Coincidence or Causality: Parathyroid Carcinoma in Chronic Kidney Disease-Case Report and Literature Review.

Parathyroid carcinoma (PC) associated with primary hyperparathyroidism (PHPT) has been well investigated in recent years. Data regarding PC evolution in secondary hyperparathyroidism (SHPT) due to chronic kidney disease (CKD) are, however, scarce. Most features that raise the suspicion of PC in PHPT are part of the usual SHPT evolution in CKD, mirroring the natural changes undergone by the parathyroid glands. Therefore, pre-surgically establishing the malignant or benign character of the lesions is cumbersome. We present two cases of PC in end-stage renal disease, one of which was bilateral, diagnosed after total parathyroidectomy in a high-volume parathyroid surgery center. A literature review of the data was also performed. A systematic search of the PubMed/MEDLINE database until January 2024 identified 42 cases of PC associated with SHPT. Understanding the PC features in CKD might improve associated bone and mineral disease management, and reduce the risk of metastasis, parathyromatosis, or recurrence. Irradiation, prolonged immunosuppression, long dialysis vintage, and genotype may predispose to the malignant transformation of chronically stimulated parathyroids. Despite postsurgical diagnosis, favorable outcomes occurred when distant metastases were absent, even without "en bloc" resection. Further research is warranted to delineate specific diagnostic and therapeutic approaches tailored to this particular patient subpopulation.

The sex-dependent impact of adipose tissue and inflammation on chronic pain - A cross-sectional study from the all of us research program.

Emerging evidence suggests an association between chronic pain and elevated body fat. We sought to determine if individuals with higher body fat, measured by hip circumference (HC) and waist circumference (WC), are at risk for chronic pain when they demonstrate higher expression of inflammatory markers. We investigated the incidence and severity of pain in patients with varying WC/HC and inflammatory markers (C-Reactive Protein, IL-6, leptin) using the NIH-sponsored All of Us Database. For each inflammatory marker and sex, participants were divided into four groups based on combinations of normal/high marker levels and small/large WC/HC. We used statistical analysis to compare WC/HC and pain severity (mean NRS pain score) between groups of the same sex. In females, but not males, combinations of elevated CRP with large WC/HC exerted additive effects on the incidence of chronic pain (p < 0.01) and severe pain (p < 0.001), as well as on the severity of pain evaluated by the mean NRS pain score (p < 0.01). This relationship held true for females with high IL-6 or leptin and large WC or HC (p < 0.001 for chronic pain and severe pain incidence, and p < 0.05 for pain severity). Neither IL-6 nor leptin showed any significant impact on pain in males. Obesity status and CRP exert additive prognostic effects for chronic pain in females, but not in males. The concomitant evaluation of other inflammatory factors, such as IL-6 or leptin in females, may further augment the prediction of chronic pain. PERSPECTIVE: This article investigates the relationship between chronic pain, obesity, and inflammatory markers. It could help elucidating sex difference in pain mechanisms, as well as the risk factors for chronic pain, potentially improving patient diagnosis, follow-up and treatment.

New insights into the metabolic-bone crosstalk in active acromegaly.

INTRODUCTION: Body composition (BC) and adipokines share bone active properties and display an altered profile in acromegaly. The fibroblast growth factor 23 (FGF23)/α-Klotho system, also involved in bone metabolism, is upregulated in growth hormone (GH) excess states. Hence, we aimed to investigate their impact on bone in active acromegaly, compared to controls. MATERIAL AND METHODS: BC, bone mineral density (BMD) (via dual X-ray absorptiometry), serum adipokines (leptin, adiponectin, resistin), parathyroid hormone (PTH), FGF23, α-Klotho, and osteocalcin were assessed in a cross-sectional study enrolling 35 patients with active acromegaly (Acro), compared to 35 sex, age, and body mass index (BMI) one-to-one matched healthy controls (CTL). RESULTS: The Acro group had higher bone density scores (p < 0.05), lower visceral fat depots (p = 0.011), and lower serum leptin (p < 0.001) but elevated adiponectin (p < 0.001) and resistin (p = 0.001) concentrations when compared to the CTL group. α-Klotho was not related to the GH/IGF1 axis in the Acro group. Resistin was higher in both diabetic and non-diabetic Acro compared to CTL (p < 0.05). Age and BC were the main independent BMD predictors in regression analysis in both groups, while IGF1 was a positive predictor of osteocalcin levels in the Acro (ß = 0.48, p = 0.006). The correlations between adipokines, the FGF23/α-Klotho system, and bone parameters, respectively, were lost after adjusting for age and BC. CONCLUSIONS: Age and BC were the main independent BMD predictors in the acromegalic patients with active disease, while IGF1 was independently associated with serum osteocalcin concentrations. The role of α-Klotho in evaluating acromegaly and the associated osteopathy in the long-term appears to be limited. Our study is among the first to report significant serum resistin changes in patients with active acromegaly, opening new insights in the GH-mediated insulin resistance. The GH-resistin relationship merits further investigations.

Progesterone in gestational diabetes mellitus: guilty or not guilty?

Insulin resistance is one of the metabolic changes in pregnancy, but only a fraction of women develop overt impaired glucose tolerance or frank diabetes. Most women are able to compensate this altered metabolic state by increasing the amount of insulin produced by the pancreatic beta cells. Progesterone might well be the key to the development of gestational diabetes. Previously high progesterone levels have already been shown to be correlated with the development of glucose abnormalities in pregnancy and now, in a new paper, progesterone receptor-knockout mice are found to have improved glucose tolerance. These mice showed increased insulin secretion, which is probably linked to the presence of increased numbers of beta cells in their pancreas. Is progesterone therefore the 'ultimate bad guy', prohibiting normal adaptation of the pancreatic beta-cell reserve during pregnancy?