ACTA ENDOCRINOLOGICA (BUC)

Context. Primary hyperparathyroidism (PHPT) is often associated with thyroid disorders like nodular goiter, Hashimoto’s thyroiditis (HT) and Graves’ disease. Objective. Our aim was to explore whether the coexistence with HT affects bone metabolism in patients with PHPT. Design. This was a comparative cross-sectional study carried out in a tertiary inpatient endocrine center from January 2018 through December 2020. Subjects and Methods. A total of 234 patients were diagnosed with PHPT at our endocrine center. One hundred of them were included in the study - 50 with PHPT only and 50 with PHPT and HT. Two control groups were defined: 37 with HT and 37 without PHPT and HT. Serum markers of calcium-phosphate metabolism, bone markers (RANKL, Osteoprotegerin, β-CTX, Osteocalcin) and interleukin-17A were measured. Results. The frequency of HT among patients with PHPT was 37.6% (95% CI 31-43%) and did not differ significantly from that in the general population, 32.5% (95% CI 30-35%). Age, BMI, markers of calciumphosphate metabolism, bone markers and interleukin-17A weren’t significantly different in PHPT with and without HT or between the two control groups. The participants with PHPT had higher levels of interleukin-17A, β-CTX and Osteocalcin (p<0.05) than those without the PHPT. RANKL and Osteoprotegerin in these groups did not differ. Interleukin-17A correlated positively with serum calcium, PTH and RANKL and negatively with serum inorganic phosphate and 25(OH)D. Controlling for HT and age did not change the correlation. Conclusions. In our study, HT has not additional effect on bone metabolism in the patients with PHPT. Higher levels of interleukin-17A in PHPT suggest a possible role in the PTH-induced bone remodeling.

Context. Endothelial dysfunction and diabetic cardiomyopathy are critical complications of diabetes. Gallic acid (GA) plays a significant role in cardiovascular disorders resulted from diabetes. In addition, increased plasma miR-24, miR-126 associated with endothelial dysfunction. Aim. The current study was designed to assess the effects of GA on plasma miR-24, miR-126 levels in the diabetic rats. Animals and Methods. Adult male Sprague-Dawley rats were divided into three groups (n=8): control (C), diabetic (D) and diabetic group treated with GA (D+G, 25 mg/kg, by gavage) for eight weeks. The blood glucose level, body weight, lipid profile, blood pressure, plasma miR-24 and miR-126 levels, antioxidant and inflammatory biomarkers were measured. Results. The plasma levels of miR-24, miR-126, body weight, high-density lipoprotein cholesterol (HDL-c), total anti-oxidant capacity (TAC) and the systolic blood pressure significantly reduced and blood glucose, total cholesterol (TC), triglycerides (TG), very low-density lipoprotein cholesterol (VLDL-c), malondialdehyde (MDA), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and low-density lipoprotein cholesterol (LDL-c) significantly elevated among the diabetic rats compared with the control group. However, GA restored body weight, blood pressure, TC, TG, VLDL-c, TNF-α, miR- 126, blood glucose, HDL-c, MDA, TAC, miR-24 and IL-6 among the GA treated rats compared with the diabetic group. Conclusion. GA improves inflammation, oxidative stress and hypotension result from diabetes. These protective effects are probably mediated via increasing plasma miR-24 and miR-126 levels.

Context. Hypothalamic-pituitary-adrenal (HPA) axis irregularities have been described both in bipolar disorder and suicidal behaviour, but few studies have examined the relationship between suicidal behaviours and cortisol levels in bipolar disorder. Objective. We compared HPA axis activity in bipolar I (BPD I) individuals with and without suicidal ideation and behaviour through multiple measurement of serum and salivary cortisol. Design. Cross-sectional, observational study. Subjects and Methods. 75 BPD I patients were assigned into 3 groups (no history of suicidal behaviour, history of suicidal ideation, history of suicide attempt), according to the C-SSRS. Socio-demographical and clinical data was obtained by using MINI 6.0 and a semi-structured questionnaire. Salivary samples were collected using Sarstedt Cortisol Salivette synthetic swab system for two consecutive days at 08:00, 16:00, 23:00 and salivary cortisol concentrations were determined by ELISA technique. A unique 1mg dose of dexamethasone was administered on the first day, at 23:00, after the collection of the saliva sample. Blood was collected on the first day at 8:00 AM and basal morning serum cortisol levels were determined by immunoassay with fluorescence detection. Results. Cortisol parameters in our BPD I sample did not vary significantly in respect to suicidal history. However, patients with a history of suicidal ideation have significantly higher total cortisol outputs than patients with no history of suicidal behaviour in the 18 to 40 age category compared with the above 40 age category. Conclusions. Total cortisol daily output varies significantly in an age-dependent manner in respect to suicidal thoughts in BPD I individuals.

Cinacalcet is used to treat tertiary hyperparathyroidism in renal failure. However, its use in pregnancy and hereditary hypophosphatemic vitamin D resistant rickets (HVDRR) has not been reported. In this study we describe the use of cinacalcet in a case of HVDRR with tertiary hyperparathyroidism diagnosed during pregnancy, in a tertiary care hospital in an academic center. A 29 year old woman with HVDRR was found to have tertiary hyperparathyroidism at week 15 of her second pregnancy: serum calcium 11.4 mg/dL, intact parathyroid hormone 307 pg/mL. Reductions in potassium phosphate and calcitriol were unsuccessful in restoring normocalcemia. Cinacalcet was started to avoid parathyroidectomy and to reduce the risk of hypercalcemia to the mother and fetus. After 10 weeks of treatment, calcium normalized but placental abruption prompted delivery at week 27 of gestation. A healthy live male was born with weight of 964 g and serum calcium of 9.0 mg/dL. After delivery cinacalcet was stopped. Eight months later, calcium was 10.0 mg/dL and intact parathyroid hormone 426 pg/mL. This case demonstrates the successful use of cinacalcet during pregnancy to manage hypercalcemia in a patient with HVDRR and treatment related tertiary hyperparathyroidism.

Introduction. Under physiological conditions, maintenance of skeletal mass is the result of a tightly coupled process of bone formation and bone resorption. Disease states,\r\nosteoporosis included, arise when this delicate balance is disrupted such as in menopause.\r\nThe aim of the present work was to study the effect of leptin supplementation on bone metabolism in ovariectomized adult female rats, by measuring indices of bone biomarkers.\r\nMaterial and methods. Forty adult female albino rats were chosen as an animal model for this study and divided into the four equal groups (n=10/group): Group I (control SHAM-operated group), Group II (ovariectomy group). Group III (alendronate group): Ovariectomized rats that received\r\nalendronate 0.1 mg/kg body weight i.p. daily for eight weeks. Group IV (leptin group): Ovariectomized rats that received leptin (10&#956;g/kg body weight) i.p. daily for eight\r\nweeks. The obtained serum is required for determination of: Serum osteocalcin, alkaline phosphatase, calcium and phosphorus levels.\r\nResults. The obtained data revealed that: Treatment with alendronate or leptin caused significant decrease of serum\r\nosteocalcin, specific bone alkaline phosphatase and urinary deoxypyridinoline levels compared to ovariectomy group.\r\nConclusions. The results obtained in the present study provide evidence that daily administration of leptin contributes significantly to improve the bone biomarkers\r\nof ovariectomy in rats. Leptin prevents ovariectomy induced increases in bone turnover in rats.

Objective. The mechanisms underlying the development of diabetic neuropathic pain (NeP) are still unknown. The aim of the study was to evaluate painful diabetic neuropathy in Type II diabetic patients with Leeds Assessment of Neuropathic Symptoms and Signs Scale (LANSS), thermal and vibratory Quantitative Sensory Testing (QST) and, EMG supported Diabetic Neuropathy Score (DNS) and to evaluate the differences in patients with and without neuropathic pain. Methods. Eighty three Type II diabetic patients (26 males, 57 females) were investigated. Patients with pain were assessed by the LANSS pain scale and a score of ≥12 was classified as NeP. All patients underwent nerve conduction studies (NCS) to obtain EMG supported diabetic neuropathy score (DNS). Cold and warm sensation thresholds and cold pain and heat pain thresholds were obtained for evaluation of A-delta and C type fibers. Vibratory perception thresholds were recorded for evaluation of thickly myelinated fibers. Results. The percentage of NeP (LANSS score ≥12) was 15.7 %. QST revealed significantly lower cold detection, higher warm detection and higher heat pain thresholds at the feet in patients with NeP compared with patients without NeP. Although small fiber dysfunction has been revealed in all patients with NeP, the percentages of the presence of small fiber neuropathy and EMG supported diabetic neuropathy were not significantly different among patients with NeP and without NeP. Conclusions. We concluded that QST is a useful and a noninvasive tool to detect small fiber dysfunction in Type II diabetic patients. QST revealed increased severity of small fiber dysfunction in patients with NeP. Although small fiber neuropathy has been revealed in all Type II diabetic patients with neuropathic pain the absence of pain does not predict preserved small fiber function.

The RET proto-oncogene is the most well-known gene involved in medullary thyroid cancer (MTC). The associations between specific RET mutations and the age of onset and aggressiveness of MTC and the presence or absence of other endocrine neoplasms such as pheochromocytoma or hyperparathyroidism have been well documented. When a new mutation is identified in the RET gene, defining that mutation’s codon-specific risk level is important in the management of patients with MTC. Case Report. Here, we present the first report of a patient with a germline variant of Ala641Thr, in the transmembrane domain of the RET gene. A 37-year-old female presented with an anterior neck mass, which was confirmed to be MTC by biochemical tests and pathologic findings. The patient had no identifiable family history of MTC or multiple endocrine neoplasia syndromes. Histology revealed a single unilateral MTC lesion (21 mm × 16 mm) in the right thyroid lobe without cervical lymph node metastasis. Genetic testing revealed a germline Ala641Thr missense mutation in the RET gene. The RET gene variant was inherited by one of her children. Conclusion. Although this novel variant has unknown clinical significance at present, the causative role of this genetic variant in MTC pathogenesis could be clarified by further molecular structure-function studies and additional clinical cases showing a genotype-phenotype relationship.

Graves&#8217; orbitopathy usually occurs in thyrotoxic patients at the presentation of the\r\nhyperthyroidism.\r\nAim: we conducted a cross sectional study over 8 and a half years of the relation\r\nbetween Graves&#8217; orbitopathy and thyroid status in patients presenting to our joint thyroidophthalmology\r\nclinic at University Hospital of Wales.\r\nMethods: Patients with active orbitopathy were diagnosed clinically and with\r\nappropriate imaging where necessary. This series excluded patients previously treated with\r\nradioiodine or surgery for Graves&#8217; disease. Of 259 patients 140 (54%) had not had 131I or\r\nsurgical therapy. Thirty four percent of the 140 had never been hyperthyroid of whom 19\r\n(13.5%) were euthyroid. Twenty nine of the 140 (20.7%) were hypothyroid receiving\r\nlevothyroxine at referral. There were no significant differences between the hyperthyroid\r\nand non hyperthyroid groups in the incidence of cigarette smoking, family history of thyroid\r\ndisease or maximum proptosis at presentation.\r\nResults: We found a higher prevalence of smokers than reported in the literature in\r\nmoderate and severe TAO across all thyroid status groups including hypothyroid only\r\npatients. This study has emphasized the occurrence of Graves&#8217; orbitopathy in hypothyroid\r\npatients as well as euthyroid individuals.

Objective. Thyroid diseases coexisting with primary hyperparathyroidism (PHPT) may individually change the diagnosis, treatment and follow-up of the patients. In our study, we aimed to investigate the thyroid diseases coexisting with PHPT and the relation between\r\nthese two clinical situations.\r\nMethods. We retrospectively investigated 255 patients who were diagnosed as PHPT between 2004-2009 in our clinic. The general characteristics of the patients, laboratory tests,\r\nwhich were performed preoperatively, neck ultrasonography, thyroid and parathyroid scintigraphy and fine needle aspiration biopsy (FNAB) results were assessed. Cytological\r\nresults of the nodules with preoperative FNAB were compared with the postoperative histological results.\r\nResults. Of the patients, 49 were male (19.2%) and 206 were female (80.8%). Mean age was 54.5?12.8. Bilateral neck exploration (BNE) was performed on 69 cases (27%),\r\nminimal invasive parathyroidectomy (MIP) on 78 cases (30.5%) and BNE plus thyroidectomy on 108 cases (42.5%). When all thyroid diseases were taken into account,\r\nprevalence of the coexisting thyroid disease was 65%, prevalence of nodular thyroid disease 52.1%, thyroid cancer 16.7% and thyroid dysfunction 11.8%. The mean age of the patients with a nodular goitre was significantly higher than of the patients who did not have nodules\r\n(p<0.001). General demographic data, calcium and PTH levels did not show any difference. Number of nodules was correlated with age (p<0.001, r=0.227).\r\nConclusion. The relation between PHPT and nodular thyroid diseases is coincidental and this can be explained by the fact that both diseases occur in advanced age.