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Rachel Fourneaux, Marie Vermalle, Frederique Albarel, Isabelle Morange, Thomas Graillon, Vincent Amodru, Thomas Cuny, Henry Dufour, Thierry Brue, and Frederic Castinetti

Objective

A relative can be an asset in dealing with chronic illnesses, such as acromegaly, where quality of life (QoL) is altered even after remission. However, it has been shown that quality of life of caregivers can also be impacted. Our main objective was to compare the perception of acromegaly in remission in the patient–relative dyad.

Methods

In this observational study, 27 patients in remission and relatives were first asked to complete QoL, anxiety/depression and coping strategy questionnaires. Then, the patient’s body image and self-esteem were evaluated from both the patient’s and the relative’s point of view using the same questionnaires with modified instructions.

Results

Relatives had overall an accurate estimation of patient body image using the Figure Rating Scale by Stunkard. However, there were wide variations between the patient’s and the relative’s responses regarding self-esteem and body perception. The QoL of relatives was not altered and was significantly higher in the social domain than for the patient.

Conclusions

Our results show that relatives require education concerning all the steps involved in the management of acromegaly, as they likely do not fully understand the sequelae of acromegaly.

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Tim Verweij, Tessa N A Slagboom, Nadège C van Varsseveld, Aart-Jan van der Lely, Madeleine L Drent, and Christa C van Bunderen

Context

Cardiovascular (CV) risk profile might differ between growth hormone-treated patients with craniopharyngioma and non-functioning pituitary adenoma (NFPA), since patients with craniopharyngioma more frequently suffer from hypothalamic metabolic disruption.

Objective

The aim of this study is to investigate the CV risk profile in adult patients with craniopharyngioma compared to NFPA before and after treatment with growth hormone (GH) replacement therapy due to severe GH deficiency.

Design

A sub-analysis of the Dutch National Registry of Growth Hormone Treatment in Adults was performed, in which we compared 291 patients with craniopharyngioma to 778 patients with NFPA. CV risk profile and morbidity were evaluated at baseline and during long-term follow-up within and between both groups.

Results

At baseline, patients with craniopharyngioma demonstrated higher BMI than patients with NFPA, and men with craniopharyngioma showed greater waist circumference and lower HDL compared to men with NFPA. During follow-up, BMI, as well as diastolic blood pressure among patients using antihypertensive drugs, deteriorated in the craniopharyngioma group compared to the NFPA group. Lipid profile improved similarly in both groups over time. No differences were found between groups in the occurrence of diabetes mellitus, cerebrovascular accidents, CV disease, or overall mortality.

Conclusion

This study suggests that overall CV risk profile is worse in craniopharyngioma patients with GH deficiency compared to patients with NFPA. During GH replacement therapy, patients with craniopharyngioma demonstrated an increase in BMI over time, where BMI remained stable in patients with NFPA. Also, diastolic blood pressure did not improve with antihypertensive drugs in craniopharyngioma patients as seen in patients with NFPA.

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Sara Storvall, Helena Leijon, Eeva M Ryhänen, Tiina Vesterinen, Ilkka Heiskanen, Camilla Schalin-Jäntti, and Johanna Arola

Objective

Parathyroid carcinoma (PC), atypical parathyroid tumours (APT) and parathyroid adenoma (PA), all present with hypercalcemia. Diminished calcium-sensing receptor (CaSR) expression is reported in PC but is rare in benign tumours. Filamin A (FLNA) binds to the CaSR and activates the mitogen-activated protein kinase (MAPK) signalling pathway. FLNA is related to tumour aggressiveness in several cancers, but its role in parathyroid neoplasia is unknown.

Design

We examined FLNA, CaSR and parafibromin expression in PCs (n = 32), APTs (n = 44) and PAs (n = 77) and investigated their potential as diagnostic and/or prognostic markers.

Methods

Tissue microarray slides were immunohistochemically stained with antibodies for FLNA, CaSR and parafibromin. Staining results were correlated with detailed clinical data.

Results

All tumours stained positively for CaSR, with two tumours (one PC and one APT) showing diminished expression. Carcinomas were characterized by increased cytoplasmic FLNA expression compared to APTs and PAs (P  = 0.004). FLNA expression was not correlated with Ki-67 proliferation index or loss of parafibromin expression. Cytoplasmic FLNA expression was also associated with higher serum calcium, PTH concentrations and male sex (P  = 0.014, P  = 0.017 and P  = 0.049 respectively). Using a combined marker score, we found that parathyroid tumours with low FLNA expression and positive parafibromin staining were extremely likely to be benign (P  < 0.001).

Conclusion

Cytoplasmic and membranous FLNA expression is increased in parathyroid carcinomas compared to benign tumours. A combined FLNA and parafibromin expression score shows potential as a prognostic predictor of indolent behaviour in parathyroid neoplasms.

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Marloes Nies, Eus G J M Arts, Evert F S van Velsen, Johannes G M Burgerhof, Anneke C Muller Kobold, Eleonora P M Corssmit, Romana T Netea-Maier, Robin P Peeters, Anouk N A van der Horst-Schrivers, Astrid E P Cantineau, and Thera P Links

Context

Whilst radioactive iodine (RAI) is often administered in the treatment for differentiated thyroid carcinoma (DTC), long-term data on male fertility after RAI are scarce.

Objective

To evaluate long-term male fertility after RAI for DTC, and to compare semen quality before and after RAI.

Design, setting, and patients

Multicenter study including males with DTC ≥2 years after their final RAI treatment with a cumulative activity of ≥3.7 GBq.

Main outcome measure(s)

Semen analysis, hormonal evaluation, and a fertility-focused questionnaire. Cut-off scores for ‘low semen quality’ were based on reference values of the general population as defined by the World Health Organization (WHO).

Results

Fifty-one participants had a median age of 40.5 (interquartile range (IQR): 34.0–49.6) years upon evaluation and a median follow-up of 5.8 (IQR: 3.0–9.5) years after their last RAI administration. The median cumulative administered activity of RAI was 7.4 (range: 3.7–23.3) GBq. The proportion of males with a low semen volume, concentration, progressive motility, or total motile sperm count did not differ from the 10th percentile cut-off of a general population (P = 0.500, P = 0.131, P = 0.094, and P = 0.500, respectively). Cryopreserved semen was used by 1 participant of the 20 who had preserved semen.

Conclusions

Participants had a normal long-term semen quality. The proportion of participants with low semen quality parameters scoring below the 10th percentile did not differ from the general population. Cryopreservation of semen of males with DTC is not crucial for conceiving a child after RAI administration but may be considered in individual cases.

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Bertrand Baussart, Chiara Villa, Anne Jouinot, Marie-Laure Raffin-Sanson, Luc Foubert, Laure Cazabat, Michèle Bernier, Fideline Bonnet, Anthony Dohan, Jerome Bertherat, Guillaume Assié, and Stephan Gaillard

Objective

Microprolactinomas are currently treated with dopamine agonists. Outcome information on microprolactinoma patients treated by surgery is limited. This study reports the first large series of consecutive non-invasive microprolactinoma patients treated by pituitary surgery and evaluates the efficiency and safety of this treatment.

Design

Follow-up of a cohort of consecutive patients treated by surgery.

Methods

Between January 2008 and October 2020, 114 adult patients with pure microprolactinomas were operated on in a single tertiary expert neurosurgical department, using an endoscopic endonasal transsphenoidal approach. Eligible patients presented with a microprolactinoma with no obvious cavernous invasion on MRI. Prolactin was assayed before and after surgery. Disease-free survival was modeled using Kaplan–Meier representation. A cox regression model was used to predict remission.

Results

Median follow-up was 18.2 months (range: 2.8–155). In this cohort, 14/114 (12%) patients were not cured by surgery, including ten early surgical failures and four late relapses occurring 37.4 months (33–41.8) after surgery. From Kaplan–Meier estimates, 1-year and 5-year disease free survival was 90.9% (95% CI: 85.6–96.4%) and 81% (95% CI: 71.2–92.1%) respectively. The preoperative prolactinemia was the only significant preoperative predictive factor for remission (P < 0.05). No severe complication was reported, with no anterior pituitary deficiency after surgery, one diabetes insipidus, and one postoperative cerebrospinal fluid leakage properly treated by muscle plasty.

Conclusions

In well-selected microprolactinoma patients, pituitary surgery performed by an expert neurosurgical team is a valid first-line alternative treatment to dopamine agonists.

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George J Kahaly and Luigi Bartalena

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Danae A Delivanis, Maria D Hurtado Andrade, Tiffany Cortes, Shobana Athimulam, Aakanksha Khanna, Elizabeth Atkinson, Travis McKenzie, Naoki Takahashi, Michael R Moynagh, and Irina Bancos

Objective

Increased visceral fat and sarcopenia are cardiovascular risk factors that may explain increased cardiovascular morbidity and frailty in patients with adrenal adenomas. Our objective was to compare body composition measurement of patients with adrenal adenomas to referent subjects without adrenal disease.

Design

Cross-sectional study, 2014–2018.

Methods

Participants were adults with nonfunctioning adrenal tumor (NFAT), mild autonomous cortisol secretion (MACS), and Cushing syndrome (CS) and age, sex, and BMI 1:1 matched referent subjects without adrenal disorders. Main outcome measures were body composition measurements calculated from abdominal CT imaging. Intra-abdominal adipose tissue and muscle mass measurements were performed at the third lumbar spine level.

Results

Of 227 patients with adrenal adenomas, 20 were diagnosed with CS, 76 with MACS, and 131 with NFAT. Median age was 56 years (range: 18–89), and 67% were women. When compared to referent subjects, patients with CS, MACS, and NFAT demonstrated a higher visceral fat (odds ratio (OR): 2.2 (95% CI: 0.9–6.5), 2.0 (1.3–3.2), and 1.8 (1.2–2.7) and a lower skeletal muscle area (OR: 0.01 (95% CI: 0–0.09), 0.31 (0.18–0.49), and 0.3 (1.2–2.7)) respectively. For every 1 µg/dL cortisol increase after overnight dexamethasone, visceral fat/muscle area ratio increased by 2.3 (P = 0.02) and mean total skeletal muscle area decreased by 2.2 cm2 (P = 0.03).

Conclusion

Patients with adrenal adenomas demonstrate a lower muscle mass and a higher proportion of visceral fat when compared to referent subjects, including patients with NFAT. Even a subtle abnormality in cortisol secretion may impact health of patients with adenomas.

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Yu Xie, Changzhi Huang, Xingchen Zhu, Jiayu Wang, Xikang Fan, Zan Fu, Yanan Ma, and Dong Hang

Background

Insulin-like growth factor 1 (IGF1) is an important growth factor modulating development, homeostasis, and aging. However, whether and how circulating IGF1 concentrations influence early death risk in the general population remains largely unknown.

Methods

We included 380 997 participants who had serum IGF1 measurement and no history of cancer, cardiovascular disease (CVD), or diabetes at baseline from UK Biobank, a prospective cohort study initiated in 2006–2010. Restricted cubic splines and Cox proportional hazards regression models were used to assess the association between baseline IGF-1 concentrations and all-cause and cause-specific mortality.

Results

Over a median follow-up of 8.8 years, 10 753 of the participants died, including 6110 from cancer and 1949 from CVD. Dose–response analysis showed a U-shaped relationship between IGF1 levels and mortality. Compared to the fifth decile of IGF1, the lowest decile was associated with 39% (95% CI: 29–50%), 20% (95% CI: 8–34%), and 39% (95% CI: 14–68%) higher risk of all-cause, cancer, and CVD mortality, respectively, while the highest decile was associated with 17% (95% CI: 7–28%) and 38% (95% CI: 11–71%) higher risk of all-cause and CVD mortality, respectively. The results remained stable in detailed stratified and sensitivity analyses.

Conclusions

Our findings indicate that both low and high concentrations of serum IGF1 are associated with increased risk of mortality in the general population. Our study provides a basis for future interrogation of underlying mechanisms of IGF1 in early death occurrence and possible implications for mitigating the risk.

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Zhi-Hao Li, Pei-Dong Zhang, Qing Chen, Xiang Gao, Vincent C H Chung, Dong Shen, Xi-Ru Zhang, Wen-Fang Zhong, Qing-Mei Huang, Dan Liu, Pei-Liang Chen, Wei-Qi Song, Xian-Bo Wu, Virginia Byers Kraus, and Chen Mao

Objective

To examine the association of incident type 2 diabetes (T2D) risk with sleep factors, genetic risk, and their combination effects.

Design

Large prospective population-based cohort study.

Methods

This population-based prospective cohort study included 360 403 (mean (s.d.) age: 56.6 (8.0) years) participants without T2D at baseline from the UK Biobank. Genetic risk was categorised as high (highest quintile), intermediate (quintiles: 2–4), and low (lowest quintile) based on a polygenic risk score for T2D. Sleep scores, including long or short sleep duration, insomnia, snoring, late chronotype, and excessive daytime sleepiness, were categorized as an unfavourable, intermediate, or favourable sleep and circadian pattern.

Results

During a median follow-up of 9.0 years, 13 120 incident T2D cases were recorded. Among the participants with an unfavourable sleep and circadian pattern, 6.96% (95% CI: 6.68–7.24%) developed T2D vs 2.37% (95% CI: 2.28–2.46%) of participants with a favourable sleep and circadian pattern (adjusted hazard ratio (HR): 1.53, 95% CI: 1.45–1.62). Of participants with a high genetic risk, 5.53% (95% CI: 5.36–5.69%) developed T2D vs 2.01% (95% CI: 1.91–2.11%) of participants with a low genetic risk (adjusted HR: 2.89, 95% CI: 2.72–3.07). The association with sleep and circadian patterns was independent of genetic risk strata. Participants in the lowest quintile with an unfavourable sleep and circadian pattern were 3.97-fold more likely to develop T2D than those in the lowest quintile with a favourable sleep and circadian pattern.

Conclusions

Sleep and circadian patterns and genetic risk were independently associated with incident T2D. These results indicate the benefits of adhering to a healthy sleep and circadian pattern in entire populations, independent of genetic risk.