How does pregnancy affect the patients with pituitary adenomas: a study on 113 pregnancies from Turkey.

OBJECTIVE: Data regarding pregnancies in relation to pituitary tumors are limited. The effects of pregnancy on pituitary adenomas and the effects of adenoma itself (hormonal activity, mass effects and pituitary insufficiency) and/or treatment on the ongoing gestation and developing fetus were evaluated. METHODS: The study was a retrospective study. A questionnaire involving questions regarding medical history before index gestation, history of related pregnancy, result of index gestation and postpartum follow-up of the patients was filled by the investigator in one of the eight Referral Endocrinology Centers from Turkey. RESULTS: One hundred and thirteen (83 prolactinoma, 21 acromegaly, 8 NFPA and 1 plurihormonal pituitary adenoma) pregnancies of 87 (60 prolactinoma, 19 acromegaly, 7 NFPA and 1 plurihormonal pituitary adenoma) patients were reviewed. The clinically important pregnancy-related tumor growth of pituitary adenomas was found to be low in previously treated adenomas. Prolactinomas were more likely to increase in size during pregnancy especially if effective prior treatment was lacking. The risk of hypopituitarism is also minimal due to pituitary adenomas during pregnancy. The results of pregnancies did not differ in patients who were on medical treatment or not for prolactinomas and acromegaly during gestation. Neural tube defect and microcephaly associated with maternal cabergoline use; Down syndrome and corpus callosum agenesis associated with maternal bromocriptine use; unilateral congenital cataract, craniosynostosis and microcephaly associated with maternal acromegaly were detected for the first time. CONCLUSION: Medical treatment can be safely done stopped in patients with prolactinoma and acromegaly when pregnancy is confirmed and reinstituted when necessary. Prospective studies may help to determine the effects of medical treatment during gestation on the mother and fetus.

Effect of Vitamin D Treatment on Serum Sclerostin Level.

Objective Sclerostin is an osteocyte-secreted endogenous inhibitor of Wnt signaling. Several systemic and local factors have been suggested as possible regulators of sclerostin expression by osteocytes. In this study, we examined the effect of vitamin D treatment on sclerostin levels. Subject and Methods 44 patients with diagnosis of vitamin D deficiency (25(OH)D≤20 ng/ml) were involved in the study. Patients had monthly intramuscular injection of 300.000 IU cholecalciferol for 3 consecutive months. Sclerostin, 25(OH)D, parathyroid hormone (PTH), calcium, phosphorus and alkaline phosphatase (ALP) levels were measured during the diagnosis and after the replacement of vitamin D. Results 8 male and 36 female patients were enrolled in the study. Minimum age, maximum age and average age were 21, 55 and 32.02±9.26 years, respectively. A statistically significant difference was observed between the pre-treatment and post-treatment values in 25(OH)D levels (p:0.001, 10.27±4.62 ng/ml and 51.40±14.62 ng/ml, respectively), PTH levels (p:0.001, 50.32±19.05 pg/ml and 33.97±13.12 pg/ml, respectively) and sclerostin levels (p:0.002, 858.98±351.63 pg/ml and 689.52±197.92 pg/ml, respectively). No statistically significant difference, however, was found between the pre-treatment and post-treatment calcium, phosphorus and ALP levels. Correlation analysis made on pre-treatment and post-treatment sclerostin levels and 25(OH)D, PTH, calcium, phosphorus and ALP levels revealed no statistically significant correlation. Conclusion Our findings show that the sclerostin level of patients with vitamin D deficiency decreases considerably through treatment.

Evaluation of Ovarian Reserve with AMH Level in Patients with Well-Differentiated Thyroid Cancer Receiving Radioactive Iodine Ablation Treatment.

Introduction: Radioactive iodine (RAI) ablation treatment is used for patients diagnosed with well-differentiated thyroid cancer in order to reduce the risk of recurrence. RAI ablation treatment can adversely affect gonads in males and females. In this study, we aimed to determine ovary damage and infertility risk due to RAI, using serum anti-Müllerian hormone (AMH) level, in females who received RAI ablation treatment. Materials and Methods: 45 female patients who have not gone through the menopause and had received RAI ablation treatment for well-differentiated thyroid cancer in premenopausal period, and 40 healthy females as control groups were included in this study. The serum AMH, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), thyroid stimulating hormone (TSH) and creatinine levels of the patients included in the study were analyzed and compared to those of the control group with similar demographical characteristics. Results: No differences were found between the patient group and control group in terms of age, height, weight, body mass index, LH, E2 and creatinine. The difference in AMH, FSH and TSH between both groups were found to be significant. There was no statistically significant relation between the age and AMH levels. Similarly, no statistically significant relation between RAI exposure duration and AMH levels was determined. When the patients below and above the age of 35 were compared with regard to AMH (2.95±1.79 and 2.75±1.94, respectively) and FSH (5.45±1.63 and 5.99±3.06, respectively), the difference between them was found to be statistically insignificant. Oligo/anovulation was detected in 7 patients (15.6% of the patient group) after RAI treatment, 8 (17.8%) patients became pregnant after RAI treatment, and none of the patients, who were actively trying to get pregnant, were unable to achieve it. Conclusion: According to these results, it may be concluded that low AMH levels due to RAI treatment can cause damage to the ovaries of patients; nevertheless, considering the AMH levels and the absence of infertility in the patients, the infertility risk was found to be low.

Correlations between the expression levels of micro-RNA146b, 221, 222 and p27Kip1 protein mRNA and the clinicopathologic parameters in papillary thyroid cancers.

CONTEXT: It has been shown that miRNA 221, 222 and 146b are increasingly expressed while p27(Kip1) is suppressed in papillary thyroid cancer (PTC). OBJECTIVE: We investigated the association between the disease recurrence risk and the expression of miRNA 221, 222, 146b and p27(Kip1) protein mRNA in these tumors. We also measured the changes in miRNAs in the presence of Hashimoto's thyroiditis (HT). METHODS: We examined formalin fixed tissue samples obtained from 77 patients. 11 out of 77 samples were identified as well differentiated tumor with uncertain malignant potential (WDT-UMP), 46 were PTC and 20 were normal thyroid tissue. RESULTS: Data analysis revealed that the higher risk of recurrence was associated with the higher miRNA expression levels in thyroid cancers. Higher expression levels of miRNA 146b, 221 and 222 were detected in thyroid cancer patients presenting with capsule invasion, vascular invasion or lymph node metastasis, when compared to the patients lacking these features. Furthermore miRNA expression levels were found to be significantly elevated in patients with distant metastases. A negative correlation was found between the p27(Kip1) protein mRNA level and the expression levels of miRNA 221, 222 and 146b. While the expression levels of miRNA 221, 222 and 146b were found to be higher in the cases of WDT-UMP comparing to normal thyroid tissue, the p27Kip1 protein mRNA expression level was lower. No difference was found between the patients with HT and without HT regarding miRNAs expression levels. CONCLUSIONS: The expression levels of miRNA 221, 222 and 146b were found to be increased in cases of thyroid cancer with a high risk of recurrence. It is important to understand that these molecular changes such as miRNA expression may eventually be used to predict risk of recurrence.

Etiology of hypopituitarism in tertiary care institutions in Turkish population: analysis of 773 patients from Pituitary Study Group database.

Hypopituitarism in adult life is commonly acquired and the main causes are known as pituitary tumors and/or their treatments. Since there are new insights into the etiology of hypopituitarism and presence of differences in various populations, more studies regarding causes of hypopituitarism are needed to be done in different ethnic groups with sufficient number of patients. Therefore, we performed a multi-center database study in Turkish population investigating the etiology of hypopituitarism in 773 patients in tertiary care institutions. The study was designed and coordinated by the Pituitary Study Group of SEMT (The Society of Endocrinology and Metabolism of Turkey). Nineteen tertiary reference centers (14 university hospitals and 5 training hospitals) from the different regions of Turkey participated in the study. It is a cross-sectional database study, and the data were recorded for 18 months. We mainly classified the causes of hypopituitarism as pituitary tumors (due to direct effects of the pituitary tumors and/or their treatments), extra-pituitary tumors and non-tumoral causes. Mean age of 773 patients (49.8 % male, 50.2 % female) was 43.9 ± 16.1 years (range 16-84 years). The most common etiology of pituitary dysfunction was due to non-tumoral causes (49.2 %) among all patients. However, when we analyze the causes according to gender, the most common etiology in males was pituitary tumors, but the most common etiology in females was non-tumoral causes. According to the subgroup analysis of the causes of hypopituitarism in all patients, the most common four causes of hypopituitarism which have frequencies over 10 % were as follows: non-secretory pituitary adenomas, Sheehan's syndrome, lactotroph adenomas and idiopathic. With regard to the type of hormonal deficiencies; FSH/LH deficiency was the most common hormonal deficit (84.9 % of the patients). In 33.8 % of the patients, 4 anterior pituitary hormone deficiencies (FSH/LH, ACTH, TSH, and GH) were present. Among all patients, the most frequent cause of hypopituitarism was non-secretory pituitary adenomas. However, in female patients, present study clearly demonstrates that Sheehan's syndrome is still one of the most important causes of hypopituitarism in Turkish population. Further, population-based prospective studies need to be done to understand the prevalence and incidence of the causes of hypopituitarism in different countries.

Comparison of primary octreotide-lar and surgical treatment in newly diagnosed patients with acromegaly.

OBJECTIVE: The primary aim of the study was to compare the efficacy of Oct-LAR and surgery in terms of controlling IGF-1 and GH levels and tumour volumes. The second aim was to compare two primary treatment modalities in terms of side effects such as pituitary insufficiency, cholelithiasis, metabolic parameters and the effect on quality of life (QoL). DESIGN: The study was a randomized, prospective study. PATIENTS: The 22 patients were consecutively randomized to Oct-LAR and surgical treatment groups. RESULTS: Baseline serum IGF-1 level, tumour volume and GH levels were comparable in the Oct-LAR and surgery groups. No significant differences were detected between the Oct-LAR and the surgery groups in terms of IGF-1 and GH levels at the 3rd and 6th months, but at 12th month, preglucose GH was found to be lower in the surgical treatment group. IGF-1 control and complete biochemical response rates were found to be 27% and 64%, in the Oct-LAR and surgical treatment groups, respectively. The mean percentage of tumour volume reduction was found to be 26%, 30% and 31% in the Oct-LAR group vs 64%, 74% and 79% in the surgery group at the 3rd, 6th and 12th months, respectively. CONCLUSION: Primary surgical treatment seems to be slightly more effective than Oct-LAR in terms of biochemical response and IGF-1 control, besides tumour volume reduction, in patients with acromegaly with noninvasive tumours. Oct-LAR is associated with more side effects such as cholelithiasis and glucose metabolism disorders and is more expensive.

Development of pituitary apoplexy during TRH/GnRH test in a patient with pituitary macroadenoma.

Pituitary apoplexy occurs as a very rare complication following pituitary function tests. Signs and symptoms are due to the rapid expansion of an infarcted and/or haemorrhagic pituitary adenoma. We report a case of macroadenoma, in which pituitary apoplexy developed 30 minutes after administration of thyrotropin-releasing hormone (TRH) and gonadotropin-releasing hormone (GnRH) injections. Magnetic resonance (MR) imaging had earlier revealed several haemorrhagic zones. After the TRH and GnRH injections, the patient complained of visual defect. MR imaging demonstrated an increase in the size of the pituitary adenoma and several haemorrhagic zones that formed a fluid-fluid level at the centre of the lesion. The pituitary mass was removed using the transsphenoidal approach. On immunostaining, follicle-stimulating and luteinising hormones were strongly positive, while prolactin was weakly positive. Pituitary functions were evaluated by dynamic function tests at six weeks post operation. The patient's pituitary functions and visual acuity were found to be normal.

Investigation of pituitary functions in patients with acute meningitis: a pilot study.

OBJECTIVE: Although long-term pituitary consequences of tuberculous meningitis are well documented in the literature, there have been few case reports of pituitary dysfunction after acute bacterial or viral meningitis. In this preliminary study, we have assessed the pituitary functions in adult patients who had acute bacterial or viral meningitis. DESIGN AND METHODS: Fourteen patients (8 men, 6 women; mean age 35.3+/-13.3) were included in the study. The diagnosis of bacterial and viral meningitis was proven by clinical findings, cerebrospinal fluid (CSF) examination, gram staining, and blood and CSF cultures. Pituitary functions were evaluated ranging from 6 to 48 months (mean 20 months) after acute meningitis. GH deficiency was investigated by the GHRH+arginine stimulation test. RESULTS: Four of 14 patients (28.6%) had isolated GH deficiency. In GH-deficient patients, the earliest duration was 6 months and the latest duration was 48 months after the diagnosis of acute meningitis. Three of the GH-deficient patients had acute bacterial meningitis and 1 patient had acute viral meningitis. Pituitary magnetic resonance imaging revealed normal pituitary gland in the patients with GH deficiency. CONCLUSIONS: This is the first systematic study evaluating the anterior pituitary function long term after the diagnosis of acute meningitis. Based on the present study, it is tempting to speculate that pituitary dysfunction is a more common sequel of acute bacterial or viral meningitis than hitherto reported. Studies with high numbers of patients are warranted to ascertain the prevalence of meningitis-induced hypopituitarism.

The evaluation of the role of beta-hydroxy fatty acids on chronic inflammation and insulin resistance.

Beta-hydroxy fatty acids are a major component of lipid A moiety of lipopolysaccharide. We aimed to investigate the role of free beta-hydroxy fatty acids on inflammation, as well as to evaluate their effects on cytokine release from human blood cells, and whether they exist in plasma of patients with chronic inflammatory diseases with/without insulin resistance. Peripheral venous blood was incubated with beta-hydroxy lauric and beta-hydroxy myristic acids (each 100 ng, 1 microg, 10 microg/mL) up to 24 hours. Cytokines were measured from culture media and plasma. Free fatty acids and biochemical parameters were also measured from patients' plasma. Only beta-hydroxy lauric acid significantly stimulated interleukin-6 production at 10 microg/mL compared to control (533.9 +/- 218.1 versus 438.3 +/- 219.6 pg/mL, P < .05). However, free beta-hydroxy lauric and myristic acids were not found in patients' plasma. Therefore, free beta-hydroxy lauric and myristic acids do not seem to have a role on sterile inflammation in chronic inflammatory diseases associated with insulin resistance.

Prevalence of Helicobacter pylori in patients with primary hyperparathyroidism.

Dyspeptic symptoms are common in patients with primary hyperparathyroidism (PHPT) and have been attributed to hypercalcemia; however, they may also become permanent after parathyroid surgery. We aimed to evaluate the prevalence of Helicobacter pylori in patients with PHPT and to see whether there is a relationship between dyspeptic complaints and H. pylori infection. Of 21 patients with PHPT, 18 patients had dyspeptic complaints. These 18 female patients with PHPT and dyspeptic symptoms were the study population, and 20 female volunteers with dyspeptic symptoms were the controls. An endoscopic examination was performed in all controls and in patients before parathyroid surgery. H. pylori was assessed by serological and histological evaluation. H. pylori was identified upon histological evaluation in 17 patients (94.4%) and serologically in 17 patients (94.4%). Active macroscopic and microscopic gastritis were found in 15 (83.3%) and in 17 (94.4%) of the patients, respectively. In the control group, H. pylori was identified histologically in 13 subjects (65%) and serologically in 17 subjects (85%). The prevalence of H. pylori assessed by histological examination was significantly (P < 0.05) different between patients and controls. There was a significant association between H. pylori infection identified by histology and/or serology and the presence of microscopic (r = 1; P < 0.001), as well as macroscopic (r = 0.54; P < 0.05), gastritis. In conclusion, this study showed that H. pylori infection was found frequently (85.7%) in patients with PHPT. In the management of PHPT with or without surgery, patients, especially those with dyspeptic symptoms, should be evaluated for H. pylori infection, which can be effectively eradicated by appropriate therapy.

Relationship between bone mineral density and insulin resistance in polycystic ovary syndrome.

The aim of the present study was to evaluate whether there is a relationship between bone mineral density (BMD) and insulin resistance and hyperinsulinemia in women with polycystic ovary syndrome (PCOS). The study consisted of 28 amenorrheic women with PCOS and 11 amenorrheic women without PCOS. Fifteen healthy women with normal ovulatory function, matched for age and body mass index (BMI), served as controls. BMD was measured at the lumbar spine and left femoral neck with dual-energy X-ray absorptiometry. Blood samples were obtained to measure serum levels of insulin, follicle-stimulating hormone, luteinizing hormone, sex hormone-binding globulin (SHBG), total and free testosterone, androstenedione and estradiol by radioimmunassay. Insulin resistance was estimated by the in sulin tolerance test (ITT), and K(ITT) was taken as the insulin sensitivity index. In the PCOS group, K(ITT) was significantly lower and insulin levels were higher than in either of the control groups (P < 0.001). BMD in the PCOS group was lower than in the healthy group and higher than in the amenorrheic control group (P < 0.05). In the PCOS group, there were positive correlations of BMD of the lumbar spine with insulin (r = 0.42: P < 0.05) and negative correlations of BMD with K(ITT) (r = -0.58; P < 0.001) and SHBG (r = -0.38; P < 0.05). The inverse association of BMD and K(ITT) was independent of BMI, insulin, SHBG, androstenedione, and free testosterone. In conclusion, insulin resistance and hyperinsulinemia in women with PCOS may be a relative protective factor against bone mineral loss.

A comparison between the 1-microg adrenocorticotropin (ACTH) test, the short ACTH (250 microg) test, and the insulin tolerance test in the assessment of hypothalamo-pituitary-adrenal axis immediately after pituitary surgery.

The short ACTH stimulation test is an easy, reliable, and extensively used test in the assessment of the hypothalamo-pituitary-adrenal (HPA) axis. However, its use immediately after pituitary surgery is a matter of debate. The insulin tolerance test (ITT) is the gold standard in the evaluation of the HPA axis, but it is not always without side effects and may be unpleasant early after pituitary surgery. Our aim was to investigate the value of the 1-microg ACTH test in the assessment of the HPA axis early after pituitary surgery. We also aimed to determine the value of the 1-microg and 250-microg ACTH tests and the ITT in the estimation of HPA axis status after 3 months postoperatively. Nineteen patients subjected to pituitary tumor surgery were included in the study, and the ITT and the 1-microg and 250-microg ACTH tests were performed between the 4th and 11th days of surgery. The tests were repeated at the first month in 3 patients with subnormal peak cortisol responses (454, 125, and 301 nmol/L) and in 18 patients at the third month postoperatively. ACTH stimulation tests were performed by using 1 microg and 250 microg ACTH iv as a bolus injection, and blood samples were drawn at 0, 30, and 60 min for measurement of serum cortisol levels. The ITT was performed by using iv regular insulin, and serum glucose and cortisol levels were measured. The 1-microg and 250-microg ACTH stimulation tests and the ITT were performed consecutively. At least 48 h were allowed between each test. A peak serum cortisol level of 550 nmol/L or greater was considered as a normal response for both the ITT and the ACTH tests. The serum cortisol level was measured by RIA using commercial kits. Serum glucose was determined by glucose oxidase method. There were correlations between the peak cortisol response to the ITT and the 1-microg ACTH test (r = 0.39, P < 0.05) in the early postoperative period. No correlation was found between the ITT and the 250-microg ACTH test responses. In the early postoperative period, two patients showed normal cortisol responses (> or =550 nmol/L) to the 1-microg ACTH test and five patients showed normal cortisol responses to the 250-microg ACTH test among the six patients with subnormal cortisol responses to the ITT. Three patients with subnormal cortisol responses to ITT and baseline cortisol values less than 240 nmol/L showed normal HPA axis at the end of the first month. In the late postoperative period, at the third month, all the patients showed normal HPA axis. In the early postoperative period of pituitary surgery, the 1-microg ACTH test results are more concordant than the 250-microg ACTH test in comparison with the ITT. Our results also indicate that HPA axis dysfunction shown by ACTH stimulation tests and the ITT in early postoperative period may be normalized 1-3 months after surgery. For this reason, we think that dynamic tests including the ITT may not be useful early after pituitary surgery.

Pituitary apoplexy probably due to TRH and GnRH stimulation tests in a patient with acromegaly.

Pituitary apoplexy is the most serious and life-threatening complication of pituitary adenomas. Most of the cases occur spontaneously but it may occur also after a number of events such as the pituitary stimulation tests. We report a case of acromegaly due to a giant pituitary adenoma in which pituitary apoplexy developed 88 hours after TRH/GnRH stimulation test. The patient had severe headaches, nausea, vomiting, visual disturbance and mental alteration and the computed tomography (CT) scans revealed intratumoral and intraventricular bleeding. The pituitary mass was removed by transsphenoidal approach. The patient developed pneumonia and died on the 9th postoperative day. Pituitary apoplexy was confirmed at surgery and on histological examination. Immunohistochemical staining was positive for GH and PRL. This case indicates that pituitary apoplexy may develop several days after TRH/GnRH stimulation test.

Platelet aggregation size and volume in chronic obstructive pulmonary disease.

In this study the effect of hypoxia on thrombocytes was investigated in patients with a chronic obstructive pulmonary disease (COPD). 15 Hypoxic (group 1), 15 nonhypoxic (group 2) patients with COPD and 10 healthy persons (group 3) were included in the study. The differences in haemoglobin, hematocrit and PaCO2 values of group 1 and group 2 were insignificant, but there was a significant difference between group 3 and the other two groups. The differences in blood pH values in the above groups were insignificant, but the differences in FEV1, FVC and PaO2 values were significant. We found that thrombocyte aggregation increased significantly in group 1 and group 2. Also the platelet count decreased and mean platelet volume increased significantly in group 1. As a result, we think that in hypoxic patients with COPD, thrombocyte count decreases, volume and aggregation formation increases and oxygen plus antiaggregation therapy may have positive effects on the survival and life quality of these patients.