Journal of Clinical Endocrinology & Metabolism最新文献

Fine-needle-aspiration-cytology (FNAC) is safe and cost-effective procedure for evaluating thyroid nodules. The non-negligible rate of indeterminate thyroid nodule (ITN) cytology warrants diagnostic surgery for histological assessment, in some cases. Two recent studies (from Europe and the United States) reported that the clinical behavior of a histologically proven thyroid cancer (TC) varies according to its presurgical FNAC results. Despite differences in study design, inclusion criteria, and the use of different cytology classification systems (Italian and Bethesda), the overall results were comparable. In order to further discuss these results and to provide additional perspective on the topic, the senior authors of the 2 studies invited other thyroid experts and cytologists not involved in the previous studies to participate in the present commentary. The strong, consistent clinical message that emerges, especially regarding PTC, is that TC with an initial diagnosis of ITN has a less aggressive clinical presentation, lower rates of (1) lymph node metastasis; (2) more aggressive variants; and (3) BRAFV600E mutations compared with differentiated thyroid cancer (DTC) with an initial diagnosis of "suspicious for malignancy" or "malignant." These results were consistent in both studies and strongly point toward a more indolent clinical phenotype of DTC with a preoperative diagnosis of ITN as opposed to suspicious for malignancy or malignant. Further understanding the clinical implications of these data appears of clinical relevance and will be discussed from both the endocrinologist and the cytologist point of view. The here overviewed data provide the foundation for beginning to examine the impact of less aggressive therapies for TC with an initial ITN diagnosis.

Background: Prepubertal children with obesity frequently have enhanced growth, accelerated skeletal maturation, and changes in the growth hormone-insulin-like growth factor (GH-IGF) axis. However, the involvement of pappalysins (PAPP-A, PAPP-A2) and stanniocalcins (STC1, STC2) as regulators of IGF bioavailability has not been studied in obesity.

Objective: We aimed to determine the effects of childhood obesity and weight reduction on serum levels of PAPP-A, PAPP-A2, STC1, and STC2 and their relationship with IGF bioavailability, growth, and other components of the GH-IGF system.

Methods: Prepubertal children with severe obesity (150, 50% males/females, age: 7.72 ± 2.05 years, BMI z-score: 4.95 ± 1.70, height z-score: 1.28 ± 1.04) were studied at diagnosis and after a minimum of 0.5 BMI z-score reduction. Two hundred and six healthy age- and sex-matched children were used as controls.

Results: Children with obesity had decreased serum concentrations of PAPP-A, PAPP-A2 and STC2, but increased total and free IGF-I, intact IGFBP-3, acid-labile subunit (ALS), IGF-II, and insulin levels, with no difference in the free IGF-I/total IGF-I ratio. Neither the standardized body mass index (BMI) nor height correlated with any biochemical parameter analyzed. A decrease in IGF-II, insulin, and ALS with an increase in IGFBP-2 and -5, STC2, and PAPP-A were observed after weight loss.

Conclusion: Increased circulating total and free IGF-I, insulin, and IGF-II may all contribute to the increased rate of prepubertal growth and bone maturation observed in children with obesity, with STC2 possibly being involved.

Objective: To investigate the clinical features, imaging characteristics, and molecular profile of sellar neurocytoma (SN).

Methods: Clinical, imaging, and pathological features of 11 cases of SN were retrospectively analyzed. Electron microscopy was performed in 5 cases. Molecular features were detected in tumor tissue by RNA sequencing, quantitative polymerase chain reaction, and immunohistochemistry.

Results: The clinical features of SN patients showed a high incidence of hyponatremia (73%, 8/11), and the tumors tended to invade the lateral side of the saddle area from preoperative imaging analysis. The tumors had positive NeuN, synaptophysin, neurofilament, somatostatin receptor 2 (SSTR2) immunohistochemistry staining. Tumor transcriptomic analysis suggested a new LMCD1-AS1:GRM7-AS1 fusion gene event and increased expression of 10 hypothalamus-secreted hormones in SN. Fifteen differentially expressed genes were verified for quantitative polymerase chain reaction verification. SSTR2 has been verified by immunohistochemistry.

Conclusion: Hyponatremia is the dominant clinical features of SN. Preoperative imaging suggests that growth toward the dorsal region is the imaging feature of SN. SSTR2 expression and LMCD1-AS1:GRM7-AS1 fusion gene event expected to become a new molecular marker for SN. Somatostatin receptor ligand therapy may be a potential therapy for SN.

Context: For some common thyroid-related conditions with high prevalence and long follow-up times, ChatGPT can be used to respond to common thyroid-related questions.

Objective: In this cross-sectional study, we assessed the ability of ChatGPT (version GPT-4.0) to provide accurate, comprehensive, compassionate, and satisfactory responses to common thyroid-related questions.

Methods: First, we obtained 28 thyroid-related questions from the Huayitong app, which together with the 2 interfering questions eventually formed 30 questions. Then, these questions were responded to by ChatGPT (on July 19, 2023), a junior specialist, and a senior specialist (on July 20, 2023) separately. Finally, 26 patients and 11 thyroid surgeons evaluated those responses on 4 dimensions: accuracy, comprehensiveness, compassion, and satisfaction.

Results: Among the 30 questions and responses, ChatGPT's speed of response was faster than that of the junior specialist (8.69 [7.53-9.48] vs 4.33 [4.05-4.60]; P < .001) and the senior specialist (8.69 [7.53-9.48] vs 4.22 [3.36-4.76]; P < .001). The word count of the ChatGPT's responses was greater than that of both the junior specialist (341.50 [301.00-384.25] vs 74.50 [51.75-84.75]; P < .001) and senior specialist (341.50 [301.00-384.25] vs 104.00 [63.75-177.75]; P < .001). ChatGPT received higher scores than the junior specialist and senior specialist in terms of accuracy, comprehensiveness, compassion, and satisfaction in responding to common thyroid-related questions.

Conclusion: ChatGPT performed better than a junior specialist and senior specialist in answering common thyroid-related questions, but further research is needed to validate the logical ability of the ChatGPT for complex thyroid questions.

Context: Renin-angiotensin-aldosterone system (RAAS) activation is closely linked to obesity; however, the sex-specific associations between RAAS activity and body composition among individuals without obesity are not well understood.

Objective: To investigate the associations of aldosterone and renin with body composition according to sex in the general population.

Design: Population-based cohort study.

Setting: Québec (Canada).

Participants: Adults aged 40 to 69 years enrolled in CARTaGENE between 2009 and 2010 (N = 3687).

Exposures: Plasma aldosterone and renin concentrations.

Main outcome measures: Body composition assessed via anthropometrics (waist circumference and waist-to-hip ratio), bioelectrical impedance (lean body mass, fat mass, and muscle mass), and cardiac magnetic resonance imaging (epicardial and pericardial adipose tissue volumes).

Results: The mean (SD) age and body mass index were 55 (8) years and 27.3 (4.8) kg/m2, respectively. Among males, higher aldosterone and renin were associated with increased waist circumference, increased waist-to-hip ratio, increased fat mass, decreased lean body mass, and decreased muscle mass (P < .05). Aldosterone (P = .02), but not renin (P = .43), was associated with increased ectopic cardiac adiposity in males. In contrast, higher renin (P < .05), but not aldosterone (P ≥ .05), was associated with increased waist circumference, increased waist-to-hip ratio, and increased cardiac adiposity in females. Among females, higher renin and aldosterone were associated with increased fat mass (P < .05) but were not associated with lean body mass or muscle mass (P ≥ .05). All aforementioned associations were independent of body weight.

Conclusion: Independent of body weight, increased RAAS activity is associated with unfavorable differences in body composition; however, the strength and pattern of association varies by sex.

Graves' disease (GD) is the leading cause of hyperthyroidism in children. However, compared to adults, GD in children is a rare condition. In a recent guideline issued by the European Thyroid Association, the diagnostic evaluation and treatment of pediatric GD is described extensively. In this article, we go beyond the guideline and describe the potential challenges of establishing the right etiology of thyrotoxicosis in children, illustrated by cases of thyroid hormone resistance, autonomous functioning thyroid nodules, and subacute thyroiditis with a thyrotoxic phase. In addition, we report therapeutic challenges in pediatric GD such as recurrent immunological flare-ups under antithyroid drug (ATD) treatment, innovative ways to improve ATD compliance and the role of definitive treatment in persistent complaints of malaise under ATD treatment.

Despite best practice replacement therapy with corticosteroids, patients with adrenal insufficiency report diminished quality of life and face increased mortality and morbidity. Conventional formulations of hydrocortisone have short half-lives (about 90 minutes) requiring multiple dosing during the day. Since 2011, extended-release hydrocortisone (ER-HC) formulations have been available enabling once-, sometimes twice-daily dosing. Most studies comparing ER-HC formulations with conventional hydrocortisone therapy report reduction in body weight, blood pressure and glucose levels, and improved quality of life. However, it is still unclear if the reported beneficiary effects are due to differences in cortisol exposure or alterations in pharmacokinetics. Here, we review studies comparing conventional and ER-HC treatment in adrenal insufficiency and discuss whether these novel formulations are safe and offer clinically significant benefits.

Context: The 2018 International Evidence-Based Guidelines (IEBG) for polycystic ovary syndrome (PCOS) were created, in part, in response to poor patient satisfaction on international surveys. Patient satisfaction in the United States before and after these guidelines has not yet been characterized.

Objective: To evaluate care patterns and patient attitudes among US women with PCOS before and after IEBG.

Methods: This was a cross-sectional study of a population-based community sample of US women with confirmed PCOS who completed standardized questionnaires on care patterns and satisfaction in care.

Results: Among 1056 respondents, aged 23 ± 6 years at diagnosis, 69.2% had to wait ≥ 1 year and 72.9% saw > 1 provider prior to receiving a diagnosis. Less than 45% strongly agreed or agreed with statements regarding trusting their doctor and < 27% were very or somewhat satisfied with care across all questions. In multivariable analyses, composite outcome of trusting your physician was associated with insurance type (uninsured vs private) (odds ratio [95% CI] 0.5 [0.3-0.9], P = .020), race (Hispanic vs Caucasian) (0.6 [0.5-0.9], P = .007), (Black vs Caucasian) (1.6 [1.0-2.4], P = .045) and timing of diagnosis (within 5 years vs > 5 years) (1.3 [1.0-1.7], P = .038). Care satisfaction was associated with insurance type (public vs private) (0.6 [0.4-0.9], P = .010), (uninsured vs private) (0.5 [0.3-0.9], P = .021), and timing of diagnosis (within 5 years vs > 5 years) (1.4 [1.1-1.9], P = .010).

Conclusion: Satisfaction and trust in care is overall poor among US patients with PCOS. Higher scores among those diagnosed within the past 5 years, compared to those with a more remote diagnosis, may indicate an improving trend in care.

Normocalcemic primary hyperparathyroidism (NPHPT), a phenotype of primary hyperparathyroidism, is characterized by elevated parathyroid hormone levels in the setting of persistently normal serum calcium. Diagnosis of NPHPT can be challenging and requires that secondary causes of hyperparathyroidism be excluded. The natural history of NPHPT remains inconclusive. Although biochemically less severe, the skeletal and renal complications of NPHPT vary across studies, primarily due to underlying selection bias. Due to limited data, there is currently no consensus regarding medical and surgical treatment. Recent studies on parathyroidectomy have indicated that normocalcemic patients present more often with negative preoperative localization studies and multiglandular disease, which complicates successful surgical management. In addition, postoperative improvements in bone mineral density and nephrolithiasis vary, raising questions about the optimal treatment approach. Further studies are needed to provide better evidence-based guidance for normocalcemic patients.

Background: Growth differentiation factor 15 (GDF15), a divergent member of the TGF-β superfamily, signals via the hindbrain glial-derived neurotrophic factor receptor alpha-like and rearranged during transfection receptor co-receptor (GFRAL-RET) complex. In nonclinical species, GDF15 is a potent anorexigen leading to substantial weight loss. MBL949 is a half-life extended recombinant human GDF15 dimer.

Methods: MBL949 was evaluated in multiple nonclinical species, and then in humans, in 2 randomized and placebo-controlled clinical trials. In the phase 1, first-in-human, single ascending dose trial, MBL949 or placebo was injected subcutaneously to overweight and obese healthy volunteers (n = 65) at doses ranging from 0.03 to 20 mg. In phase 2, MBL949 or placebo was administered subcutaneously every other week for a total of 8 doses to obese participants (n = 126) in 5 different dose regimens predicted to be efficacious based on data from the phase 1 trial.

Results: In nonclinical species, MBL949 was generally safe and effective with reduced food intake and body weight in mice, rats, dogs, and monkeys. Weight loss was primarily from reduced fat, and metabolic endpoints improved. A single ascending dose study in overweight or obese healthy adults demonstrated mean terminal half-life of 18 to 22 days and evidence of weight loss at the higher doses. In the phase 2, weight loss was minimal following biweekly dosing of MBL949 for 14 weeks. MBL949 was safe and generally tolerated in humans over the dose range tested, adverse events of the gastrointestinal system were the most frequent observed.

Conclusion: The prolonged half-life of MBL949 supports biweekly dosing in patients. MBL949 had an acceptable safety profile. The robust weight loss observed in nonclinical species did not translate to weight loss efficacy in humans.