Hypocalcemia in combination with hyperphosphatemia impairs muscle cell differentiation in vitro.

PURPOSE: Hypoparathyroidism is a rare endocrine disorder characterized by low or absent secretion of parathyroid hormone (PTH), which leads to decreased calcium and increased phosphorus levels in the serum. The diagnosis of hypoparathyroidism is based on the identification of the aforementioned biochemical abnormalities, which may be accompanied by clinical manifestations. Symptoms of hypoparathyroidism, primarily attributed to hypocalcemia, include muscle cramps or spasms, facial, leg, and foot pain, seizures, and tingling in the lips or fingers. The treatment of hypoparathyroidism depends on the severity of symptoms and the underlying pathology. Over the long term, calcium supplements, active vitamin D analogs, and thiazide diuretics may be needed. In fact, in patient cohorts in which optimal disease control still remains elusive, replacement therapy with recombinant parathyroid hormone analogs may be contemplated. Despite the predominantly neuromuscular symptoms of hypoparathyroidism, further effects of parathyroid hormone deficiency at the muscle cell level remain poorly understood. Thus, the aim of our study was to evaluate the effects of hypocalcemia in combination with hyperphosphatemia on muscle cells differentiation in vitro. METHODS: C2C12 cells, an in vitro model of muscle cells, were differentiated for 2 or 6 days in the presence of hypocalcemia (CaCl2 0.9 mmol/l) and moderate (PO4 1.4 mmol/l) or severe (PO4 2.9 mmol/l) hyperphosphatemia, or combinations of both conditions. Cell differentiation and expression of genes linked to muscle differentiation were evaluated. RESULTS: The combination of hypocalcemia with hyperphosphatemia induced a significant reduction (50%) in differentiation marker levels, such as MyoD (protein 1 for myoblast determination) and myogenin on the 1st day of differentiation, and MHC (myosin heavy chains) after 6 days of differentiation compared to control. Furthermore, this condition induced a statistically significant reduction of insulin-like growth factor-1 (IGF-1) mRNA expression and inhibition of IGF signaling and decrease in ERK phosphorylation compared to control cells. CONCLUSIONS: Our results showed that a condition of hypocalcemia with hyperphosphatemia induced an alteration of muscle cell differentiation in vitro. In particular, we observed the reduction of myogenic differentiation markers, IGF-1 signaling pathway, and ERK phosphorylation in differentiated skeletal myoblasts. These data suggest that this altered extracellular condition might contribute to the mechanisms causing persistence of symptoms in patients affected by hypoparathyroidism.

The effects of non-andrological medications on erectile dysfunction: a large single-center retrospective study.

PURPOSE: To evaluate the association among andrological diseases at the first outpatient visit and the medications taken by patients for other comorbidities, as well as the differential impact between specific medication and relative comorbidities. METHODS: This is a single-center retrospective study based on subjects who referred to the Andrology Unit with a well-defined andrological diagnosis. RESULTS: A total of 3752 subjects were studied (mean age ± DS 46.2 ± 16.5 years). A total of 19 categories of andrological diseases and 110 type of medications for other comorbidities were identified. ED was the most frequent andrological pathology at the first andrological examination (28.7%), followed by infertility (12.4%). The couple of variables that were statistically significant in the univariate association analysis (p < 0.001) were: ED and (a) antihypertensives; (b) antihyperglycemics; (c) lipids-lowering; (d) psychotropics. The univariate and multivariate regression analyses confirmed the association. All the related comorbidities were also significantly associated with the univariate analysis, and all remained significantly associated with multivariate analysis. A multivariate analysis was also conducted to analyze the association between ED and the following pairs of variables "DM-antihyperglycemics", "dyslipidemia-lipids-lowering", and "hypertension-antihypertensives". In all cases, the pathology, but not the specific treatment, was significantly associated with ED. CONCLUSION: ED is significantly associated with antihypertensive, antihyperglycemic, lipid-lowering, psychotropic drugs' intake. Anyway, ED appears to be more related to the diseases than to the specific therapies. The definitive cause/effect relationship should be established based on future prospective studies.

Bone quality in endocrine diseases: determinants and clinical relevance.

PURPOSE: Bone is one of the main targets of hormones and endocrine diseases are frequent causes of secondary osteoporosis and fractures in real-world clinical practice. However, diagnosis of skeletal fragility and prediction of fractures in this setting could be a challenge, since the skeletal alterations induced by endocrine disorders are not generally captured by dual-energy X-ray absorptiometry (DXA) measurement of bone mineral density (BMD), that is the gold standard for diagnosis of osteoporosis in the general population. The aim of this paper is to review the existing evidence related to bone quality features in endocrine diseases, proposing assessment with new techniques in the future. METHODS: A comprehensive search within electronic databases was performed to collect reports of bone quality in primary hyperparathyroidism, hypoparathyroidism, hyperthyroidism, hypercortisolism, growth hormone deficiency, acromegaly, male hypogonadism and diabetes mellitus. RESULTS: Using invasive and non-invasive techniques, such as high-resolution peripheral quantitative computed tomography or DXA measurement of trabecular bone score (TBS), several studies consistently reported altered bone quality as predominant determinant of fragility fractures in subjects affected by chronic endocrine disorders. CONCLUSIONS: Assessment of skeletal fragility in endocrine diseases might take advantage from the use of techniques to detect perturbation in bone architecture with the aim of best identifying patients at high risk of fractures.

The role of thyroid function in female and male infertility: a narrative review.

PURPOSE: We herein aimed to review the new insights into the impact of impaired thyroid function on male and female fertility, spacing from spontaneous pregnancy to ART, with the objective of providing an updated narrative revision of the literature. METHODS: This narrative review was performed for all available prospective, retrospective and review articles, published up to 2021 in PubMed. Data were extracted from the text and from the tables of the manuscript. RESULTS: Thyroid dysfunction is frequently associated with female infertility, whereas its link with male infertility is debated. Female wise, impaired function is detrimental to obstetric and fetal outcomes both in spontaneous pregnancies and in those achieved thanks to assisted reproduction technologies (ART). Furthermore, the reference range of TSH in natural pregnancy and ART procedures has recently become a matter of debate following recent reports in this field. On the other hand, the impact of thyroid function on the male reproductive system is less clear, although a possible role is suggested via modulation of Sertoli and Leydig cells function and spermatogenesis. CONCLUSION: Thyroid function should be carefully monitored in both male and female, in couples seeking spontaneous pregnancy as well as ART, as treatment is generally immediate and likely to improve chances of success.

Erectile dysfunction as a marker of endocrine and glycemic disorders.

PURPOSE: The aim of this study was to evaluate in a population of patients with erectile dysfunction (ED): (a) the prevalence of a previously unknown endocrine/glycemic disorders; (b) the correlation between ED severity and endocrine/glycemic disorders. METHODS: 1332 patients referred for ED from 2013 to 2020 were included. The ED diagnosis was made using the International-Erectile-Function-Index-5 questionnaire. ED severity was considered according to presence/absence of spontaneous erections, maintenance/achievement deficiency. All patients were subjected to search for sociodemographic and clinical characteristics: age, ethnicity, marital status, previous use of PDE5i, previous prostatectomy, diabetes mellitus (DM), prediabetes, endocrine dysfunctions. RESULTS: The mean ± SD age was 54.3 ± 13.7 years. The 19.1% (255/1332) of patients were already in treatment for prediabetes/diabetes or endocrine dysfunctions. Among the remaining 1077, the prevalence of previously unknown endocrine and glycemic disorders was 30% (323/1077). Among them, 190/323 subjects (58.8%) were affected by hypogonadism, with high estradiol level observed in 8/190 (4.2%). The prevalence of new glycemic alterations was 17.3% (56/323) [specifically, 32/56 (57.1%) DM, and 24/56 (42.9%) prediabetes]. A thyroid dysfunction was observed in 40/323 subjects (12.3%) and hyperprolactinemia in 37/323 (11.5%). Patients with new diagnosis of DM showed more severe form of ED compared to the total group {difficulty in the achievement of erection: 46/56 [82.2%, vs 265/1332 (19.9%), p < 0.05]; absence of spontaneous erection 23/56 [41.1%, vs 321/1332 (24.1%), p < 0.05]}. CONCLUSION: ED is an early marker of endocrine/glycemic disorder, and a previously unknown dysfunction was found in more than a quarter of patients. A newly diagnosed DM is associated with ED severity, especially in elderly man and in presence of hypertension.

The gut microbiome as possible mediator of the beneficial effects of very low calorie ketogenic diet on type 2 diabetes and obesity: a narrative review.

Several studies have shown a strong correlation between the different types of diets and gut microbiota composition on glycemia and weight loss. In this direction, low-carbohydrate and ketogenic diets have gained popularity, despite studies published so far leading to controversial results on subjects with diabetes. In this narrative review, firstly, we aimed to analyze the role of very-low-calorie ketogenic diets (VLCKDs) in type 2 diabetes (T2DM) and obesity management. Secondly, in this context, we focused attention on gut microbiota as a function of VLCKD, particularly in T2DM and obesity treatment. Finally, we reported all this evidence to underline the importance of gut microbiota to exalt new nutritional strategies for "tailor-made" management, treatment, and rehabilitation in subjects with T2DM and obesity, even with diabetic complications. In conclusion, this narrative review outlined the beneficial impact of VLCKD on gut microbiota even in subjects with T2DM and obesity, and, despite inner VLCKD short-duration feature allowing no sound-enough provisions for long-term outcomes, witnessed in favor of the short-term safety of VLCKD in those patients.Level of evidence Level V: Opinions of authorities, based on descriptive studies, narrative reviews, clinical experience, or reports of expert committees.

Diabetes and disordered bone metabolism (diabetic osteodystrophy): time for recognition.

Diabetes and osteoporosis are rapidly growing diseases. The link between the high fracture incidence in diabetes as compared with the non-diabetic state has recently been recognized. While this review cannot cover every aspect of diabetic osteodystrophy, it attempts to incorporate current information from the First International Symposium on Diabetes and Bone presentations in Rome in 2014. Diabetes and osteoporosis are fast-growing diseases in the western world and are becoming a major problem in the emerging economic nations. Aging of populations worldwide will be responsible for an increased risk in the incidence of osteoporosis and diabetes. Furthermore, the economic burden due to complications of these diseases is enormous and will continue to increase unless public awareness of these diseases, the curbing of obesity, and cost-effective measures are instituted. The link between diabetes and fractures being more common in diabetics than non-diabetics has been widely recognized. At the same time, many questions remain regarding the underlying mechanisms for greater bone fragility in diabetic patients and the best approach to risk assessment and treatment to prevent fractures. Although it cannot cover every aspect of diabetic osteodystrophy, this review will attempt to incorporate current information particularly from the First International Symposium on Diabetes and Bone presentations in Rome in November 2014.

Effect of diet on type 2 diabetes mellitus: a review.

Type 2 diabetes mellitus is one of the fastest growing diseases; the number of people affected by diabetes will soon reach 552 million worldwide, with associated increases in complications and healthcare expenditure. Lifestyle and medical nutrition therapy are considered the keystones of type 2 diabetes prevention and treatment, but there is no definite consensus on how to treat this disease with these therapies. The American Diabetes Association has made several recommendations regarding the medical nutrition therapy of diabetes; these emphasize the importance of minimizing macrovascular and microvascular complications in people with diabetes. Four types of diets were reviewed for their effects on diabetes: the Mediterranean diet, a low-carbohydrate/high-protein diet, a vegan diet and a vegetarian diet. Each of the four types of diet has been shown to improve metabolic conditions, but the degree of improvement varies from patient to patient. Therefore, it is necessary to evaluate a patient's pathophysiological characteristics in order to determine the diet that will achieve metabolic improvement in each individual. Many dietary regimens are available for patients with type 2 diabetes to choose from, according to personal taste and cultural tradition. It is important to provide a tailor-made diet wherever possible in order to maximize the efficacy of the diet on reducing diabetes symptoms and to encourage patient adherence. Additional randomized studies, both short term (to analyse physiological responses) and long term, could help reduce the multitude of diets currently recommended and focus on a shorter list of useful regimens.

The role of ejaculatory dysfunction on male infertility.

BACKGROUND: The aim of this study was to evaluate: 1) the prevalence of male infertility due to ejaculatory dysfunction (premature ejaculation-PE, intravaginal ejaculatory dysfunction-IVEjD, anejaculation-AE, and retrograde ejaculation-RE); and 2) the hormonal profile and semen characteristics of such subjects. METHODS: N.3280 subjects who were referred to our andrology unit for infertility were studied. Exclusion criteria: the presence of known causes of male infertility and erectile dysfunction. In all subjects were performed: medical history and andrological physical examination; hormonal profile; semen analysis or centrifugation/resuspension of post-orgasmic urine; IIEF-5 questionnaire for the diagnosis of ED; PEDT questionnaire for the diagnosis of EP. RESULTS: the prevalence of ejaculatory dysfunctions in infertile males was 1.8% (59/3280). The causes were: a) absence of ejaculation in 37/3280 subjects (1.1%); among them, 23/3280 (0.7%) subjects showed a condition of RE and 14/3280 (0.4%) of AE; b) PE in 16/3280 subjects (0.5%); and c) IVEjD in 6/3280 subjects (0.2%). Hormonal values and seminal parameters (when semen analysis was possible) were within the normal ranges in all the cases. In subjects with RE, sperm recovery was possible in 69.9% (16/23) subjects after centrifugation and resuspension of post-orgasmic urine. CONCLUSIONS: The prevalence of male infertility due to ejaculatory dysfunctions is overall just under 2%. The main cause is retrograde ejaculation; psychogenic origins could also have an important role. It is important to identify the cause of ejaculatory dysfunction in order to decide upon correct management (PE treatment, centrifugation and resuspension of post-orgasmic urine, penile vibratory stimulation, and psychological counselling).

The CATCH checklist to investigate adult-onset hypogonadism.

Adult-onset hypogonadism is a syndrome often underdiagnosed, undertreated, or incompletely explored. There are various reasons for this: firstly, undefined age range of men in whom testosterone levels should be investigated and then no definitive serum cutoff point for the diagnosis of hypogonadism; and finally, variable and non-specific signs and symptoms; men and physicians do not pay adequate attention to sexual health. All these factors make the diagnostic criteria for hypogonadism controversial. The evaluation of the clinical features and causes of this syndrome, its link with age, the role of testosterone and other hormone levels, and the presence of any comorbidities are all useful factors in the investigation of this population. The purpose of this manuscript, after an accurate analysis of current literature, is to facilitate the diagnosis of hypogonadism in men through the use of the CATCH acronym and a checklist to offer a practical diagnostic tool for daily clinical practice. A narrative review of the relevant literature regarding the diagnosis of late-onset hypogonadism or adult-onset hypogonadism was performed. PubMed database was used to retrieve articles published on this topic. A useful new acronym CATCH (Clinical features [symptoms] and Causes, Age, Testosterone level, Comorbidities, and Hormones) and a practical checklist to facilitate the evaluation of hypogonadism in aging men were used. The evaluation of the clinical features and causes of hypogonadism, the link with age, the role of Testosterone and other hormones, and the evaluation of comorbidities are important in investigating adult-onset hypogonadism. The CATCH checklist could be helpful for clinicians for an early diagnosis of both hypogonadism and associated comorbidities. We suggest the use of this acronym to advocate the investigation of declining testosterone in aging men.