The hypertonic saline test can lead to hyperkalemia, especially in patients with primary polydipsia who experience a longer test duration. Monitoring potassium levels in these patients is recommended.