ACTA ENDOCRINOLOGICA (BUC)

Background. Heterozygous gain-of-function mutations in the glucokinase (GCK) gene cause hyperinsulinaemic hypoglycaemia (GCK-HI), while lossof- function mutations lead to a monogenic type of diabetes (GCK-MODY). We, herein, report a heterozygous GCK gene mutation in a large family with GCK-MODY and insulinoma in one individual from the same family. Patients and methods. The proband, an 11-yearold male, was referred for asymptomatic mild hyperglycemia (fasting glucose:121 mg/dL) and HbA1c of 6.1%. Segregation analysis of the family revealed multiplex members with asymptomatic fasting hyperglycaemia or non-insulindependent diabetes and 33-year-old maternal uncle of the proband case had a history of distal pancreatectomy due to the diagnosis of insulinoma. His preoperative investigations were revealed fasting glucose of 31 mg/dL, insulin: 7μU/ mL, C-peptide: 2.6 mg/dL, and a low HbA1c(4.0%) which was suggestive for recurring hypoglycaemia episodes. Postpancreatectomy he developed mild fasting hyperglycemia (115-136 mg/dL). Results. Genetic analysis revealed heterozygous p.Ser453Leu(c.1358C> T) mutation in the GCK gene in the proband. In segregation analysis, the identical heterozygous p.Ser453Leu(c.1358C> T) GCK gene mutation was detected in all of the other affected family members for whom a DNA analysis was applicable. The maternal uncle was first diagnosed with insulinoma and underwent a pancreatectomy. He also had an identical mutation in a heterozygous state. Conclusion. We, to the best of our knowledge, firstly identified these two entirely distinct phenotypes of glucose metabolism, GCK-MODY and GCK-HI, due to an identical heterozygous p.Ser453Leu (c.1358C> T) mutation in the GCK. Further studies required to elucidate this new phenomenon and understanding the genotype-phenotype relationship of GCK gene mutations.

Background. The COVID-19 pandemic hit the world in late 2019, and by 2020, everyone was affected. Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) belongs to the beta-coronavirus genre and uses the angiotensin-converting enzyme 2 (ACE2) receptor to penetrate cells. Thyroid cells are rich in such receptors. Therefore, this gland is frequently involved alongside other organs in the COVID-19 disease. Aim. To describe COVID-19 inflammation and, eventually, dysregulations of normal thyroid function in a case series of patients diagnosed in a tertiary endocrinology care centre. Patients and Methods. We described subacute thyroiditis cases related to COVID-19 infection or vaccination against SARS-CoV2 infection (clinical manifestations and evolution). We also reviewed the literature data regarding COVID-19 infection or vaccination implications in thyroid pathology. Results. The literature describes two types of thyroid involvement in SARS-CoV2 infection or vaccination: subacute thyroiditis (SAT) and non-thyroidal illness syndrome (NTIS). In our case series, 5 patients (3 males), aged 41-54 years, developed the classical clinical manifestation of SAT related to COVID-19 infection (3 patients, concomitantly to upper respiratory infection or a few weeks apart) or anti-SARS-CoV2 ARNm vaccination (1-2 weeks after the vaccine administration). Clinical, laboratory and imaging findings and the evolution (steroid anti-inflammatory treatment used in 4/5 cases) were unremarkable compared to other SAT etiologies. Conclusion. We found no differences between the ”typical” viral and post-COVID-19 SAT regarding clinical presentation, severity, response to treatment, and thyroid function alteration. The only remarkable difference is the association of SAT with anti-SARS-CoV2 ARNm vaccination

Context. Impaired flow mediated dilatation (FMD) and increased carotid intima media thickness (CIMT) are the antecedent forms of atherosclerosis. Objective. The aim of this study was to evaluate vascular structural and functional changes in patients with asymptomatic primary hyperparathyroidism (APHPT), and whether biochemical alterations, related with PHPT and oxidative stress marker serum advanced oxidation protein products (AOPPs), may have influence on vascular alterations. Design. This is a cross sectional clinical study. Subject and Methods: Thirty-four patients with APHPT and 29 sex- and age and cardiovascular risk factors matched control cases were included in this study. Endothelial function was evaluated by FMD of the brachial artery; CIMT was measured by ultrasonography; in addition serum AOPPs and biochemical parameters were determined. Results. Serum Ca levels were higher in the patient group [10.93±0.60mg/dL vs. 9.45±0.31; p<0.001]. FMD measurement was significantly lower in patients group [0.07 (0.01-0.26) % vs. 0.14 (0.04-0.22) %; p=0.01]. CIMT measurements were comparable between the groups [52 (35- 69) mm vs. 56 (38-70) mm; p=0.821]. AOPPs levels were significantly higher in the patients [136.43 (55.14-1352) mmol/L vs. 84 (53.18-595.48) mmol/L; p=0.026]. There were significant negative correlations between FMD and serum Ca (r=–0.339, p<0.001); and serum AOPPs levels (r=–0.275, p<0.005). Serum Ca (p=0.007, β=–0.353) and AOPPs (p=0.024, β=–0.243) levels and hyperlipidemia (p=0.024, β=–0.288) were the predictors of FMD. Conclusions. Vascular endothelial function is impaired in patients with APHPT. Hypercalcemia, increased oxidative stress and hyperlipidemia may have role in the pathogenesis of endothelial dysfunction in patients with APHPT.

Streptococcus pneumoniae generally causes pneumonia or meningitis. The psoas abscess and osteomyelitis is mainly caused by Staphylococcus aureus. We report here on a patient with type 2 diabetes mellitus who had a psoas abscess and foot ulcer caused by Streptococcus pneumoniae after acupuncture\r\nand moxibustion.

A 54 years old man, who had undergone a cystectomy and urinary diversion surgery 31 years previously, complained of progressive generalized bone pain, muscle weakness and walking abnormality for six months. Laboratory investigations revealed elevated alkaline phosphatase, high serum chloride level and metabolic acidosis. Osteomalacia was suspected due to clinical and laboratory findings. Osteomalacia due to hyperchloremic metabolic acidosis is a complication of urinary diversion. Regular monitoring of pH, chloride, bicarbonate, and calcium-phosphorus metabolism is therefore essential for early diagnosis and treatment.

Aim. This study aimed to investigate the clinical presentation and treatment outcomes of newly diagnosed acromegaly patients treated with various combinations\r\nof treatment modalities.\r\nMaterials and Methods. Eighty-four acromegaly patients (42 female, 42 male, mean age 40.29?13.32 y), followed and\r\ntreated between 2000 and 2010 were included. Data on patient demographics, delay between onset of symptoms and the\r\ndiagnosis, details of treatments, and treatment- or disease-related morbidity and mortality were collected and analyzed. The median delay time for diagnosis was 60.71 ? 56.19 months. Patients received various combinations of surgery, gamma knife radiotherapy or conventional radiotherapy,\r\nlong acting somatostatin analogue, and dopamine agonist.\r\nResults. After ten years of treatment, median GH and IGF-1 values decreased from 13.7 ng/mL (IQR: 5.3- 34) to 1.04\r\nng/mL (IQR: 0.52-2.7) and from 600 &#956;g/L (IQR: 460.5-787.5) to 194 &#956;g/L (IQR :157-356), respectively (p<0.0001).\r\nMedian GH during 75 g oral glucose tolerance test (OGTT) decreased from 4.35 ng/mL (IQR: 1.87-13.15) to 1.40 ng/mL\r\n(IQR: 0.60-3.40) (p<0.0001). Fifty patients (59.5%) were in remission according to IGF-1 values and 52 patients (62 %) were cured according to nadir GH during OGTT respectively. The mortality rate was 5.9%.\r\nIn conclusion. Strict biochemical control following appropriate intervention significantly reduces both morbidity and mortality in acromegaly patients.

Aim. Histology and cytology consultations of thyroid fine needle aspiration biopsy (FNAB) of thyroidectomy specimens can change management of the patient. We aimed to determine compliance rates of pathology results between urban centers and a tertiary institution and its impact on patient management.\r\nMethods. This retrospective study includes 101 patients, who were referred to our center, between January 2008 and December 2008. After admission, all FNAB or thyroidectomy specimens of patients managed elsewhere were consulted by the pathology department. Comparison of FNAB and histology reports of our institution and the medical centers elsewhere had been carried out.\r\nResults. A total of 76% concordance rate was found between the FNAB results of other centers and consultation results. The highest concordance was observed in the malignant cytology group (77%). The cytological or histological outcomes of 24 (23.7%) patients were interpreted differently. After second opinion, patient management\r\nchanged in 21 of the 101 patients.\r\nConclusion. Since FNAB results can change the type of surgical treatment and the management plan, the results especially reported as suspicious may need a second\r\nopinion. We suggest that cytology or histology results of thyroid patients referred to tertiary centers for further evaluation and treatment should always be reviewed.

We describe clinical features of women with extremely low bone density, and investigate secondary causes of osteoporosis. Our hypothesis was that this population would be enriched in identifiable causes of osteoporosis. We performed a retrospective review of medical records of all women seen at our university over 4 years with T-score on bone densitometry at/below -4 at any site. Historical and fracture details were abstracted. We considered a thorough work up to include Vitamin D, PTH, CBC, chemistry panel, cortisol, transglutaminase, myeloma screen, tryptase and 24-hour urine calcium. Results. 137 women were identified with T-score at/below -4. Percent identified as Asian was 26% (higher than local prevalence of 8%). Average BMI was 21.6 kg/ m2. Clearly identifiable causes of osteoporosis were noted in 57% (inflammatory disorder, glucocorticoid or antacid exposure, prolonged immobilization and alcoholism were most prevalent). Of the remainder, full work up was performed only in 8%. Endocrine consultation and white race predicted thoroughness of secondary work-up. Conclusion. Fragility fractures, leanness and Asian race were common in women with very low T-score. However, few new causes were identified. Underlying etiology was either immediately evident or inadequately studied, especially in minorities.

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The role of osteocalcin in atherogenesis is unclear. We investigated the association between osteocalcin and carotid atherosclerosis in Chinese middle-aged and elderly male adults and further determined whether osteocalcin is independently associated with the carotid intima-media thickness (CIMT) in hyperglycemia subgroups. Subjects and methods. A total of 84 male participants (mean age, 59.13 years) were enrolled in groups of normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) according to the oral glucose tolerance test. A standard interview, anthropometric measurements and laboratory analyses were performed for each participant. Bilateral carotid intima–media thicknesses (CIMT) were measured using ultrasonography. The circulating osteocalcin was measured using quantitative enzyme immunoassay. Results. Both IGT and newly diagnosed T2DM groups had significantly lower osteocalcin levels compared with the NGT group (5.01 ± 0.68 μg/L, and 6.173 ± 0.68 ng/mL vs. 11.55 ± 0.57 μg/L, respectively). Multivariate linear stepwise regression analysis demonstrated that waisthip ratio(WHR) (standardized β = -0.408, P = 0.000), 2 hour plasma glucose after glucose load, (PPG) (standardized β = -0.235, P = 0.025), homeostasis model of assessment for insulin resistance index(HOMA-IR) (standardized β = -0.287, P = 0.004), and Glycosylated haemoglobin (HbA1c) (standardized β = -0.250, P = 0.015) were independently and inversely associated with serum osteocalcin in hyperglycemia subgroups; PPG(standardized β = -0.476, P = 0.015), osteocalcin(standardized β = -0.486, P = 0.001) were negatively associated with CIMT, while TG (standardized β = 0.647, P = 0.000) was positively associated with CIMT in T2DM. Conclusion. These results showed that osteocalcin is independently associated with carotid atherosclerosis in men with T2DM. It is tempting to suggest that osteocalcin may be implicated atherosclerosis.