Association of ADAMTS4 and ADAMTS9 levels with cardiovascular risk in patients with primary hyperparathyroidism.

PURPOSE: Primary hyperparathyroidism (PHPT) has been associated with increased incidence of morbidity and mortality of the cardiovascular system. The pathogenetic mechanisms underlying this association are still not completely clear. A disintegrin and metalloproteinase with thrombospondin-like motifs (ADAMTS) play a critical role in atherosclerosis. This study aimed to investigate the levels of ADAMTS4 and ADAMTS9 and relationship between these proteoglycanases and cardiometabolic abnormalities in PHPT. MATERIALS AND METHODS: A case-control study was performed in a training and research hospital. Fifty-six patients with PHPT and 61 healthy volunteers were recruited. The Framingham score was used to calculate cardiovascular risk (CVR). Serum ADAMTS levels were determined by a human enzyme-linked immunoassay in all subjects. RESULTS: The ADAMTS9 concentration was significantly higher in patients with PHPT than in the control group (p < 0.05); however, there were no significant differences in ADAMTS4 levels between the groups (p > 0.05). In ROC curve analysis, PHPT can be predicted by the use of ADAMTS9 at a cut-off value of 30.7 pg/mL (69% sensitivity, 65% specificity). CVR score was significantly increased in the PHPT than controls (p < 0.05). ADAMTS4 and ADAMTS9 levels had positive correlations with CVR score (r = 0.322, p = 0.017; r = 0.275, p = 0.044 respectively). CONCLUSIONS: Based on the results of the present study, cardiovascular risk is increased in PHPT and associated with ADAMTS4 and ADAMTS9. Further efforts are needed to establish the function of ADAMTS proteases in both PHPT and atherosclerosis.

SERUM LEVELS OF FIBROBLAST GROWTH FACTOR-23, OSTEOPROTEGERIN, AND RECEPTOR ACTIVATOR OF NUCLEAR FACTOR KAPPA B LIGAND IN PATIENTS WITH PROLACTINOMA.

OBJECTIVE: The aim of this study to was to evaluate the effect of fibroblast growth factor-23 (FGF-23), osteoprotegerin (OPG), receptor activator nuclear κB ligand (RANKL), and vitamin D hormones on bone loss in patients with hyperprolactinemia due to pituitary prolactinoma. METHODS: We recruited 46 premenopausal female patients with prolactinoma and age and sex-matched healthy controls (Group 3, n = 20) for this cross-sectional study. Prolactinoma patients were divided into 2 groups as patients newly diagnosed (Group 1, n = 26) and those under cabergoline treatment (Group 2, n = 20). Anthropometric and metabolic variables; hormonal profiles; and osteocalcin, deoxypyridinoline (DOP), and bone mineral density measurements were performed for all participants. FGF-23, OPG, and RANKL levels were analyzed in all groups. RESULTS: FGF-23, OPG, calcium, phosphorus, and parathormone levels were similar between all groups despite significantly higher levels in the control group in terms of vitamin D and RANKL levels than in patients. Bone loss was found more in Group 2, particularly observed in Z scores of femur and spinal bone (P<.05). Correlation analysis revealed a negative correlation between FGF-23 and femur neck T score (r = -0.0433, P = .05) in patients with active prolactinoma. A positive correlation was also observed between parameters of DOP and OPG (r = 0.673, P = .02). In patients with remission there were a negative correlation between prolactin and luteinizing hormone (r = -600, P = .08). Additionally, a negative correlation was found between osteocalcin and osteoprotegerin in patients in remission (r = -0.73, P = .01). CONCLUSION: Our data indicated that FGF-23 and OPG levels do not play a critical role on the development of bone decrease in patients with hyperprolactinemia. However, further prospective studies in larger numbers of participants should be designed to clarify this issue. ABBREVIATIONS: BFP = body fat percentage BMD = bone mineral density BMI = body mass index CV = coefficient of variation DOP = deoxypyridinoline ELISA = enzyme-linked immunosorbent assay FGF-23 = fibroblast growth factor-23 HOMA-IR = homeostatic model assessment of insulin resistance OPG = osteoprotegerin RANKL = receptor activator nuclear κB ligand.

The need of prophylactic central lymph node dissection is controversial in terms of postoperative thyroglobulin follow-up of patients with cN0 papillary thyroid cancer.

PURPOSE: The objective of this study was to investigate whether prophylactic central lymph node dissection (pCLND) facilitates postoperative thyroglobulin (Tg) follow-up in the patients with papillary thyroid carcinoma (PTC). We also questioned whether radioactive iodine (RAI) remnant ablation provides any further advantage in this regard. METHODS: The records of patients with low-intermediate risk PTC who underwent either only total thyroidectomy (TT) or TT in conjunction with pCLND were reviewed. Adjuvant RAI ablation was performed depending on tumor diameter, multifocality, the presence of positive lymph nodes and adverse histopathologic features. Pre-ablative and post-ablative Tg levels, post-operative complications and clinico-pathological characteristics were compared between the two groups (TT alone and TT with pCLND). RESULTS: Among the 302 patients, TT was performed in 140 (46.4%) and TT with pCLND in 162 (53.6%). More than half of all patients in both groups had papillary microcarcinoma (58.0% and 53,1%, respectively). Postoperatively, the median preablative Tg level was higher in the TT only group than that of the TT with pCLND group (0.96 vs 0.27 ng/ml, respectively). The post-ablative Tg levels were undetectable in both groups at the last follow-up visit. Also, a subgroup of patients (19.5%) who did not receive RAI ablation all became athyroglobulinemic at one year after surgery. CONCLUSIONS: Although performing pCLND with TT seems to have an advantage over TT alone as to achieve lower Tg levels in the early post-operative period, Tg levels become comparable following RAI ablation. On the other hand, the patients who have not been treated with adjuvant RAI ablation, also became athyroglobulinemic regardless of the surgical method.

The relationship between cytotoxin-associated gene A positive Helicobacter pylori infection and autoimmune thyroid disease.

OBJECTIVE: The aim of this study was to determine whether there is an association between cagA [cytotoxin-associated gene A] positivity and thyroid autoimmunity and thyroid volume. METHODS: This prospective study included 78 Helicobacter pylori-positive (H. pylori) dyspeptic patients in the study group, and 50 age-, gender-, and body mass index-matched H. pylori-negative dyspeptic patients in the control group. All the controls were evaluated via upper gastrointestinal endoscopic biopsy or breath test, and were found as H. pylori negative. Gastric biopsy specimens were obtained via endoscopy and histological examination was performed for documentation of H. pylori. RESULTS: In all, 55.1% (n = 43) of the H. pylori-positive patients were cagA positive. There was no significant difference in metabolic syndrome parameters or thyroid function test results between the study and control groups. The frequency of anti-TPO and Hashimoto's thyroiditis positivity was significantly higher in the study group than in the control group. Thyroid volume was higher and severe parenchymal heterogeneity was more common in the H. pylori-positive patients. CONCLUSIONS: H. pylori infection might be a risk factor for autoimmune thyroid disease and high thyroid volume in patients diagnosed with histological evaluation. However, cagA positivity has no additional effect on these parameters.

Isolated vitamin D deficiency is not associated with nonthyroidal illness syndrome, but with thyroid autoimmunity.

AIM: This study aimed to compare thyroid functions, thyroid autoantibodies, and the existence of nonthyroidal illness syndrome (NTIS) according to vitamin D level. MATERIALS AND METHODS: The study included age- and BMI-matched healthy volunteers with and without vitamin D deficiency. In addition, the nonthyroidal illness syndrome status was evaluated. RESULTS: Anti-TPO positivity was significantly more common in those with severe and moderate vitamin D deficiency, as compared to those with a normal 25(OH)D level. Furthermore, TSH levels were significantly lower in those with severe and moderate vitamin D deficiency than in those with a normal 25(OH)D level. In addition, there was a significant weak inverse correlation between anti-TPO positivity and the 25(OH)D level and a positive correlation between the TSH level and 25(OH)D level. Only 1 thyroid function test result was compatible with NTIS among the participants with moderate vitamin D deficiency; therefore the difference was not significant. CONCLUSIONS: The prevalence of thyroid autoantibody positivity was higher in those with severe and moderate vitamin D deficiency than in those with a normal 25(OH)D level. Additional large-scale studies must be conducted to determine if vitamin D deficiency plays a causal role in the pathogenesis of Hashimoto's thyroiditis and NTIS.

Preclinical atherosclerosis in patients with prolactinoma.

OBJECTIVE: The aim of this study was to evaluate the effect of hyperprolactinemia on body fat, insulin sensitivity, inflammatory markers, and cardiovascular risk in patients with prolactinoma. METHODS: The study included 35 untreated hyperprolactinemic patients with pituitary adenomas, and 36 age-, gender-, and body mass index (BMI)-matched healthy controls without any known disease. Serum glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR, lipid profile, high-sensitivity C-reactive protein (hs-CRP), and heart-type fatty acid binding protein (H-FABP) levels were measured. Waist and hip circumference (WC and HC) were measured in all the participants. The body fat percentage was measured, and the visceral fat and abdominal fat percentages were measured via bioelectrical impedance (BIA). In addition, carotid intima media thickness (CIMT) was measured using high-resolution B-mode ultrasound. RESULTS: The serum glucose level, HOMA-IR, triglyceride level, and SC were significantly higher in the patient group than in the control group. The hs-CRP level and CIMT were significantly higher in the hyperprolactinemic patients. Visceral and truncal fat percentages were significantly higher in the patients with prolactinoma. H-FABP levels were similar in the 2 groups, and there was a positive correlation between the prolactin (PRL) and H-FABP protein levels. CONCLUSIONS: Based on the present findings, hyperprolactinemia is associated with preclinical atherosclerosis and metabolic abnormalities. Patients with hyperprolactinemia might experience cardiovascular disease in the long term. Metabolic control should be achieved in addition to the control of hyperprolactinemia in the clinical management of patients diagnosed with prolactinoma.

Hyperprolactinaemia associated with increased thyroid volume and autoimmune thyroiditis in patients with prolactinoma.

OBJECTIVE: The aim of this investigation was to evaluate the effects of hyperprolactinaemia on thyroid function, volume and nodularity in patients with prolactinoma. CONTEXT: Hyperprolactinaemia has been associated with various autoimmune diseases; however, the data on the correlation between the level of prolactin (PRL) and thyroid disorders have not been adequately clarified. DESIGN: Case-control study. PATIENTS: Forty-eight subjects with new diagnosis of hyperprolactinaemia (group 1) and 39 subjects undergoing treatment for prolactinoma (group 2) were recruited from our outpatient clinic. Fifty-two healthy subjects were included as a control group (group 3). MEASUREMENTS: The serum PRL, thyroid-stimulating hormone (TSH), thyroxine (free T4), thyroidal microsome (anti-TPO) and antithyroglobulin antibodies (TgAb) levels were evaluated, and ultrasonographic thyroid volume was calculated. RESULTS: The frequencies of positive anti-TPO and TgAb were significantly higher in group 1 than in groups 2 and 3 (P = 0·008). Also, the percentage of patients with thyroid heterogeneity were significantly higher in groups 1 and 2 than in group 3 (P < 0·05). The percentage of patients with thyroid nodules were higher in group 1 than in groups 2 and 3 (p1-2 = 0·03, p1-3 = 0·05 and p2-3 = 0·637). The mean thyroid volume was significantly higher in group 1 (P = 0·001), and a positive correlation was found between thyroid volume and the level of PRL (r = 0·616; P = 0·0001). Prolactin had a significant effect on the total volume according to stepwise multiple linear regression analysis (adjusted R(2) is 0·268; P < 0·0001). CONCLUSIONS: Patients with hyperprolactinaemia have significantly increased thyroid volume, thyroid autoimmunity and nodule prevalence.

Systematic review of COVID-19 and autoimmune thyroiditis.

COVID-19 is a severe acute respiratory syndrome. Recent reports showed that autoimmune thyroiditis might occur following COVID-19 infection. We aimed to review the literature to assess the prevalence, clinical features and outcome of autoimmune thyroid disorders triggered by COVID-19. We reviewed case reports, case series, and observational studies of autoimmune thyroiditis including Graves' disease, Hashimoto thyroiditis, and silent thyroiditis developed in COVID-19 patients by searching PubMed, SCOPUS and Web of Science and included in the systematic review. Our search yielded no prevalence study. We noted 20 reported cases: Fourteen cases of Graves' disease, 5 cases of hypothyroidism due to Hashimoto's thyroiditis and one case of postpartum thyroiditis. The majority (16/20, 80%) were middle-aged (mean age: 40 years) female patients. Autoimmune thyroiditis was diagnosed either concomitantly or 7-90 days after the COVID-19 infection. Eight out of 14 cases with Graves' disease had a known thyroid disorder and they were stable in remission. One out of 5 cases with Hashimoto's thyroiditis had known prior hypothyroidism. The majority of the patients achieved remission within 3 months. One patient with thyroid storm due to Graves' disease and one patient with myxedema coma have died. Current data suggest that COVID-19 may cause autoimmune thyroid disease or exacerbate the underlying thyroid disease in remission. It is reasonable to routinely assess the thyroid functions both in the acute phase and during the convalescence so as not to overlook a thyroid disorder and not to delay treatment especially in patients with preexisting autoimmune thyroid diseases.

A rare case of ectopic ACTH syndrome originating from malignant renal paraganglioma.

Ectopic adrenocorticotropic hormone (ACTH) syndrome is characterized by hypercortisolism due to the hypersecretion of a non-pituitary ACTH-secreting tumor leading to Cushing's syndrome. Only a few cases have been reported previously as causing ectopic ACTH related to paraganglioma. Herein, we present a case of Cushing's syndrome, in who was proved to be attributable to an ACTH-secreting renal malignant paraganglioma. A 40-year-old woman presented with a five-month history of newly diagnosed hypertension and diabetes, weakness, hyperpigmentation, oligomenorrhea, hirsutism, and acneiform lesions. She showed cushingoid features, including moon face, facial hirsutism, facial and truncal acne, hyperpigmentation, and severe muscle weakness of the limbs. She did not have other findings such as striae, supraclavicular fat accumulation, and buffalo hump. Laboratory examination showed the presence of hypopotasemia, hyperglycemia, hyperthyroidism, and leukocytosis. The serum levels of ACTH, cortisol, and urine-free cortisol were markedly elevated. Results of an overnight 2-mg dexamethasone suppression test included a basal serum cortisol of 61.1 mcg/dL (normal range: 4.6-22.8 mcg/dL) and a cortisol value of 46.1 mcg/dL after dexamethasone administration. There was no suppression found after 2-day 8-mg dexamethasone administration. Magnetic resonance imaging (MRI) of the pituitary gland indicated two microadenomas. An abdominal MRI scan revealed horseshoe kidney, bilateral adrenal hyperplasia, and masses with dimensions of 35 x 31 mm in the left kidney. Inferior petrosal sinus sampling showed no evidence of a central-to-peripheral gradient of ACTH. A positron emission tomography/computed tomography scan showed intense increased activity in the lower pole of the left kidney. Left adrenalectomy and left partial nephrectomy were performed. The resected tumor was diagnosed as the ACTH-secreting paraganglioma in the pathological examination, which was confirmed by immunohistochemical studies with chromogranin A, synaptophysin, and ACTH. Only a few cases of paragangliomas as a cause of ectopic ACTH syndrome have been reported. To our knowledge, this is the first case of renal paraganglioma resulting in Cushing's syndrome due to ectopic ACTH hypersecretion.

Frequency of nodular goiter and autoimmune thyroid disease and association of these disorders with insulin resistance in polycystic ovary syndrome.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a frequent endocrine disease in women. Nodular goiter and autoimmune thyroid disease (AITD) are endocrinologic abnormalities that have high prevalence. The purpose of our study was to detect the prevalence of AITD and nodular goiter in patients with PCOS and investigate whether PCOS-related hormones and metabolic factors affect these thyroid disorders. MATERIAL AND METHODS: Ninety-seven women with PCOS and 71 healthy female volunteers were recruited into the study. Serum-free thyroxine, thyroid-stimulating hormone, anti-thyroperoxidase antibody and anti-thyroglobulin antibody levels were evaluated. Thyroid volume (TV) was calculated using ultrasonography. RESULTS: The body mass index (BMI), Waist/Hip ratio, homeostasis model assessment insulin resistance (HOMA-IR), fasting blood glucose, triglyceride and low-density lipoproteins, and fasting insulin were significantly higher in the PCOS group (p<.05). The control group had significantly higher serum high density lipoprotein cholesterol results (p=.005). The mean TV was 11.4±4.7 mL in the PCOS group and 9.9±2.8 mL in the controls (p=.022). Twenty-nine patients with PCOS (29/97; 29.9%) had thyroid nodules, whereas only eleven control subjects had thyroid nodules (11/71; 15.5%) (p=.043). The frequency of AITD was significantly higher in the PCOS group (p=.001). A statistically significant relationship was found between TV and age, fasting glucose, HOMA-IR, BMI, and fasting insulin (p<.05). Participants with thyroid nodules were older and had higher fasting glucose, BMI, fasting insulin, and HOMA-IR values compared with those without thyroid nodules (p<.05). CONCLUSION: We demonstrated that TV and frequency of nodular goiter were increased in patients with PCOS. This result was related with insulin resistance. Therefore, we recommend that patients with PCOS must be investigated for the development of nodular goiter and AITD.

Effect of lifestyle interventions with or without metformin therapy on serum levels of osteoprotegerin and receptor activator of nuclear factor kappa B ligand in patients with prediabetes.

Osteoprotegerin has been shown to be increased in cardiovascular disorders and type 2 diabetes mellitus. Prediabetes represents a high risk condition for diabetes and diabetic complications. Therefore, we aimed to find the relationship between prediabetes and osteoprotegerin with nuclear factor-B ligand, carotid intima media thickness, and metabolic markers. A total of 54 participants with prediabetes including impaired fasting glucose (n = 21), impaired glucose tolerance (n = 8), impaired fasting glucose and impaired glucose tolerance (n = 25), and 60 healthy individuals as a control were admitted to the study. Metabolic and anthropometric parameters, insulin resistance variables, osteoprotegerin, and nuclear factor-B ligand markers, carotid intima media thickness were examined at baseline for all participants. To evaluate the effect of therapy we determined the same parameters after the end of the study. Measurements of waist circumference, body mass index, body fat percentage and levels of fasting blood glucose, fasting insulin, homeostatic model assessment of insulin resistance, triglyceride levels and hsCRP and carotid intima media thickness were significantly higher in patients with prediabetes (p < 0.05). We also found higher osteoprotegerin and lower nuclear factor-B ligand levels in patients than in controls however, the value was non-significant (p > 0.05). Patients with prediabetes were under lifestyle interventions with (group 1, n = 33) or without metformin (group 2, n = 21) therapy. Baseline anthropometric and metabolic characteristics were not found statistically different in group 1 and group 2. Mean follow up period of the patients were 7.9 ± 2.2 month (min-max: 6-12 months). After the follow up period we evaluated the same parameters and found significant differences between waist circumference, body mass index, body fat percentage, fasting insulin, homeostatic model assessment of insulin resistance, and osteoprotegerin levels (p < 0.05). However, carotid intima media thickness, and nuclear factor-B ligand levels significantly different only in the group treated with metformin (p < 0.05). We also compared the variables after the treatment period with the control group and found significantly lower levels in terms of fasting insulin, homeostatic model assessment of insulin resistance, waist circumference, body mass index, body fat percentage, carotid intima media thickness, osteoprotegerin, and nuclear factor-B ligand values (p < 0.05). Correlation analysis revealed a negative relationship between nuclear factor-B ligand and body mass index, and body fat percentage in group 1 (p = 0.05, r = -0.646, p = 0.01, r = -0.585). Therapy of prediabetes was associated with a significant decrease in osteoprotegerin and certain metabolic variables together with an increase in nuclear factor-B ligand levels particularly in patients with under metformin therapy.

Serum heart type fatty acid binding protein levels are not changed in hyperthyroidism.

BACKGROUND: Heart type fatty acid binding protein (H-FABP) is a small protein and released into the circulation when myocardial damage has occurred. Previous studies have demonstrated that H-FABP is closely associated with cardiac and some endocrinologic disorders including prediabetes, metabolic syndrome, and acromegaly. Hyperthyroism is a well-known disorder associated with cardiovascular diseases. We aimed to investigate the effect of hyperthyrodism on H-FABP levels. METHODS: Forty six patients with hyperthyroidism with no known history of coronary artery disease and 40 healthy controls are involved in the study. Serum H-FABP levels are measured using sandwich enzyme-linked immunosorbent assay. RESULTS: There was no significant difference between serum H-FABP levels of patients with hyperthyroidism and controls (871±66 pg/mL, and 816±66 pg/mL, respectively P=0.56). There was no significant correlation between H-FABP, free triiodothyronine (fT3), free thyroxine (fT4), and thyroid stimulating hormone (TSH) levels in patients and controls. CONCLUSIONS: Serum H-FABP levels are not altered in patients with hyperthyroidism.

Transformation of nonfunctioning pancreatic tumor into malignant insulinoma after 3 years: an uncommon clinical course of insulinoma.

A 62-year-old man admitted to our outpatient clinic with two months of recurrent life threatening hypoglycemia episodes. He was diagnosed as malignant insulinoma with multiple metastases of liver and peripancreatic lymph nodes. Liver biopsy specimen was demonstrated grade 2 neuroendocrine tumor compatible with clinical and radiological results. He was followed under the treatment of continuous intravenous glucose infusion during the diagnostic procedures. He had a pancreatic lesion history measured 20 x 12 mm in diameter via the abdominal tomography examination approximately two years before the diagnosis. Unusual course of this case suggests the transformation of nonfunctioning pancreatic neuroendocrine tumor into functional insulin secreting tumor with metastases. The patient was found inoperable and started on chemotherapy.

Hyperprolactinemia has no effect on plasma ghrelin levels in patients with prolactinoma.

OBJECTIVE: Accumulating evidence suggests that prolactin is a modulator of body weight and composition and that it regulates some transporters in adipose tissue. It was demonstrated that hyperprolactinemia is associated with weight gain and obesity. Ghrelin is a novel hormone secreted from many organs including the pituitary gland. Ghrelin acts by regulating energy homeostasis and stimulating appetite. The aim of this study is to investigate whether ghrelin has a role in the case of weight gain in patients with prolactinoma. MATERIAL AND METHODS: Forty-four patients with prolactinoma, both newly diagnosed and undergoing cabergoline treatment, were included in this study. Age- and sex-matched healthy subjects were included in the control group. Serum fasting glucose, insulin, lipid profile, and ghrelin levels were measured. Homeostasis model assessment of insulin resistance (HOMA-IR) was also calculated. Body mass index (BMI) and total fat ratio (%) of all the participants were assessed by bioelectrical impedance analysis using TBF-310GS™ (Tanita Corporation, Tokyo, Japan). RESULTS: Patients with prolactinoma demonstrated significantly higher serum levels of fasting insulin, triglyceride, and waist and hip circumference measurement. No significant difference was found between the fasting glucose, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and HOMA-IR levels. BMI was significantly higher in the patients with prolactinoma than that in the control group (p<0.05). Additionally, the total body fat percentage was higher in the patients with prolactinoma than that in the control group; however, the difference was not significant (p>0.05). Furthermore, there was no significant difference in terms of the ghrelin levels between these groups. There was a correlation with serum ghrelin and growth hormone levels (p<0.02, rho=0.489). However, no significant correlation was obtained between serum prolactin or ghrelin levels and body fat percentage. CONCLUSION: According to the results of our study, ghrelin has no effect on weight gain in patients with prolactinoma. Further studies are needed to evaluate whether ghrelin affects the prevalence of obesity in patients with prolactinoma.

Insulin-like growth factor 1, liver enzymes, and insulin resistance in patients with PCOS and hirsutism.

AIM: Hyperinsulinemia and insulin resistance are commonly seen in patients with hirsutism and polycystic ovary syndrome (PCOS), and are associated with cardiovascular disease risk. However, it is not yet known whether insulin-like growth factor I (IGF-I) and alanine transaminase (ALT) produced by the liver play roles in hyperinsulinemia and subclinical atherosclerotic process in patients with PCOS and idiopathic hirsutism (IH). MATERIALS AND METHODS: This was a prospective case-controlled study. The study population consisted of 25 reproductive-age PCOS women, 33 women with IH, and 25 control subjects. RESULTS: Mean IGF-I levels and median ALT levels were higher in patients with IH and PCOS than controls, but these differences were not statistically significant. The participants who had a homeostasis model assessment insulin resistance index (HOMA-IR) greater than 2.7 had significantly higher IGF-1 and ALT levels. ALT levels were positively correlated with body mass index, FG, insulin and HOMA-IR. CONCLUSION: The study illustrated that IGF-1 and ALT levels were significantly higher in patients with increased insulin resistance. Due to short disease duration in younger participants, we did not observe any correlation between IGF-1 and hyperinsulinemia. These findings suggest that increased hepatic production of IGF-I and ALT might be an early indicator of insulin resistance in hirsutism.

The relationship between LH and thyroid volume in patients with PCOS.

BACKGROUND: Thyroid volume (TV) has been found to be associated with age, anthropometry, smoking, iodine status and hyperinsulinemia. Hyperinsulinemia is frequent finding in patients with PCOS and has associations with TV. However, the TV has been evaluated only a few studies in patients with PCOS. Therefore, the aim of this study was to evaluate the biochemical and hormonal variables in patients with PCOS comparing with the controls and their relationships between TV. METHODS: This was a case-control study conducted in a training and research hospital. The study population consisted of 47 reproductive-age PCOS women and 30 control subjects. We evaluated anthropometric, biochemical and hormonal parameters as well as thyroid volume in PCOS patients and controls. Insulin resistance was calculated using the homeostasis model assessment insulin resistance index (HOMA-IR). RESULTS: Mean age, BMI, thyroid stimulant hormone (TSH) levels and TV were similar between groups (p<0.05). The HOMA-IR and free T4 levels were higher in patients with PCOS. However, hyperinsulinemia and insulin resistance were not found to be associated with TV. Thyroid volume was positively correlated with the LH and anti TPO levels. The participants were divided into 2 groups according to HOMA-IR levels. The mean TV measurement was higher in group with higher HOMA-IR levels, but the difference was not significant in young age PCOS patients. CONCLUSION: In early age PCOS patients it was observed that insulin resistance had no effect on TV. In this case, anti TPO and LH have dominant effect on TV. Chronic stimulation with LH and insulin may lead to increase in TV in later stages of the PCOS diseases.

A rare case of ectopic ACTH syndrome originating from malignant renal paraganglioma

SUMMARY Ectopic adrenocorticotropic hormone (ACTH) syndrome is characterized by hypercortisolism due to the hypersecretion of a non-pituitary ACTH-secreting tumor leading to Cushing's syndrome. Only a few cases have been reported previously as causing ectopic ACTH related to paraganglioma. Herein, we present a case of Cushing's syndrome, in who was proved to be attributable to an ACTH-secreting renal malignant paraganglioma. A 40-year-old woman presented with a five-month history of newly diagnosed hypertension and diabetes, weakness, hyperpigmentation, oligomenorrhea, hirsutism, and acneiform lesions. She showed cushingoid features, including moon face, facial hirsutism, facial and truncal acne, hyperpigmentation, and severe muscle weakness of the limbs. She did not have other findings such as striae, supraclavicular fat accumulation, and buffalo hump. Laboratory examination showed the presence of hypopotasemia, hyperglycemia, hyperthyroidism, and leukocytosis. The serum levels of ACTH, cortisol, and urine-free cortisol were markedly elevated. Results of an overnight 2-mg dexamethasone suppression test included a basal serum cortisol of 61.1 mcg/dL (normal range: 4.6-22.8 mcg/dL) and a cortisol value of 46.1 mcg/dL after dexamethasone administration. There was no suppression found after 2-day 8-mg dexamethasone administration. Magnetic resonance imaging (MRI) of the pituitary gland indicated two microadenomas. An abdominal MRI scan revealed horseshoe kidney, bilateral adrenal hyperplasia, and masses with dimensions of 35 x 31 mm in the left kidney. Inferior petrosal sinus sampling showed no evidence of a central-to-peripheral gradient of ACTH. A positron emission tomography/computed tomography scan showed intense increased activity in the lower pole of the left kidney. Left adrenalectomy and left partial nephrectomy were performed. The resected tumor was diagnosed as the ACTH-secreting paraganglioma in the pathological examination, which was confirmed by immunohistochemical studies with chromogranin A, synaptophysin, and ACTH. Only a few cases of paragangliomas as a cause of ectopic ACTH syndrome have been reported. To our knowledge, this is the first case of renal paraganglioma resulting in Cushing's syndrome due to ectopic ACTH hypersecretion.

Transformation of nonfunctioning pancreatic tumor into malignant insulinoma after 3 years: an uncommon clinical course of insulinoma

A 62-year-old man admitted to our outpatient clinic with two months of recurrent life threatening hypoglycemia episodes. He was diagnosed as malignant insulinoma with multiple metastases of liver and peripancreatic lymph nodes. Liver biopsy specimen was demonstrated grade 2 neuroendocrine tumor compatible with clinical and radiological results. He was followed under the treatment of continuous intravenous glucose infusion during the diagnostic procedures. He had a pancreatic lesion history measured 20 x 12 mm in diameter via the abdominal tomography examination approximately two years before the diagnosis. Unusual course of this case suggests the transformation of nonfunctioning pancreatic neuroendocrine tumor into functional insulin secreting tumor with metastases. The patient was found inoperable and started on chemotherapy. Arch Endocrinol Metab. 2015;59(3):270-2.