The acromegaly registry of ten different centers in Turkey.

OBJECTIVES: To describe biochemical and clinical features, and therapeutic outcomes of acromegaly patients in Turkey. METHODS: Retrospective multicenter epidemiological study of 547 patients followed in 10 centers of the Turkish Acromegaly registry. RESULTS: A total of 547 acromegaly patients (55% female) with a median age of 41 was included in this study. Majority of patients had a macroadenoma (78%). Transsphenoidal surgery was performed as primary treatment in 92% of the patients (n = 503). Surgical remission rate was 39% (197/503) in all operated patients. Overall disease control was achieved in 70% of patients. Remission group were significantly older than non-remission group (p = .002). Patients with microadenomas had significantly higher remission rates than patients with macroadenomas (p < .001). Patients with microadenomas were significantly older at the time of diagnosis when compared to patients with macroadenomas (p < .001). Preoperative growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels were significantly lower in the remission group (p < .001). Initial IGF-1 and GH levels were significantly higher in macroadenomas compared to microadenomas (p < .001). Medical treatment was administered as a second-line treatment (97%) in almost all patients without remission. Radiotherapy was preferred in 21% of the patients mostly as a third line treatment. CONCLUSIONS: This is one of the largest real life studies evaluating the epidemiological characteristics and treatment outcomes of patients with acromegaly who were followed in different centers in Turkey. Transsphenoidal surgery in the treatment of acromegaly still remains the most valid method. Medical treatment options may improve long-term disease outcomes in patients who cannot be controlled with surgical treatment (up to 70%).

Serum betatrophin levels are reduced in patients with full-blown polycystic ovary syndrome.

Betatrophin is defined as a new marker in glucose homeostasis and lipid metabolism. We aimed to investigate the role of serum betatrophin in full-blown polycystic ovary syndrome (PCOS) patients and 47-aged healthy women, 51 full-blown PCOS patients were included in this cross-sectional study. Betatrophin concentrations were significantly lower in PCOS group and displayed a positive correlation only with serum tryglyceride in control group (p < .05). A cutoff level (464.5 ng/L) was determined for betatrophin according to Receiver Operating Characteristic curve. Using this value, 64.7% of PCOS patients were classified as below the cutoff and in this group betatrophin was found to correlate negatively with fasting glucose, fasting insulin, and homeostasis model assessment of insulin resistance (p = .038, p = .020, and p = .014, respectively), and positively with total testosterone (p = .041). In the rest of PCOS cases (35.3%) who had betatrophin higher than cutoff, positive correlation was found with low-density lipoprotein cholesterol (p = .009). In conclusion, betatrophin levels are reduced in full-blown PCOS patients who had worse metabolic phenotype.

Mean Platelet Volume in Graves' disease: A Sign of Hypermetabolism Rather than Autoimmunity?

OBJECTIVE: To evaluate the impact of mean platelet volume (MPV) on predicting disease course among patients with Graves' disease (GD). METHODS: This retrospective study was performed between 2013-2016 at the Outpatient Endocrinology Clinic of Baskent University Faculty of Medicine, Adana hospital on 65 patients with GD. Among participants, 30 cases experienced thyrotoxicosis again during the first six months after discontinuing anti-thyroid drug (ATD) sessions that had been carried out for at least 12 months prior to stopping (Relapse group). We also observed 35 patients who exhibited normal thyroid functions within six months following ATD withdrawal (Remission group). MPV levels and thyroid function tests were recorded and total duration of ATD therapy was calculated for all participants. RESULTS: The mean MPV level that was measured at the time of drug withdrawal did not differ between groups, being 8.0±1.2 fL in the Relapse group vs. 8.0±1.0 fL in the Remission group (p=0.81). However, we found that the relapse MPV was higher than the withdrawal MPV in the Relapse group (9.2±1.3 fL) than it was in the Remission group (8.0±1.2 fL, p=0.00). CONCLUSIONS: Higher relapse MPV in Relapse group but similar MPV levels in both groups at ATD withdrawal may be attributed to hypermetabolism or hyperthyroidism rather than autoimmunity of GD. Abbreviations:BMI: Body mass index GD: Graves' disease MPV: Mean platelet volume TSH: Thyroid-stimulating hormone TRAbs: Thyrotropin receptor antibodies ATD: Anti-thyroid drug fT4: Free thyroxine fT3: Free triiodothyronine CBC: Complete blood count PTC: Papillary thyroid carcinoma.

Body Mass Index below Obesity Threshold Implies Similar Cardiovascular Risk among Various Polycystic Ovary Syndrome Phenotypes.

OBJECTIVE: The aim of this study was to determine the cardiometabolic risk factors in different polycystic ovary syndrome (PCOS) phenotypes. SUBJECTS AND METHODS: This cross-sectional study was performed between 2010 and 2011. Eighty-nine patients with PCOS and 25 age- and weight-matched healthy controls were included in the study. Patients were grouped using the Rotterdam 2003 criteria as: group 1, oligomenorrhea and/or anovulation (ANOV) and hyperandrogenemia (HA) and/or hyperandrogenism (n = 23); group 2, ANOV and polycystic ovaries (PCO; n = 22); group 3, HA and PCO (n = 22); group 4, ANOV, HA and PCO (n = 22); group 5, controls (n = 25). Laboratory blood tests for diagnosis and cardiometabolic risk assessments were performed. Insulin resistance (IR) was calculated in all patients with the homeostasis model assessment of IR (HOMA-IR) formula. An euglycemic hyperinsulinemic clamp test was performed on 5 randomly selected cases in each subgroup, making 25 cases in total, and indicated as the 'M' value (mg/kg/min), which is the total body glucose disposal rate. RESULTS: The mean BMl values of the groups were: group 1, 26.1 ± 5.3; group 2, 27.9 ± 5.2; group 3, 24.3 ± 4.2; group 4, 27.9 ± 7.5; group 5, 24.7 ± 5.2 (p > 0.05). There were no differences in the lipid profile, plasma glucose, HOMA-IR, insulin and M values between the groups (p > 0.05). Phenotypes with oligomenorrhea/anovulation (groups 1, 2 and 4) were more obese than group 3 (p = 0.039). CONCLUSIONS: The cardiometabolic risk profile was similar among the PCOS subgroups. This finding could be attributed to the mean BMl values, which, being below 30, were not within the obesity range. Obesity appeared to be an important determinant of high cardiovascular risk in PCOS.

Plasma fetuin-A levels are reduced in patients with hypothyroidism.

OBJECTIVE: To determine plasma fetuin-A levels in hypothyroid patients before and after treatment with l-thyroxine (T4) and to determine the relation between plasma fetuin-A levels with cardiovascular risk factors. DESIGN: A prospective, controlled, single-blind study. METHODS: Forty-four treatment-naive female patients diagnosed with hypothyroidism and 39 age- and sex-matched control subjects were enrolled. Anthropometric measurements, blood pressure, plasma TSH, fetuin-A, free T4, LDL-cholesterol, triglyceride, C-reactive protein, fibrinogen levels, and brachial artery flow-mediated dilatation were measured. All measurements were repeated after 3 months in the control group and 3 months after the attainment of euthyroidism with l-T4 replacement in the hypothyroid group. Baseline data were compared between the two groups. Posttreatment plasma fetuin-A levels of hypothyroid patients were compared with baseline levels of both groups. The relationship between plasma fetuin-A, TSH levels, and other cardiovascular risk factors was evaluated. RESULTS: Plasma fetuin-A levels were ∼20% lower in hypothyroid female patients compared with the controls (P=0.0001). Fetuin-A levels increased by ∼20% in hypothyroid patients after achievement of euthyroidism (P=0.0001) and were no longer different compared with controls (P=0.38). There was a negative correlation between plasma TSH and fetuin-A levels (r=-0.79; P=0.001). There was no significant correlation between plasma fetuin-A levels and cardiovascular risk factors within or between groups. The fetuin-A levels were normalized with thyroid hormone treatment. CONCLUSION: Plasma fetuin-A levels are reduced in female patients with hypothyroidism, which are restored to normal during restoration of euthyroidism. There was no relation with cardiovascular risk factors.

Successful management of a giant pituitary lactosomatotroph adenoma only with cabergoline.

Although advances in endocrinologic and neuroradiologic research allow easier recognition of pituitary adenomas, giant pituitary tumours are relatively rare. In the literature, the term "giant" is generally used when a pituitary tumour becomes larger than 4 cm in diameter. Cabergoline is a potent and long-acting inhibitor of prolactin secretion, which exhibits high specificity and affinity for dopamine D2 receptor. Herein, we report a 46-year-old woman with a giant lactosomatotroph pituitary adenoma, sized 6 × 5 × 5.5 cm, who is treated successfully only with cabergoline. The patient showed dramatic response to cabergoline treatment by means of clinical, biochemical and radiological imaging findings. Cabergoline seems to be safe and effective in the treatment of prolactin and growth hormone cosecreting pituitary adenomas as well as prolactinomas. However, surgical or more aggressive approach must be considered where indicated.

A case of inoperable malignant insulinoma with resistant hypoglycemia who experienced the most significant clinical improvement with everolimus.

Metastatic insulinomas may sometimes present with recurrent life-threatening hypoglycemia episodes. Such patients usually fail to respond to various therapeutic agents which causes constant dextrose infusion requirement. Herein, we present a resistant case of inoperable malignant insulinoma who was treated with many therapeutic agents and interventions including somatostatin analogues, Yttrium-90 radioembolization, everolimus, radiotherapy, and chemoembolization. Close blood sugar monitorization during these therapies showed the most favourable response with everolimus. Everolimus treatment resulted in rapid improvement of hypoglycemia episodes, letting us discontinue dextrose infusion and discharge the patient. However, experience with everolimus in such patients is still limited, and more precise data can be obtained with the increasing use of this agent for neuroendocrine tumours.

Depression in patients with euthyroid chronic autoimmune thyroiditis.

Depression and chronic autoimmune thyroiditis are common diseases. The aim of this study was to determine whether the frequency of depression is elevated in patients with chronic autoimmune thyroiditis and normal thyroid function. A total of 201 subjects were included, of whom 107 and 94 participants were healthy or had euthyroid chronic autoimmune thyroiditis, respectively. Serum thyroid hormone levels and thyroid auto-antibodies were measured in all subjects. All participants were evaluated with Hamilton Depression Rating Scale (HDRS). HDRS scores of patients with euthyroid chronic autoimmune thyroiditis were higher than in healthy participants. This study suggests a possible association between depression and chronic autoimmune thyroiditis. The depression risk may be increased in patients with chronic autoimmune thyroiditis and normal thyroid function.

Macroprolactinemia, like hyperprolactinemia, may promote platelet activation.

Insulin resistance, which provides a convenient milieu for platelet activation, has been closely associated with atherosclerotic disorders. Although it often accompanies hyperprolactinemia, findings conflict concerning its clinical impact in macroprolactinemia. In order to investigate the relationship between hyperprolactinemia and platelet activation evidenced by ADP-stimulated P-selectin expression on flow cytometry, we studied hyperprolactinemic, macroprolactinemic, and normoprolactinemic subjects. Thirty-four hyperprolactinemic and 44 age- and body mass index-matched euprolactinemic premenopausal women were included. They were matched regarding insulin sensitivity status, waist circumference, blood pressures, and plasma lipids. In order to detect macroprolactinemia among hyperprolactinemic cases, prolactin was measured before and after polyethylene glycol (PEG) precipitation in patients' sera. P-selectin expression was significantly higher in the hyperprolactinemic group (P =0.001), and 41.2% of them exhibited macroprolactinemia. Expression of P-selectin was comparable between the macroprolactin-negative (monomeric hyperprolactinemia; n = 20) and -positive (n = 14) subgroups (P = 0.90). Both subgroups showed greater expression compared with normoprolactinemic controls (P = 0.014 and 0.005, respectively). Platelet activation accompanies the atherosclerotic disorders closely associated with insulin resistance. Among groups matched with regard to insulin-sensitivity markers, both monomeric hyperprolactinemia and macroprolactinemia appeared to promote platelet activation.

Lanreotide autogel and insulin sensitivity markers: report of 5 acromegalic patients and literature review.

OBJECTIVE: To evaluate the short-term effects of Lanreotide Autogel on insulin sensitivity markers among acromegalic patients with pituitary tumors. DESIGN: Prospective clinical trial with six months of follow-up. SETTING: A tertiary endocrinology clinic. MATERIALS AND METHODS: Naïve patients (patient No. 1 and patient No. 3) and patients who experienced prior somatostatin analogue treatment (patient No. 2, patient No. 4, and patient No. 5) were included. Before and after 6 months of Lanreotide Autogel therapy, insulin sensitivity in each subject was determined using homeostasis model assessment of insulin resistance and beta-cell function formula. Euglycemic hyperinsulinemic clamp test was also performed to evaluate whole insulin sensitivity and was indicated as an 'M' index. RESULTS: All patients experienced reduction in their HOMA-beta. We noted major HOMA-beta decreases accompanied by pronounced increases in M indices for patients Nos. 1, 2 and 3 (1.03 vs. 8.22, 2.98 vs. 4.70, and 5.09 vs. 13.09, respectively). The increases in M indices of these patients were with marked decreases in GH levels (34.20 vs. 15.30 microg/l, 4.25 vs. 0.74 and 5.0 vs. 0.66 ng/mL, respectively). Minor decline in HOMA-beta and worsened M index and almost stable GH were observed in patients Nos. 4 and 5. Except for patient No. 3, all participants showed declining HOMA-IR. CONCLUSIONS: Short-term Lanreotide Autogel treatment has been observed to improve M indices of acromegalic patients whose GH levels exhibited marked reduction. This amelioration seemed to be related to decreases in GH levels rather than to a direct drug effect.

A new perspective in diagnosing polycystic ovary syndrome.

Recently, the term of "possible" polycystic ovary syndrome (PCOS) has been used for defining cases in which biochemical evaluations are incomplete but clinical phenotypes are suggestive of PCOS. The aim of this study was, by using Rotterdam 2003 criteria, to detect possible PCOS cases and compare their characteristics and insulin sensitivity status with confirmed PCOS subjects. One-hundred-eighteen women who admitted with complaints and symptoms suggesting PCOS were included. Insulin sensitivity status of the cases was calculated with Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Cases fulfilling Rotterdam 2003 criteria were defined as confirmed PCOS, whereas indeterminate subjects as possible PCOS. Confirmed PCOS was detected in 70 (59.3%) and possible PCOS in 48 (40.7%) cases. Confirmed PCOS was most prevalent among subjects with hirsutism and menstrual dysfunction; 32 (80.0%) vs. 8 (20%), (p=0.000). Body mass index and HOMA-IR values did not differ between groups: confirmed PCOS versus possible PCOS; 25.46+/-5.55 kg/m(2) vs. 26.75+/-7.55 kg/m(2), 3.37+/-4.12 vs. 3.21+/-2.50, (p>0.05). Family history of type-2 diabetes mellifus was similar within both groups (p>0.05). Many PCOS patients seem to be undiagnosed due to inadherence to diagnostic work-up and/or to not fulfill Rotterdam 2003 criteria. These criteria may not be sufficient to cover the entire spectrum of PCOS.