Clinical Endocrinology最新文献

Objectives

Pheochromocytomas and paragangliomas (PPGLs) are manifestations of von Hippel-Lindau (VHL) disease. This study aims to describe the clinical features of PPGLs in VHL patients and the distinctions between VHL disease-related PPGLs and sporadic PPGLs.

Design, Patients and Measurements

The study included all patients with VHL disease and PPGLs treated in a single centre from 2007 to 2023. A total of 145 patients were included in the sporadic PPGLs group. Their clinical data were retrospectively reviewed. Genetic testing for VHL mutation was conducted using Sanger sequencing. Statistical analysis was performed using SPSS 22.

Results

Fifty-nine (65.6%) of the 90 VHL disease patients had PPGLs (male: female, 38:21; age at diagnosis, 25.0 ± 13.3 years). 42 (71.2%) patients had lesions only in the adrenal gland, and 16 (27.1%) patients had lesions both in and out of the adrenal gland. 45 (76.3%) patients had multiple lesions. Eighteen (45.0%) patients developed recurrence after surgery. Fifty-eight patients with PPGLs underwent genetic testing and had pathogenic or likely pathogenic mutations in the VHL gene. Fifty-three (91.4%) patients had missense mutations, 34 of which were located in the Elongin-C binding domain. The hotspot mutation sites were codon 161 and codon 167. Five novel mutations were identified. The clinical characteristics showed no significant differences between groups with different mutation sites. Compared to sporadic PPGLs, VHL disease-related PPGLs were more frequently located in the adrenal gland (71.2% vs. 49.0%, p < 0.001), had a higher prevalence of multiple lesions (76.3% vs. 11.0%, p < 0.001), and secreted noradrenaline (80.4% vs. 43.2%, p < 0.001). They were also more likely to relapse after surgery (45.0% vs. 15.3%, p < 0.001).

Conclusion

VHL disease-related PPGLs were often multifocal and noradrenergic, and more likely to relapse compared with sporadic PPGLs. No relationships were identified between the mutation sites and the clinical characteristics of PPGLs.

Macro-thyroid-stimulating hormone (macro-TSH) is a complex formed by monomeric TSH with anti-TSH antibodies, causing falsely elevated TSH levels and potential misdiagnosis of hypothyroidism. Identification of macro-TSH is essential for proper treatment and patient follow-up. Its diagnostic gold standard is gel filtration chromatography (GFC), which is very expensive, time-consuming, and rarely available. Polyethylene glycol (PEG) precipitation is more accessible and inexpensive. The aim of the study was to review evidence on PEG precipitation for the detection of macro-TSH to standardize its application in clinical practice.

Methods

According to PRISMA guidelines, we conducted up to August 2024 a comprehensive search of PubMed and Scopus databases, using terms related to macro-TSH and PEG precipitation.

Results

We included 23 studies with 4476 subjects, encompassing 10 observational studies and 13 case series/reports. All studies showed a low risk of bias. They were conducted in tertiary centres and included newborns to elderly subjects. The most of evidence about the procedure has been achieved with PEG concentrations of 12.5%. The PEG-precipitable TSH of the macro-TSH cases was always higher than 75% ranging on average from 81% to 90%. No-macro-TSH cases (controls) showed a PEG-precipitable TSH percentage ranging from 44.1% to 61.8%.

Conclusions

PEG precipitation can be taken into account as a useful diagnostic tool for macro-TSH. However, it is necessary to perform PEG precipitation in cases with a highly suspicious clinical picture and at the same time perform all available ancillary tests. PEG-precipitable TSH > 75% can be considered a reliable diagnostic threshold for macro-TSH cases.

Objective

The effects of pheochromocytomas and paragangliomas (PPGLs)-induced catecholamine overproduction on vascular and cardiac function are generally thought to be reversible after PPGLs removal. However, a sizable proportion of patients who were free of the recurrent disease still faced high risks of cardiovascular problems after successful surgery. We aim to identify incidence and risk factors for long-term cardiovascular complications in PPGLs patients after surgery.

Design

We retrospectively reviewed 602 patients who underwent surgery for sporadic PPGLs at three centers between January 2012 and October 2022. Demographic characteristics and perioperative data were recorded. Multiple logistic regression was used to determine the risk factors for postoperative long-term cardiovascular complications.

Results

Finally, a total of 602 patients were included in the analysis, comprising 460 (76.4%) patients with pheochromocytomas and 142 (23.6%) patients with paragangliomas. After a median follow-up of 64 months, 76 (12.6%) patients had developed long-term cardiovascular complications. Independent risk factors included pheochromocytomas (odds ratio [OR] = 4.13, 95% confidence interval [CI]: 1.425–11.965, p = 0.009), had low preoperative left ventricular ejection fraction (LVEF, OR = 5.659, 95% CI: 2.141–14.955, p < 0.001), experienced intraoperative hemodynamic instability (HDI, OR = 2.498, 95% CI: 1.423–4.385, p = 0.001), suffered from postoperative in-hospital cardiovascular complications (OR = 5.723, 95% CI: 2.078–15.758, p = 0.001) and long-term persistent hypertension (OR = 3.552, 95% CI: 1.580–7.988, p = 0.002).

Conclusions

Long-term cardiovascular complications commonly occur in patients with surgical-cured PPGLs. Pheochromocytomas, had low preoperative LVEF, experienced intraoperative HDI, suffered from postoperative in-hospital cardiovascular complications, and persistent hypertension were determined as the risk factors for long-term cardiovascular complications. These findings may help to improve follow-up management.

Objective

To estimate the incidence, prevalence, patient characteristics and healthcare utilization patterns of moderate to severe thyroid eye disease (TED) in the United States.

Design

Retrospective review of medical and prescription claims data from the Inovalon deidentified claims database.

Patients

Patients with moderate to severe TED were identified based on specific and sensitive definitions using International Classification of Diseases (ICD) codes selected by a group of TED specialists.

Results

The incident moderate to severe TED population included 3364 and 1730 patients using the sensitive and specific definitions, respectively. After adjusting for age and gender, corresponding incidence rates in the sensitive and specific populations were 8.97 (13.49 in women and 4.27 in men) and 4.37 (6.59 in women and 2.05 in men) per 100,000 person-years, respectively. The prevalent population included 16,310 and 8018 patients using the sensitive and specific definitions, respectively, corresponding to adjusted prevalence rates of 44.13 (66.00 in women and 21.39 in men) and 20.55 (31.18 in women and 9.50 in men) per 100,000 persons. A preponderance of women was observed, and comorbidity rates were high, with > 40% of prevalent patients experiencing hypertension. Steroids were the most frequently prescribed medication. The impact of teprotumumab was not captured, since this study only included claims data through 2019.

Conclusions

The estimated incidence and prevalence rates of TED demonstrate the considerable impact of this disease in the United States, making the creation of a specific ICD code imperative for effective healthcare planning and management.

Objective

Different definitions of thyroid dysfunction during pregnancy may lead to under or overtreatment. The aims of this study were to (1) define population-based pregnancy-specific reference ranges for thyroid dysfunction during early pregnancy in Nepal and assess the impact of antibody positivity, (2) quantify the diagnostic impact of population-based reference ranges compared with current practice and (3) assess the determinants of thyroid function and antibody positivity.

Methods

A total of 800 healthy pregnant women aged 20–40 years in the Bhaktapur municipality were included. Population-based reference ranges for thyroid hormones levels were defined as 2.5th and 97.5th percentiles using competitive immunoluminometric assay design. Thyroid disease cases and those with recommended treatment indications were calculated using current non-pregnancy new reference ranges. Multivariate regression analyses were performed to identify the determinants of thyroid hormones and antibody levels.

Results

Median gestational age was 11 weeks. The reference interval was 0.05–3.69 µLU/mL for thyroid stimulating hormone (TSH) and 8.89–15.28 pg/mL for free tetraiodothyronine (fT4) after excluding thyroid peroxidase antibody-positive women. Compared with the current non-pregnancy reference ranges, the new calculations increased the number of women who required treatment from 5 to 12 (0.9% increase). We identified 19 women (2.4%) who were positive for TSH receptor antibody (TRAb). We could not identify the determinants of TRAb positivity, and TRAb positivity was not associated with TSH or fT4 levels.

Conclusions

We found meaningful changes using population-based pregnancy-specific TSH and fT4 reference intervals and encourage further studies in other low- and middle-income settings. Our findings suggest that population screening for TRAb is not clinically meaningful.

Trial Registration

Clinical Trial Registration: U1111-1183-4093.

Objective

Poirier-Bienvenu neurodevelopmental syndrome (POBINDS) is a rare neurodevelopmental syndrome, resulting from germline heterozygous CSNKB2 pathogenic variants. The main presentations are severe epilepsy, delayed psychomotor development, and/or profound intellectual disability. More recently, CSNK2B pathogenic variants have been reported in patients with mild intellectual disability and no history of epileptic symptoms. Short stature is present in 66% of patients, in half of these cases due to proven growth hormone deficiency.

Methods

Whole genome sequencing (WGS) was performed through a French genomic program for a patient with isolated growth hormone deficiency after negative next generation sequencing (NGS) results. NGS panel analysis of CSNK2B and genes involved in isolated growth hormone deficiency (IGHD) was performed in 44 patients from the Genhypopit network (n = 2144) with growth hormone deficiency (GHD) and intellectual disability (ID) or epilepsy and in a convenience cohort of 68 GHD patients.

Results

We present the first case of POBINDS presenting mainly as growth delay due to GHD. Genome analysis revealed a de novo pathogenic variant in the translation initiation codon of CSNK2B (c.1 A > G, p.(Met1?)). The patient had mild intellectual disability and subsequent analysis of the patient's clinical history revealed that he had had febrile convulsions, compatible with POBINDS. No CSNK2B pathogenic variants were identified among the 44 selected patients with GHD and ID or epilepsy, or in a convenience cohort of 68 patients with GHD.

Conclusion

Although rare, pediatricians should be aware that POIBNDS syndrome may present as IGHD with mild ID.

Background

Growth hormone (GH) treatment is effective in restoring normal growth in children with GH deficiency (GHD). However, individual responses to GH treatment vary, necessitating predictive models to estimate growth outcomes. This study aimed to develop and validate a predictive model for GH treatment response during the first 2 years in patients with idiopathic GHD using the LG growth study (LGS) database.

Methods

This observational study included 669 prepubertal patients with idiopathic GHD from the LGS registry who received GH treatment for at least 2 years. Clinical and laboratory data were collected at baseline and every 6 months thereafter. Stepwise multivariate regression analysis was performed to develop prediction models for the treatment period.

Results

The mean age of patients with GDH was 6.0 ± 1.8 years. Height standard deviation score (SDS) significantly increased from −2.50 ± 0.71 to −1.66 ± 0.71 in the first year and −1.35 ± 0.71 in the second year. The first-year growth velocity was 9.06 ± 1.51 cm, decreasing to 7.42 ± 1.37 cm in the second year. The prediction models incorporated variables such as age, birth weight, bone age, initial height SDS, body mass index SDS, mid-parental height, GH dose and first year of height after GH treatment, explaining 76.9% and 84.1% of the variability in height SDS changes in the first and second years, respectively.

Conclusions

GH treatment significantly improves height outcomes in prepubertal children with GHD. The developed predictive models demonstrated accuracy, facilitating personalized GH therapy. Future research should focus on refining these models and exploring the long-term effects of GH treatment in pubertal patients.

Trial Registration

ClinicalTrials.gov identifier: NCT01604395.

Background

A previous study had established the safety and preserved of quality of life in patients with adrenal insufficiency (AI) who received prednisolone 5 mg once daily at sahur (predawn) during Ramadan fasting. It has been postulated that a lower dose of prednisolone between 2 and 3 mg may be sufficient for glucocorticoid replacement in this group of patients. This study aimed to assess the safety and effect on quality of life in patients with AI given prednisolone 2.5 mg during Ramadan fasting.

Methods

Patients with AI on twice-daily hydrocortisone, who had low or moderate risk of adrenal crisis and intended to fast, were recruited. Patients were given prednisolone 2.5 mg once daily taken at sahur(predawn) and Ramadan education was given. Weight, sleep duration, physical activity, biochemical parameters and quality of life measurements (SF-36 questionnaire) were analysed at the end of Ramadan and compared against the patient's own baseline readings before the start of Ramadan.

Results

A total of 16 patients (10 men, median age 60 [50.3, 68] years) were recruited. All patients were on 15–20 mg of hydrocortisone (in divided doses) before Ramadan, and intended to fast. Five of the participants had type 2 diabetes with low IDF-DAR risk category. 18.7% of the participants were unable to complete all 29 days of fasting. Up to 62.5% of the participants reported at least one adverse event. There was a statistically significant reduction in weight (median: −1.6 [−2.5, −0.3] kg, p < .01), systolic blood pressure (median: −17.0 (−28.8, −4.3) mmHg, p < .01) and diastolic blood pressure (median: −13.0 (−17.8, −3.8) mmHg, p < .01). Quality of life measures were preserved in all domains.

Conclusion

With prednisolone 2.5 mg daily in Ramadan fasting, more than half of the participants experienced symptoms of AI, with significant reduction in weight and blood pressure. We conclude that prednisolone 2.5 mg daily is insufficient during the somewhat stressful state of Ramadan fasting. Further studies with prednisolone 3–4 mg daily in settings with readily available prednisolone 1 mg tablets may further elucidate the safety of using lower dose prednisolone in Muslim patients who fast with AI during Ramadan.