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.

Introduction. We aimed to investigate Cardiotrophin-1 (CT-1) levels along with other markers of cardiovascular disease and the association of androgen levels with these parameters in both lean and overweight or obese PCOS patients. Material and Methods. The study included 90 overweight or obese PCOS patients with metabolic syndrome (MS) and 80 lean PCOS patients without MS. The control group consisted of 140 healthy females. Anthropometric measurements, plasma glucose, insulin, lipid and hormone profile, homocysteine, hs-CRP, CT-1 levels and carotid-IMT were evaluated in all study subjects. Results. Fasting insulin, HOMA values were significantly higher in obese PCOS patients. Total testosteron levels were higher in both PCOS groups with respect to both controls. Serum homocysteine, hs-CRP, CT-1 and carotid- IMT values were significantly higher in both PCOS groups compared to controls (p=0.001, pCIMT: 0.005). CT-1 was positively correlated with insulin, HOMA, total testosterone, homocysteine, hs-CRP and carotid IMT. After multiple regression analysis, CT-1 was significantly positively correlated with total testosterone, hs-CRP and carotid IMT. Conclusions. CT-1 was associated with other cardiovascular risk markers and its use as a cardiovascular risk marker might be suggested. Cardiovascular risk was increased even in lean PCOS patients without MS and it might be associated with elevated androgen levels.

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.

Context. Although, many studies have been made on the clinical course of autoimmune thyroiditis, this study focused on women and the factors effecting the natural course such as Selenium. Objective. The study aimed to determine Hashimoto’s thyroiditis (HT) clinical course in adults and the factors that could affect it. Design. The study was in a retrospective manner between 2010-2018. Subjects and Methods. 101 patients with HT were followed for 60.7±32.7 months. Biochemical and ultrasonographic data were collected. We investigated whether the age at diagnosis, family history, smoking habits, levothyroxine replacement therapy, and serum selenium (Se) levels influenced the disease course. Results. No relationship was observed between age and thyroid functions, thyroid volumes (TV), and autoantibody (Ab) levels at diagnosis. Ab levels were irrelevant with TV, echogenicity, and nodularity at diagnosis. However, initial TSH levels were significantly associated with anti-TPO levels (p=0.028, r=0.218). In the untreated group, thyroid functions seemed to be stable. TV decreased significantly in both treated and untreated patients (p<0.001). The decrease in TV was significantly higher in the treatment group (p=0.002). In euthyroid and subclinical hypothyroid patients, levothyroxine therapy did not affect the decrease in TV. Ab levels remained stable in untreated patients, but anti-TPO levels significantly decreased in treated patients (p<0.001). Smoking seemed to increase only anti-Tg levels (p=0.009). Family history was not associated with any of the studied parameters. Serum Se level was negatively correlated only with thyroid echostructure and only in treated patients. TV showed a “Gaussian distribution” in all patients at the diagnosis and at the end, independent of levothyroxine treatment. Conclusions. Most euthyroid patients remained euthyroid during five years of follow-up. The decrease in TV was significantly prominent with LT4 treatment. Importantly, TV followed a normal distribution instead of the bimodal distribution that is classically described.

Context. The aim of this study was to explore the prognostic significance correlation between the endocrinopathy and the size of the pituitary adenoma with the sellar floor bone mineral density values using microfocus computerized tomography (μCT) analysis. Subjects and Methods. 16 consecutive patients with pituitary adenomas had full endocrinological and radiological work up prior to endoscopic transnasal transsphenoidal surgery. Multiple bony samples were collected from the sellar floor during surgery, and labeled and analyzed in a double blind fashion. Each bone sample was analyzed for bone mineral density (BMD) and Hounsfield units (HU) with microfocus CT. Results. There was no correlation between adenoma size and BMD values of sella floor but grade IV macroadenomas were found to have lower BMD levels. Statistical analysis showed that the level of correlation between grouped BMD (<1.0 and >1.0) data with ACTH (<46 and >46), IGF (<303 and >303), and PRL (<29.93 and >29.93) levels were insignificant (P=.569, P=.315, and P=1.00, respectively) Conclusion. We have found no clinical relationship between sellar floor BMD values and endocrinopathy and the size of the adenoma. However, it was found out that preoperative conventional CT evaluation seemed insufficient in predicting the sellar floor bone integrity and may mislead the surgeon.

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.

Diabetic ketoacidosis (DKA) is a common medical emergency situation. In rare cases, glycemic changes associated with the menstrual cycle may create a predisposing factor for DKA. In the absence of facilitating factors that may cause DKA, catamenial DKA should be considered. In the patients with catamenial DKA, increasing the insulin dose 1-2 days before menstruation may prevent the development of hyperglycemia or DKA associated with menstrual cycle. In this study, we present a 21-year-old female with type 1 diabetes mellitus (DM) that recurrently applied to our hospital due to DKA a few days prior to menstrual bleeding.