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- Abstract: adrenarche x
- Abstract: amenorrhoea x
- Abstract: fertility x
- Abstract: Gender x
- Abstract: Hypogonadism x
- Abstract: infertility x
- Abstract: Kallmann x
- Abstract: Klinefelter x
- Abstract: menarche x
- Abstract: menopause x
- Abstract: puberty x
- Abstract: testes x
- Abstract: Turner x
- Abstract: ovary x
- Abstract: follicles x
Diabetes and Endocrine Unit, National Hospital, Kandy, Sri Lanka
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Refractory hypothyroidism is associated with high morbidity and increased healthcare expenditure. In general, the use of the levothyroxine absorption test looks promising in evaluating refractory hypothyroidism but has shown significant variability in protocols in multiple settings. We intended to assess the usefulness of the levothyroxine absorption test in a low-resource setting and to assess the factors associated with refractory hypothyroidism. A cross-sectional study among age-matched 25 cases of refractory hypothyroidism and 24 treatment-responsive hypothyroid controls was conducted. A supervised levothyroxine absorption test was performed with levothyroxine 1000 μg tablets after a 10-h fast, and serum free tetraiodothyronine (FT4) levels were measured at 0, 1, 2, 3, 4, and 5 h. Descriptive statistics, chi-square test, Student’s t-test, and logistic regression were used in the analysis. Results showed no significant difference in age, body weight, etiology of hypothyroidism, interfering medications, thyroxine storage, and ingestion technique in cases and controls. Cases had a longer duration of hypothyroidism and males had a higher peak FT4 concentration. During pooled analysis, serum FT4 peaked at 3 h with an increment of 149.4% (128.4–170.5%) from baseline and plateaued thereafter. The absolute value of FT4 at 3 h was 41.59 (s.d. 14.14) pmol/L (3.23 ng/dL). We concluded that there was no significant difference in the pattern of levothyroxine absorption in both groups. The most common cause of refractory disease was pseudo-malabsorption. Rapid supervised levothyroxine absorption test with two blood samples for FT4 at baseline and at the peak of absorption (3 h) is simple, convenient, and cost-effective, particularly in low-resource settings.
Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark
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Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark
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Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark
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Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark
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Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark
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Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark
Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark
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Objective
Growth hormone deficiency (GHD) is the most common endocrine late effect in irradiated survivors of childhood brain tumors. This study aimed to determine the prevalence of GHD in adults treated with proton or photon irradiation for a brain tumor in childhood and to detect undiagnosed GHD.
Design
This study is a cross-sectional study.
Methods
We investigated GHD in 5-year survivors from two health regions in Denmark treated for childhood brain tumors with cranial or craniospinal irradiation in the period 1997–2015. Medical charts were reviewed for endocrinological and other health data. Survivors without a growth hormone (GH) test at final height were invited to a GH stimulation test.
Results
Totally 41 (22 females) survivors with a median age of 21.7 years (range: 15.1–33.8 years) at follow-up and 14.8 years (range: 5.1–23.4 years) since diagnosis were included; 11 were treated with proton and 30 with photon irradiation; 18 of 21 survivors were previously found to have GHD; 16 of 20 survivors with no GH test at final height were tested, 8 (50 %) had GHD. In total, 26 of 41 patients (63%) had GHD. Insulin-like growth factor-1 (IGF-1) is associated poorly with the insulin tolerance test (ITT).
Conclusion
This study identified a high prevalence of undiagnosed GHD in survivors with no GH test at final height. The results stress the importance of screening for GHD at final height in survivors of childhood brain tumors with prior exposure to cranial irradiation, irrespective of radiation modality and IGF-1.
Significance statement
This cross-sectional study reports a prevalence of 63% of GHD in irradiated childhood brain tumor survivors. Furthermore, the study identified a considerable number of long-term survivors without a GH test at final height, of whom, 50% subsequently were shown to have undiagnosed GHD. Additionally, this study confirmed that a normal serum IGF-1 measurement cannot exclude the diagnosis of GHD in irradiated survivors. This illustrates the need for improvements in the diagnostic approach to GHD after reaching final height in childhood brain tumor survivors at risk of GHD. In summary, our study stresses the need for GHD testing in all adult survivors treated with cranial irradiation for a brain tumor in childhood irrespective of radiation modality.
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Department of Cardiology, Department of Growth and Reproduction, Faculty of Health Sciences, Nephrology and Endocrinology H, Hillerød University Hospital, Dyrehavevej 29, DK-3400 Hillerød, Denmark
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Department of Cardiology, Department of Growth and Reproduction, Faculty of Health Sciences, Nephrology and Endocrinology H, Hillerød University Hospital, Dyrehavevej 29, DK-3400 Hillerød, Denmark
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Objective
GH is implicated in the counter-regulatory response to hypoglycemia. We tested whether IGF1 levels are associated with occurrence of severe hypoglycemic events in patients with type 1 diabetes and whether the IGF1 concentration is influenced by glycemic control.
Methods
A total of 228 outpatients with type 1 diabetes were included in a post hoc analysis of a 1-year observational study on severe hypoglycemia. Serum total IGF1 was measured at entry into the study. The occurrence of severe episodes of hypoglycemia, mild symptomatic, and biochemical as well as hypoglycemia awareness status was assessed. Also patients were included in a multiple regression analysis to investigate the role of HbA1c in the IGF1 concentration.
Results
IGF1 levels were associated with neither severe hypoglycemia in the entire cohort (P=0.30) nor in any gender nor when confining the analysis to those with long-standing diabetes (>20 years) (n=112, P=0.68) and those with both long-standing diabetes and undetectable C-peptide (n=51, P=0.067). Levels of IGF1 were associated with neither mild symptomatic hypoglycemia (P=0.24) nor biochemical hypoglycemia (0.089) nor hypoglycemia awareness (P=0.16). At a multiple regression analysis, HbA1c was negatively associated with IGF1 (P=0.001).
Conclusion
In type 1 diabetes, circulating IGF1 levels are negatively associated with glycemic control. However, IGF1 levels were not associated with occurrence of hypoglycemia or hypoglycemia awareness in these patients.
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The association between oral lichen planus (OLP) and hypothyroidism has been debated with conflicting results: some authors detected a statistically significant association between these two, while others did not confirm it. The aim of this study was to evaluate the thyroid status in patients with newly diagnosed OLP to test the null hypothesis that thyroid disease is not associated with an increased incidence of oral lesions, with a prospective case-control approach. A total of 549 patients have been evaluated, of whom 355 were female. Odds ratio (OR) and 95% confidence intervals (CIs) were obtained. Patients suffering from thyroid diseases were associated with an almost 3-fold increased odds of having OLP (OR 2.85, 95% CI: 1.65–4.94), after adjusting this analysis for age, gender, body mass index, smoking status, diabetes, hypertension and hepatitis C infection. It would be appropriate to further investigate the possible concomitance of OLP among patients with thyroid disorder; endocrinologists should be aware of this association, especially because OLP is considered a potentially malignant oral disorder.
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Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London, UK
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Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London, UK
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Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London, UK
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Endogenous Cushing’s syndrome (CS) poses considerable diagnostic challenges. Although late-night salivary cortisol (LNSC) is recommended as a first-line screening investigation, it remains the least widely used test in many countries. The combined measurement of LNSC and late-night salivary cortisone (LNS cortisone) has shown to further improve diagnostic accuracy. We present a retrospective study in a tertiary referral centre comparing LNSC, LNS cortisone, overnight dexamethasone suppression test, low-dose dexamethasone suppression test and 24-h urinary free cortisol results of patients investigated for CS. Patients were categorised into those who had CS (21 patients) and those who did not (33 patients). LNSC had a sensitivity of 95% and a specificity of 91%. LNS cortisone had a specificity of 100% and a sensitivity of 86%. With an optimal cut-off for LNS cortisone of >14.5 nmol/L the sensitivity was 95.2%, and the specificity was 100% with an area under the curve of 0.997, for diagnosing CS. Saliva collection is non-invasive and can be carried out at home. We therefore advocate simultaneous measurement of LNSC and LNS cortisone as the first-line screening test to evaluate patients with suspected CS.
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Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark
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Steno Diabetes Center Aarhus (SDCA), Aarhus University Hospital, Aarhus, Denmark
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Background
The diagnosis of the polyuria–polydipsia syndrome is challenging. Copeptin is a robust biomarker of arginine vasopressin (AVP) secretion. Arginine, which stimulates growth hormone (GH), has been shown also to stimulate copeptin secretion via unknown mechanisms.
Aim
The aim was to investigate copeptin levels in response to three different GH stimulation tests in patients suspected of GH deficiency.
Methods
In this cross-sectional study, we measured plasma copeptin levels at baseline and at 60, 105, and 150 min in patients undergoing a stimulation test for growth hormone deficiency with either arginine (n = 16), clonidine (n = 8) or the insulin tolerance test (ITT) (n = 10).
Results
In patients undergoing the arginine test, the mean age was 9 years, and 10 years for clonidine. The ITT was only performed in adult patients (>18 years) with a mean age of 49 years. Copeptin level increased significantly from baseline to 60 min after arginine (P <0.01) and ITT (P < 0.01). By contrast, copeptin level tended to decrease after clonidine stimulation (P = 0.14).
Conclusion
These data support that infusion of arginine increases plasma copeptin levels and reveal a comparable response after an ITT. We hypothesize that the underlying mechanism is abrogation of somatostatin-induced AVP suppression.
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Shanghai Center of Thyroid Diseases, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
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Shanghai Center of Thyroid Diseases, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
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Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University, Shanghai, China
Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China
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Thyroid fine needle aspiration biopsy (FNAB) remains indeterminate in 16–24% of the cases. Molecular testing could improve the diagnostic accuracy of FNAB. This study examined the gene mutation profile of patients with thyroid nodules and analyzed the diagnostic ability of molecular testing for thyroid nodules using a self-developed 18-gene test. Between January 2019 and August 2021, 513 samples (414 FNABs and 99 formalin-fixed paraffin-embedded (FFPE) specimens) underwent molecular testing at Ruijin Hospital. Sensitivity (Sen), specificity (Spe), positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated. There were 457 mutations in 428 samples. The rates of BRAF, RAS, TERT promoter, RET/PTC, and NTRK3 fusion mutations were 73.3% (n = 335), 9.6% (n = 44), 2.8% (n = 13), 4.8% (n = 22), and 0.4% (n = 2), respectively. The diagnostic ability of cytology and molecular testing were evaluated in Bethesda II and V–VI samples. For cytology alone, Sen, Spe, PPV, NPV, and accuracy were 100%, 25.0%, 97.4%, 100%, and 97.4%; these numbers were 87.5%, 50.0%, 98.0%, 12.5%, and 86.2% when considering positive mutation, and 87.5%, 75.0%, 99.0%, 17.6%, and 87.1% when considering positive cytology or and positive mutation. In Bethesda III–IV nodules, when relying solely on the presence of pathogenic mutations for diagnosis, Sen, Spe, PPV, NPV, and AC were 76.2%, 66.7%, 94.1%, 26.8%, and 75.0%, respectively. It might be necessary to analyze the molecular mechanisms of disease development at the genetic level to predict patients with malignant nodules more accurately in different risk strata and develop rational treatment strategies and definite management plans.
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Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, Genova, Italy
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Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, Genova, Italy
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Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, Genova, Italy
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Objective
This retrospective study aimed to evaluate children observed for suspected precocious puberty in five Italian centers of Pediatric Endocrinology during the first wave of coronavirus disease 2019 pandemic (March–September 2020), compared to subjects observed in the same period of the previous year.
Design
The study population (490 children) was divided according to the year of observation and final diagnosis: transient thelarche, non-progressive precocious puberty, central precocious puberty (CPP), or early puberty.
Results
Between March and September 2020, 338 subjects were referred for suspected precocious puberty, compared to 152 subjects in the same period of 2019 (+122%). The increase was observed in girls (328 subjects in 2020 vs 140 in 2019, P < 0.05), especially during the second half of the period considered (92 girls from March to May vs 236 girls from June to September); while no difference was observed in boys (10 subjects in 2020 vs 12 in 2019). The percentage of girls with confirmed CPP was higher in 2020, compared to 2019 (135/328 girls (41%) vs 37/140 (26%), P < 0.01). Anthropometric and hormonal parameters in 2019 and 2020 CPP girls were not different; 2020 CPP girls showed more prolonged use of electronic devices and a more sedentary lifestyle both before and during the pandemic, compared to the rest of the 2020 population.
Conclusions
The present findings corroborate the recently reported association between the complex lifestyle changes related to the lockdown and a higher incidence of CPP in Italian girls.
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Objective
To investigate the impact of early exposure to androgen excess on gonadotropin-dependent puberty (GDP) and final height (FH) of patients with androgen-secreting adrenocortical tumors (ACT) in childhood.
Methods
Retrospective cohort study. Occurrence of GDP and achievement of FH were evaluated. Central precocious puberty (CPP) and early fast puberty (EFP) were considered pubertal disorders. Patients with normal puberty and pubertal disorders were compared.
Results
The study included 63 patients (44F), followed in a single institution from 1975 until 2017. At diagnosis of ACT, median age was 25.8 months; duration of signs, 6 months; stature SDS, 0.5 (−3.6 to 3.9) and bone age advancement, 14.7 months (−27.9 to 85.4). To date, 37 patients developed GDP: 26 had normal puberty; one, precocious thelarche; seven, CPP and three, EFP. GnRHa effectively treated CPP/EFP. Tall stature and older age at diagnosis of ACT were associated with risk of CPP alone (RR 4.17 (95% CI 1.17–14.80)) and CPP/EFP (RR 3.0 (95% CI 1.04–8.65)). Recurrence/metastasis during follow-up were associated with risk of CPP alone (RR 4.17 (95% CI 1.17–14.80)) and CPP/EFP (RR 3.0 (95% CI 1.12–8.02)). Among the 19 patients that reached FH, stature SDS dropped from 1.4 to −0.02 since diagnosis of ACT (P = 0.01). Seventeen achieved normal FH. There was no difference in FH SDS between patients with normal puberty and pubertal disorders (P = 0.75).
Conclusions
Gonadotropin-dependent pubertal disorders are common in patients with androgen-secreting ACT in childhood. FH is usually not impaired. The study reinforces the importance of close follow-up after surgery to identify and treat consequences of early exposure to androgen excess.
Unit for Thrombosis Research, Department of Regional Health Research, University of Southern Denmark, Denmark
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Department of Clinical Research, University of Southern Denmark, Odense, Denmark
OPEN, Open Patient data Explorative Network, Odense University Hospital, Region of Southern Denmark, Odense, Denmark
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Unit for Thrombosis Research, Department of Regional Health Research, University of Southern Denmark, Denmark
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Unit for Thrombosis Research, Department of Regional Health Research, University of Southern Denmark, Denmark
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Department of Clinical Research, University of Southern Denmark, Odense, Denmark
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Unit for Thrombosis Research, Department of Regional Health Research, University of Southern Denmark, Denmark
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Introduction
Hypogonadism is prevalent during opioid treatment, and low testosterone concentrations are associated with cardiovascular disease. The effect of testosterone replacement therapy (TRT) on the coagulation system in men with hypogonadism is not clarified. We investigate the effects of TRT on the tissue factor (TF) and contact activation pathways of coagulation in opioid-treated men.
Materials and methods
This was a double-blinded, placebo-controlled study in 37 men with total testosterone < 12 nmol/L randomized to 24 weeks of testosterone injections (n = 17) or placebo (n = 20). Variables of the coagulation system were analysed at baseline and after 24 weeks. Measurements included the TF pathway (endogenous thrombin potential (ETP) and peak thrombin), the contact activation pathway (endogenous kallikrein potential (EKP) and peak kallikrein), coagulation factors (FVII, FX, prothrombin, and FXII), and inhibitors (tissue factor pathway inhibitor (TFPI), protein C, protein S, antithrombin, and C1 esterase inhibitor (C1inh)). Between-group differences at 24 weeks were determined with analysis of covariance. Within-group changes in TRT and placebo were analysed with paired t-test.
Results
Between-group differences at 24 weeks were observed for ETP (P = 0.036), FVII (P = 0.044), FX (P = 0.015), prothrombin (P = 0.003), protein C (P = 0.004), and protein S (P = 0.038). Within the TRT group, ETP, peak thrombin, FVII, FX, prothrombin, TFPI, protein C, FXII, and C1inh decreased and protein S increased (all P < 0.05). Within the placebo group, coagulation outcomes were unchanged.
Conclusion
TRT affects the coagulation system in an anticoagulant direction through suppressed TF pathway in men with opioid-induced hypogonadism.
