Hot thyroid nodules are mostly benign and rarely show a malignant nature. Here we present the case of a 45-year-old man with a hypercaptant but ultrasound suspicious nodule; he underwent fine needle aspiration (FNA) and subsequent thyroidectomy. Pathology revealed a papillary thyroid carcinoma (PTC) with focal tall cell features, positivity to BRAF V600E and focal hyperspression of p53. A multidisciplinary clinicopathological approach is crucial for the correct diagnosis.
Adrenal insufficiency (AI) is diagnosed with morning cortisol but ACTH stimulation test is usually needed to confirm the diagnosis. In this study we investigated different morning cortisol thresholds that can safely rule out AI without requiring a confirmatory ACTH stimulation test.
Retrospective cohort study.
We included patients aged 18 and above who underwent the 250 mcg ACTH stimulation test from June 2018 to June 2022. Basal and post-ACTH serum cortisol values at 30 and 60 min were documented. Sensitivity, specificity and logistic regression analysis were employed to assess morning cortisol level's ability to predict AI as confirmed by ACTH stimulation test.
237 patients were included, 66 diagnosed with AI and 171 had normal ACTH results. Hypertension and type 2 Diabetes correlated with lower AI incidence. Median morning cortisol was 138.0 nmol/L for AI group and 286.0 nmol/L for non-AI patients. A morning cortisol of 285 nmol/L had 90.6 % sensitivity, 50.3 % specificity, and a negative predictive value of 93.3 % for ruling out AI. A threshold of 306 nmol/L increased sensitivity to 95.3 % with 40 % specificity.
Morning cortisol is an effective diagnostic tool for ruling out AI. Using multiple thresholds based on clinical suspicion and the integration of predictive pre-test probability can reduce the need for excessive ACTH stimulation tests. This study contributes to the growing evidence of utilizing morning serum cortisol in the diagnosis of adrenal insufficiency.
Diagnosing Adrenal Insufficiency (AI) can be challenging due to debate regarding the cortisol cut-off value that can exclude AI without additional tests. The confirmatory short synacthen test has certain limitations including financial implications and time restrictions. We investigated the performance of various morning cortisol levels that can diagnose AI without additional testing.
Hypoglycemia has long been recognized as a dangerous adverse effect of the treatment of diabetes mellitus with insulin or insulin secretagogues.
Our study was aimed to identify the number of diabetic patients presenting to the emergency department (ED) with hypoglycemia, contributing risk factors for hypoglycemia (including antidiabetic medication regimens), the number of episodes of hypoglycemia requiring medical attention, and how many patients were prescribed glucagon at discharge.
Our study is a retrospective analysis across two hospitals from October 2019 to March 2022, including the population of adult persons with diabetes mellitus, above 18 years of age, presenting to the emergency department with hypoglycemia.
Of the women were 2 African Americans, 25 Caucasians, 17 Hispanics, and 39 from other ethnicities. Of the men were 8 African Americans, 32 Caucasians, 27 Hispanics, and 44 from other ethnicities. The mean age of males was 66.2 years, and females was 72.9 years. 131 patients had no prior visits for hypoglycemia. Of the 194 patients, 54 were discharged from the ED, and 140 were admitted to the hospital. The most common risk factors associated with hypoglycemia requiring medical attention were age > 65, having more than one comorbidity, decreased oral intake, and poor socioeconomic status. Regarding recurrent presentations with hypoglycemia, there was a significant association with insulin use (p-value = 0.0007), with a higher-than-expected number of insulin users having a previous visit for hypoglycemia. Only 16.7 % of non-insulin-using patients had prior visits, compared to 40.6 % of insulin users. Pairwise Chi-square testing did not reveal a significant association between any other medication class and prior visits for hypoglycemia, nor was there an association between risk factors and prior visits. To obtain optimal glycemic control, early identification of hypoglycemia risk factors, self-monitoring of blood glucose, and proper selection of anti-diabetic regimens are important to prevent long-term complications.
Unfortunately, the three elements that would prevent subsequent severe hypoglycemic events (i.e., education, adjustment of medication, and glucagon prescription) are underutilized. Hypoglycemia is more common in the elderly population which remains an unmodifiable risk factor. Identifying patients with persistent poor oral intake is extremely important as they may be prone to hypoglycemic episodes on their current anti-diabetic regimen and will need medication adjustments accordingly. Our future research focuses on whether giving glucagon prescriptions to patients with diabetes mellitus at discharge prevents recurrent ED visits for hypoglycemia.
It is still controversial about the efficacy of Diptptidyl peptidase-4 (DPP4) inhibitors in the treatment of autoimmune diabetes, especially it is unclear whether different drugs have different efficacy for different subtypes of autoimmune diabetes.
To evaluated the efficacy and safety of different DPP-4 inhibitors (Sitagliptin or saxagliptin) combined with insulin in the treatment of different subtypes of autoimmune diabetes.
We searched PubMed, Embase, Cochrane library, Web of Science, Wanfang and CNKI databases from inception to August 2022 to identify correlational studies. Then, RevMan 5.4 and Stata 17.0 software were used to make forest plots. Weighted mean difference (WMD) or odds ratio (OR) with 95 %CI to evaluated the outcomes of Saxagliptin or Sitagliptin combined with insulin in the treatment of autoimmune diabetes.
18 studies consisting of 811 patients were included. Our study revealed Sitagliptin or Saxagliptin both have decrease insulin dose without increase the occurrence of hypoglycemia and adverse event, regardless of subtypes of autoimmune diabetes. Saxagliptin did not statistically improve in glucose control and beta cell function in both LADA and T1DM. However, compared with T1DM, Sitagliptin decreased HbA1c and improved islet beta cell function in patients with LADA.
Sitagliptin combined with insulin therapy in patients with LADA significantly improve glucose control and beta cell function, decrease insulin dose without increasing the occurrence of hypoglycemia and adverse event. Further research in this field is required.
DPP-4 inhibitors combined with insulin therapy in patients with autoimmune diabetes significantly reduced blood glycemic, preserve islet beta cell function, decrease insulin dose, BMI and the incidence of hypoglycemia, and do not increase the incidence of adverse events.
Pancreatic neuroendocrine neoplasms (pNENs) are histologically classified as well-differentiated, poorly-differentiated, or mixed neuroendocrine-non-neuroendocrine neoplasms. There are unresectable pNENs owing to metastases or invasion in not only functional pNENs but also non-functional. However, the exact origin of pNENs has not been elucidated. This study aims to characterize the molecular biology of pNENs based on clinical information and histopathological analysis and identify prognostic biomarkers.
We investigated the relationship between the biological characteristics and immunostaining of pathological tissues in 75 patients. Staining density was evaluated on a 4-point scale from 0 to 3, and the percentage of tumor cells was calculated and scored from 0 to 300 (H-score). We performed receiver operating characteristic (ROC) curve analysis of the H-score. Progression-free survival and overall survival analyses were performed based on the Kaplan–Meier curves.
The H-score showed that patients who died of pNEN had high Ki-67 and low somatostatin receptor (SSTR) 2 levels, and those who relapsed had high Ki-67 and low SSTR5 levels. The ROC showed that the SSTR2 H-score > 80.25 was associated with lower mortality, which was further confirmed by Kaplan–Meier curves [hazard ratio (HR): 6.039, 95 % confidence interval (CI): 1.233–29.59, P = 0.0006). SSTR5 H-score > 93.9 had less recurrence, which was confirmed using Kaplan–Meier curves (HR: 3.321, 95 % CI: 1.426–7.734, P = 0.0336).
Ki-67 > 4.95 is associated with a significantly increased risk of death. Quantification of SSTR2 and SSTR5 immunostaining using the H-score may serve as prognostic markers.
Papillary thyroid cancers are relatively common endocrine malignancies. Risks include obesity, smoking, family history, and radiation exposure. Estrogens may be associated with an increased risk; the implications for transgender women, who use estrogen for gender-affirming hormone therapy (GAHT), are unclear.
3 transgender female veterans seen at sites within our VA Health System were diagnosed with papillary thyroid cancer. All three had started some form of estrogenic GAHT prior to the diagnosis, between 3 months to 5 years earlier. One veteran had radiation exposure, one had a smoking history, and 2 were obese. 2 were treated with thyroidectomy, and one had a recurrence treated with RAI. Each veteran had started GAHT before coming to the VA, and one started without physician support.
Thyroid cancer prevalence in the transgender female population is not yet well-established. These 3 transgender female veterans each had risk factors associated with cancer development. Based on limited existing data, it is conceivable but not clear that GAHT treatment could have impacted their course.
Further investigation of thyroid cancer among transgender women in general, and into the impact of GAHT on disease burden in particular, is needed. Clinicians should also be aware that patients may be receiving hormonal therapy from nontraditional sources with unforeseen and unknown associated risks.
Haemoglobin A1c (HbA1c) levels might inaccurately represent long-term glycaemic control in type 2 diabetes mellitus (T2DM) patients with chronic kidney disease (CKD) owing to anaemia. Fructosamine, which reflects glycaemic control, remains unaffected by anaemia.
This study sought to assess whether fructosamine levels or fructosamine-albumin (FA) ratios could be biomarkers for glycaemic control in T2DM patients, with and without CKD. HbA1c and fructosamine levels were measured, and comparisons were made using the area under the curve and receiver operating characteristic curves. Youden's index was utilized to pinpoint the cut-off points. Predictive values for complications were also assessed.
Our study underscores the close association between HbA1c and blood glucose concentrations among T2DM patients, regardless of kidney function status (r = 0.758). Conversely, fructosamine levels and FA ratios only displayed moderate correlations with FBG among those without CKD (r = 0.466 and r = 0.436, respectively). In a similar manner, the estimated blood glucose (eBG) levels derived from HbA1c were better than the ones from fructosamine levels and FA ratios in terms of comparation to actual fasting blood glucose (FBG) levels across various eGFR levels.
Our findings suggest that HbA1c remains a conventional gauge for glycaemic control among T2DM outpatients, regardless of CKD status. However, for short-term glycaemic monitoring in T2DM outpatients with CKD and low eGFR levels, fructosamine, and FA ratios emerge as potential biomarkers worthy of consideration.
Neck circumference is a low-cost and simple anthropometric measure that has been proven to accurately assess central obesity. However, evidence of its use and feasibility in low-resource settings is limited. We aimed to compare the utility of neck circumference with standard physical measures of obesity in northern Peru. This was a retrospective, cross-sectional study conducted among adults screened for metabolic syndrome. Body mass index, waist circumference, neck circumference, and additional measurements for metabolic syndrome were obtained. Assessments were performed following the WHO STEPS Surveillance Manual. Pearson correlation coefficients and multiple linear regression models were used to estimate the relationship of neck circumference to waist circumference and body mass index. Data from 250 participants showed a normal, homogeneous distribution in both men and women with respect to age and physical/biochemical measurements. The mean age was 53.6 years. A positive correlation of neck circumference with body mass index (r = 0.51 for women and 0.65 for men) and waist circumference (r = 0.6 for women and 0.74 for men) was observed. Multiple linear regression showed that a 1-cm increase in neck circumference increased body mass index by 0.72 kg/m2 (p < 0.001) in men and 0.94 kg/m2 (p < 0.001) in women, and waist circumference by 2.20 cm (p < 0.001) in men and 2.27 cm (p < 0.001) in women. Our findings suggest that neck circumference is a valid and reliable measure that will replace body mass index and waist circumference in Peruvian adults with central obesity; due to the strong correlation that exists between the NC and these anthropometric measurements, mainly because it is an easy, quick measurement and is less vulnerable to errors such as in the measurement of abdominal circumference or variabilities in weight.
Reproductive processes in fishes are regulated by the hypothalamic-pituitary-gonadal (HPG) axis, much like in tetrapods. Within this system, Gonadotropin-Releasing Hormone (GnRH) is released by the hypothalamus, binding to GnRH receptors in the pituitary gland and stimulating the secretion of gonadotropin hormones. The current study aimed to analyze the GnRH receptor in Oncorhynchus mykiss (rainbow trout) using a computational and structural biology approach. The GnRH receptor gene of O. mykiss comprises a nucleotide sequence of 1707 base pairs with an open reading frame of 1251 base pairs, which is responsible for encoding 416 amino acids. It was found that the GnRH receptor contains leucine (L) as the most abundant amino acid. The secondary structure revealed that alpha helices constitute the largest percentage (36 %) with 153 residues, followed by extended strands with 77 residues (17.51 %). The GnRH receptor contains 26 negatively charged and 37 positively charged amino acid residues. The highest hydrophilicity was observed for lysine (K) at position 310, with a value of −3.900, while the highest hydrophobicity was found for leucine (L) at position 290, with a value of 3.80. Molecular docking analysis showed that the most favorable binding energy was observed for Gestrinone (−7.8 kcal/mol). Gestrinone was found to form hydrogen bonds with MET160, LUE245, LUE62, TYR216, and GLN209 residues of GnRH. Moreover, molecular dynamics revealed that the complexes form robust and enduring connections, indicating their structural integrity throughout the simulation. The results of this study provide insights into the protein modeling, molecular docking, and virtual screening of antagonist ligands against the GnRH receptor. Additionally, they may significantly aid in the advancement and improvement of therapeutic strategies targeted at treating various fish reproductive dysfunctions.
Atypical primary hyperparathyroidism (PHPT), which includes normocalcemic and normohormonal variants, can be a diagnostic challenge. We sought to create a machine learning model to predict the probability of a patient having atypical presentations of PHPT.
A model was constructed using logistic regression of PHPT patients and were compared to controls. Variables included sex, body mass index (BMI), calcium, PTH, 25-hydroxyvitamin D, phosphorus, chloride, sodium, alkaline phosphatase, and creatinine. The performance of the model was evaluated using the area under the curve (AUC).
The study included 4987 controls and 433 patients with atypical PHPT. Calcium, PTH, vitamin D, phosphorus, BMI, and sex were found to significantly contribute to the performance of the model, achieving an AUC of 0.999. The sensitivity, specificity, positive and negative predictive values were 92.9 %, 99.7 %, 96.3 % and 99.4 %, respectively.
Machine learning can reliably aid in the recognition of PHPT in patients with atypical variants.
When evaluating patients with atypical variants of primary hyperparathyroidism, the clinician needs to be able to identify subtle relationships in the patient laboratory test to make the diagnosis. These relationships can be found with machine learning and incorporated to predictive models which can ease and improve the diagnosis.
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