Endocrines, Volume 3, Issue 2 (June 2022) – 14 articles

Endometriosis is a benign, hormone-responsive chronic disease that affects women of reproductive age; long-term treatment to balance satisfactory tolerability with clinical efficacy is necessary for these patients. The first-line therapy for endometriosis is predominantly medical treatment, in order to improve symptoms or prevent post-surgical disease recurrence. Multiple factors including age and women preference, pain severity, and endometriosis stage must be considered in the choice of the most suitable therapy. Estrogen-progestogins are generally used as first-line hormone therapies among different medical options currently effective for endometriosis management. Several studies have shown that they are able to improve pain symptoms in most patients, are well tolerated, and are inexpensive. Combined hormonal contraception treatment, administered cyclically or continuously, with different types of hormones and route of administration, results in clinically noticeable decrease in dysmenorrhea, noncyclic pelvic pain, dyspareunia, and recurrence rate after surgery, and also in quality of life improvement. Full article

Prader–Willi Syndrome (PWS, OMIM #176270) is a rare complex genetic disorder due to the loss of expression of paternally derived genes in the PWS critical region on chromosome 15q11-q13. It affects multiple neuroendocrine systems and may present failure to thrive in infancy, but then, hyperphagia and morbid obesity starting in early childhood became the hallmark of this condition. Short stature, hypogonadism, sleep abnormalities, intellectual disability, and behavioral disturbances highlight the main features of this syndrome. There have been a significant number of advances in our understanding of the genetic mechanisms underlying the disease, especially discoveries of MAGEL2, NDN, MKRN3, and SNORD116 genes in the pathophysiology of PWS. However, early diagnosis and difficulty in treating some of the disease’s most disabling features remain challenging. As our understanding of PWS continues to grow, so does the availability of new therapies and management strategies available to clinicians and families. Full article

The transgender concept is described as a clinically significant distress due to the incongruity between the experienced gender and assigned gender. A transgender person carries a gender identity that is different from their assigned sex at birth. Transgender people may be binary: male to female (transgender women) or female to male (transgender men) or genderqueer (non-binary, fluid or variable gender expression). The binary concept has been described in transgender population, where the term transwomen is used to describe people assigned male at birth (AMAB) who are recognized as females during gender transition; with the term transmen where they are assigned female at birth (AFAB) and are then recognized as males in gender transition. According to the DSM-5 classification, gender dysphoria is described when a transgender person develops clinically relevant bio-psychosocial suffering. Currently, the transgender population has gained massive public awareness through social media and gained a considerable level of attention globally. Several studies on transgender populations from different parts of the world have shown real discrimination and stigma towards transgender people, which sometimes acts as a barrier to the provision of the required care for them. Lack of access to the required information, legal issues, lack of solutions to fertility problems, financial constraints, and psychological and emotional obstacles, together with risk of sexually transmitted infections, including human immunodeficiency virus (HIV), all make the life of a transgender person more complicated. Testosterone therapy is a hormone-based therapy for transgender men that provides a body image tallying with the favored gender identification, whereas estrogen and androgen-suppressing agents are used in transgender females to produce changes compatible with their required gender identity. Gender affirmation surgery is a broad term, under which the genital reconstruction is described as a major component. Psychological conditions such as depression, substance abuse, suicidal deaths, and sexually transmitted infections, particularly among males having sex with males, are reported at a significantly higher rate among transgender populations. Cardiovascular morbidity is higher among this population, and continuous medical surveillance is warranted. Medical care provision to transgender populations should be handled with great care, while attending to the unmet needs of this population, as this care should extend beyond routine hormonal therapy and gender reassignment surgery. Full article

Since phosphate is indispensable for skeletal mineralization, chronic hypophosphatemia causes rickets and osteomalacia. Fibroblast growth factor 23 (FGF23), which is mainly produced by osteocytes in bone, functions as the central regulator of phosphate metabolism by increasing the renal excretion of phosphate and suppressing the production of 1,25-dihydroxyvitamin D. The excessive action of FGF23 results in hypophosphatemic diseases, which include a number of genetic disorders such as X-linked hypophosphatemic rickets (XLH) and tumor-induced osteomalacia (TIO). Phosphate-regulating gene homologous to endopeptidase on the X chromosome (PHEX), dentin matrix protein 1 (DMP1), ectonucleotide pyrophosphatase phosphodiesterase-1, and family with sequence similarity 20c, the inactivating variants of which are responsible for FGF23-related hereditary rickets/osteomalacia, are highly expressed in osteocytes, similar to FGF23, suggesting that they are local negative regulators of FGF23. Autosomal dominant hypophosphatemic rickets (ADHR) is caused by cleavage-resistant variants of FGF23, and iron deficiency increases serum levels of FGF23 and the manifestation of symptoms in ADHR. Enhanced FGF receptor (FGFR) signaling in osteocytes is suggested to be involved in the overproduction of FGF23 in XLH and autosomal recessive hypophosphatemic rickets type 1, which are caused by the inactivation of PHEX and DMP1, respectively. TIO is caused by the overproduction of FGF23 by phosphaturic tumors, which are often positive for FGFR. FGF23-related hypophosphatemia may also be associated with McCune-Albright syndrome, linear sebaceous nevus syndrome, and the intravenous administration of iron. This review summarizes current knowledge on the pathogenesis of FGF23-related hypophosphatemic diseases. Full article

Background: Polycystic ovary syndrome (PCOS) is a frequent reproductive disease characterized by hyperandrogenism, oligo /anovulation, and polycystic aspects at ultrasound. In these last years, a body of evidence disclosed the frequent occurrence in PCOS patients of insulin resistance (IR) and compensatory hyperinsulinemia. Aim: To evaluate whether any relationship exists between IR, compensatory hyperinsulinemia and familial predisposition to diabetes. Methods: A group of overweight/obese PCOS patients (n = 84) was selected from our Clinic database according to the Rotterdam criteria and the following parameters were extracted from the database: insulin, C Peptide, aspartate amino transferase (AST), alanine amino transferase (ALT), HOMA (Homeostasis Model Assessment) index, total cholesterol, LDL (Low Density Lypoprotein), HDL (High Density Lypoprotein), and body mass index (BMI). The presence and absence of diabetes among first grade relatives (parents and/or grandparents) were also considered. The Hepatic Insulin Extraction (HIE) index was computed as a ratio between insulin and C-Peptide plasma levels. Results: PCOS patients with familial diabetes showed higher levels of ALT, AST, HOMA index, and HIE. Baseline insulin levels above 12 μU/mL were more frequently observed in PCOS with familial diabetes. HIE index, ALT, and AST were higher in these latter PCOS patients than in PCOS without diabetic first grade relatives, sustaining the hypothesis of an impaired liver clearance of insulin in the case of familial diabetes. Conclusions: According to our study, the presence of anamnestic evidence of familial diabetes together with baseline levels of insulin higher that 12 µIU/mL and elevated transaminase levels should be considered as a consistent clinical suspect of liver impairment that might trigger compensatory hyperinsulinemia and lead to NAFLD and liver steatosis. Full article

The importance of functional food and nutraceutical products to deal with cardiometabolic diseases (CMDs) and metabolic syndrome (MetS) has gained attention in the past few years. The aim of this narrative review is to highlight the potential and effectiveness of nutraceutical in the improvement of CMDs and MetS biomarkers, alongside their burden of disease and economic health expenditure. A science database search was conducted between May and June 2021. A total of 35 studies were included in this paper. We included male and female subjects, children, and adults, in good health or with cardiovascular or metabolic disease. CMDs and MetS have gradually become worldwide health problems, becoming two of the major causes of morbidity and mortality in western countries. The results indicate a positive link between daily consumption of nutraceutical products and an improvement in cardiometabolic and anthropometric biomarkers. In this paper we included a wide range of nutraceutical products. Most of them showed promising data, indicating that nutraceuticals could provide a new therapeutic treatment to reduce prevalence and pharmaceutical expenditures attributed to CMDs and MetS. Unfortunately, there is a huge vacuum of data on nutraceutical usage, savings, and burden reduction. Therefore, further clinical and pharmaco-economic research in the field is highly required. Full article

Turner syndrome (TS) affects approximately 1 out of every 1500–2500 live female births, with clinical features including short stature, premature ovarian failure, dysmorphic features and other endocrine, skeletal, cardiovascular, renal, gastrointestinal and neurodevelopmental organ system involvement. TS, a common genetic syndrome, is caused by sex chromosome aneuploidy, mosaicism or abnormalities with complete or partial loss of function of the second X chromosome. Advances in genetic and genomic testing have further elucidated other possible mechanisms that contribute to pathogenic variability in phenotypic expression that are not necessarily explained by monosomy or haploinsufficiency of the X chromosome alone. The role of epigenetics in variations of gene expression and how this knowledge can contribute to more individualized therapy is currently being explored. TS is established as a multisystemic condition, with several endocrine manifestations of TS affecting growth, puberty and fertility having significant impact on quality of life. Treatment guidelines are in place for the management of these conditions; however, further data on optimal management is needed. Full article

Diagnosing thyroid carcinoma is not always easy on basic haemtoxylin and eosin staining since nuclear features are inconsistent and controversial. In view of this, studies on the role of immunohistochemical markers in the diagnosis of malignant thyroid carcinoma are necessary. Proposed immunohistochemical markers for papillary thyroid cancer include Hector Battifora mesothelial-1 (HBME-1), and Galectin-3 (Gal-3) which have been studied in this project. Immunohistochemical staining of fifty-eight formalin-fixed paraffin embedded surgically removed thyroid tissue from the years 2008 and 2013 was undertaken to determine the diagnostic accuracy of these two markers. We have concluded that both Gal-3 and HBME-1 are useful markers to aid in the diagnosis of papillary thyroid carcinoma and also in distinguishing between benign and malignant thyroid lesions. The sensitivity and specificity of Gal-3 over the 2years studied was found to be 96.2% and 92.6%, respectively, whilst HBME-1 was found to have sensitivity of 93.6% and specificity of 69.02%. Full article

Endometriosis is one of the most common diseases in women of reproductive age, and although there are many theories to explain this enigmatic disease, such as reflux theory, metastasis theory, and metaplasia theory, there is still no single theory that can wholly explain the pathogenesis of the disease, and it is considered a mysterious disease until now [...] Full article

Self-monitoring of blood glucose (SMBG) is common in patients with diabetes. The aim of this study was to explore how frequency/behavior of SMBG affect glucose control in patients with type 2 diabetes. This cross-sectional study was conducted at a regional teaching hospital in Taiwan. All participants completed a structured questionnaire about the frequency and behavior of SMBG, and hemoglobulin A1C (A1C) data were recorded from medical records. A total of 382 diabetes outpatients participated in the study. In the patients using insulin injections, A1C was better in patients with SMBG ≥ 28 times than in those with SMBG < 28 times per month (7.82 ± 1.86% vs. 8.33 ± 1.31%, p = 0.025). In the patients not using insulin, A1C was better in patients with SMBG > 14 times than those with SMBG ≤ 14 times per month (7.08 ± 0.23% vs. 7.55 ± 0.08%, p = 0.038). The patients who more frequently reviewed the causes of hypoglycemia and hyperglycemia had a better A1C level (p for linear trend <0.001). Our study suggested that SMBG ≥ 28 and >14 times could improve glycemic control for insulin-requiring and non-insulin-requiring type 2 diabetes patients, respectively. Further exploration of the cause of hyperglycemia or hypoglycemia shown by SMBG could also improve blood glucose control. Full article

Thyroid diseases in children and adolescents include acquired or congenital conditions, including genetic disorders either isolated or part of a syndrome. Briefly, we will review the physiology and pathophysiology of the thyroid gland and its disorders. The aim of this chapter is to describe genetic abnormalities of the thyroid gland. Full article

The intricacies of human adrenal development have been under scrutiny for decades. Each year marks the identification of new genes and new interactions between gene products that ultimately will act to produce the fully functioning adult gland. Due to the complexity of this process, genetic missteps may lead to a constellation of pathologies. Recent years have identified several novel genetic causes of adrenal dysgenesis and provided new insights into previously delineated processes. SF1, DAX1 (NR0B1), CDKN1C, SAMD9, GLI3, TPIT, MC2R, MRAP, NNT, TXNRD2, AAAS, and MCM4 are among the genes which have had significant contributions to our understanding of the development and function of both adrenals and gonads. Collection and elucidation of these genetic and clinical insights are valuable tools for clinicians who diagnose and manage cases of adrenal dysfunction. Full article

Background and study aims—Albuminuria, defined as an enhanced urine albumin/creatinine ratio (ACR) on a spot sample, is a validated biomarker of glomerular damage. However, it cannot always detect early renal failures in patients with type 2 diabetes (T2D), thus prompting the search for more sensitive and specific parameters. Herein, we investigated the differential role of plasma and urine neutrophil-gelatinase-associated lipocalin (NGALp,—NGALu) for the detection of diabetic kidney disease (DKD). Methods—Traditional glomerular (serum creatinine, cystatin C, ACR) damage biomarkers were evaluated in 84 patients with T2D and in 21 metabolically healthy controls. Diabetic patients were stratified into four groups based on T2D duration (less or more than 5 years) and presence and severity of DKD (early- or advanced-stage), as defined by the ACR and estimated glomerular filtration rate (eGFR). NGALp and NGALu were determined by ELISA methodology and compared among groups. Results—There was no difference in NGALp and NGALu levels between the metabolically healthy individuals and the age-matched, newly diagnosed diabetic patients in the absence of DKD. However, in contrast to NGALu, NGALp was found to be substantially increased in patients with long-standing diabetes without biochemical evidence of DKD, closely mirroring the modest, but still accelerated, decline in the eGFR typical of this chronic dysmetabolic condition, and remained overexpressed throughout the stages of DKD progression. Increased NGALu levels were, instead, rather specific in patients with biochemical evidence of DKD (i.e., marked by increased albuminuria), regardless of T2D duration. Spearman’s correlation and regression analyses showed that patient age and T2D duration could exert a strong positive impact exclusively on NGALp concentrations (ρ = 0.419, p < 0.001 for age; ρ = 0.581, p < 0.001 for T2D), and none on NGALu. Furthermore, receiver operating characteristic (ROC) analysis showed the best performance of NGALp compared to NGALu for the detection of DKD (AUC = 0.817 for NGALp, AUC = 0.711 for NGALu). Conclusions—Our data suggest a different pathophysiological and predictive role for urine and plasma NGAL in the context of T2D and DKD. Full article

The kisspeptin system includes the cleavage products Kiss1 precursor and kisspeptin receptor (Kiss1R). It was originally discovered and studied in cancer metastasis, but the identification of KISS1/KISS1R gene mutations causing hypogonadotropic hypogonadism (HH) revealed unexpected effects in reproduction. Nowadays, the kisspeptin system is the main central gatekeeper of the reproductive axis at puberty and adulthood, but it also has a widespread functional role in the control of endocrine functions. At the periphery, Kiss1 and Kiss1R are expressed in the testes, but the need for kisspeptin signaling for spermatogenesis and sperm quality is still unclear and debated. This brief manuscript summarizes the main findings on kisspeptin and male reproduction; upcoming data on sperm maturation are also discussed. Full article