Journal of the Endocrine Society最新文献

In the last 10 years the field of prenatal diagnosis has been significantly reshaped followed by the implementation of noninvasive prenatal cell-free DNA (cfDNA) testing methodologies in clinical practice. Based on a superior performance and higher sensitivity and specificity than the former practice of biochemical markers screening, the American College of Obstetricians and Gynecologists and American College of Medical Genetics and Genomics recommend noninvasive prenatal cfDNA screening for trisomy 21, 18, 13, and sex chromosome aneuploidy to all pregnant people. While cfDNA screening is helpful in risk assessment for the most common autosomal trisomies, cfDNA also provides information about fetal sex chromosomes. Prediction of fetal sex is highly desired by the parents and also useful to healthcare providers for management of pregnancies that are at-risk for X-linked conditions. In fact, utilization of cfDNA screening has resulted in a significant number of referrals to evaluate discordant results for cfDNA sex prediction and appearance of fetal genitalia by prenatal ultrasound scan or at birth raising concerns about the fetus/infant atypical sex development known as a difference in sex development (DSD). In this mini-review, we outline principles and limitations of cfDNA technology, summarize recent findings related to cfDNA test performance in prediction of sex chromosome abnormalities and DSD conditions, define the technical and biological causes of discrepant results, provide recommendations to consolidate efforts by prenatal and clinical management teams in challenging situations, and discuss ethical considerations associated with fetal sex prediction and prenatal DSD diagnosis.

Context: Literature suggests patients with thyroid cancer have unmet informational needs in many aspects of care. Patients often turn to online resources for their health-related information, and generative artificial intelligence programs such as ChatGPT are an emerging and attractive resource for patients.

Objective: To assess the quality of ChatGPT's responses to thyroid cancer-related questions.

Methods: Four endocrinologists and 4 endocrine surgeons, all with expertise in thyroid cancer, evaluated the responses to 20 thyroid cancer-related questions. Responses were scored on a 7-point Likert scale in areas of accuracy, completeness, and overall satisfaction. Comments from the evaluators were aggregated and a qualitative analysis was performed.

Results: Overall, only 57%, 56%, and 52% of the responses "agreed" or "strongly agreed" that ChatGPT's answers were accurate, complete, and satisfactory, respectively. One hundred ninety-eight free-text comments were included in the qualitative analysis. The majority of comments were critical in nature. Several themes emerged, which included overemphasis of diet and iodine intake and its role in thyroid cancer, and incomplete or inaccurate information on risks of both thyroid surgery and radioactive iodine therapy.

Conclusion: Our study suggests that ChatGPT is not accurate or reliable enough at this time for unsupervised use as a patient information tool for thyroid cancer.

Appetite-related hormones are secreted from the gut, signaling the presence of nutrients. Such signaling allows for cross-talk between the gut and the appetite-control regions of the brain, influencing appetite and food intake. As nutritional requirements change throughout the life course, it is perhaps unsurprising that appetite and eating behavior are not constant. Changes in appetite-related gut hormones may underpin these alterations in appetite and eating. In this article, we review evidence of how the release of appetite-related gut hormones changes throughout the life course and how this impacts appetite and eating behaviour. We focus on hormones for which there is the strongest evidence of impact on appetite, food intake, and body weight: the anorexigenic glucagon like peptide-1, peptide tyrosine tyrosine, and cholecystokinin, and the orexigenic ghrelin. We consider hormone concentrations, particularly in response to feeding, from the very early days of life, through childhood and adolescence, where responses may reflect energy requirements to support growth and development. We discuss the period of adulthood and midlife, with a particular focus on sex differences and the effect of menstruation, pregnancy, and menopause, as well as the potential influence of appetite-related gut hormones on body composition and weight status. We then discuss recent advancements in our understanding of how unfavorable changes in appetite-related gut hormone responses to feeding in later life may contribute to undernutrition and a detrimental aging trajectory. Finally, we briefly highlight priorities for future research.

Adrenal dysfunction due to over-the-counter (OTC) health supplements containing unlabeled glucocorticoids has been previously reported. Here, we present a case series of 12 patients at an urban safety net medical center evaluated by endocrinology for iatrogenic adrenal dysfunction, Cushing syndrome (CS) and/or adrenal insufficiency (AI), associated with use of OTC arthritis supplements surreptitiously containing glucocorticoids. There were 12 patients using OTC arthritis supplements (Artri King [n = 8], Ardosons [n = 3], Ajo Rey [n = 1]) included. The mean age was 51.6 years and 33.3% were female. Findings of CS were identified in 10/12 (83.3%) patients, including moon facies (66%), central adiposity (66%), and abdominal striae (50%). Symptoms of AI were identified in 8/12 (66.7%) patients, including nausea/vomiting (42%), fatigue (42%), and abdominal pain (33%). Of 10/12 (83.3%) patients initially needing glucocorticoid replacement therapy, 4 continue to require treatment, 3 have successfully discontinued treatment, and 3 have been lost to follow-up. The literature reviewed identified 10 cases in 7 previously published reports, which did not include consistent follow-up data on adrenal function after discontinuation of the supplement. This case series demonstrates possible presentations of CS and/or AI from glucocorticoid exposure in patients taking these OTC arthritis supplements. Including more cases than all previously published reports combined, this series expands data for cortisol levels, cosyntropin test results, and glucocorticoid replacement needs for these patients and highlights the necessity for vigilant identification of supplement sources of exogenous steroids and the recognition of possible AI when such supplements are discontinued.

[This corrects the article DOI: 10.1210/jendso/bvae010.].

"Pseudo-endocrine disorders" refer to proposed conditions that have never been scientifically proven to exist but, due to widespread misinformation available on the internet and other media, are relatively commonly diagnosed and treated with equally unproven and sometimes dangerous treatments. Adrenal fatigue is a nonexistent condition that supposedly results from adrenal exhaustion and atrophy due to chronic stress and has been promoted as a potential explanation for a variety of symptoms. Testing consists of nonvalidated online surveys and salivary cortisol profiles while treatment is not evidence-based at best and can be dangerous. Wilson's syndrome and reverse T3 syndrome are also nonexistent conditions that supposedly result from impaired T4 to T3 conversion and competition of excess reverse T3 with T3 for T3 receptors. Testing involves measurement of axillary temperature and treatment consists of T3 therapy, often at very high and dangerous doses. Hypogonadism ("low T") is frequently diagnosed in "men's health" clinics and other venues without actual hormone testing or further evaluation and is often treated with supraphysiologic testosterone therapy that suppresses endogenous gonadal testosterone and sperm production, leads to a lifelong need for testosterone therapy, and may have numerous other harmful effects. Low-dose naltrexone (LDN) therapy has been proposed as a treatment for multiple disorders including autoimmune conditions and other disorders resulting from aberrant immune mechanisms, but there is no valid evidence that LDN has any benefits. Management of patients with pseudo-endocrine disorders must involve careful listening, patient education, healthy lifestyle measures, and honesty, encouragement, and compassion.

Context: Polycystic ovary syndrome (PCOS) affects 10% of women of reproductive age. The genetic architecture of the disease is emerging, but there is little data exploring the effect of genetic risk on clinical presentation.

Objective: We hypothesized that genetic risk loci would influence measurable phenotypic traits.

Methods: This retrospective cohort study, conducted at an academic medical center, included women of European ancestry with PCOS (n = 404), as diagnosed by the National Institutes of Health criteria, and controls with regular menses and no hyperandrogenism (n = 408). We identified association between genetic risk variants and measured phenotypic traits using linear regression.

Results: In a combined analysis of cases and controls, 2 variants in loci containing the genes PRSS23 (P < .001) and FSHB (P < .001) were associated with gonadotropin levels. Two variants in loci containing NEIL2/GATA4 (P = .002) and CYP3 (P < .001) were associated with androgen levels. Three variants in loci containing SHBG (P = .001), ZBTB16 (P < .001), and CYP3 (P < .001) were associated with ovarian morphology. One variant in the locus containing FTO (P = .001) was associated with hip circumference and was influenced by body mass index.

Conclusion: These results demonstrate that PCOS genetic risk variants may influence hormone levels and ovarian morphology and increase the risk of obesity. Increased genetic risk for PCOS appears to drive traits that underly the classical clinical presentation of PCOS.

Context: Studies describing the coagulation profile in adrenal adenomas still need to be added.

Objective: We explored how sex and mild autonomous cortisol secretion (MACS) affect coagulation parameters in patients with adrenal adenomas.

Design: Cross-sectional study.

Methods: From January 2019 until April 2023, participants in the Impact of Adrenal IncidenTalomas and Possible Autonomous Cortisol Secretion on Cardiovascular and Metabolic Alterations trial (NCT04127552) diagnosed with adrenal adenoma were categorised according to the 1 mg overnight dexamethasone-suppression test (1 mg-DST). Coagulation parameters were evaluated, and two-way ANOVA was used to elucidate the cortisol-by-sex interaction.

Results: Of 153 patients screened, 90 were enrolled (62.2% female, mean age 62 ± 10 years): 41 with non-functioning adrenal tumour (1 mg-DST ≤ 1.8 µg/dL), and 49 with a MACS (1 mg-DST > 1.8 µg/dL). Platelet counts were higher in the MACS group (P = .01). Regression analysis identified female sex (B = 36.603, P = .011), 1mg-DST (B = 0.238, P = .042), and younger age (B = -1.452, P = .038) as independent predictors for elevated platelet count. In patients with MACS, women exhibited higher levels of procoagulant factors fibrinogen (P = .004) and factor VIII (P < .001), and coagulation inhibitors protein C (P = .003) and antithrombin III (P = .005) than males. No differences were observed in the non-functioning adrenal tumour group, providing a cortisol-by-sex interaction regarding fibrinogen (P = .047), factor VIII (P = .046), and protein C (P = .028).

Conclusion: Our findings revealed a worse coagulation profile in women with MACS, underscoring the need for a sex-specific approach in clinical practice to manage thrombotic risks effectively. Dedicated prospective studies are needed to validate and integrate these findings into clinical strategies for thromboprophylaxis.

Context: Subclinical hypothyroidism (SCH) is characterized by elevated thyroid-stimulating hormone (TSH) levels and normal free thyroxine (fT4) levels. In upper normal TSH levels, thyrotropin-releasing hormone (TRH) stimulation test proved to be useful in identifying an exaggerated TSH response.

Objective: We aimed to evaluate the incidence and predictive ability of basal TSH, anti-thyroid peroxidase antibodies (TPOAb), and anti-thyroglobulin antibodies (TgAb) for exaggerated TRH stimulation test in SCH.

Methods: A total of 952 subjects with SCH (TSH 4.01-10.00 mIU/L) found during health checkups were evaluated for TSH response to TRH stimulation testing and autoantibodies. Exaggerated TSH response was defined as ΔTSH (peak serum TSH level after TRH injection minus basal TSH level) of > 25.00 mIU/L.

Results: The prevalence of exaggerated TSH responses in SCH was 66% (n = 633). The proportion of exaggerated TSH response tended to increase as basal TSH levels increased (P for trend <.001). Also, the proportion of positive TPOAb or TgAb tended to increase as basal TSH levels increased (P for trend <.05). Analysis of predictive ability of basal TSH, positive TPOAb, or TgAb for exaggerated TRH stimulation test revealed that positive TPOAb or TgAb showed high specificity (> 90%) for positive TRH stimulation test but low sensitivity. Basal TSH showed low sensitivity and specificity.

Conclusion: Two-thirds of SCH showed exaggerated TRH stimulation test. Positive TPOAb or TgAb showed high specificity (> 90%) for positive TRH stimulation test but basal serum TSH levels showed low predictability. The TRH stimulation test may be a valuable guide to identify SCH patients with hypothyroid state.