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.

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.

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.