Ilkay Cakir

Investigation of insulin resistance in patients with normocalcemic primary hyperparathyroidism.

While derangements in glucose metabolism in patients with primary hyperparathyroidism are well-defined, this issue is not investigated in patients with normocalcemic primary hyperparathyroidism (NPHPT). The aim of this study was to investigate the presence of insulin resistance in patients with NPHPT. Eighteen patients with NPHPT (two males and 16 females) and 18 healthy volunteers were enrolled into the study. Secondary causes of parathyroid hormone elevations were excluded in all patients. Blood samples were obtained for the measurement of serum calcium, phosphate, alkaline phosphatase (ALP), albumin, creatinine, glucose, and serum lipid levels. Glucose and insulin responses to oral glucose tolerance test (OGTT) were obtained. Homeostasis model assessment (HOMA-IR) was also used as an indice of insulin resistance. Patients and control subjects had similar age, body mass index, and sex distribution. Although within normal limits, serum calcium and ALP levels were higher in patients than in the control subjects. None of the patients and the control subjects had diabetes mellitus, while eight patients and six control subjects had impaired glucose tolerance. Insulin responses to OGTT and HOMA-IR were not significantly different among the patient and control subjects. In addition, both groups have similar serum lipid levels. Patients with NPHPT do not exhibit insulin resistance and glucose intolerance. Since so little is known about this form of disease, subjects should be monitored regularly for the metabolic aspects of the disease as well as the progression of their disease.

Obstructive sleep apnoea syndrome is associated with relative hypocortisolemia and decreased hypothalamo–pituitary–adrenal axis response to 1 and 250 μg ACTH and glucagon stimulation tests

OBJECTIVE The investigations regarding the effect of obstructive sleep apnoea syndrome (OSAS) on hypothalamo-pituitary-adrenal (HPA) axis revealed conflicting results. We aimed to evaluate the effects of OSAS on HPA-axis with dynamic tests. METHODS This study was carried out on 26 patients with OSAS and 15 subjects without OSAS which, were defined according to the International Classification of Sleep Disorders. Patients were enrolled from either Endocrinology outpatient clinic or Neurology Sleep Center. Participants for the control group were included from the patients admitting to Endocrinology Department with the complaint of obesity or volunteers from hospital staff. All the participants were evaluated by polysomnography (PSG) and dynamic tests of HPA axis (dexamethasone suppression test, 1 and 250μg ACTH and glucagon stimulation tests). RESULTS Serum basal and peak cortisol levels were found to be lower in OSAS patients when compared to the control group during 1μg ACTH and glucagon stimulation tests. When the area under curve (AUC) of cortisol responses to dynamic stimulation tests were calculated according to trapezoid formula, patients with OSAS were found to have lower values compared to control group. AUC responses of all three dynamic stimulation tests were found to be negatively correlated with AHI. CONCLUSION OSAS is associated with relative hypocortisolemia in the morning with reduced responses to 1 and 250μg ACTH and glucagon stimulation tests.

Micronucleus evaluation in mitogen-stimulated lymphocytes of patients with acromegaly

Acromegaly is a syndrome characterized by a sustained elevation of circulating growth hormone and insulin-like growth factor-1 (IGF-1). Insulin-like growth factor-1 is a potent mitogen and has a role in the transformation of normal cells to malignant cells. This study aims to evaluate the spontaneous micronucleus (MN) frequency by using the cytokinesis-block MN assay to determine genetic damage in the lymphocytes of patients with acromegaly. The study was carried out in 20 patients who had active acromegaly and in 20 age- and sex-matched healthy controls. The MN values were measured in binucleated cells obtained from mitogen-stimulated lymphocytes of patients and control subjects. The distribution of binucleated cells with 1, 2, 3, or more MNs was also measured. We found significantly higher MN frequency values in the lymphocytes of acromegalic patients than in those of the control subjects (2.23 ± 0.68 vs 1.03 ± 0.54, P = .001). The MN frequency increased with increasing IGF-1 levels of acromegalic patients (P = .036, R = 0.47). We observed that the number of binucleated cells with 2 MNs was higher for the majority of patients with acromegaly than for control subjects. Furthermore, the receiver operating characteristic curve (area under the curve = 0.914, P < .0001) was calculated to assess the discriminative power of the MN frequency. Our results indicate that increased MN frequency in the lymphocytes of patients with acromegaly may reflect genomic instability and this increased MN frequency may be associated with elevated levels of circulating growth hormone and IGF-1.

Evaluation of coagulation and fibrinolytic parameters in adult onset GH deficiency and the effects of GH replacement therapy: A placebo controlled study

OBJECTIVE Increased cardiovascular mortality/morbidity observed in patients with hypopituitarism is ascribed to growth hormone deficiency (GHD) because of its unfavorable cardiovascular risk profile. Abnormalities in the coagulation system may also contribute to increased cardiovascular morbidity/mortality. To get a better insight into the role of hemostasis in GHD we assessed several hemostatic markers at baseline and after 6 months of GH replacement therapy (GHRT). DESIGN-PATIENTS: Nineteen patients with adult onset GHD were enrolled (twelve patients into the treatment and seven patients into the placebo group) into the study. Platelet count, collagen/epinephrine closure time, collagen/ADP closure time, fibrinogen, prothrombin time (PT), activated partial thromboplastin time (aPTT), antithrombin III (AT III), protein C activity, protein S activity, lupus anticoagulant, antiphospholipid antibody immunoglobulin M, and antiphospholipid antibody immunoglobulin G were measured at baseline and 6 months after treatment. RESULTS The investigated parameters in the groups were similar at baseline except for low protein S (PS) activity. Protein S deficiency was observed in three of the patients in the GH treatment group at baseline, however the PS activity values normalized following GHRT. AT III and protein C activities decreased when compared to baseline values in the treatment group but not in the placebo group. CONCLUSIONS We observed protein S deficiency more frequent than seen in the general population and normalization of protein S activity and decreases, in other natural anticoagulants following GHRT. Further studies are required to understand the impact of these changes in cardiovascular morbidity and mortality in this patient population.

Acromegaly is associated with decreased skin transepidermal water loss and temperature, and increased skin pH and sebum secretion partially reversible after treatment.

BACKGROUND Acromegaly is characterized by an acquired progressive somatic disfigurement, mainly involving the face and extremities, besides many other organ involvement. Wet and oily skin was described in acromegaly patients and it was attributed to hyperhidrosis and increased sebum production but this suggestion has not been evaluated with reliable methods. OBJECTIVE The aim of this study was to examine the skin parameters of patients with acromegaly using measurements of skin hydration, sebum content, transepidermal water loss, pH and temperature and particularly the effects of 12 months of treatment on these parameters. METHODS 52 patients with acromegaly and 24 healthy control subjects were included in this two blinded prospective study. Skin properties were measured on forehead and forearm by Corneometer CM825, Sebumeter SM810, Tewameter TM210 and Phmeter PH900 as non-invasive reliable measuring methods. Serum GH, IGF-1 and all measurements of skin properties on forehead and forearm were repeated at the end of the 3, and 6 months of therapy in 20 cases. Patients were treated with appropriate replacement therapy for deficient pituitary hormones. RESULTS The sebum content and pH of the skin of acromegalic patients were significantly higher and transepidermal water loss and skin temperature were found to be significantly lower in acromegalic patients when compared to the control group both on forehead and forearm. GH and IGF-1 levels were positively correlated with sebum levels and negatively correlated with skin temperature on both forehead and forearm. The sebum levels of the patients were significantly decreased both on forehead and forearm at 3rd and 6th months of treatment. CONCLUSION The present study demonstrated increased sebum secretion, decreased transepidermal water loss, alkali and hypothermic skin surface in patients with acromegaly by reliable methods for the first time. These data suggest that GH and/or IGF-I may have a modulatory role on several skin characteristics which can be at least partially reversible with treatment.

Increased micronucleus, nucleoplasmic bridge, nuclear bud frequency and oxidative DNA damage associated with prolactin levels and pituitary adenoma diameters in patients with prolactinoma

Prolactinoma is the most common pituitary tumor. Most pituitary tumors are benign, but they often are clinically significant. We investigated cytokinesis-block micronucleus cytome (CBMN cyt) assay parameters and oxidative DNA damage in patients with prolactinoma to assess the relations among age, prolactin level, pituitary adenoma diameter and 8-hydroxy-2’-deoxyguanosine (8-OHdG) level in patients with prolactinoma. We investigated 27 patients diagnosed with prolactinoma and 20 age- and sex-matched healthy controls. We measured CBMN cyt parameters and plasma 8-OHdG levels in peripheral blood lymphocytes of patients with prolactinoma and controls. The frequencies of micronucleus (MN), nucleoplasmic bridge, nuclear bud, apoptotic and necrotic cells, and plasma 8-OHdG levels in patients with prolactinoma were significantly greater than controls. MN frequency was correlated positively with age, prolactin levels and pituitary adenoma diameters in patients with prolactinoma. The increased chromosomal and oxidative DNA damage, and the positive correlation between MN frequency, prolactin levels and pituitary adenoma diameters may be associated with increased risk of cancer in patients with prolactinoma, because increased MN frequency is a predictor of cancer risk.

The Effects of Gonadotropin Replacement Therapy on Metabolic Parameters and Body Composition in Men with Idiopathic Hypogonadotropic Hypogonadism

Testosterone replacement therapy (TRT) in idiopathic hypogonadotrophic hypogonadism (IHH) slows the process of metabolic syndrome (MetS), diabetes mellitus, and cardiovascular diseases by its inversing effects on insulin resistance, dyslipidemia, and blood pressure. Since there are not enough data regarding the effects of gonadotropin replacement therapy (GRT), we aimed to investigate the impact of GRT on MetS parameters in IHH patients. Sixteen patients with IHH and 20 age and body mass index (BDI)-matched healthy controls were enrolled into the study. Patients were evaluated at baseline and 6 months after the GRT. Sex hormones, insulin like growth factor-1, prolactin, insulin, C-reactive protein (CRP), homocysteine, and lipid levels were measured at baseline and after the treatment. Anthropometric measurements, including BMI, body fat ratio (BFR), fat free mass (FFM), waist circumference, and waist-to-hip ratio (WHR), were also performed. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) index was calculated. Body fat ratio, triglyceride, HOMA-IR, and CRP levels were higher, whereas bone age, fat free mass, and creatinine levels were lower in the patients with hypogonadism. HOMA-IR indices and basal insulin levels decreased significantly after 6 months of GRT compared with baseline levels. Triglyceride levels, and BFRs diminished significantly by an accompanying decline in WHR. FFM of the patients increased following the GRT. No significant changes were detected in CRP, homocysteine, total and LDL-cholesterol levels. Similar to TRT, hCG treatment decreases HOMA-IR, triglyceride levels, BFR and WHRs, and increases FFM in patients with IHH.

Ectopic ACTH Syndrome Caused by Multifocal Pulmonary Carsinoids with 18f-FDG Uptake: Case Report

Ectopic ACTH secretion [EAS] and bronchopulmonary carcinoids are both rare diseases, although lung carsinoids account for the most common source of EAS. Surgical resection of the tumor is selected treatment when the source of EAS could be determined. We report a patient with signs and symptoms suggestive of hypercortisolism, admitted to hospital with weight gain. Laboratory tests were in favour of ACTH-dependent Cushing’s syndrome, a normal pituitary MRI and no central-to-peripheral ACTH gradient in bilateral inferior petrosal sinus sampling are suggested ectopic ACTH secretion. Thoracic CT scan revealed two lesions at the left lung, with 18fFDG-uptake at PET scan. The patient was successfully treated with lobectomy and histological examination confirmed an atypical bronchial carcinoid tumor with positive ACTH immunoreactivity. Although functional imaging modalities that target somatostatin receptors in neuroendocrine tumours are favourible, FDG-PET imaging may also be a useful and more available tool for evaluation of thoracic carcinoid tumors.