Ozlem Celik

Gammaknife radiosurgery in patients with acromegaly.

We aimed to evaluate the efficacy and reliability of gamma-knife radiosurgery (GKR) in 22 patients with acromegaly at the Endocrinology-Metabolism Clinic of Cerrahpasa Medical School. We collected data retrospectively from hospital records on disease activity and other pituitary functions, pituitary MRI and visual fields, before GKR and 6, 12, 24, 36, 48 and 60 months after GKR. The median follow-up duration after GKR was 60 months (interquartile range [IQR]: 24-60 months). The remission rate was 54.5% after the 60 months of follow-up. The median growth hormone (GH) level at 60 months after GKR (0.99 ng/mL [IQR: 0.36-2.2]) was significantly lower than the median GH level before GKR (5.65 ng/mL [IQR: 3.85-7.2] (p=0.002). The median insulin-like growth factor-1 (IGF-1) level 60 months after GKR (221.5 ng/mL [IQR: 149-535]) was significantly lower than the median IGF-1 level before GKR (582.5 ng/mL [IQR: 515-655]) (p=0.008). Tumour growth was well controlled in 20 patients (95.2%). Six patients (28.6%) developed new-onset hypopituitarism. We concluded that GKR is an effective adjuvant treatment to control tumour growth, lower GH and IGF-1 levels, and to increase remission rates in patients with acromegaly who were refractory to surgical and medical treatment.

Effect of stressful life events on the initiation of graves’ disease

Objective. The aim of this study was to investigate the relationship between stressful life events (LESs) and its effect on the initiation of Graves’ disease (GD) and toxic nodular goitre (TNG). Patients and method. Forty-five patients with GD, 24 patients with TNG and 36 healthy control (CG) were included to the study. Graves and TNG patients had diagnosed within the last 12 months, with clinical and biochemical confirmation in Endocrinology Metabolism Outpatient Clinic of Cerrahpasa Medical School. The Holmes–Rahe Stress Scale and the Life Experience Survey (LES) was the psychological evaluation instrument used in this study. Results. There was no significant difference according to Holmes–Rahe scale (Graves & TNG P = 0.329, Graves & Control P = 0.115, TNG and control P = 0.571). According to LES scale when negative event number, positive event number, neutral events and their effects are considered, between Graves and TNG groups no statistically difference was observed (P = 0.139, P = 0.083, P = 0.167, P = 0.162, P = 0.861). The number and impact of negative SLEs were significantly higher in GD compared to CG (P = 0.015, P < 0.001). Conclusion. According to LES scale GD patients has significant difference with respect to CG when negative event number and impact are considered.

Ornithine transcarbamylase deficiency diagnosed in pregnancy

Urea cycle enzymes deficiencies are rare metabolic disorders. Ornithine transcarbamylase (OTC) deficiency is the most common type. The syndrome results from a deficiency of the mitochondrial enzyme OTC which catalyses the conversion of ornithine and carbamoyl phosphate to citrulline. It shows X-linked inheritance and typically remains asymptomatic until late infancy or early childhood. The severity of the symptoms depends on the age of the patient and the duration of hyperammonemia. Female heterozygotes are more difficult to diagnose. They suffer from hyperammonemic periods which can be triggered by trauma, infections, surgery, childbirth, parenteral nutrition, and by the initiation of sodium valproate therapy. The prognosis of OTC deficiency is better for those with an onset after infancy, but morbidity from brain damage does not appear to be linked to the number of episodes of hyperammonemia that have occurred. However, early diagnosis and prompt initiation of ammonia-lowering treatment are essential for survival of these patients. This case presents a patient who was diagnosed with OTC deficiency following mental confusion during pregnancy.

Lipodystrophy during pegvisomant therapy: a case report and review of the literature

Acromegaly is a serious, chronic endocrine disorder characterized by exaggerated growth hormone (GH) secretion and increased levels of insulin‐like growth factor‐1 (IGF‐1). Treatment modalities include somatostatin analogues and pegvisomant and/or radiotherapy following pituitary tumor resection.1 Pegvisomant is a pegylated analogue of human GH and functions as a GH receptor antagonist. Pegvisomant acts in the periphery and significantly decreases serum IGF‐1 levels.2 Various studies have shown that pegvisomant is safe and well‐tolerated and is an effective therapy for acromegaly patients. Possible adverse effects of pegvisomant treatment include self‐limited erthematous injection‐site reactions, mild liver toxicity, influenza‐like syndrome and headache.3 Here, we describe an acromegalic patient who developed lipohypertrophy following initiation of pegvisomant therapy.

The association of carotid cavernous fistula with Graves' ophthalmopathy.

Graves’ ophthalmopathy (GO) is one of the frequent manifestations of the disorder which is an inflammatory process due to fibroblast infiltration, fibroblast proliferation and accumulation of glycosaminoglycans. Eye irritation, dryness, excessive tearing, visual blurring, diplopia, pain, visual loss, retroorbital discomfort are the symptoms and they can mimic carotid cavernous fistulas. Carotid cavernous fistulas are abnormal communications between the carotid arterial system and the cavernous sinus. The clinical manifestations of GO can mimic the signs of carotid cavernous fistulas. Carotid cavernous fistulas should be considered in the differential diagnosis of the GO patients especially who are not responding to the standard treatment and when there is a unilateral or asymmetric eye involvement. Here we report the second case report with concurrent occurrence of GO and carotid cavernous fistula in the literature.

Atherosclerotic risk factors and premature atherosclerosis in acromegaly before and after 48 months of octreotide-LAR treatment.

We studied premature atherosclerosis with carotid Doppler ultrasonography in active acromegaly before and after treatment. Patients (n = 27) with active acromegaly and 12 age-, gender-, and body mass index-matched healthy individuals were included in the study. Carotid intima–media thickness was decreased significantly in the inactive group after treatment (median: 0.6 mm, interquartile range [IQR]: 0.55-0.80]) when compared with the active group (median: 0.9 mm [IQR: 0.75-1.15], P < .0001), but there was no significant difference between the inactive and control groups. There was a correlation between homeostasis model of assessment–insulin resistance (P = .01, r = .41) and growth hormone (GH; P < .0001, r = .46). In conclusion, premature atherosclerosis was demonstrated in active acromegaly patients probably as a consequence of insulin resistance and direct vascular effects of GH and/or insulin-like growth factor 1.

Investigation of insulin resistance gene polymorphisms in patients with differentiated thyroid cancer

We aimed to investigate insulin receptor substrate-1 (IRS-1), insulin receptor substrate-2 (IRS-2), insulin-like growth factor binding protein-3 (IGFBP-3) genotypes, which are thought to be involved in the pathogenesis of many solid tumors and have thus far not been studied in patients with differentiated thyroid cancer (DTC). The study consisted of 93 patients diagnosed with DTC (79 females, 14 males) and 111 healthy control subjects (63 females, 48 males). The anthropometric measurements, lipid profiles, thyroid function tests and homeostatic model assessment (HOMA) as an indicator of insulin resistance (IR) of all patients were recorded. In addition IRS-1, IRS-2 and IGFBP-3 gene polymorphisms were determined by using polymerase chain reaction and restriction fragment length polymorphism. Hardy–Weinberg equilibrium was tested for each gene polymorphisms, and genetic effects were evaluated by the Chi Square test and multiple logistic regression. Homeostasis model assessment of insulin resistance (HOMA-IR), body mass index, waist circumference and serum total cholesterol levels were significantly higher in patients with DTC than in the control group. There was no difference between the two groups with respect to IRS-1, IRS-2 and IGFBP-3 gene polymorphisms. In addition, these gene polymorphisms were found to have no effect on lymph node metastases or tumor staging. While, obesity and increased HOMA-IR may be risk factors in DTC development, we suggest that IRS-1, IRS-2 and IGFBP-3 gene polymorphisms do not play an important role in pathogenesis of DTC.

Pheochromocytoma presenting with rhabdomyolysis and acute renal failure: a case report

Abstract Rhabdomyolysis ranges from an asymptomatic illness with elevated creatine kinase levels to a life-threatening condition associated with extreme elevations in creatine kinase, electrolyte imbalances, acute renal failure, and disseminated intravascular coagulation. The most common causes are crush injury, overexertion, alcohol abuse, certain medicines, and toxic substances. A number of electrolyte abnormalities and endocrinopathies, including hypothyroidism, thyrotoxicosis, diabetic ketoacidosis, nonketotic hyperosmolar state, and hyperaldosteronism, cause rhabdomyolysis. Rhabdomyolysis and acute renal failure are unusual manifestations of pheochromocytoma. There are a few case reports with pheochromocytoma presenting rhabdomyolysis and acute renal failure. Herein, we report a case with pheochromocytoma crisis presenting with rhabdomyolysis and acute renal failure.

Iatrogenic Cushing’s syndrome with inhaled steroid plus antidepressant drugs

Current guidelines recommend the use of inhaled corticosteroids (ICS) for suppression of airway inflammation in patients with asthma. Although it is well known that ICS cause dose-related adrenocortical suppression, it is less known that they can lead to iatrogenic Cushing’s syndrome (CS). Fluticasone propionate (FP) is an ICS more potent than beclomethasone and budesonide. FP is metabolized as mediated by cytochrome P450 3A4 in the liver and the gut. Systemic bioactivity of FP can increase with the use of drugs that affect the cytochrome P450. Herein, we report the rapid development of iatrogenic CS in a patient receiving paroxetine and mirtazepine for 12 weeks in addition to inhaled FP.

Association of three SNPs in the PARP-1 gene with Hashimoto's thyroiditis.

Poly(ADP-ribose) polymerase-1 (PARP-1) has a vital role in the progression of the inflammatory response, and its inhibition confers protection in various models of inflammatory disorders. Therefore, we investigated the effect of promoter and exon variations of the PARP-1 gene on the risk for the inflammatory disease Hashimoto’s thyroiditis (HT). This case–control association study was comprised of 141 HT patients and 150 controls from a group of women in a Turkish population. Two polymorphisms in the promoter region of the PARP-1 gene, rs2793378 and rs7527192, were analyzed using the PCR-RFLP method. In addition, single nucleotide polymorphism (SNP) rs1136410, which is located at codon 762, was analyzed using bidirectional sequencing. The combined genotype and haplotype analyses of these polymorphisms were performed using SPSS 18 and Haploview 4.2. The results were statistically analyzed by calculating the odds ratios and 95% confidence interval using Pearson’s χ2-test and Fisher’s exact test (two-sided). Although we had a number of significant results, the associations became nonsignificant following a Bonferroni correction for multiple comparisons. Nonetheless, a protective factor against HT was still observed for the heterozygous genotype (TC) of SNP rs1136410 (P=0.001), even following Bonferroni correction, and according to the rs2793378–rs7527192 combined analysis, the occurrence of the TT/GA combined genotype was significantly higher in the controls (P=0.007). These results prove that the heterozygosity of SNP rs1136410 provides a protective effect against HT disease in a group of women in a Turkish population.