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Daan M van Velzen, Nienke M Nota, Suat Simsek, Elfi B Conemans, Guy T’Sjoen, and Martin den Heijer

Objective

Transgender individuals sometimes report a lack of physical change during hormone treatment, such as alterations in muscle tone or fat distribution. Identifying characteristics of this subgroup could be a step toward individualizing hormone therapy in transgender individuals. Therefore, we study the variation of changes in body composition and characteristics associated with a lack of change.

Design and methods:

Body composition measures were recorded in 323 transmen and 288 transwomen at every visit from the start of hormone therapy to a maximum of 24 months follow-up. Absence of change was defined as transmen with a decrease in lean body mass or transwomen with a decrease in fat percentage.

Results

A lack of change at 24 months was observed in 19 of 94 (20.2%) transmen and in 9 of 96 (9.4%) transwomen. The risk of not achieving change in body composition was related to lower testosterone levels and less suppression of LH in transmen (OR: 0.67, 95% CI: 0.48–0.94 per SD increase in testosterone and OR: 1.36, 95% CI: 1.01–1.83 per SD increase in LH).

Conclusions:

There is a large variation in body composition changes during hormone therapy, with a substantial proportion of individuals with no measurable effects. In transmen, serum testosterone and LH were associated with a lack of change, but serum hormone levels were not associated with body composition changes in transwomen. The results provide a rationale for individualizing hormone therapy in transmen, by considering individual effects rather than solely relying on a standardized dosage of hormone therapy.

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Aoife Garrahy, Martín Cuesta, Brian Murphy, William Tormey, Michael W O'Reilly, Mark Sherlock, and Chris J Thompson

Objective:

Severe hyponatraemia (plasma sodium concentration, pNa <120 mmol/L) is reported to be associated with mortality as high as 50%. Although there are several international guidelines for the management of severe hyponatraemia, there are few data on the impact of treatment.

Design and Methods:

We have longitudinally reviewed rates of specialist input, treatment outcomes and mortality rates in patients with severe hyponatraemia (pNa <120 mmol/L) in 2005, 2010 and 2015, and compared the recent mortality rate with that of patients admitted with pNa 120-125 mmol/L.

Results:

Between 2005 and 2010 there was a doubling in the rate of specialist referral (32% to 68%, p=0.003) and an increase in the use of active management of patients with pNa <120 mmol/L (63% to 88%, p=0.02), associated with a reduction in mortality from 51% to 15% (p=0<0.001). The improved rates of intervention were maintained between 2010 and 2015, but there was no further reduction in mortality. When data from all three reviews were pooled, specialist consultation in patients with pNa <120 mmol/L was associated with 91% reduction in mortality risk, RR 0.09 (95% CI 0.03-0.26), p<0.001. Log-rank testing on in-hospital survival in 2015 found no significant difference between patients with pNa <120 mmol/l and pNa 120-125 mmol/L (p=0.56).

Conclusion:

Dedicated specialist management of severe hyponatraemia is associated with a reduction in mortality, to rates comparable with moderate hyponatraemia.

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Marie-Josée Desrochers, Matthieu St-Jean, Nada El Ghorayeb, Isabelle Bourdeau, Benny So, Éric Therasse, Gregory Kline, and André Lacroix

Context:

Unilateral aldosteronomas should suppress renin and contralateral aldosterone secretion. Complete aldosterone suppression in contralateral adrenal vein sample (AVS) could predict surgical outcomes.

Objectives:

To retrospectively evaluate the prevalence of basal contralateral suppression using Aldosterone (A)contralateral(CL)/Aperipheral(P) as compared to (A/Cortisol(C)CL)/(A/C)P ratio in primary aldosteronism (PA) patients studied in two Canadian centers. To determine the best cut-off to predict clinical and biochemical surgical cure. To compare the accuracy of ACL/AP to the basal and post-ACTH lateralization index (LI) in predicting surgical cure.

Methods:

In total, 330 patients with PA and successful AVS were included; 124 lateralizing patients underwent surgery. Clinical and biochemical cure at 3 and 12 months were evaluated using the PASO criteria.

Results:

Using ACL/AP and (A/C)CL/(A/C)P at the cut-off of 1, the prevalence of contralateral suppression was 6 and 45%, respectively. Using ROC curves, the ACL/AP ratio is associated with clinical cure at 3 and 12 months and biochemical cure at 12 months. (A/C)CL/(A/C)P is associated with biochemical cure only. The cut-offs for ACL/AP offering the best sensitivity (Se) and specificity (Sp) for clinical and biochemical cures at 12 months are 2.15 (Se: 63% and Sp: 71%) and 6.15 (Se: 84% and Sp: 77%), respectively. Basal LI and post-ACTH LI are associated with clinical cure but only the post-ACTH LI is associated with biochemical cure.

Conclusions:

In lateralized PA, basal contralateral suppression defined by ACL/AP is rare and incomplete compared to the (A/C)CL/(A/C)P ratio and is associated with clinical and biochemical postoperative outcome, but with modest accuracy.

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Giorgio Radetti, Antonio Fanolla, Fiorenzo Lupi, Alessandro Sartorio, and Graziano Grugni

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Srdjan Pandurevic, Luca Bergamaschi, Carmine Pizzi, Laura Patton, Paola Rucci, Francesca Corzani, Carolina Cecchetti, Carla Pelusi, Paola Altieri, Valentina Vicennati, Guido De Dalmazi, Flaminia Fanelli, Djuro Macut, Uberto Pagotto, and Alessandra Gambineri

Research into cardiovascular disease (CV) prevention has demonstrated a variety of ultrasound (US) markers predicting risk in the general population, but which have been scarcely used for polycystic ovary syndrome (PCOS). Obesity is a major factor contributing to CV disease in the general population, and it is highly prevalent in PCOS. However, it is still unclear how much risk is attributable to hyperandrogenism. This study evaluates the most promising US CV risk markers in PCOS and compares them between different PCOS phenotypes and BMI values.

Women fulfilling the Rotterdam criteria for PCOS were recruited from our outpatient clinic for this cross-sectional study.

Participants (n = 102) aged 38.9±7.4 years were stratified into the four PCOS phenotypes and the three BMI classes (normal-weight, overweight, obese). They were assessed for clinical and biochemical parameters together with the following US markers: coronary intima-media thickness (cIMT), flow-mediated vascular dilation (FMD), nitroglycerine-induced dilation (NTG), and epicardial fat thickness (EFT).

There was no statistical difference among the four phenotypes in terms of cIMT, FMD, NTG or EFT, however all the US parameters except NTG showed significant differences among the three BMI classes. Adjusting for confounding factors in multiple regression analyses, EFT retained the greatest direct correlation with BMI, and cIMT remained directly correlated but to a lesser degree.

This study showed that obesity rather than the hyperandrogenic phenotype negatively impacts precocious US CV risk markers in PCOS. In addition, EFT showed the strongest association with BMI, highlighting its potential for estimating CV risk in PCOS.

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Mette Hansen Viuff, Kirstine Stochholm, Angela Lin, Agnethe Berglund, Svend Juul, and Claus Højbjerg Gravholt

Objective: Although the overall risk of cancer is not increased in Turner syndrome, the pattern of cancer occurrence differs from the general population. We aim to describe the cancer morbidity pattern in Turner syndrome and evaluate the effect of long-term hormone replacement therapy (HRT).

Design: Nationwide epidemiological study.

Methods: 1,156 females with Turner syndrome diagnosed during 1960-2014, were linked with data from the Danish National Patient Registry. Statistics Denmark randomly identified 115,578 female controls. Stratified Cox regression was used to analyze cancer morbidity, mortality and effect of HRT.

Results: Overall risk of cancer was not elevated (Hazard ratio 1.04 (95%CI 0.80-1.36)). The risk of skin cancer and benign skin neoplasms was two-fold increased, while the risk of breast cancer was decreased (Hazard ratio 0.4 (0.2-0.9)). Turner syndrome (45,X) had a two- to five-fold increased risk of benign central nervous system tumors, colon and rectal cancers, benign skin neoplasms and skin cancer. Turner syndrome women with a 45,X/46,XX karyotype had increased risk of tongue cancer. HRT had no impact on the risk of any cancer investigated in this study.

Conclusions: The lack of one X chromosome might play a role in skin neoplasms, central nervous system tumors, colon and rectal cancers. The risk of breast cancer is lower than in the general population. Long-term HRT during the premenopausal age range seem not to exert a cancerous effect in Turner syndrome. Increased vigilance concerning specific types of cancer in Tuner syndrome harboring a 45,X karyotype is needed.

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Fatemeh Majidi, Samuela Martino, Mustafa Kondakci, Christina Antke, Matthias Haase, Vasileios Chortis, Wiebke Arlt, Cristina L Ronchi, Martin Fassnacht, Claire Laurent, Jean-Michel Petit, Olivier Casasnovas, Amir Mouhammed Habra, Aleem Kanji, Roberto Salvatori, An Thi Nhat Ho, Ariadni Spyroglou, Felix Beuschlein, Diego Villa, Wasithep Limvorapitak, Björn Engelbrekt Wahlin, Oliver Gimm, Martina Rudelius, Matthias Schott, Ulrich Germing, Rainer Haas, and Norbert Gattermann

Purpose:

We sought to refine the clinical picture of primary adrenal lymphoma (PAL), a rare lymphoid malignancy with predominant adrenal manifestation and risk of adrenal insufficiency.

Methods:

Ninety-seven patients from 14 centers in Europe, Canada and the United States were included in this retrospective analysis between 1994 and 2017.

Results:

Of the 81 patients with imaging data, 19 (23%) had isolated adrenal involvement (iPAL), while 62 (77%) had additional extra-adrenal involvement (PAL+). Among patients who had both CT and PET scans, 18FDG-PET revealed extra-adrenal involvement not detected by CT scan in 9/18 cases (50%). The most common clinical manifestations were B symptoms (55%), fatigue (45%), and abdominal pain (35%). Endocrinological assessment was often inadequate. With a median follow-up of 41.6 months, 3-year progression-free (PFS) and overall (OS) survival rates in the entire cohort were 35.5% and 39.4%, respectively. The hazard ratios of iPAL for PFS and OS were 40.1 (95% CI: 2.63–613.7, P = 0.008) and 2.69 (95% CI: 0.61–11.89, P = 0.191), respectively. PFS was much shorter in iPAL vs PAL+ (median 4 months vs not reached, P = 0.006), and OS also appeared to be shorter (median 16 months vs not reached), but the difference did not reach statistical significance (P = 0.16). Isolated PAL was more frequent in females (OR = 3.81; P = 0.01) and less frequently associated with B symptoms (OR = 0.159; P = 0.004).

Conclusion:

We found unexpected heterogeneity in the clinical spectrum of PAL. Further studies are needed to clarify whether clinical distinction between iPAL and PAL+ is corroborated by differences in molecular biology.

Open access

Carmina Teresa Fuss, Katharina Brohm, Max Kurlbaum, Anke Hannemann, Sabine Kendl, Martin Fassnacht, Timo Deutschbein, Stefanie Hahner, and Matthias Kroiss

Objective: Saline infusion testing (SIT) for confirmation of primary aldosteronism (PA) is based on impaired aldosterone suppression in PA compared to essential hypertension (EH). In the past, aldosterone was quantified using immunoassays (IA). Liquid chromatography tandem mass spectrometry (LC-MS/MS) is increasingly used in clinical routine. We aimed at a method-specific aldosterone threshold for the diagnosis of PA during SIT and explored diagnostic utility of steroid panel analysis.

Design: Retrospective cohort study of 187 paired SIT samples (2009-2018). Diagnosis of PA (n=103) and EH (n=84) was established based on clinical routine workup without using LC-MS/MS values.

Setting: Tertiary care center.

Methods: LC-MS/MS using a commercial steroid panel. Receiver operator characteristics analysis was used to determine method-specific cut-offs using a positive predictive value (PPV) of 90% as criterion.

Results: Aldosterone measured by IA was on average 31 ng/L higher than with LC-MS/MS. The cut-offs for PA confirmation were 54 ng/L for IA (sensitivity: 95%, 95%-CI 89.0-98.4; specificity: 87%, 95%-CI 77.8-93.3; area under the curve (AUC) 0.955, 95%-CI 0.924-0.986; PPV: 90%, 95%-CI 83.7-93.9) and 69 ng/L for LC-MS/MS (79%, 95%-CI 69.5-86.1; 89%, 95%-CI 80.6-95.0; 0.902, 95%-CI 0.857-0.947; 90%, 95%-CI 82.8-94.4). Other steroids did not improve SIT.

Conclusions: Aldosterone quantification with LC-MS/MS and IA yields comparable SIT-cut-offs. Lower AUC for LC-MS/MS is likely due to the spectrum of disease in PA and previous decision making based on IA results. Until data of a prospective trial with clinical endpoints are available, the suggested cut-off can be used in clinical routine.

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Hao Jin, Weidong Lin, Ligong Lu, and Min Cui

Objective: The complications and treatment effects of conventional thyroidectomy and thyroid thermal ablation should be compared in order to identify the best intervention for patients with benign thyroid nodules.

Methods: Patients (18-50 years old) who had benign thyroid nodules and were eligible for both thyroidectomy and thyroid thermal ablation were randomly allocated (1:1) to either conventional thyroidectomy group or thyroid thermal ablation group. Patients’ satisfaction and condition-specific quality of life were measured with the Thyroid-Specific Quality-of-Life Questionnaire Scale (QoL) at the 15th post-randomization month and were set as the co-primary outcome.

Results: A total of 450 patients were enrolled and randomized (225 patients in each group). At the 15th month after randomization, more patients in the thyroid thermal ablation group were satisfied with the treatment effects compared to those in the conventional thyroidectomy group. More patients in the thyroid thermal ablation group have a QoL score of 410 (QOL scores ranges from 0 to 410) than patients in conventional thyroidectomy. Eight (4%) of the 209 patients in conventional thyroidectomy group and 6 (3%) of the 208 patients in thyroid thermal ablation group had at least one severe postoperative complication. The time to achieve volume reduction was longer in the thermal ablation group.

Conclusion: Thyroid thermal ablation is superior to conventional thyroidectomy in terms of patients satisfaction, postoperative quality of life, and shorter hospital stay, but takes longer to achieve BTNs volume reduction. The complication rates between the two groups were similar.

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A B Hansen, D Wøjdemann, C H Renault, At Pedersen, K M Main, L L Raket, Rikke Beck Jensen, and A Juul

This review aims to cover the subject of sex steroid action in adolescence. It will include situations with too little sex steroid action, as seen in e.g Turners syndrome and androgen insensitivity issues, too much sex steroid action as seen in adolescent PCOS, CAH and gynecomastia, too late sex steroid action as seen in constitutional delay of growth and puberty and too early sex steroid action as seen in precocious puberty.

This review will cover the etiology, the signs and symptoms which the clinician should be attentive to, important differential diagnoses to know and be able to distinguish, long-term health and social consequences of these hormonal disorders and the course of action with regards to medical treatment in the pediatric endocrinological department and for the general practitioner.

This review also covers situations with exogenous sex steroid application for therapeutic purposes in the adolescent and young adult. This includes gender-affirming therapy in the transgender child and hormone treatment of tall statured children. It gives some background information of the cause of treatment, the patient’s motivation for medicating (or self-medicating), long-term consequences of exogenous sex steroid treatment and clinical outcome of this treatment.