Osteoporosis and dermatoporosis: a review on the role of vitamin D.

Osteoporosis (OP) and Dermatoporosis (DP) are expressions of the aging process at the skin and bone levels, respectively. Both conditions are associated with increased morbidity for elderly people, and this requires necessary interventions. They share many common risk factors; among these, vitamin D (VD) deficiency appears to have a role. VD is involved in either disease with many mechanisms, among which immunomodulation. VD deficiency has been linked to OP because it inhibits the body's capacity to absorb calcium and maintain optimal bone health. Available evidence suggests that proper vitaminosis D also appears to be vital in preventing skin age-related issues. DP is often seen in elderly individuals, particularly those with long-term sun exposure and a history of chronic sun damage. VD deficiency can be linked to DP, since its involvement in collagen production, epidermal barrier function, inflammation regulation, wound healing, and sun protection. Aim of this review is to summarize the most updated existing evidence on the role of VD in the development of fragility syndromes such as DP and OP and the possible benefits of VD supplementation as a simple and harmful weapon against aging.

Long-Term Safety of Growth Hormone Deficiency Treatment in Cancer and Sellar Tumors Adult Survivors: Is There a Role of GH Therapy on the Neoplastic Risk?

Experimental studies support the hypothesis that GH/IGF-1 status may influence neoplastic tissue growth. Epidemiological studies suggest a link between GH/IGF-1 status and cancer risk. However, several studies regarding GH replacement safety in childhood cancer survivors do not show a prevalence excess of de novo cancers, and several reports on children and adults treated with GH have not shown an increase in observed cancer risk in these patients. The aim of this review is to provide an at-a-glance overview and the state of the art of long-term effects of GH replacement on neoplastic risk in adults with growth hormone deficiency who have survived cancer and sellar tumors.

Severe impact of late diagnosis of congenital adrenal hyperplasia on gender identity, sexual orientation and function: case report and review of the literature.

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) represents the most frequent form of CAH and of 46, XX disorder of sex development in female newborns. In the majority of cases, particularly in developed countries, female patients suffering from the classic forms of CAH reach the diagnosis at birth or in the early childhood, allowing a prompt treatment with a correct gender assignment. The current manuscript describes an unusual case of an Italian 46-year-old woman, homeborn in the 60s, receiving an extraordinarily late diagnosis of simple virilising classic form of CAH due to 21-OHD, determining a relevant impairment of both physical and psychosexual development. The patient presented primary amenorrhea, height under target, overweight with visceral adiposity, hypercholesterolemia and insulin resistance, hirsutism with a typical male-pattern hair growth, external genital ambiguity, and a severe impairment in the entire series of psychological dimensions, particularly severe depressive symptoms, together with gender dysphoria relative to the female gender assigned at birth, cross-gender behaviours, and body image discomfort, which were associated with homosexual orientation, and sexual dysfunction. Following diagnosis and glucocorticoid (GC) replacement therapy, the hyperandrogenism control and familial and socio-cultural factors changes, particularly, living alone and the interruption of social isolation, were accompanied by menarche appearance, improvement in hirsutism and metabolic profile, and a resolution in all psychological dimensions, depressive symptoms, and gender dysphoria. The patient began to perceive homosexual orientation without discomfort, and ameliorating sexual function. Few cases of female patients with CAH due to 21-OHD receiving an extremely delayed diagnosis have been published. However, to the best of our knowledge, this is the first case including a complete psychosexual assessment at diagnosis with a detailed re-evaluation after 5 years of disease treatment.

Craniopharyngioma and Metabolic Syndrome: A 5-Year Follow-Up Single-Center Experience.

Patients with craniopharyngioma often have comorbidities, such as obesity and hypopituitarism. These two conditions affect each other and worsen the quality of life of patients, which lead to a higher risk of morbidity and mortality. In addition, abdominal obesity, measured as waist circumference (WC), is together with other parameters [arterial hypertension, hyperglycemia, hypertriglyceridemia, and reduced levels of high-density lipoprotein (HDL) cholesterol], one of the components of metabolic syndrome (MS). Each one of these morbidities occurs in patients with craniopharyngioma more frequently than in the remaining population. On these bases, we evaluated metabolic parameters in patients with craniopharyngioma at the time of diagnosis and after a 5-year follow-up, which compares these data with those of age-, gender-, WC-, and body mass index (BMI)-matched controls. In addition, we evaluated the prevalence of MS according to IDF criteria (MS-IDF) and the prevalence of MS according to ATP III (MS-ATPIII) criteria in patients and controls at baseline and after 5 years. We recruited 20 patients with craniopharyngioma (age 38.5 ± 15 years, 10 M) and 20 age-, gender-, WC- and BMI-matched controls (age 34.16 ± 13.19 years, 10 M). In all patients and controls, we evaluated the following: anthropometric features [height, weight, BMI, WC, hip circumference (HC) and waist-to-hip ratio (WHR)], systolic blood pressure (SBP) and diastolic blood pressure (DBP), lipid profile [total cholesterol (TC), HDL, low-density lipoprotein (LDL) cholesterol, triglycerides (TG)], and blood glucose at baseline and after 5 years. The prevalence of MS, according to IDF and ATPIII criteria, was calculated in the two groups at baseline and after 5 years. According to our results, at baseline, patients with craniopharyngioma had a worse metabolic profile than controls and a higher prevalence of MS. Besides, at a 5-year follow-up, patients still had impaired metabolic characteristics and more frequent MS (according to IDF and ATPIII criteria) when compared to controls. These data confirm that MS in patients with craniopharyngioma is unresponsive to life-changing interventions and to a common pharmacological approach. Other factors may be involved in the evolution of these conditions; so, further studies are needed to establish the correct management of these patients.

Multidisciplinary management of osteoporotic vertebral fractures.

Vertebral fractures represent the most frequent complication associated with osteoporosis. Patients harboring a vertebral fracture complain physical impairment including low back pain and spine balance alteration, i.e., kyphosis, leading to subsequent systemic complication, with an increase in morbidity and mortality risk. Different strategies are available in the management of osteoporotic vertebral fractures: medical therapy acts as a prevention strategy while surgical vertebral augmentation procedures, when correctly indicated, aim to reduce pain and to restore the physiological vertebral height. Considering the growing prevalence and incidence of this condition and its socio-economic burden, prevention, diagnosis and treatment of osteoporotic vertebral fractures are of utmost importance. Our aim is to review the current strategies for the management of osteoporotic vertebral fractures providing an integrated multidisciplinary endocrinological, radiological and neurosurgical point of view.

Vitamin D deficiency and tumor aggressiveness in gastroenteropancreatic neuroendocrine tumors.

PURPOSE: Data regarding vitamin D status in patients affected by gastroenteropancreatic (GEP) neuroendocrine tumor (NET) are limited and often showing contrasting results. The aim of the study was to evaluate the incidence of vitamin D deficiency (<20 ng/mL) in GEP-NET patients and compare the 25-hydroxyvitamin D (25(OH)D) levels with clinicopathological parameters and clinical outcome. METHODS: A retrospective cross-sectional study including 75 low grade (G1-G2) GEP-NETs and 123 healthy controls matched for age, sex, and body mass index, was performed. RESULTS: GEP-NET patients had significantly lower 25(OH)D levels compared to controls (17.9 ± 7.8 vs 24.2 ± 7.7 ng/mL, p < 0.0001). Ileal NETs were associated to lower 25(OH)D levels compared to other primary tumor sites (p = 0.049) and small bowel resection posed a significant increased risk of severe vitamin D deficiency (OR = 2.81, 95% CI = 1.25-3.37, p = 0.018). No correlation with somatostatin analogs treatment was found. 25(OH)D levels were significantly lower in G2 compared to G1 GEP-NETs (15.6 ± 7.8 vs 19.9 ± 7.4 ng/mL, p = 0.016) and in patients with progressive disease (12.6 ± 5.7 ng/mL) compared to those with stable disease (mean 21.5 ± 8.2 ng/mL, p = 0.001) or tumor free after surgery (19.6 ± 7.3 ng/mL, p = 0.002). Patients with vitamin D deficiency and insufficiency had shorter progression-free survival compared to those with sufficiency (p = 0.014), whereas no correlation was found with disease-specific survival. CONCLUSIONS: Vitamin D deficiency is highly prevalent among GEP-NETs and could be associated with high tumor grade and disease progression. Therefore, the monitoring of 25(OH)D levels is relevant in these patients and vitamin D supplementation should be considered in the management of GEP-NET patients with vitamin D deficiency or insufficiency.

Craniopharyngioma, Chronotypes and Metabolic Risk Profile.

AIM: To investigate the potential association among Craniopharyngioma (CP), chronotypes and metabolic risk profile. SUBJECTS AND METHODS: The study population included 28 patients (46.4% males; 42.6 ± 15.8 years) and 28 controls, age, gender and BMI matched (46.4% males; 46.5 ± 12.9 years). In this study sample, we evaluated: anthropometric measurements (waist circumference, WC; BMI), plasma glucose, lipid profile, and systolic (SBP) and diastolic (DBP) blood pressure. Morningness-Eveningness was measured with the Horne-Ostberg Morningness-Eveningness Questionnaire (MEQ), which included 19 questions about preferred sleep time and daily performance. RESULTS: in both patients and controls grade I obesity was detected in 15 subjects (53.6%), grade II obesity in 13 subjects (46.4%). In the patient group, the mean score of chronotype was 47.8 ± 12.6. In particular, 9 patients (32.1%) exhibited the morning chronotype, 6 (21.4%) the intermediate chronotype and 13 (46.4.%) the evening chronotype. No significant difference was found in gender and age among the chronotype categories. Patients with the evening chronotype had higher blood pressure values and worse metabolic parameters than those with the morning chronotype. In the control group, the mean score of the chronotype was 57.6 ± 9.5. In particular, 16 (57.1%) subjects exhibited the morning chronotype, 10 (35.7%) the intermediate chronotype and only 2 (7.1.%) the evening chronotype. The prevalence of intermediate and evening chronotypes was higher in females than males (p = 0.021), while males have a higher prevalence of the morning chronotype. Subjects with intermediate and evening chronotypes had worse metabolic parameters than those with the morning chronotype. In patients, the chronotype score was inversely correlated to WC, BMI, SBP, DBP, plasma glucose, total cholesterol, triglycerides, LDL cholesterol and positively correlated with HDL cholesterol. No correlation was found between age and chronotype. In controls, the chronotype score was inversely correlated to WC, BMI, plasma glucose, total cholesterol, LDL cholesterol. No correlation was found among chronotype and age, blood pressure, triglycerides, HDL cholesterol. Considering the whole population of the study (patients and controls), at logistic regression the chronotype score was significantly associated with the presence of CP. CONCLUSIONS: for the first time thus far, our study puts the light on the association of the CP with chronotypes and metabolic alterations in this disease, which are the main determinants of the reduced quality of life, higher morbidity and mortality in this setting of patients. This finding suggests that alterations of chronotype might represent an adjunctive risk for CP patients and a possible target for their integrate management.

Magnetic resonance imaging is a valuable tool to evaluate the therapeutic efficacy of burosumab in children with X-linked hypophosphatemia.

PURPOSE: To examine the MRI diagnostic performance in the assessment of therapeutic response to burosumab in children with X-linked hypophosphatemia (XLH). DESIGN: Prospective longitudinal open cohort. PATIENTS: Seventeen children with XLH, average age of 10.2 ± 2.7 years, had a knee MRI at baseline and after 1 year of burosumab. INTERVENTION: Children received burosumab at an average dose of 1.4 ± 0.5 mg/kg during 1 year for the treatment of severe rickets (the target serum phosphate ≥ 1.2 mmol/L (≥3.7 mg/dL). The primary endpoint was the change from baseline to 12 months in rachitic lesions on knee MRI. Secondary endpoints were changes in biochemical parameters of phosphate and alkaline phosphatase (ALP). RESULTS: One year of treatment with burosumab significantly reduced radiological disease activity on knee MRI (by 44 ± 29% in the transverse extent of widening) which was accompanied by a significant reduction in biochemical activity, namely in serum ALP activity, by 28 ± 17%. Additionally, MRI parameters after 1 year of treatment with burosumab (the maximum width of medial physis at 12 months and the change from baseline in the maximum width of lateral physis) were associated with ALP activity at 12 months. CONCLUSION: We suggest that MRI is a valuable and quantitative tool to evaluate the therapeutic response to burosumab. MRI could be an excellent alternative to standard bone radiographs for evaluation of the rachitic lesions in a clinical setting avoiding repeated exposition to ionizing radiation.

Impact of Long-Term Growth Hormone Replacement Therapy on Metabolic and Cardiovascular Parameters in Adult Growth Hormone Deficiency: Comparison Between Adult and Elderly Patients.

Growth hormone deficiency (GHD) in adults is due to a reduced growth hormone (GH) secretion by the anterior pituitary gland which leads to a well-known syndrome characterized by decreased cognitive function and quality of life (QoL), decreased bone mineral density (BMD), increased central adiposity with a reduction in lean body mass, decreased exercise tolerance, hyperlipidemia and increased predisposition to atherogenesis. Considering some similar features between aging and GHD, it was thought that the relative GH insufficiency of the elderly person could make an important contribution to the fragility of elderly. GH stimulation tests are able to differentiate GHD in elderly patients (EGHD) from the physiological reduction of GH secretion that occurs with aging. Although there is no evidence that rhGH replacement therapy increases the risk of developing Diabetes Mellitus (DM), reducing insulin sensitivity and inducing cardiac hypertrophy, long-term monitoring is, however, also mandatory in terms of glucose metabolism and cardiovascular measurements. In our experience comparing the impact of seven years of rhGH treatment on metabolic and cardiovascular parameters in GHD patients divided in two groups [adult (AGHD) and elderly (EGHD) GHD patients], effects on body composition are evident especially in AGHD, but not in EGHD patients. The improvements in lipid profile were sustained in all groups of patients, and they had a lower prevalence of dyslipidemia than the general population. The effects on glucose metabolism were conflicting, but approximately unchanged. The risk of DM type 2 is, however, probably increased in obese GHD adults with impaired glucose homeostasis at baseline, but the prevalence of DM in GHD is like that of the general population. The increases in glucose levels, BMI, and SBP in GHD negatively affected the prevalence of Metabolic Syndrome (MS) in the long term, especially in AGHD patients. Our results are in accordance to other long-term studies in which the effects on body composition and lipid profile are prominent.

Treatment of Paget's disease of the bone: long-term effect of neridronate in a real-life setting.

BACKGROUND: Bisphosphonates represent the gold standard treatment for Paget's disease of bone. Neridronate is a potent bisphosphonate, licensed in Italy for this use, but only few clinical trials have investigated the outcomes of this treatment. The aim of our study was to report our long-term experience with intravenous Neridronate. METHODS: This is a 48 months observational, descriptive and prospective study on patients with active Paget's disease of bone treated with intravenous Neridronate. Patients underwent laboratory tests (total alkaline phosphatase (ALP), calcium, phosphate, 25 OH Hydroxivitamin D, serum protein electrophoresis, parathyroid hormone) at the time of diagnosis and every 6 months. In all subjects, mutations in the SQSTM1 and ZNF687 genes were searched. The primary endpoint was the treatment efficacy in term of rate of therapeutic response at 48 months (normalization of ALP levels or a reduction of at least 75% in total ALP excess). RESULTS: Fifteen patients (10 female, mean age 70.3 years) were enrolled at our division from 2016 to 2020. One was positive for the ZNF687 gene mutation. After 48-month follow-up, the therapeutic response was maintained in 80% of patients treated with intravenous neridronate. ALP values were higher at 48 months than at 6 months, but this difference was not clinically relevant because the percentage of subjects who maintained a therapeutic response at 48 months was not significantly different from that observed at 6 months (80% vs. 86.6%, P=0.62). One patient had a biochemical relapse, and was retreated with the same therapeutic regimen, achieving a good response. CONCLUSIONS: Treatment with intravenous neridronate is effective in inducing and maintaining sustained remission in patients with PDB for at least 48 months. Administration in single intravenous infusion may improve long-term compliance compared to oral formulations.

Papillary thyroid carcinoma arising in ectopic thyroid tissue within sternocleidomastoid muscle: a review of current literature.

The prevalence of ectopic thyroid tissue as consequence of an aberrant migration of thyroid during embryogenesis ranges up to 10% in autopsy studies. The differential diagnosis between the relatively rare occurrence of a primary carcinoma arising in ectopic thyroid tissue and the more frequent presence of cervical lymph node metastasis from papillary thyroid carcinoma (PTC) might represent a difficult challenge in the clinical practice. The clinical relevance of these lesions lies in their risk of hidden primary thyroid cancer. Our intention is to provide in this review the current limited data available and to report an unusual localization of primary PTC arising from an extra-thyroid area, responsible for a solitary cervical mass as initial manifestation. The tumor developed in an ectopic thyroid tissue embedded within the clavicular head of the sternocleidomastoid muscle and was completely separated from the thyroid. Surgical excision of ectopic thyroid tissue with clavicular head of sternocleidomastoid muscle along with total thyroidectomy and central and selective lateral neck dissection were carried out. Histopathology was diagnostic for ectopic PTC and no primary lesions in the thyroid gland neither metastatic lymph nodes were found. Tumor cells were positive for thyroid transcription factor-1and thyroglobulin, and negative for CD56. A postoperative adjuvant radioiodine ablation was given after recombinant human thyroid-stimulating hormone (TSH) stimulation and the post-treatment whole body scan was negative. After the evaluation at six months showing negative neck ultrasound and undetectable thyroglobulin levels, while TSH suppressed and after recombinant human TSH stimulation, the patient was re-evaluated every six months. At two years, the patient remained completely free of disease and is currently on substitutive dose of l-thyroxine. Endocrinologists and neck surgeons must be aware of the rare possibility of primary PTC arising from ectopic thyroid tissue within the sternocleidomastoid muscle.

Treatment of Acromegalic Osteopathy in Real-life Clinical Practice: The BAAC (Bone Active Drugs in Acromegaly) Study.

BACKGROUND: Vertebral fractures (VFs) are a frequent complication of acromegaly, but no studies have been so far published on effectiveness of antiosteoporotic drugs in this clinical setting. OBJECTIVE: To evaluate whether in real-life clinical practice bone active drugs may reduce the risk of VFs in patients with active or controlled acromegaly. STUDY DESIGN: Retrospective, longitudinal study including 9 tertiary care endocrine units. PATIENTS AND METHODS: Two hundred and forty-eight patients with acromegaly (104 males; mean age 56.00 ±â€…13.60 years) were evaluated for prevalent and incident VFs by quantitative morphometric approach. Bone active agents were used in 52 patients (20.97%) and the median period of follow-up was 48 months (range 12-132). RESULTS: During the follow-up, 65 patients (26.21%) developed incident VFs in relationship with pre-existing VFs (odds ratio [OR] 3.75; P < .001), duration of active acromegaly (OR 1.01; P = .04), active acromegaly at the study entry (OR 2.48; P = .007), and treated hypoadrenalism (OR 2.50; P = .005). In the entire population, treatment with bone active drugs did not have a significant effect on incident VFs (P = .82). However, in a sensitive analysis restricted to patients with active acromegaly at study entry (111 cases), treatment with bone active drugs was associated with a lower risk of incident VFs (OR 0.11; P = .004), independently of prevalent VFs (OR 7.65; P < .001) and treated hypoadrenalism (OR 3.86; P = .007). CONCLUSIONS: Bone active drugs may prevent VFs in patients with active acromegaly.

The Sun's Vitamin in Adult Patients Affected by Prader-Willi Syndrome.

Prader-Willi syndrome (PWS) is a genetic disorder characterized by hyperphagia with progressive, severe obesity, and an increased risk of obesity-related comorbidities in adult life. Although low dietary vitamin D intake and low 25-hydroxy vitamin D (25OHD) levels are commonly reported in PWS in the context of bone metabolism, the association of low 25OHD levels with fat mass has not been extensively evaluated in PWS adults. The aims of this study were to investigate the following in PWS adults: (1) 25OHD levels and the dietary vitamin D intake; (2) associations among 25OHD levels with anthropometric measurements and fat mass; (3) specific cut-off values for body mass index (BMI) and fat mass predictive of the 25OHD levels. In this cross-sectional, single-center study we enrolled 30 participants, 15 PWS adults (age 19-41 years and 40% males) and 15 control subjects matched by age, sex, and BMI from the same geographical area (latitude 40° 49' N; elevation 17 m). Fat mass was assessed using a bioelectrical impedance analysis (BIA) phase-sensitive system. The 25OHD levels were determined by a direct competitive chemiluminescence immunoassay. Dietary vitamin D intake data was collected by three-day food records. The 25OHD levels in the PWS adults were constantly lower across all categories of BMI and fat mass compared with their obese counterpart. The 25OHD levels were negatively associated with BMI (p = 0.04), waist circumference (p = 0.03), fat mass (p = 0.04), and dietary vitamin D intake (p < 0.001). During multiple regression analysis, dietary vitamin D intake was entered at the first step (p < 0.001), thus explaining 84% of 25OHD level variability. The threshold values of BMI and fat mass predicting the lowest decrease in the 25OHD levels were found at BMI ≥ 42 kg/m2 (p = 0.01) and fat mass ≥ 42 Kg (p = 0.003). In conclusion, our data indicate that: (i) 25OHD levels and dietary vitamin D intake were lower in PWS adults than in the control, independent of body fat differences; (ii) 25OHD levels were inversely associated with BMI, waist circumference, and fat mass, but low dietary vitamin D intake was the major determinant of low vitamin D status in these patients; (iii) sample-specific cut-off values of BMI and fat mass might help to predict risks of the lowest 25OHD level decreases in PWS adults. The presence of trained nutritionists in the integrated care teams of PWS adults is strongly suggested in order to provide an accurate nutritional assessment and tailored vitamin D supplementations.

Bone metabolism, bone mass and structural integrity profile in professional male football players.

BACKGROUND: Physical exercise plays an important role in bone mineralization as well as factors involved in bone metabolism influence the athletic performance. In European countries, soccer is the most popular sport. The aim of the study was to investigate bone metabolism, bone mass and structural integrity profile in professional male adult football players. METHODS: Sixteen professional male football players from a single team of the Second division Italian League (mean age 22.4±0.7 years) were enrolled. Bone biochemical parameters, including serum calcium, phosphorus, albumin, creatinine, alkaline phosphatase, intact plasma PTH, 25-hydroxy-vitamin D (25-OHD), 24-h urinary calcium and phosphorus, and calcaneal quantitative ultrasound (QUS), were evaluated at the beginning (October 2012) and at the end of the League (May 2013). RESULTS: 25-OHD levels were significantly lower at the end of the League compared to the beginning (27.1±5.9 vs. 36.6±9.5 ng/mL, fold change [FC]=0.25, P=0.008), and the prevalence of 25-OHD deficiency increased from 25% to 73%. Moreover, higher rate of previous bone, cartilage or ligament injuries correlated with 25-OHD deficiencies (P=0.014). T-score and Z-score were at the upper limits of the normality ranges, without significant difference between the beginning and end of the League. Phosphaturia was slightly decreased at the end of the League (691.0±364.5 vs. 934.0±274.3 mg/24h, FC=0.26, P=0.06). A significant correlation was found between phosphaturia and BQI (R2=0.28, P=0.03), and both T-s and Z-s (R2=0.28, P=0.03) at the beginning of the League. CONCLUSIONS: With this pilot study, we demonstrated that vitamin D status significantly worsened at the end of the League. Therefore, vitamin D supplementation might be suggested in adult football players in order to prevent vitamin D deficiency and improve the athletic performance.

Vitamin D and Sleep Regulation: Is there a Role for Vitamin D?

BACKGROUND: Vitamin D exerts multiple pleiotropic effects beyond its role in calcium-phosphate metabolism. Growing evidence suggests an association between hypovitaminosis D and sleep disorders, thus increasing the interest in the role of this vitamin in the regulatory mechanisms of the sleep-wake cycle. OBJECTIVE: The study aimed to explore and summarize the current knowledge about the role of vitamin D in sleep regulation and the impact of vitamin D deficiency on sleep disorders. METHODS: The main regulatory mechanisms of vitamin D on sleep are explained in this study. The literature was scanned to identify clinical trials and correlation studies showing an association between vitamin D deficiency and sleep disorders. RESULTS: Vitamin D receptors and the enzymes that control their activation and degradation are expressed in several areas of the brain involved in sleep regulation. Vitamin D is also involved in the pathways of production of Melatonin, the hormone involved in the regulation of human circadian rhythms and sleep. Furthermore, vitamin D can affect sleep indirectly through non-specific pain disorders, correlated with alterations in sleep quality, such as restless legs syndrome and obstructive sleep apnea syndrome. CONCLUSION: Vitamin D has both a direct and an indirect role in the regulation of sleep. Although vitamin D deficiency has been associated to sleep disorders, there is still scant evidence to concretely support the role of vitamin D supplementation in the prevention or treatment of sleep disturbances; indeed, more intervention studies are needed to better clarify these aspects.

Increased prevalence of overweight and obesity in children with X-linked hypophosphatemia.

BACKGROUND/AIM: X-linked hypophosphatemia (XLH) is a rare disease characterized by low phosphate levels. Scientific evidence points to a link between hypophosphatemia and obesity in general population. The aim of our longitudinal observational study was to investigate the prevalence of obesity and associated factors in a large cohort of children with XLH. PATIENTS/METHODS: We studied 172 XLH-children 5-20 years of age (113 girls/59 boys). Anthropometric parameters (weight, height, and BMI) were collected at birth and during follow-up at mean ages of 5.3, 8.2, 11.3, and 15.9 years (groups 1, 2, 3, and 4, respectively). In each group, subjects were classified based on International Obesity Taskforce (IOTF) cut off values of BMI for age and sex as overweight or obese (IOTF 25-30 or ≥30 kg/m2, respectively). RESULTS: In each age-group, almost 1/3 of XLH-patients were classified as overweight or obese (29.4, 28.7, 27.5, and 36.7% in groups 1, 2, 3, and 4, respectively). Children without a XLH-family history had higher BMI-IOTF at every point of follow-up, compared to those with positive XLH-family history. Similarly, higher BMI-IOTF was significantly associated with treatment duration (23.3 ± 4.4 vs 23.8 ± 3.8 vs 25.2 ± 4.5 kg/m2, for subjects with treatment duration of <5, 5-10 and >10 years, respectively, P for trend = 0.025). Multiple regression analysis confirmed an association of treatment duration and lack of XLH-family history with higher BMI-IOTF. CONCLUSION: One out of three of XLH-children have phenotypically unfavourable metabolic profile expressed as increased prevalence of overweight or obesity in comparison to general population. Both the lack of XLH family history and the duration of treatment increase the risk of higher BMI-IOTF. BMI should be carefully monitored in children, and later in adults, with XLH.

Somatotropic Axis and Obesity: Is There Any Role for the Mediterranean Diet?

Obesity is associated with reduced spontaneous and stimulated growth hormone (GH) secretion and basal insulin-like growth factor I (IGF-1) levels-which in turn is associated with increased prevalence of cardiovascular risk factors. The aim of this study was to investigate: (1) the association of somatotropic axis with cardiometabolic status; (2) the association of somatotropic axis with the Mediterranean diet and nutritional pattern in people with obesity. Cross-sectional observational study was carried out in 200 adult women, aged 36.98 ± 11.10 years with severe obesity (body mass index-BMI of 45.19 ± 6.30 kg/m2). The adherence to the Mediterranean diet and the total calorie intake was assessed. Anthropometric measurements, body composition and biochemical profile were determined along with Growth Hormone (GH)/Insulin like Growth Factor 1 (IGF-1) axis and insulin resistance (homeostatic model assessment for insulin resistance-HoMA-IR). The enrolled subjects were compared after being divided according to GH peak response and according to IGF-1 standard deviation scores (SDS). Derangements of GH peak were detected in 61.5% of studied patients while IGF-1 deficiency was detected in 71% of the population. Both blunted GH peak response and IGF-1 SDS were indicators of derangements of somatotropic axis and were associated with comparable results in terms of cardiometabolic sequelae. Both GH peak and IGF-1 levels were inversely associated with anthropometric and metabolic parameters. The adherence to the Mediterranean diet predicts GH peak response. Fatty liver index (FLI), fat mass (FM) and phase angle (PhA) were predictive factors of GH peak response as well. In conclusion derangements of somatotropic axis is associated with a worse cardiometabolic profile in people with obesity. A high adherence to the Mediterranean diet-and in particular protein intake-was associated with a better GH status.

Phase Angle: A Possible Biomarker to Quantify Inflammation in Subjects with Obesity and 25(OH)D Deficiency.

Obesity is associated to chronic low-grade metabolic inflammation and hypovitaminosis D. Among extra-skeletal effects, an important role in inflammation has been described for vitamin D (25(OH)D). Phase angle (PhA) is a bioelectrical impedance analysis (BIA) parameter that represents an indicator of cellular health in chronic inflammatory states. However, it is still unknown whether a low 25(OH)D levels might correlate with PhA in obesity. Considering the lack of evidence correlating the 25(OH)D levels with PhA in obesity, the aim of this study was to investigate their possible relationship in a group of patients with obesity stratified according to body mass index (BMI) categories. Four hundred and fifty-five adult subjects (219 males and 236 females; 36 ± 11 years) were enrolled. Body composition, including PhA, was assessed using a BIA phase-sensitive system. Serum levels of 25(OH)D was determined by a direct competitive chemiluminescence immunoassay. Most of the participants were affected by grade III obesity (24%) and had 25(OH)D deficiency (67%). Subjects with 25(OH)D deficiency had highest BMI (p < 0.001). Stratifying the sample population according to the BMI classes, 25(OH)D levels decreased significantly along with the increase in BMI (p < 0.001), with the lowest 25(OH)D levels in the class III obesity. In addition, stratifying the sample population according to 25(OH)D categories, BMI and fat mass (FM) decreased, while PhA increased significantly along with the 25(OH)D categories (p < 0.001). The 25(OH)D levels showed significant positive associations with PhA (r = -0.59, p < 0.001), and this association remained significant also after adjusting for BMI and FM (r = 0.60, p < 0.001). The lowest values of PhA were significantly associated with the severity of obesity (OR 0.3, p < 0.001) and of 25(OH)D deficiency (OR 0.2, p < 0.001). To compare the relative predictive power of body composition parameters associated with the 25(OH)D levels, we performed a multiple linear regression analysis. The most sensitive and specific cut-off for 25(OH)D levels to predict the PhA above the median was >14 ng/mL (p < 0.001). In conclusion, we provided preliminary insights into a novel link between 25(OH)D levels and PhA in the setting of obesity. This association uncovered a new potential usefulness of PhA as expression of cell membrane integrity and predictor of inflammation in low 25(OH)D status that might help in identifying high-risk patients with obesity who could benefit from careful 25(OH)D supplementation.

Acromegaly and Heart Failure.

In patients with acromegaly, chronic GH and IGF-I excess commonly causes a specific cardiomyopathy characterized by a concentric cardiac hypertrophy associated with diastolic dysfunction and, in later stages, with systolic dysfunction ending in heart failure in untreated and uncontrolled patients. Additional relevant cardiovascular complications are represented by arterial hypertension, valvulopathies, arrhythmias, and vascular endothelial dysfunction, which, together with the respiratory and metabolic complications, contribute to the development of cardiac disease and the increase cardiovascular risk in acromegaly. Disease duration plays a pivotal role in the determination of acromegalic cardiomyopathy. The main functional disturbance in acromegalic cardiomyopathy is the diastolic dysfunction, observed in 11% to 58% of patients, it is usually mild, without clinical consequence, and the progression to systolic dysfunction is generally uncommon, not seen or observed in less than 3% of the patients. Consequently, the presence of overt CHF is rare in acromegaly, ranging between 1 and 4%, in patients with untreated and uncontrolled disease. Control of acromegaly, induced by either pituitary surgery or medical therapy improves cardiac structure and performance, limiting the progression of acromegaly cardiomyopathy to CHF. However, when CHF is associated with dilative cardiomyopathy, it is generally not reversible, despite the treatment of the acromegaly.

Calcium and Vitamin D Supplementation. Myths and Realities with Regard to Cardiovascular Risk.

Vitamin D and calcium are considered crucial for the treatment of bone diseases. Both vitamin D and calcium contribute to bone homeostasis but also preserve muscle health by reducing the risk of falls and fractures. Low vitamin D concentrations result in secondary hyperparathyroidism and contribute to bone loss, although the development of secondary hyperparathyroidism varies, even in patients with severe vitamin D deficiency. Findings from observational studies have shown controversial results regarding the association between bone mineral density and vitamin D/calcium status, thus sparking a debate regarding optimum concentrations of 25-hydroxyvitamin D and calcium for the best possible skeletal health. Although most of the intervention studies reported a positive effect of supplementation with calcium and vitamin D on bone in patients with osteoporosis, this therapeutic approach has been a matter of debate regarding potential side effects on the cardiovascular (CV) system. Thus, the aim of this review is to consider the current evidence on the physiological role of vitamin D and calcium on bone and muscle health. Moreover, we provide an overview on observational and interventional studies that investigate the effect of vitamin D and calcium supplementation on bone health, also taking into account the possible CV side-effects. We also provide molecular insights on the effect of calcium plus vitamin D on the CV system.