ACTA ENDOCRINOLOGICA (BUC)

Introduction. Biotin treatment causes false-low or false-high results in some immunoassays methods. This phenomenon is called as biotin interference. In the present article, a seven-month-old male, with renal failure and laboratory hyperthyroidism due to biotin interference is presented. Case report. High free T4 (fT4), free T3 (fT3), antithyroid peroxidase antibody (anti-TPO), anti-thyroglobulin antibody (anti-TG) and low thyroid stimulating hormone (TSH) levels were detected in a seven-month-old male patient who has metabolic acidosis, renal failure, and suspected of metabolic disease. Anti-thyroid drug therapy was started. However, when he was re-evaluated due to the absence of euthyroidism with anti-thyroid therapy (methimazole 0.8 mg/ kg /day), it was found that the patient had been given 20 mg/ day biotin for acidosis for two months. Biotin interference was considered in hormone measurement. Thyroid function tests were found to be normal 12 days after discontinuation of biotin therapy. Conclusion. Immunoassay measurements which use biotin should be done 2-7days after the last dose of biotin in patients under biotin treatment, but this time may need be much longer in renal failure patients. During this period or if the biotin therapy cannot be stopped, alternative methods should be preferred for analysis.

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. Relative adrenal insufficiency (RAI) is the inadequate production of cortisol due to dysfunction of the hypothalamic–pituitary–adrenal (HPA) axis during a severe illness. We evaluated the HPA axis and RAI in a tertiary pediatric intensive care unit (PICU). Methods. A total of 100 PICU patients were included in this prospective cohort study. Basal serum levels of adrenocorticotropic hormone (ACTH), cortisol values were compared with those in the control group. A low-dose ACTH stimulation test was performed in patients with basal cortisol levels below 18 μg/dL. Results. The basal cortisol levels of the PICU patients were significantly higher than those of the control group (P < 0.05). All tested patients (n= 24) had delta cortisol levels > 9 μg/dL and a peak cortisol response > 18 μg/dL. Basal cortisol levels were positively correlated with Pediatric Risk of Mortality (PRISM) III scores (P < 0.05; r = 0.363). The basal or stimulated cortisol levels of the patients who received glucocorticoid treatment were higher than the cut-off levels. Conclusions. High basal or stimulated cortisol levels are indicative of disease severity in the acute phase of stress. Patients with very high cortisol levels should be particularly carefully monitored because of the high mortality risk.

Objective. Parathyroid gland hyperplasia is diffuse or nodular in secondary hyperparathyroidism (sHPT) in patients with renal failure. Whether the nodular growth starts from the beginning or is the transformation of a diffusely-growing gland into nodular hyperplasia in parallel\r\nwith increases in the severity of the disease is unknown. The disease might be unresponsive to medical treatment when\r\nnodular hyperplasia develops. This study aims to differentiate the characteristics of the parathyroid glands with and without nodular hyperplasia in sHPT, and to\r\ninvestigate if there is any similarity between the nodular hyperplastic glands of sHPT and the parathyroid adenomas of primary hyperparathyroidism.\r\nMaterials and Methods. Hyperplasia types (nodular or diffuse) and parathyroid cell types, and the expression of\r\nproliferating cell nuclear antigen (PCNA) and Ki-67 in parathyroid tissue were investigated histopathologically and\r\nimmunohistochemically in 94 parathyroid glands of 42 patients with hyperparathyroidism.\r\nResults and Discussion. 63 glands showed nodular hyperplasia and 16 diffuse hyperplasia in sHPT. Chief cells predominated across the whole series. Vacuolated chief cells most frequently accompanied chief cells in both nodular\r\nhyperplasia (28.6%) and adenomas (53%). The median ratio of PCNA LI (labelling index) was 30/10? (min: 4-max: 720) cells in nodular hyperplasia, 16/10? (min: 2-max: 180) cells in diffuse hyperplasia and 30/10? (min: 10-max: 707) cells in adenomas (p>0.05). The highest PCNA LI according to all the cell types in the series was in chief cell and vacuolated chief cell combinations (53/10?, p=0.04). These findings suggest that parathyroid adenoma and nodular hyperplasia have histopathologically- and immunohistochemically - simil ar characteristics suggesting that both have aggressive cell proliferation.