Ayse Kubat Uzum

Transient gestational diabetes insipidus diagnosed in successive pregnancies: review of pathophysiology, diagnosis, treatment, and management of delivery

Gestational diabetes insipidus (GDI) is a rare disorder characterised by polyuria, polydypsia, and excessive thirst usually manifesting in the third trimester of pregnancy. The etiology is thought to depend on excessive vasopressinase activity, a placental enzyme that degrades arginine-vasopressin (AVP), but not 1-deamino-8-d-arginine vasopressin (dDAVP), which is a synthetic form. This is a transient syndrome and may be associated with acute fatty liver of pregnancy and preeclampsia. The use of dDAVP in symptomatic cases has been proven as a safe method for both the mother and the fetus during the pregnancy. We report a case of recurrent gestational diabetes insipidus in successive pregnancies, which responded to dDAVP and subsided after delivery.

Effects of vitamin D replacement therapy on serum FGF23 concentrations in vitamin D-deficient women in short term

OBJECTIVE Fibroblast growth factor 23 (FGF23), a phosphatonin, inhibits renal phosphate reabsorption and suppresses 1-α hydroxylase activity. Calcitriol stimulates FGF23 synthesis in bone. We aimed to determine the effect of vitamin D replacement therapy on serum FGF23 concentrations in vitamin D-deficient women and to compare the FGF23 concentrations of vitamin D-deficient patients with healthy subjects and patients with genetically determined hypophosphatemic rachitis. DESIGN AND METHODS The study group was composed of vitamin D-deficient females (n=18, mean age 29.1 ± 9.9 years), vitamin D-sufficient healthy females (control group; n=19, mean age 28.5 ± 5.2 years), and patients with genetically determined hypophosphatemic rachitis (n=13, mean age 26.5 ± 15.1 years). The groups were compared for serum FGF23, 1,25-dihydroxyvitamin D3 (1,25(OH)2D), calcium, phosphate, bone turnover markers, intact parathyroid hormone (PTH), and urinary excretion of calcium and phosphate. The vitamin D-deficient group was re-evaluated after a standard treatment regimen. RESULTS Serum FGF23 concentrations were significantly lower in vitamin D-deficient patients than in vitamin D-sufficient women and hypophosphatemic rachitis group. Serum FGF23 and phosphate concentrations further decreased significantly during replacement of vitamin D (P<0.05). A significant negative correlation was evident between FGF23 and PTH before vitamin D replacement in the patients (r=-0.469, P<0.05). CONCLUSION Decreased FGF23 concentrations, which further decline during vitamin D replacement therapy, may have favorable action on bone mineralization by counterregulatory effect on phosphate homeostasis. Lower 1,25(OH)2D concentrations at baseline and hypophosphatemia during treatment may have dominating effects on FGF23 concentrations in vitamin D deficiency, leading to decreased FGF23 concentrations at baseline and during replacement therapy.

Evaluation of the effect of L-thyroxin therapy on endothelial functions in patients with subclinical hypothyroidism

Subclinical hypothyroidism (SH) is characterized by normal serum free T4 (FT4), free T3 (FT3) levels and increased serum thyroid-stimulating hormone (TSH) levels. Endothelial dysfunction, which is an early step of atherosclerosis, has been reported in patients with subclinical hypothyroidism. The aim of this study is to evaluate endothelial functions and the effect of l-thyroxin (L-T4) therapy on endothelial functions in SH. Twenty-seven patients with SH and 22 healthy controls were evaluated in terms of endothelial functions, using brachial artery Doppler ultrasonography. After restorating euthyroidism, measurements were repeated. Baseline and nitroglycerin induced diameter (NID) of brachial artery were similar in patients with SH and the control group. Compared to the control group, the patients with SH showed significantly reduced flow-mediated diameter (FMD). Baseline and NID values were significantly higher after LT4 therapy in SH group. FMD also significantly increased after LT4 therapy. Hypothyroidism accelerates atherogenesis through modification of athero-sclerotic risk factors and direct effects on the blood vessels. In this study, we observed marked improvement in endothelial functions after L-T4 therapy in SH patients. We suggest that thyroid hormone replacement therapy may help to prevent atherosclerosis in this group of patients.

Comparison of 68Ga-DOTATATE PET-CT, 18F-FDG PET-CT and 99mTc-(V)DMSA scintigraphy in the detection of recurrent or metastatic medullary thyroid carcinoma

PurposeWe aimed to compare the efficacies of gallium-68 (68Ga) DOTATATE PET-computed tomography (CT), fluorine-18 fluorodeoxyglucose (18F-FDG) PET-CT and technetium-99m (99mTc)-(V)DMSA scintigraphy in the detection of residual/metastatic medullary thyroid carcinoma (MTC). Materials and methodWe retrospectively evaluated DOTATATE PET-CT, 18F-FDG PET-CT and (V)DMSA scintigraphy of 22 MTC patients, all taken within a 6-month period in each patient, because of high levels of calcitonin (Ct) and carcinoembryonic antigen (CEA). We investigated the relationships between the results of the imaging modalities and tumour marker levels and the sporadic versus hereditary nature of the disease, as well as the effect of imaging results on patient management. ResultsThe ages of the patients at diagnosis were between 20 and 69 years. The median levels of Ct and CEA were 871.5 pg/ml and 11.2 ng/ml, respectively. In the patient-based analysis, we observed at least one focus of abnormal uptake in 15 of 22 DOTATATE PET-CT (68.2% sensitivity), eight of 18 18F-FDG PET-CT (44.4% sensitivity) and five of 15 (V)DMSA scans (33.3% sensitivity). These data showed a significant difference between DOTATATE PET-CT and (V)DMSA scintigraphy (P=0.016), whereas the relationships between DOTATATE PET-CT and 18F-FDG PET-CT and between 18F-FDG PET-CT and (V)DMSA scintigraphy showed no significant differences (P>0.05). In the lesion-based analysis, 134 lesions were detected with DOTATATE PET-CT, 76 lesions with 18F-FDG PET-CT and nine lesions with (V)DMSA scintigraphy. ConclusionDOTATATE PET-CT is an efficient imaging modality in MTC patients with increased Ct and CEA (especially >1000 pg/ml and 50 ng/ml, respectively) for localizing recurrent or metastatic disease. 18F-FDG PET-CT can be performed if DOTATATE PET-CT is not available, but (V)DMSA scintigraphy is not recommended.

Serum ghrelin and adiponectin levels are increased but serum leptin level is unchanged in low weight Chronic Obstructive Pulmonary Disease patients

BACKGROUND Weight loss and muscle wasting are common features reported in COPD patients and they are all related with systemic inflammation. In this study, the relationship between pulmonary functions and inflammatory and metabolic parameters in low weight COPD patients were investigated. METHODS Fifty male COPD patients were grouped according to the Global Initiative for Chronic Obstructive Lung Disease criteria. Group 1: Mild-moderate COPD patients (n=18; with a mean age of 66.4 ± 9.2 yrs; body mass index (BMI):19.7 ± 1.5 kg/m(2)), group 2: Severe-very severe COPD patients (n=32; with a mean age of 65.9 ± 10.0 yrs; BMI:19.3 ± 1.6 kg/m(2)), group 3: Control group composed of healthy nonsmoking males (n=17; with a mean age of 50.2 ± 8.4 yrs; BMI:21.85 ± 1.5 kg/m(2)). Anthropometric parameters, serum levels of adiponectin (ApN), ghrelin, leptin, hsCRP, IL-6, IL-1β, IL-8, TNF-α and pulmonary functions were compared. RESULTS Adiponectin concentration was higher in group 1 (43.3 ± 28.6 ng/mL; p<0.05) and group 2 (59.9 ± 31.8 ng/mL; p<0.001) when compared with the control group (23.5 ± 13.6 ng/mL). Ghrelin concentrations were higher in COPD groups (1281.0 ± 1173.7 and 1840.0 ± 403.6 pg/mL; p<0.05) compared to the control subjects (554.0 ± 281.9 pg/mL). When the groups were compared, no significant difference was found for leptin, IL-1β, TNF-α, and IL-8. Interleukin-6 and hsCRP levels were higher in group 1 than in the control group. ApN was negatively correlated with BMI and FEV1. In all groups, FEV1 showed positive correlation with BMI, skinfold thicknesses, insulin and triglyceride; negative correlation with age, pack/years, HDL-Chol and ApN. Increased SHBG with decreased insulin level and HOMA-IR may indicate increased insulin sensitivity in COPD groups. CONCLUSION The anti-inflammatory effect of ApN and ghrelin is more evident in severe-very severe COPD patients.

Leptin concentration indexed to fat mass is increased in untreated anorexia nervosa (AN) patients

Context  Data regarding serum adipocytokine and ghrelin concentrations in different stages of anorexia nervosa (AN) is conflicting.

Unchanged serum adipokine concentrations in the setting of short-term thyroidectomy-induced hypothyroidism.

OBJECTIVE To investigate short-term effects of thyroidectomy-induced hypothyroidism on leptin, adiponectin, and resistin concentrations in association with anthropometric data. METHODS Thirty premenopausal women with euthyroid nodular goiter-mean age, 44.0 ± 11.6 years; mean body mass index (BMI), 28.6 ± 5.9 kg/m2; 13 obese, 7 overweight, and 10 normal weight subjects-scheduled for total thyroidectomy were included in the study. Serum leptin, adiponectin, resistin, free triiodothyronine, free thyroxine, thyroid-stimulating hormone, glucose, insulin, and C-reactive protein concentrations, lipid profile, and anthropometric variables were determined in the euthyroid state (preoperatively) and the hypothyroid state (postoperatively, with a thyroid-stimulating hormone concentration >30 mIU/L). RESULTS Body weight, BMI, waist and hip circumferences, body fat mass, and serum lipid concentrations increased significantly after thyroidectomy. No significant difference was found between preoperative and postoperative serum leptin, adiponectin, and resistin concentrations. Fat tissue mass-corrected leptin, adiponectin, and resistin concentrations did not differ significantly between euthyroid and hypothyroid periods. Thyroid hormone concentrations showed no significant correlations with adipokine levels. CONCLUSION Serum adipokine concentrations seem not to change significantly during short-term thyroidectomy-induced hypothyroidism despite significant increases in body weight, BMI, fat mass, and lipid concentrations.

Clinical presentations, metabolic abnormalities and end-organ complications in patients with familial partial lipodystrophy

OBJECTIVE Familial partial lipodystrophy (FPLD) is a rare genetic disorder characterized by partial lack of subcutaneous fat. METHODS This multicenter prospective observational study included data from 56 subjects with FPLD (18 independent Turkish families). Thirty healthy controls were enrolled for comparison. RESULTS Pathogenic variants of the LMNA gene were determined in nine families. Of those, typical exon 8 codon 482 pathogenic variants were identified in four families. Analysis of the LMNA gene also revealed exon 1 codon 47, exon 5 codon 306, exon 6 codon 349, exon 9 codon 528, and exon 11 codon 582 pathogenic variants. Analysis of the PPARG gene revealed exon 3 p.Y151C pathogenic variant in two families and exon 7 p.H477L pathogenic variant in one family. A non-pathogenic exon 5 p.R215Q variant of the LMNB2 gene was detected in another family. Five other families harbored no mutation in any of the genes sequenced. MRI studies showed slightly different fat distribution patterns among subjects with different point mutations, though it was strikingly different in subjects with LMNA p.R349W pathogenic variant. Subjects with pathogenic variants of the PPARG gene were associated with less prominent fat loss and relatively higher levels of leptin compared to those with pathogenic variants in the LMNA gene. Various metabolic abnormalities associated with insulin resistance were detected in all subjects. End-organ complications were observed. CONCLUSION We have identified various pathogenic variants scattered throughout the LMNA and PPARG genes in Turkish patients with FPLD. Phenotypic heterogeneity is remarkable in patients with LMNA pathogenic variants related to the site of missense mutations. FPLD, caused by pathogenic variants either in LMNA or PPARG is associated with metabolic abnormalities associated with insulin resistance that lead to increased morbidity.

Amyloid Goiter Associated with Amyloidosis Secondary to Rheumatoid Arthritis

Amyloidosis refers to a variety of conditions in which amyloid proteins are abnormally deposited in organs and/or tissues. The most common forms of systemic amyloidosis are primary amyloidosis (PA) of light chains and secondary amyloidosis (SA) caused by chronic inflammatory diseases such as rheumatoid arthritis (RA). Although involvement of the thyroid gland by amyloid is a relatively common phenomenon, clinically significant enlargement of the thyroid owing to amyloid deposition is a rare occurrence. In SA, the deposition of amyloid associated (AA) protein is associated with atrophy of thyroid follicles. The clinical picture of these patients is characterized by rapid, painless thyroid gland enlargement which may be associated with dysphagia, dyspnea, or hoarseness. Thyroid function is not impaired in most cases. Although amyloid goitre secondary to systemic amyloidosis due to chronic inflammatory diseases is relatively common, specifically related to RA is much more uncommon one and it is reported less in the literature. In this report, A 52-old-year female patient with amyloid goiter associated with amyloidosis secondary to rheumatoid arthritis is presented.

Evaluation of the eff ect of L-thyroxin therapy on cardiac functions by using novel tissue Doppler-derived indices in patients with subclinical hypothyroidism

Objectives Subclinical hypothyroidism (SH) is characterized by normal serum free T4 (fT4), free T3 (fT3) levels and increased serum thyroid stimulating hormone (TSH) levels. The aim of this study was to assess the validity of tissue Doppler imaging (TDI) in evaluating cardiac eff ects of SH and to demonstrate the improving eff ects of L-thyroxin(L-T4) on TDI parameters. Methods Twenty-seven patients with SH and 22 healthy controls were evaluated by standard echocardiography and TDI. TDI-derived systolic velocities [isovolumic myocardial acceleration (IVA), peak myocardial velocity during isovolumic contraction (IVV), peak systolic velocity during ejection period (Sa)] and diastolic indices (peak early (Ea) and late diastolic (Aa) velocities, Ea/Aa, E/Ea ratios and Tei index) were measured. After restoring euthyroidism, all measurements were repeated. Results At baseline, left ventricular (LV) systolic velocities (IVV and IVA) and diastolic indices were signifi cantly impaired in the SH group. After L-T4 therapy, left ventricular systolic and diastolic functions were improved. Right ventricular (RV) systolic velocities were similar between the study group and the healthy controls but diastolic functions were impaired in the SH group, at baseline. Tei index of the RV was improved after L-T4 therapy. RV IVA remained unchanged after hormone replacement therapy. Conclusions SH is associated with biventricular systolic and diastolic dysfunction. IVA which is an accurate estimate of subclinical systolic dysfunction, was signifi cantly impaired in the left ventricle and had improved after L-T4 therapy. We found that IVA is able to detect early eff ects of subclinical hypothyroidism on LV systolic functions and L-T4 therapy can improve ventricular functions.