Endocrines, Volume 4, Issue 3 (September 2023) – 13 articles

Pituitary apoplexy (PA) is a rare medical emergency. The sudden pressure increase in the sella turcica may determine compression on the surrounding structures determining the classical symptomatology associated, especially visual field impairment and/or ocular palsies and hypopituitarism; hypotonic hyponatremia may occur too, even if it is not common. Although already described in the literature, cases of isolated III cranial nerve palsies are extremely rare events. We report the case of a mid-60-year-old man with a known pituitary adenoma accessing the Emergency Department (ED) for worsening headaches unresponsive to analgesics, with a morphological picture consistent with ischemic PA, despite no dimensional increase of the pituitary lesion; upon ED access, a mild paucisymptomatic hyponatremia was also observed. Dexamethasone and mannitol were empirically introduced upon neurosurgical indication and tramadol and ketorolac were promptly administered as well, but without benefit. In the next days, a severe hypotonic hyponatremia was evidenced and a clear left III cranial nerve palsy developed, but no clear signs of cerebral bleeding or ischemia, nor a significant compression on the homolateral cavernous sinus, were observed. Upon ruling out other possible causes, a likely diagnosis of syndrome of inappropriate antidiuresis (SIAD) was made, confirmed by the quick response to fluid restriction. Overall, the sudden fall in tonicity plasma levels seemed to contribute to the exacerbation of the neurological deficit since the normalization of sodium levels was associated with a rapid and complete reversion of the III cranial nerve palsy. Full article

We report a case of a 19-year-old male referred to the Endocrine Unit because of gynecomastia. Initial investigation revealed elevated levels of estradiol (E2) along with secondary hypogonadism (hypotestosteronemia and severe oligoasthenoteratozoospermia (OAT)) despite normal testicular volume (12 mL) and secondary sexual characteristics. Surprisingly, an ultrasound examination revealed a small hypoechoic mass (1.1 cm) with intense intralesional vascularization within the right testicle, even though tumor markers were normal. Surgical removal of testicular mass led to the identification of Leydigioma, and the patient showed regression of gynecomastia during the nine-month follow-up. Unexpectedly, hypergonadotropinemia manifested along with normal testosterone (T) levels and significant improvement in OAT. Magnetic resonance imaging (MRI) showed pituitary hyperplasia (PH). Gynecomastia represents an atypical manifestation of Leydig cell tumors and typically resolves after surgical removal. However, unilateral orchiectomy may determine compensatory PH. Currently, it is uncertain whether the shift from hypogonadotropic to permanent hypergonadotropinemia was the only factor responsible for the high sperm count occurring in our patient. Further research is needed to elucidate the underlying mechanisms. Full article

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors were once known as a class of glycemic-lowering agents to treat type 2 diabetes. As the evolving evidence from recent cardiorenal trials on these agents has shown—e.g., EMPA-REG OUTCOME, DECLARE-TIMI 58, CANVAS Program, DAPA-CKD—disclosing their benefits beyond glycemic management, SGLT-2 inhibitors have stimulated a shift in the management of T2DM and its comorbidities, specifically preventing cardiovascular events in people with ASCVD, preventing heart failure hospitalizations, and delaying the progression of chronic kidney disease. As a result, their usage beyond glycemic management has been included in clinical practice guidelines. Although SGLT-2 inhibitors have shown promising results in cardiorenal outcomes, patients have not had equal access to these agents, at least in the United States, suggesting a systemic issue of health inequity. This review article explores the mechanisms by which cardiorenal benefits are offered, the results of the landmark clinical trials for these agents, and their place in therapy. Full article

Corosolic acid (CA), a natural compound derived from the Banaba tree (Lagerstroemia speciosa), has attracted attention for its potential therapeutic properties in the management of metabolic diseases. This narrative review aims to summarize the current evidence on the anti-dyslipidemic, anti-diabetic, and anti-inflammatory effects of CA and to understand the pharmacokinetics and molecular mechanisms through the analysis of preclinical and clinical studies. Full article

Phosphorus is essential for all living organisms. It plays an important role in maintaining biological functions, such as energy metabolism, cell membrane formation, and bone mineralization. Various factors in the intestine, kidneys, and bones regulate the homeostasis of the inorganic phosphate (Pi) concentration in the body. X-linked hypophosphatemia (XLH), the most common form of hereditary hypophosphatemic rickets, is characterized by an impaired mineralization of the bone matrix, hypertrophic chondrocytes with hypophosphatemia, and active vitamin D resistance in childhood. Phosphate-regulating gene with homologies to endopeptidases on the X chromosome was recognized as the responsible gene for XLH. XLH is classified as fibroblast growth factor 23 (FGF23)-related hypophosphatemic rickets. The enhanced FGF23 stimulates renal phosphate wasting by downregulating sodium-dependent Pi cotransporters, NaPi2a and NaPi2c proteins, in the proximal tubules. Recently, transmembrane protein (Tmem) 174 has been identified as a novel regulator of phosphate transporters. This review introduces the role of Tmem174 in the Pi homeostasis in the body. Full article

The association between type 1 diabetes (T1D) and coeliac disease (CD) is well known. Metabolic control of thirty-seven patients aged between 1 and 18 years, with coexisting T1D and CD were evaluated. The control group includes 37 patients affected only by diabetes. All data relating to the metabolic control of all patients were acquired through examination of medical records and CMG reports available on dedicated online platforms. Glucose variability was expressed as Coefficient of Variation (CV) and Standard Deviation of blood glucose values (SD). The formula used for CV computation is: CV (%) = 100 × SD (daily glycemia)/Mean (daily glycemia). Patients with T1D and CD showed a significant reduction in rapid pre-prandial insulin. The same reduction was present if we consider only patients using CGM. In patients without CGM, there was no difference in the doses of basal, pre-prandial and total insulin. Indicators of metabolic control were overlapping between the two groups in patients who used CGM. On the contrary, diabetic and coeliac patients without CGM had increased levels of glycaemic variability indicators and HbA1c. Finally, the percentage of target glycaemic values and >250 mg/dL glycaemic values were significantly decreased and increased, respectively in T1D and CD patients without CGM. With this study we wanted to demonstrate if CGM could improve metabolic control of patients with coexisting T1D and CD. Our data show a worse metabolic control in patients with T1D and CD who did not use CGM. Instead, patients who use CGM, regardless of the concomitant CD, manage to achieve the same glycaemic targets through an adjustment of titration of pre-prandial insulin doses. Full article

Leydig cells, located in the testis interstitial space, are the primary source of testosterone in males. Testosterone plays critical roles in both reproductive and metabolic functions and therefore is essential for male health. Steroidogenesis must be properly regulated since dysregulated hormone production can lead to infertility and metabolic disorders. Leydig cell steroidogenesis relies on the coordinated interaction of various factors, such as hormones and signaling molecules. While luteinizing hormone (LH) is the main regulator of Leydig cell steroidogenesis, other molecules, including growth hormones (GH), prolactin, growth factors (insulin, IGF, FGF, EGF), and osteocalcin, have also been implicated in the stimulation of steroidogenesis. This review provides a comprehensive summary of the mechanisms and signaling pathways employed by LH and other molecules in the stimulation of Leydig cell steroidogenesis, providing valuable insights into the complex regulation of male reproductive and metabolic health. Full article

Background: The prevalence of thyroid disease has seen a rapid increase in recent times, primarily attributed to the fast pace of lifestyles that often result in poor dietary choices, work-life imbalances, social stress, genetic mutations, and improved diagnostic capabilities. However, the precise contribution of these factors to thyroid disease remains a subject of controversy. Consequently, there is a pressing need to gain a comprehensive understanding of the related associations in order to potentially mitigate the associated morbidity and mortality rates. Methods: This study employed association rule mining techniques to reveal hidden correlations among complex and diverse epidemiological connections pertaining to thyroid disease associations. We proposed a framework which incorporates text mining and association rule mining algorithms with exceptionality measurement to simultaneously identify common and exception risk factors correlated with the disease through real-life digital health records. Two distinctive datasets were analyzed through two algorithms, and mutual factors were retained for interpretation. Results: The results confirmed that age, gender, and history of thyroid disease are risk factors positively related to subsequent thyroid cancer. Furthermore, it was observed that the absence of underlying chronic disease conditions, such as diabetes, hypertension, or obesity, are associated with reduced likelihood of being diagnosed with thyroid cancer. Conclusions: Collectively, the proposed framework demonstrates its sound feasibility and should be further recommended for different disease in-depth knowledge discovery. Full article

Interstitial expansion is associated with glomerular filtration rate (GFR) loss in many renal diseases, including diabetic nephropathy. The Renin–Angiotensin System Study (RASS) tested whether a 5-year renin–angiotensin system (RAS) blockade with enalapril or losartan versus placebo slowed progression of early diabetic nephropathy lesions in 285 normoalbuminuric, normotensive, normal/high GFR patients with type 1 diabetes. RASS found no benefit to the RAS blockade on diabetic glomerular lesions but observed an unexpected 50% increase in the fractional volume of the renal cortex which is the interstitium. The effects of the RAS blockade on individual interstitial components––striated collagen, interstitial cells, and peritubular capillaries––were not assessed. We evaluated by electron microscopy changes in fractional volume of each component in seven patients from each group between baseline and five years. At baseline, 49% of the interstitium was collagen, 12% cells, 26% peritubular capillaries, 7% space, and 2% artifact. There was no overall change in the interstitial composition during the RASS. There were no statistically significant effects of treatment group on any interstitial components. Renal volume remained stable in all groups. The RAS blockade affected neither the approximately 50% increase in interstitium fractional volume per cortex nor the parallel increase in all interstitial components that occurred over the five years of the RASS. Full article

Primary amenorrhea (PA) describes the complete absence of menses by the age of 15 years. It is a devastating diagnosis that can affect the adolescent’s view of her femininity, sexuality, fertility and self-image. A normal menstrual cycle can occur only in the presence of: a properly functioning hypothalamus–pituitary axis, well-developed and active ovaries, outflow tract without abnormalities. Any dysfunction in any of these players can result in amenorrhea. PA evaluation includes the patient’s medical history, physical examination, pelvic ultrasonography and initial hormone evaluation, limited to the serum-follicle-stimulating hormone (FSH) and luteinizing hormone, testosterone and prolactin. A karyotype should be obtained in all adolescents with high FSH serum levels. The main causes of PA, whether or not accompanied by secondary sexual characteristics, include endocrine defects of the hypothalamus–pituitary–ovarian axis, genetic defects of the ovary, metabolic diseases, autoimmune diseases, infections, iatrogenic causes (radiotherapy, chemotherapy), environmental factors and Müllerian tract defects. PA management depends on the underlying causes. Estrogen replacement therapy at puberty has mainly been based on personal experience. PA can be due to endocrine, genetic, metabolic, anatomical and environmental disorders that may have severe implications on reproductive health later in life. In some complex cases, a multidisciplinary team best manages the adolescent, including a pediatrician endocrinologist, gynecologist, geneticist, surgeon, radiologist, and psychologist. Full article

The prevalence of diabetes is rising globally; currently, 537 million people worldwide and 37.3 million people in the US are affected. Patients with diabetes have a four-times-greater risk of hospitalization with longer hospital stays and a greater chance of readmission compared to patients without diabetes. Spending on diabetes care as a proportion of global GDP is also projected to increase from 1.8% in 2015 to 2.2% in 2030. The largest component of this medical expenditure is inpatient care in hospitalized patients, accounting for USD 69.7 billion of the total medical cost. Hospitalized patients can develop hyperglycemia without a history of pre-existing diabetes. It has been shown that hyperglycemia in patients without a history of diabetes is also associated with poor hospital outcome. In this review, we discuss the adverse effects of hyperglycemia and hypoglycemia on hospital outcomes; we review recent glycemic targets, recent guidelines’ recommendations, and landmark trials with a brief review on discharge planning, updates on hyperglycemic emergencies, and the use of newer technologies in hospitalized patients such as continuous glucose monitoring devices. Full article

The purpose of this systematic review is to synthesize available studies on sleep health characteristics in adults of African descent with or at risk for cardiometabolic conditions. PubMed, PsycINFO, CINAHL, and Web of Science were searched for original research studies on subgroups of African descent with at least one cardiometabolic risk factor. Studies published in English with measured sleep characteristics were included. Studies focused on participants with severe psychiatric illness, night shift workers, or with a pharmacologic sleep treatment focus were excluded. The risk for bias was assessed using the NHLBI 2021 Quality Assessment Tool. Two reviewers independently synthesized the results before reaching a consensus. Out of 340 studies screened, 35 studies were included. There were 631,756 participants with an average age of 44.3 combined (SD = 16.5) (53% female and 22% Black). Disparities in sleep health characteristics and cardiometabolic health among African American adults were found. Markers of poor cardiometabolic health were associated with disordered sleep. While the studies in this review captured key factors, the study measurement methods were inconsistent, and African Caribbean Americans were underrepresented. The studies demonstrated the intersectionality of poor sleep characteristics, cardiometabolic risk factors, and racial/ethnic groupings. Clinicians should consider these findings when providing care. Full article

Impaired glucagon secretion is a major component of glucose intolerance in type 2 diabetes mellitus (T2D). Glucagon secretion exhibits heterogenous patterns in individuals and across glucose tolerance diagnoses. Characterization of the range of glucagon secretion patterns can help clinicians personalize diabetes care based on glucagon characteristics in addition to glucose and insulin profiles. A total of 102 subjects with normal glucose tolerance, impaired glucose tolerance, and T2D had their glucagon profiles recorded in response to an oral glucose tolerance test. Shapelet analysis was used to identify the most descriptive patterns of early glucagon secretion, and spectral biclustering was employed to identify biclusters of associated subjects and shapelets. The dynamics of glucose, insulin, and glucagon secretion in each cluster were evaluated to identify overall patterns, and the characteristics of the subjects in each cluster were compared. Three clusters were chosen to represent the glucagon patterns. Membership in these three clusters was interpreted based on the presence or lack of extrema in the first 30 min after oral carbohydrate intake. Cluster 1 (n = 23) had a minimum at 30 min and only negative trends. Cluster 2 had a minimum at 10 min and a maximum at 20 min (n = 25). Cluster 3 (n = 40) had a maximum at 10 min and a minimum at 20 min. Subjects in cluster 1 had the lowest average fasting plasma glucose (90.17 mg/dL) and average age (41.39 years) and the highest HOMA-beta score (87.5%), while subjects in cluster 2 had the highest average fasting plasma glucose (102.56 mg/dL) and average age (53.16 years) and the lowest HOMA-beta score (55.77%). Characterization of glucagon dynamics, in addition to glucose and insulin, can aid in personalized treatment approaches and provide greater insight about the underlying dysfunction in glucose regulation. Full article