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Department of Hematology, University of Groningen, University Medical Center Groningen, The Netherlands
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Hypothyroidism is associated with a decreased health-related quality of life (HRQoL). We hypothesized that individuals with hypothyroidism (defined as use of thyroid hormone (TH)) and especially those having an impaired HRQoL are characterized by a high prevalence of comorbid disorders and that the impact of hypothyroidism and comorbidity on HRQoL is synergistic. Presence of comorbidity was based on data obtained using structured questionnaires, physical examination, biochemical measurements and verified medication use. Single morbidities were clustered into 14 different disease domains. HRQoL was measured using the RAND-36. Logistic regression analyses were used to determine the effect of TH use on the odds of having an affected disease domain and a lower score than an age- and sex-specific reference value for HRQoL. TH was used by 4537/14,7201 participants of the population-based Lifelines cohort with a mean (± s.d.) age of 51.0 ± 12.8 years (88% females). Eighty-five percent of the TH users had ≥1 affected disease domain in contrast to 71% of nonusers. TH use was associated with a higher odds of 13 out of 14 affected disease domains independent of age and sex. In a multivariable model, TH use was associated with a decreased HRQoL across six out of eight dimensions. No significant interactions between TH use and affected disease domains were observed. TH users with an impaired HRQoL had significantly more comorbidity than those not having an impaired HRQoL. In this large, population-based study, we demonstrated that TH users had more comorbidity than individuals not using TH. The coexistence of other chronic medical conditions in subjects with TH use led to further lowering of HRQoL in an additive manner.
Department of Analysis, Universidade Federal do Rio Grande do Sul (UFRGS), School of Pharmacy, Porto Alegre, RS, Brazil
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Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil
Department of Pediatrics, Universidade Federal do Rio Grande do Sul (UFRGS), Medical School, Porto Alegre, RS, Brazil
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Congenital adrenal hyperplasia (CAH) occurs due to enzyme defects in adrenal steroidogenesis. The 21-hydroxylase deficiency accounts for 90–95% of cases, triggering accumulation of 17-hydroxyprogesterone (17-OHP). Early diagnosis through neonatal screening allows adequate treatment and reduced mortality. The purpose of the study was to determine 17-OHP cutoffs for the diagnosis of CAH in a public newborn screening program in Southern Brazil. A retrospective, descriptive, cross-sectional study was conducted to analyze 17-OHP levels in dried blood samples collected on filter paper of 317,745 newborns screened at a public newborn screening center from May 2014 to April 2017. Neonatal 17-OHP was measured in DBS samples using a time-resolved fluoroimmunoassay (GSP® kit 3305-0010; PerkinElmer). Different cutoffs were determined and stratified by birth weight. The incidence of CAH was 1:15,887 live births in the state of Rio Grande do Sul, with 20 cases of classical CAH diagnosed during the study period. Most newborns (80.73%) were white, and the prematurity rate was 9.8% in the study population. The combination of different percentiles, 98.5th for birth weight 2001–2500 g and 99.8th for the other birth weight groups, decreased false-positive results and increased specificity compared with current reference values to identify classical CAH cases. The local 17-OHP cutoffs determined were higher than those currently used by this screening program for all birth weight groups. The calculation of reference values from local population data and the combination of percentiles proved to be a valuable tool for proper diagnosis of CAH and reduction in the number of false positives.
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Department and Graduate Institute of Forensic Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
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Context
Autonomous cortisol secretion (ACS) has a relatively high prevalence in patients with primary aldosteronism (PA). There is still a lack of relevant studies to analyze the influence of ACS on diagnosing and managing PA.
Objective
To evaluate the influence of ACS on image–adrenal venous sampling (AVS) correlation and the postoperative results.
Methods
This was a retrospective study using the Taiwan Primary Aldosteronism Investigation database from July 2017 to April 2020, with 327 PA patients enrolled. A total of 246 patients were included in the image–AVS analysis. Patients who had undergone unilateral adrenalectomy and a 12-month follow-up were included in the postoperative analysis.
Results
Sixty-five patients (26.4%) had ACS. The image–AVS discordance rate was higher in the ACS group compared to the non-ACS group (75.4% (n = 49) vs 56.4% (n = 102); odds ratio (OR) = 2.37 (CI: 1.26–4.48); P = 0.007). The complete biochemical success rate was higher in the non-ACS group than that in the ACS group (98.1% (n = 51) vs 64.3% (n = 9); OR = 28.333 (CI: 2.954–271.779); P = 0.001). In logistic regression analysis, ACS was the only factor associated with lower biochemical success (OR = 0.035 (CI: 0.004–0.339), P = 0.004).
Conclusion
PA patients with ACS have higher image–AVS discordance rate and worse biochemical outcomes after surgery. ACS was the only negative predictor of postoperative biochemical outcomes. Further studies and novel biomarkers for AVS are crucial for obtaining better postoperative outcomes in PA patients with ACS.
Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
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John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
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John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
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John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
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Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
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John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
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Glucocorticoids (GCs) reduce inflammation and preserve muscle function in boys with Duchenne muscular dystrophy (DMD) but cause pubertal delay. Pubertal induction with testosterone is recommended but longer-term outcome is unknown.
Objective
To assess hypothalamic–pituitary–gonadal axis, muscle volume and function 5 years after pubertal induction.
Methods
A prospective observational follow-up of a clinical study was conducted. 15 GC-treated males with DMD were treated with incremental testosterone for 2 years (end of regimen +2 years) then evaluated at +2.5 years and +5 years (final follow-up ~3 years after last injection). Data collected included testicular volume (TV), gonadotrophin, testosterone, inhibin B, muscle function, and limb muscle MRI.
Results
Participants were 18.7 years (s.d. 1.6) at the final follow-up and had been on GC for 11.2 years (s.d. 2.2). Testosterone levels were similar at +2.5 years (8.6 nmol/L (s.d. 3.4) and 5 years (11.0 nmol/L (s.d. 6.1). TV increased from 2.8 mL (s.d. 0.9) at +2 years to 7.1 mL (s.d. 1.8) then 10.6 mL (s.d. 3.5) at +2.5 years and +5.0 years (P < 0.001). Inhibin B levels increased from 55.6 pg/mL (s.d. 47.0) at baseline to 158.2 pg/mL (s.d.87.6), P =0.004 at 5 years but remained lower than reference values (mean 305 pg/mL). Muscle contractile bulk decreased.
Interpretation
Pubertal induction with testosterone in DMD is associated with HPG axis activation and ongoing increases in inhibin B, TV, and testosterone concentrations. Some patients have normal levels which is promising regarding future fertility. Given the beneficial impact of testosterone on bone health, muscle, and well-being, monitoring testosterone levels in this population and supplementation of sub-optimal levels is important.
Clinical Research Center for Metabolic Disease, Gansu Province, Lanzhou, Gansu, China
The First School of Clinical Medicine, Lanzhou University, Lanzhou, Gansu, China
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The First School of Clinical Medicine, Lanzhou University, Lanzhou, Gansu, China
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The First School of Clinical Medicine, Lanzhou University, Lanzhou, Gansu, China
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The First School of Clinical Medicine, Lanzhou University, Lanzhou, Gansu, China
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Clinical Research Center for Metabolic Disease, Gansu Province, Lanzhou, Gansu, China
The First School of Clinical Medicine, Lanzhou University, Lanzhou, Gansu, China
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Aims
Aging, obesity, and type 2 diabetes mellitus (T2DM) form a metabolic disease continuum that has a continuously increasing prevalence. Lipidomics explains the complex interactions between lipid metabolism and metabolic diseases. We aimed to systematically investigate the plasma lipidome changes induced by newly diagnosed impaired glucose tolerance (IGT) and T2DM in overweight/obese elderly individuals and to identify potential biomarkers to differentiate between the IGT, T2DM, and control groups.
Methods
Plasma samples from 148 overweight/obese elderly individuals, including 52 patients with IGT, 47 patients with T2DM, and 49 euglycemic controls, were analyzed using a high-coverage nontargeted absolute quantitative lipidomics approach.
Results
We quantified 1840 lipids from thirty-eight classes and seven lipid categories. Among overweight/obese elderly individuals, the lipidomic profiles of IGT and T2DM patients were significantly different from those of controls, while they were similar in the IGT and T2DM groups. The concentrations of diglycerides, triglycerides, phosphatidylcholines, and ceramides were obviously altered in the IGT and T2DM groups. Particularly, IGT and T2DM induced the accumulation of triglycerides with longer carbon atom numbers (C44–50) and saturated or lower double bond numbers (n (C=C) = 0–2). Furthermore, a total of 17 potential lipidic biomarkers were identified to successfully differentiate between the IGT, T2DM, and control groups.
Conclusions
In overweight/obese elderly patients, IGT and T2DM induced apparent lipidome-wide changes. This study’s results may contribute to explaining the complex dysfunctional lipid metabolism in aging, obesity, and diabetes.
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Objectives
The incidental diagnosis of nonfunctioning pituitary macroadenomas (NFPMAs) is becoming more prevalent with the spread of modern brain imaging techniques. We sought to uncover new data about their natural history and surgical outcome.
Design
This is a retrospective single-center observational study.
Methods
Among 210 patients seen for a NFPMA between 2010 and 2019, 70 (33%) were discovered incidentally (i-NFPMA). We analyzed outcomes in a total of 65 patients with available follow-up data.
Results
Mean age at diagnosis (± s.d.) was 60 ± 14 years and mean maximal diameter was 20.0 ± 7.3 mm. At diagnosis, 29 patients (45%) had pituitary hormone deficits (LH/FSH 41%, TSH 29%, ACTH 15%) and 12% had visual field deficits. 26 patients underwent initial surgery, while 12 had delayed surgery after initial surveillance. In the surveillance group, the risk of tumor growth was estimated at 10%/year. Patients with hormonal deficits at diagnosis experienced earlier growth at 24 months (P < 0.02). Overall, surgical resection of the i-NFPMA led to stable or improved endocrine function in 91% of patients, with only 6% postoperative permanent diabetes insipidus. Moreover, surgery was more effective in preserving intact endocrine function (10/12) than restoring altered endocrine function to normal (6/22, P = 0.03).
Conclusion
About one-third of NFPMAs are now discovered incidentally and a significant subset may be responsible for unrecognized endocrine and visual deficits. Under surveillance the risk of further tumor growth is significant (10%/year) and seems to occur faster in patients already harboring an endocrine deficit. Early surgical removal before onset of endocrine deficits appears to lead to better endocrine outcome.
Division of Epidemiology and Biometry, Carl von Ossietzky University, Oldenburg, Germany
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Faculty of Health Sciences and Medicine, University of Lucerne, Lucerne, Switzerland
Department of Pediatrics, McMaster Children’s Hospital and McMaster University, Hamilton, Ontario, Canada
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Background
Craniopharyngiomas (CPs) are rare embryonic tumors. Clinical presentation and outcome of patients perinatally diagnosed with congenital CP (cCP) are not clear and refer mainly to a few case reports in the literature. The aim of this study was to analyze clinical presentation and outcome in patients with cCP.
Study design
Three hundred and sixty-one patients diagnosed with adamantinomatous CP were recruited 2007–2022 in KRANIOPHARYNGEOM 2007/Registry 2019 and prospectively observed. In two cases, cCP was diagnosed prenatally and in one case on the second day of life. Pre- and perinatal diagnostic findings, postnatal evaluation, and therapeutic interventions and outcome in these three cases of cCP were analyzed.
Results
All patients survived. One patient developed psychomotor retardation and a mild hemiparesis. Prenatal routine ultrasound examination led to the diagnosis of cCP. Tumor resection was performed during the early postnatal period (range: 11–51 days of age). Functional capacity, measured by Fertigkeitenskala-Münster-Heidelberg (FMH) was reduced in three and behavioral parameters, measured by the Strength and Difficulties Questionnaire (SDQ) were abnormal in two cases.
Conclusion
cCP is a rare diagnosis with a prevalence of 0.83% in our study group. Compared to cases reported in the literature, the presented cases were treated immediately and had a better prognosis. Based on improvements of diagnostic and therapeutic techniques, prenatal diagnosis of cCP should lead to transfer prior to delivery of cCP patients to a specialized center for delivery and postnatal treatment of newborns with sellar masses by a multidisciplinary team to secure the improved prognosis of these patients.
Significance statement
We previously reported that lower event-free survival rates after craniopharyngioma are associated with younger age at diagnosis. Perinatally diagnosed congenital craniopharyngiomas are very rare. This article presents three unique cases with congenital craniopharyngioma, comparing their diagnostics, therapy, and development. All three cases had surgery during the early postnatal period with sparing of the posterior hypothalamus. In each case, endocrinopathy was present at follow-up. Low functional capacity was reported in all cases and an abnormal total difficulties score in two cases. Compared to the literature, the presented cases had better prognosis in morbidity and mortality. This report and the review of the literature confirm the importance of a multidisciplinary approach in the diagnostic and treatment of the very rare condition of congenital craniopharyngioma.
Alfred Health, Melbourne, Victoria, Australia
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Department of General Practice, Melbourne Medical School, The University of Melbourne, Victoria, Australia
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Hypogonadism can result following anabolic steroid abuse. The duration and degree of recovery from anabolic steroid-induced hypogonadism (ASIH) is immensely variable, and there is a paucity of prospective controlled data characterising the trajectory of natural recovery following cessation. This poses difficulties for users trying to stop androgen abuse, and clinicians wanting to assist them. The objective of this paper was to synthesise evidence on the physical, psychological and biochemical patterns of ASIH recovery. We present the pathophysiology of ASIH through a literature review of hypothalamic–pituitary–testosterone axis recovery in supraphysiological testosterone exposure. This is followed by a scoping review of relevant observational and interventional studies published on PubMed and finally, a conclusion that is an easy reference for clinicians helping patients that are recovering from AAS abuse. Results indicate that ASIH recovery depends on age and degree of androgen abuse, with physical changes like testicular atrophy expected to have near full recovery over months to years; spermatogenesis expected to achieve full recovery over months to years; libido returning to baseline over several months (typically less potent than during AAS use); and recovery from gynaecomastia being unlikely. For psychological recovery, data are insufficient and conflicting, indicating a transient withdrawal period which may be followed by persisting longer-term milder symptoms. For biochemical recovery, near complete recovery of testosterone is seen over months, and complete gonadotropin recovery is expected over 3–6 months. Further prospective studies are indicated to more closely describe patterns of recovery.
Division of Endocrinology and Metabolism, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
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NIHR Health Protection Research Unit on Chemical Radiation Threats and Hazards, Imperial College London, London, UK
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NIHR Health Protection Research Unit on Chemical Radiation Threats and Hazards, Imperial College London, London, UK
National Institute for Health Research (NIHR) Health Protection Research Unit in Environmental Exposures and Health, Imperial College London, London, UK
Mohn Centre for Children’s Health and Wellbeing, Imperial College London, London, UK
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NIHR Health Protection Research Unit on Chemical Radiation Threats and Hazards, Imperial College London, London, UK
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NIHR Health Protection Research Unit on Chemical Radiation Threats and Hazards, Imperial College London, London, UK
National Institute for Health Research (NIHR) Health Protection Research Unit in Environmental Exposures and Health, Imperial College London, London, UK
Mohn Centre for Children’s Health and Wellbeing, Imperial College London, London, UK
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Context
Salivary androgens represent non-invasive biomarkers of puberty that may have utility in clinical and population studies.
Objective
To understand normal age-related variation in salivary sex steroids and demonstrate their correlation to pubertal development in young adolescents.
Design, setting and participants
School-based cohort study of 1495 adolescents at two time points for collecting saliva samples approximately 2 years apart.
Outcome measures
The saliva samples were analyzed for five androgens (testosterone, androstenedione (A4), 17-hydroxyprogesterone, 11-ketotestosterone and 11β-hydroxyandrostenedione) using liquid chromatography-mass spectrometry; in addition, salivary dehydroepiandrosterone (DHEA) and oestradiol (OE2) were analysed by ELISA. The pubertal staging was self-reported using the Pubertal Development Scale (PDS).
Results
In 1236 saliva samples from 903 boys aged between 11 and 16 years, salivary androgens except DHEA exhibited an increasing trend with an advancing age (ANOVA, P < 0.001), with salivary testosterone and A4 concentration showing the strongest correlation (r = 0.55, P < 0.001 and r = 0.48, P < 0.001, respectively). In a subgroup analysis of 155 and 63 saliva samples in boys and girls, respectively, morning salivary testosterone concentrations showed the highest correlation with composite PDS scores and voice-breaking category from PDS self-report in boys (r = 0.75, r = 0.67, respectively). In girls, salivary DHEA and OE2 had negligible correlations with age or composite PDS scores.
Conclusion
In boys aged 11–16 years, an increase in salivary testosterone and A4 is associated with self-reported pubertal progress and represents valid non-invasive biomarkers of puberty in boys.
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National Center for Neurological Disorders, Shanghai, China
Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
Neurosurgical Institute of Fudan University, Shanghai, China
Shanghai Key Laboratory of Medical Brain Function and Restoration and Neural Regeneration, Fudan University, Shanghai, China
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National Center for Neurological Disorders, Shanghai, China
Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China
Neurosurgical Institute of Fudan University, Shanghai, China
Shanghai Key Laboratory of Medical Brain Function and Restoration and Neural Regeneration, Fudan University, Shanghai, China
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Purpose
We aimed to describe and predict the risk of severe hypernatremia after surgical resection of craniopharyngioma and to identify the association of water intake, urine output, and sodium level change in the patients.
Method
The outcome was postoperative severe hypernatremia. We identified risk factors associated with hypernatremia using multivariable regression. We trained machine learning models to predict the outcome. We compared serum sodium change, intravenous input, oral input, total input, urine output, and net fluid balance according to different nurse shifts.
Results
Among 234 included patients, 125 developed severe hypernatremia after surgery. The peak incidence occurred during day 0 and day 6 after surgery. The risk was increased in patients with gross total resection (odds ratio (OR) 2.41, P < 0.001), high Puget classification (OR 4.44, P = 0.026), preoperative adrenal insufficiency (OR 2.01, P = 0.040), and preoperative hypernatremia (OR 5.55, P < 0.001). The random forest algorithm had the highest area under the receiver operating characteristic curve (0.770, 95% CI, 0.727–0.813) in predicting the outcome and was validated in the prospective validation cohort. Overnight shifts were associated with the highest serum sodium increase (P = 0.010), less intravenous input (P < 0.001), and less desmopressin use (P < 0.001).
Conclusion
The overall incidence of severe hypernatremia after surgical resection of craniopharyngioma was significant, especially in patients with gross total resection, hypothalamus distortion, preoperative adrenal insufficiency, and preoperative severe hypernatremia. Less intravenous input and less desmopressin use were associated with serum sodium increases, especially during overnight shifts.
