Fibromyalgia (FM) is a chronic syndrome with an increasing prevalence, characterized by widespread musculoskeletal pain in combination with a variety of cognitive symptoms and fatigue. A plethora of scientific evidence that has accumulated during the last decades, resulted in a significant improvement of the understanding of the pathophysiology of the disease. However, current therapeutic approaches in patients with FM remains a multidimensional approach including patient education, behavioral therapy, exercise, pain management, and relief of chronic symptoms, rather than the use drug therapies, based on the mechanisms of disease development. Vitamin D, a fat-soluble vitamin derived mainly from skin synthesis through ultraviolet radiation, has been recognized to manifest a plethora of extraskeletal actions, apart from its fundamental role in skeletal and calcium homeostasis, including modulation of cell growth, neuromuscular actions, and potential anti-inflammatory properties. Recent findings indicate that hypovitaminosis D to be highly prevalent in patients with FM. Supplementation studies are limited so far, indicating potential beneficial effects on pain and severity of the disease, however specific recommendations are lacking. This review aims to summarize and critically appraise data regarding the pathophysiological interplay between vitamin D and FM, available results from observational and supplementation studies so far, with a clinical discourse on current knowledge gaps and future research agenda.

Background: Although primary hyperparathyroidism (PHPT) has been associated with diabetes mellitus (DM), the etiological link is not clear and the effect of parathyroidectomy is controversial.The aim of this observational study was to investigate the metabolic link between calciotropic hormones and glucose metabolism in PHPT patients before and after parathyroidectomy. Methods: Twenty-four consecutive patients with PHPT (Group-A) without DM were included in the study. Anthropometric characteristics and medical history were recorded. Fasting plasma glucose (FPG), fasting insulin (FI), calcium, phosphorus, parathyroid hormone (PTH) and 25-hydroxyvitamin-D [25(OH)D] were measured. Homeostasis Model Assessment was used for estimating insulin resistance (HOMA-IR) and β-cell function (HOMA-B). QUICKI index for insulin sensitivity was also calculated. In a subgroup of 13 patients (Group-B) a scheduled curative parathyroidectomy was performed and all measurements were repeated after surgery. In 10 out of 13 a 75 g OGTT was performed before and 6 weeks after surgery to further evaluate glucose response, insulin response and insulin sensitivity using Matsuda Index. SPSS 22 was used for statistical analysis. Results: Group-A had a mean age of 55±10.66 years and the female:male ratio was 19:5. Pearson and Spearman correlation coefficient was used and a statistically significant positive correlation between HOMA-B and PTH (r=0.53, P=0.008) was identified. PTH was also correlated to waist-to-hip ratio (r=0.44, P=0.03) and inversely to FPG/FI ratio (r=−0.40, P=0.056). Linear regression showed a significant linear relation between HOMA-B and PTH (P=0.006), which remained significant when adjusted for age and BMI.When subjects were classified according to their 25(OH)D levels in vitamin D sufficient [25(OH)D ≥20 ng/dl, n=16] and vitamin D insufficient (10<25(OH)D<20 ng/dl, n=8), independent samples t-test showed no significant difference in glucose homeostasis. In Group-B after surgery, calcium and PTH levels normalized and phosphorus increased. T-paired test and Wilcoxon signed rank test were used but no significant alterations were identified in FPG (P=0.56), FI (P=0.73), HOMA-IR (P=0.65), HOMA-B (P=0.53), QUICKI (P=0.90), Matsuda index (P=0.10), BMI (P=0.17).The correlation between HOMA-B and PTH remained significant after surgery (r=0.76, P=0.002). Conclusion: Findings of this small study indicate a correlation independent of vitamin D between PTH and indices of β-cell function and insulin sensitivity, in PHPT patients. This parallel increase of HOMA-B and PTH could be due to insulin resistance or reflect a potential direct action of PTH on β-cell. Larger studies will clarify the mechanisms and explain the inability of parathyroidectomy to reverse this effect.

Introduction: Prevalence of type 2 diabetes mellitus (T2DM) rises rapidly worldwide and most patients with T2DM are obese. All treatment algorithms advocate lifestyle modification and weight loss in combination with various therapeutic categories available for the treatment of T2DM, resulting in diet-antidiabetic drug combinations that are not always proper or safe for the patients. Case presentation: A 73-year-old Caucasian man presented to the emergency department of our hospital with weakness and malaise gradually deteriorating over the previous 3 days, accompanied by anorexia, nausea and vomit tendency over the last 24 hours. He had a previous history of hypertension, diagnosed 15 years ago, currently treated with felodipine and metoprolol. He also had a history of T2DM diagnosed 10 years ago, currently treated with metformin, sitagliptin and dapagliflozin. Despite his poor general condition and his reduced food intake he continued all his medications. The patient was obese, struggling with several weight loss efforts over the last ten years. The week before admission to the hospital he had started an Atkins diet. Physical examination at the time of admission revealed signs of dehydration. Patient vitals were within normal range. His point-of-care blood glucose value was 143 mg/dl. He had moderate tenderness to palpation in the upper abdomen, while the remainder of the clinical examination was normal. On admission serum creatinine and uric acid were increased while the rest of the biochemical tests were normal. Estimated serum osmolality was 308 mOsm/kg. His arterial blood gas showed a pH 7.19, PCO2 of 34 mmHg, PO2 of 103 mmHg, bicarbonate of 13.5 mmol/l and an anion gap of 24 mEq/l. He had increased blood β-hydroxybutyric acid and urine ketones in the urine analysis. The diagnosis of euglycemic diabetic ketoacidosis (euDKA) was established and he was treated with intravenous fluids, glucose and insulin. Conclusions: Sodium-glucose cotransporter-2 (SGLT2) inhibitors lower plasma glucose and favour weight loss by promoting glycosuria and inhibiting glucose reabsorption. Low carbohydrate diets force the body into ketogenesis, causing a state of relative metabolic acidosis even in non-diabetic patients. This case indicates that these diets should be avoided in T2DM patients on SGLT2 inhibitor treatment, since both SGLT2 inhibitors and low carbohydrate diets (such as Atkins diet) can induce ketogenesis or even ketoacidosis in the presence of a triggering factor, reflecting a life-threatening ketogenic combination.

Objective: To report the unusual presentation of a thyrotropinoma in a patient with: i) accelerated bone turnover, evident as osteopenia and increased serum alkaline phosphatase level, and ii) a pericardial effusion, years before diagnosis, that resolved completely following surgery and somatostatin analogue treatment. Case report: A 38-year-old man had been treated for years for presumed hypothyroidism with thyroxine supplementation based on elevated TSH levels before the clinical suspicion of a TSH secreting pituitary adenoma (TSHoma) was raised. During that time period there was a persistent elevation of alkaline phosphatase and associated osteopenia that had been attributed to vitamin D deficiency, although vitamin D supplementation was of no benefit. He concurrently developed a pericardial effusion of no apparent cause despite a comprehensive diagnostic work up and was treated surgically. Recurrence of a pericardial effusion and a pleural effusion developed a few months after initial treatment. At that time thyroxine was discontinued, a pituitary macroadenoma was diagnosed and TSHoma was confirmed by classical biochemical features and an elevated a-glycoprotein subunit. After surgery, due to incomplete resection and persistent although mild elevation of a-glycoprotein subunit, an octreoscan was performed and, based on a positive scan, treatment with octreotide long acting repeatable (LAR) was initiated, to which he had an antitumor and antisecretory response. Shortly after initiation of medical treatment a recession of the pericardial effusion was noted and alkaline phosphatase levels were normalized. Conclusion: Increased bone metabolism due to a hyperthyroid state induced by a TSHoma may be anticipated. However, effusions (pericardial, pleural) have only rarely been reported in combination with hyperthyroidism. To our knowledge this is the first case of a TSHoma accompanied by pericardial and pleural effusions that both dissolved after treatment of the adenoma.

Objective: To report a case of hypogonadism reversal and spontaneous puberty in a craniopharyngioma patient who suffered from hypopituitarism as a result of complete surgical resection. Methods: A 13-year-old boy with hypopituitarism was evaluated for right testicular sensitivity. At the age of 6 the child presented with growth arrest and a craniopharyngioma causing pituitary insufficiency was diagnosed. Treatment with hydrocortisnone and thyroxine supplementation was initiated and he was subjected to a transphenoidal surgery that resulted in complete tumor resection (adamantinoma). Postsurgical biochemical testing confirmed panhypopituitarism and he was prescribed levothyroxine, hydrocortisone and desmopressin supplementation. Recombinant growth hormone was initiated 2 years later since growth had not resumed. Gonadotropins had been undetectable since diagnosis and the last evaluation had confirmed prepubertal status. On clinical examination increased testicular volume was found (10–12 ml) with absence of pubic hair and mild sensitivity was confirmed. The Scrotum ultrasound revealed normal appearing testes with a maximal diameter of 4.5 cm left and 4.1 cm right. Testosterone and adrenal androgen levels were below normal limits but a GnRH stimulation test (2.5 μ/kg) provoked a four fold increase of LH. Onset of puberty was suspected. Results: Six months later, measurement of basal gonadotropins (FSH=1.4 U/L, LH=1.8 U/L), testosterone (98 ng/dl NL 10–572) and inhibin B (216 pg/ml NL 68–300) indicated the onset of puberty that was confirmed by a tenfold increase of LH in the GnRH stimulation test. Conclusions: Recovery of pituitary function in craniopharyngioma patients who had panhypopituitarism both prior and after complete surgical resection of the tumor has only rarely been reported. Nevertheless, this case depicts that one should consider the possibility of a functional gonadal axis prior to steroid supplementation for puberty induction to children suffering from hypopituitarism due to craniopharyngioma diagnosed and treated before the onset of puberty.