Clinical and demographic aspects of Paget disease of bone: A multicentric study from Turkey.

OBJECTIVE: Paget disease of bone (PDB) is a metabolic bone disease that has been rarely reported in the Eastern countries. This study aimed to evaluate the clinical and demographic characteristics of patients with PDB followed up at endocrinology clinics in Turkey. METHODS: An invitation was sent to tertiary endocrinology clinics to complete a survey on the demographic, clinical, radiological, and laboratory parameters, as well as treatment modalities of patients with PDB. This study enrolled clinically and radiologically proven 185 patients with PDB from 18 endocrinology centers based in 10 cities of Turkey. RESULTS: This cohort of PDB had female preponderance (women/men: 105/80) with a mean age, during diagnosis, of 57±10 years. Most of the patients (59.6%) were symptomatic at diagnosis. Bone pain and headache were the predominant clinical symptoms. Polyostotic disease was observed in 67.5% (n=125) of patients. Frequently affected bones were skull (41.6%), pelvis (53.5%), spine (41%), and femur (25.4%). Moreover, 17 patients with skull involvement had hearing loss. Mean serum alkaline phosphatase (ALP) level (552±652 IU/L; range: 280-5762 IU/L) was over the normal reference cutoff with normal serum calcium levels. Intravenous bisphosphonates (zoledronic acid, 5 mg; pamidronate, 60-90 mg) were the most used drugs (75%) for the treatment of PDB. Most of the patients (87.1%) treated with intravenous bisphosphonates responded well, with a decrease in serum ALP level (117±114 IU/L) in the 12th month of therapy. Furthermore, 16 patients relapsed after the second year of therapy; 3 patients did not respond to the initial intravenous bisphosphonate treatment. CONCLUSION: The patients with PDB followed up by endocrinology clinics of Turkey exhibited polyostotic disease with classical clinical, radiological, and biochemical features and women's predominance with good response to intravenous bisphosphonate therapy.

The relation between BRAFV600E mutation and clinicopathological characteristics of papillary thyroid cancer.

Aim BRAF mutation inhibits many tumour suppressor genes, increases pro-angiogenic molecules and reduces radioactive iodine uptake of tumour in papillary thyroid cancer (PTC), giving it more aggressive clinical characteristics. In this study, we aimed to evaluate the effect of BRAF V600E mutation on the clinicopathological features in patients with PTC. Methods The laboratory and clinical findings of 256 PTC patients who were referred to our clinic between 2007 and 2017 were assessed. Subjects involved in the study were divided into two groups depending on the presence of BRAF V600E mutation. Results BRAF V600E mutation testing gave positive results for 65 (25.4%) out of 256 patients. No significant correlation between BRAF V600E mutation, age and gender was detected. There was no difference between the groups in terms of tumour variant, tumour localization, tumour focality, and perineural invasion. In terms of histopathologic characteristics, presence of tumour capsular invasion (p=0.027), extrathyroidal extension (ETE) (p=0.002), absence of pathologically detected lymphocytic thyroiditis (p=0.006) and radio iodine I-131 treatment (p=0.001) were significantly higher in BRAF V600E (+) patients. During a followup period, four patients with BRAF V600E (+) and two patients with BRAF V600E (-) status underwent lateral neck dissection due to lymph node metastasis (p=0.01). Conclusion The presence of BRAF V600E mutation was proved to be a poor prognostic factor. However, in order to further assess the prognostic effect of BRAF V600E mutation in this group of patients and particularly its effect on mortality, long term followup results must be evaluated.

Comparison of clinicopathological features in patients with noninvasive follicular thyroid neoplasm with papillary-like nuclear features and follicular variant papillary thyroid cancer.

INTRODUCTION: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a newly defined entity accepted as a tumor precursor. OBJECTIVES: We aimed to examine the features of patients diagnosed with follicular variant papillary thyroid carcinoma (FVPTC), which are classified as NIFTP in the recent classification. This study compares clinical, radiological, histopathological, and molecular featur es of NIFTP and FVPTC. PATIENTS AND METHODS: A total of 247 patients with FVPTC were retrospectively examined and pathology specimens were reviewed. RESULTS: Patients were divided into 2 groups (NIFTP group: 107 patients; FVPTC group: 140 patients). There was a difference in terms of the percentage of pathologic nodules with irregular borders detected on preoperative neck ultrasonography (NIFTP group: 6.5%, FVPTC group: 15.7%; P = 0.02). Central lymph node dissection specimens of 50 patients in the NIFTP group were normal, while 4 of 70 patients (5.7%) in the FVPTC group had lymph node metastasis (P = 0.14). In addition, multivariable analysis (binary logistic regression) showed that FVPTC was positively associated only with irregular borders and extrathyroidal extensions (P = 0.02 and P <0.001, respectively). CONCLUSIONS: We suggest that patients diagnosed with NIFTP according to the new classification are considered lowrisk, and margin characteristics of the nodule detected on preoperative ultrasonography may be helpful in the differential diagnosis.

Benign and Malignant Thyroid Gland Diseases in the Patients with Primary Hyperparathyroidism.

INTRODUCTION: This study aimed to evaluate concurrently detected thyroid pathologies in the patients who underwent surgery for primary hyperparathyroidism (PHPT). MATERIALS AND METHODS: In this study, we retrospectively analyzed the files of the patients who underwent surgery for PHPT between 2012 and 2015. Pre- and post-operative laboratory examination results and preoperative radiological and nuclear medicine findings of the patients were retrospectively recorded. RESULTS: A total number of 41 patients with PHPT were divided into two groups as the Group 1 with PHPT and benign thyroid pathology (21 patients) and the Group 2 with PHPT and malignant thyroid pathology (20 patients). In Group 1, 18 and 3 of 21 patients were females and males, respectively. Group 2 included 15 male and 5 female patients. The mean age of the patients was found to be 55.6 and 53.9 years in Group 1 and Group 2, respectively. Both groups were matched for age and gender. In terms of thyroid pathology, 20 of 41 patients (48.7%) who underwent total thyroidectomy for PHPT were found to have thyroid papillary carcinoma while benign pathologic conditions were detected in 21 (51.3%) individuals. CONCLUSIONS: Cooccurrence of thyroid diseases and PHPT is common. Therefore, all the patients should preoperatively be evaluated for the presence of thyroid pathology to determine the technique of parathyroid surgery.

Follicular morphological characteristics may be associated with invasion in follicular thyroid neoplasms with papillary-like nuclear features.

The newly proposed nomenclature and diagnostic criteria for encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), the noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), could improve the consistency and accuracy of diagnosing this entity. Diagnosis of NIFTP requires evaluation of the complete tumor border or capsule. The presence of tumor invasion in follicular thyroid neoplasms with papillary-like nuclear features has been recently discussed by many authors. In this study, we examined the predictive value and association of follicular morphological characteristics with the tumor invasion. In addition, we analyzed the association between tumor encapsulation and molecular profile in EFVPTC/NIFTP cases. A total of 106 cases of FVPTC were included in the study. The tumors were grouped based on the presence of tumor capsule and characteristics of tumor border, as 1) completely encapsulated tumors without invasion, 2) encapsulated tumors with invasion, 3) infiltrative tumors without a capsule. Clinicopathological features, histomorphological features [nuclear criteria, minor diagnostic features, follicles oriented perpendicular to tumor border/capsule (FOPBC)] and molecular alterations in BRAF, NRAS, and KRAS genes were evaluated. FOPBC were significantly more frequently seen in encapsulated tumors with invasion (p = 0.008). The nuclear features were not associated with the presence of encapsulation and characteristics of tumor border. BRAF mutation was more frequent in infiltrative tumors, while NRAS mutation was more frequent in encapsulated tumors, but the results were not statistically significant (p = 0.917). In conclusion, FOPBC histomorphological feature may be associated with tumor invasion in EFVPTC/NIFTP. Additionally, BRAF/KRAS/NRAS mutation analysis may prevent inadequate treatment in these patients.

TERT Expression in Pituitary Adenomas.

OBJECTIVE: Although pituitary adenomas have benign histomorphological features, some of them may present in an aggressive manner. To predict the behaviour of these tumours, telomerase reverse transcriptase (TERT) activity in pituitary adenomas has been the subject of a few studies with contradictory results. This study aims to investigate whether immunohistochemical expression of TERT differs in neoplastic and nonneoplastic pituitary tissues and aims to investigate whether TERT expression is related to clinicopathological features of pituitary adenomas. MATERIAL AND METHOD: The study included 48 patients who had been diagnosed with pituitary adenomas and had clinical follow-ups. Nonneoplastic pituitary tissues were obtained from autopsy specimens (n=20). Immunohistochemistry for TERT antibody was performed. Both the nuclear and cytoplasmic expression of TERT antibody was noted, and total combined TERT staining was evaluated according to nuclear and cytoplasmic stainings. RESULTS: TERT expression did not differ between neoplastic and nonneoplastic pituitary tissues. Neither total (combined nuclear and cytoplasmic) TERT nor nuclear TERT expression revealed any statistically significant relationship with any of the clinicopathological features. Higher cytoplasmic TERT expression was observed in adenomas with recurrence than adenomas without recurrence (p=0.035). CONCLUSION: This study introduces the notion that immunohistochemical expression of TERT does not differ in neoplastic and nonneoplastic pituitary tissues. Pituitary adenomas with cytoplasmic immunohistochemical expression of TERT have significantly higher rates of recurrence. Further studies, including combined methods of immunohistochemistry and molecular analyses in larger groups, may reveal applicable results for the clinical significance of TERT in pituitary adenomas.

Relationship between lymphovascular invasion and clinicopathological features of papillary thyroid carcinoma.

Lymphovascular invasion (LVI) is an important prognostic factor in various solid tumors, however, data on the association between LVI and thyroid carcinomas are limited. In this study, we evaluated the relationship between LVI and clinicopathological features of papillary thyroid carcinoma (PTC). Six hundred seventy-eight patients diagnosed with PTC between 2012 and 2015 were included into the study. Patients were classified based on the presence or absence of LVI. Gender, age, ultrasonography (US), tumor size and multifocality, BRAFV600E mutation, perineural and capsular invasion, extrathyroid extension (ETE), nodal metastasis, and recurrences were evaluated, and risk analysis was performed for each parameter. The number of patients with LVI [LVI (+)] was 63, while the number of patients without LVI [LVI (-)] was 615. The female/male ratio was 564/114. LVI was present in 18.4% of male patients and in 7.4 % of female patients. In the age group between 17-25 years LVI was detected in 6/13 patients, and this result was statistically significant compared to other age groups (p = 0.004). Suspicious lymph nodes upon US, perineural or capsular invasion, ETE, tumor size, and nodal metastasis were significantly more frequent in LVI (+) group (p < 0.001). The frequency of BRAFV600E mutation was also significantly higher in LVI (+) group (p < 0.001). Overall, the presence of LVI was associated with gender, tumor size, age, lymph node metastasis, pathological lymph nodes, perineural and capsular invasion, ETE, and BRAFV600E mutation. These results suggest that in PTC patients undergoing thyroidectomy, the presence of LVI should be considered as an indicator of aggressive clinicopathological features and those patients should be followed up carefully for recurrences and metastasis.

Comparison of clinicopathological features in incidental and nonincidental papillary thyroid carcinomas in 308 patients.

Incidental papillary thyroid carcinomas (IPTCs) consist of a significant portion of increasing incidence in papillary thyroid carcinomas. This study investigated the clinicopathological features of IPTCs from different perspectives and by comparing nonincidental PTCs (NIPTCs) in patients who underwent total thyroidectomy and lymph node dissection. Basic results were as follows. IPTC was present in 27.9% of 308 patients. IPTCs were significantly accompanied by lymphocytic thyroiditis (LT), particularly, multinodular hyperplasia (MNH). IPTCs were more common in older patients (51.3 years vs. 47.2 years) and in female patients. IPTCs significantly differed from NIPTCs in terms of smaller tumour size, lymphatic vessel invasion (2.6% vs. 97.4%), extrathyroidal extension (4.3% vs. 95.7%), lymph node metastasis (3.6% vs. 96.4%), multifocality (21.2% vs. 78.8%), bilaterality (5.3% vs. 94.7%), and BRAFV600 mutation (6.7% vs. 93.3%). Older age, bilaterality, encapsulation, and radioactive iodine (RAI) were significantly more common in IPTCs > 5 mm than in those ≤ 5 mm. In conclusion, IPTCs are more commonly associated with LT and MNH. IPTCs may have a more favourable prognosis than NIPTCs, and tumour size > 5 mm may predict bilaterality and need for RAI. Nevertheless, the patient-based clinical approach in IPTCs may have benefits in the management of IPTCs.

Serum Adiponectin Level as a Predictor of Subclinical Cushing's Syndrome in Patients with Adrenal Incidentaloma.

Subclinical Cushing's syndrome (SCS) is a condition of slight but chronic cortisol excess in patients with adrenal incidentaloma (AI) without typical signs and symptoms of Cushing's syndrome. Adiponectin has potent roles in modulating energy balance and metabolic homeostasis and acts in opposition to glucocorticoids. This study aimed to evaluate adiponectin level in SCS and nonfunctional AI (NAI) patients and its relation with metabolic parameters. Patients with AI (n = 40) and metabolically healthy controls (n = 30) were included. In AI patients and controls, detailed medical history assessment, physical examinations, anthropometric measurements, and laboratory measurements were performed. Age, body mass index, waist circumference, and lipid profiles were significantly higher and waist-to-hip ratio and adiponectin level were significantly lower in the AI patients than in the controls. The midnight cortisol and urinary free cortisol levels were significantly higher in the SCS patients (n = 8) than in the NAI patients (n = 32). Adiponectin level of the SCS group was significantly lower than those of the NAI and control groups. The sensitivity and specificity for an adiponectin level of ≤13.00 ng/mL in predicting the presence of SCS were 87.5% and 77.4%, respectively. In conclusion, adiponectin is valuable in predicting the presence of SCS in AI patients.

Iatrogenic Cushing's Syndrome After Topical Steroid Therapy for Psoriasis.

Glucocorticoids are used for the treatment of many diseases, such as inflammatory, allergic, autoimmune, and neoplastic diseases. They can be used in the form of topical, oral, inhalable, rectal, and intra-articular agents. Many topical steroid-related iatrogenic Cushing's syndrome cases affecting especially children have been reported in the literature. Topical steroid-related Cushing's syndrome is rarely seen in adults. In this report, we present the case of a 32-year-old male patient with iatrogenic Cushing's syndrome related to long-term clobetasol propionate treatment for psoriasis. In the context of such treatment, the glucocorticoid withdrawal problem has to be overcome. At present there is no consensus on steroid withdrawal. Patients on long-term glucocorticoid treatment must be evaluated for potential adverse effects and withdrawal symptoms by their physician and their endocrinologist.

Histological perspective on the effects of tumor-associated macrophages in the tumor microenvironment surrounding papillary thyroid carcinoma.

Tumor-associated macrophages (TAMs) are one of the most noticeable elements of the tumor microenvironment. The present study investigated the relationships between the density of CD163 immunolabeled M2-like TAMs with other histological properties of the tumor microenvironment and clinipathological features in 90 patients with papillary thyroid carcinomas (PTC). The percentage of TAMs was higher in tumors with significant lymphocytic tumor response (p = 0.020), in tumors with a significant degree of stromal tumor response (p = 0.014), those with infiltrative tumor borders (p = 0.029), in conventional variant papillary carcinoma (p = 0.032), and in patients with autoantibodies for thyroid peroxidase (p = 0.014). The tumors associated with lymphocytic thyroiditis had lower numbers of TAMs (p = 0.027). In conclusion, for the first time, the present study attempts to establish a full assessment of interactions of CD163 expressing M2-like TAMs with the triad of primary tumor- tumor microenvironment- tumor behavior and above all, with markers of autoimmunity. Thus, these alternatively polarized macrophages may act in tumor progression and dissemination according to their various products, which may be ordered by tumor cells or neighboring immune cells. The molecular studies may reveal their roles in various tumors and may improve the therapy strategies targeting TAMs in various malignant tumors, including PTCs.

Histopathological Evidence of Lymph Node Metastasis in Papillary Thyroid Carcinoma.

Prophylactic lymph node dissection is still controversial due to the potentially surgery-related morbidity in management of papillary thyroid carcinomas. So, some histopathological predictors for lymph node metastasis in thyroidectomy specimens may reveal importance. The objective of this study was to define histomorphological indicators of lymph node metastasis in the patients who had been performed thyroidectomy without lymph node dissection. Clinicopathological features of patients archived in Department of Pathology at Trakya University Medical Faculty were reviewed. A total of 211 patients who had been diagnosed as papillary carcinoma and had been performed total thyroidectomy/lobectomy with central/cervical lymph node dissection were included in the study. Clinical features (age, gender, preoperative/postoperative clinical, and laboratory findings) and histopathological features (histological variant, tumor size, focality, extrathyroidal extension, tumor border, lateral tubular growth, intraglandular dissemination, stromal and lymphocytic tumor response, lymphocytic thyroiditis, lymphovascular invasion, lymph node metastasis, number of metastatic lymph nodes, extranodal extension, size of the metastatic foci) were evaluated. Male gender, conventional variant, tumor size greater than 10 mm, multifocality, extrathyroidal extension, lateral tubular growth, intraglandular dissemination, lymphocytic and stromal tumor response, and absence of lymphocytic thyroiditis were predictive, and older age (≥45 years) and follicular variant PTC were protective for lymph node metastasis. In order to optimize the management of papillary thyroid carcinomas, pathologists should search for the clues of lymph node metastasis particularly intraglandular dissemination, lateral tubular growth, tumor border and lymphocytic/stromal tumor response, multifocality, concomitant lymphocytic thyroiditis besides the actual prognostic criteria especially in younger aged male patients.

Submandibular ectopic thyroid with normally located thyroid gland.

Ectopic thyroid is a rare developmental anomaly of the thyroid gland which is defined as the presence of thyroid tissue at a site other than the pretracheal area. Nearly 1 to 3% of all ectopic thyroids are located in the lateral neck. Simultaneous submandibular ectopic thyroid tissue presenting with a functional orthotopic thyroid gland is extremely rare. In this article, we report a 37-year-old female case admitted to our clinic with a complaint of swollen neck in whom ultrasonography revealed submandibular ectopic thyroid tissue presenting with an orthotopic thyroid gland.

Propylthiouracil induced leukocytoclastic vasculitis: A rare manifestation.

Propylthiouracil (PTU) is a common drug used in patients with hyperthyroidism. It may cause perinuclearantineutrophil cytoplasmic antibodies (p-ANCA) in few patients with Graves' disease. This antibody has been associated with different forms of vasculitis. We report a patient who presented with cutaneous manifestations of leukocytoclasticvasculitis with simultaneous development of p-ANCAs during PTU therapy for Graves' disease.

Impaired glucose metabolism is a risk factor for increased thyroid volume and nodule prevalence in a mild-to-moderate iodine deficient area.

OBJECTIVE: Insulin resistance (IR) is a key factor involved in the pathogenesis of impaired glucose metabolism. IR is associated with increased thyroid volume and nodule prevalence in patients with metabolic syndrome. Data on the association of thyroid morphology and abnormal glucose metabolism are limited. This prospective study was carried out to evaluate thyroid volume and nodule prevalence in patients with pre-diabetes and type 2 diabetes mellitus (DM) in a mild-to-moderate iodine deficient area. MATERIALS AND METHODS: Data were gathered on all newly diagnosed patients with pre-diabetes and type 2 diabetes mellitus between May 2008 and February 2010. 156 patients with pre-diabetes and 123 patients with type 2 DM were randomly matched for age, gender, and smoking habits with 114 subjects with normal glucose metabolism. Serum thyroid-stimulating hormone (TSH) and thyroid ultrasonography was performed in all participants. RESULTS: Mean TSH level in the diabetes group (1.9±0.9 mIU/L) was higher than in the control group (1.4±0.8 mIU/L) and the pre-diabetes group (1.5±0.8 mIU/L) (P<0.0001 for both). Mean thyroid volume was higher in the pre-diabetes (18.2±9.2mL) and diabetes (20.0±8.2mL) groups than in controls (11.4±3.8mL) (P<0.0001 for both). Percentage of patients with thyroid nodules was also higher in the pre-diabetes (51.3%) and diabetes groups (61.8%) than in controls (23.7%) (P<0.0001 for both). CONCLUSIONS: The results suggest that patients with impaired glucose metabolism have significantly increased thyroid volume and nodule prevalence.

Fine-needle aspiration biopsy of thyroid nodules: comparison of diagnostic performance of experienced and inexperienced physicians.

OBJECTIVE: To determine whether a difference exists in terms of obtaining adequate cytologic samples from ultrasound-guided fine-needle aspiration cytology (US-FNAC) between experienced and inexperienced physicians in a tertiary referral center. METHODS: In a prospective design, all patients with thyroid nodules of at least 10 mm in diameter were referred for US-FNAC tissue sampling as a part of their diagnostic work-up. Between May 2006 and September 2009, 997 euthyroid patients with 1,320 thyroid nodules were referred for US-FNAC by the attending endocrinologist (experienced physician) or 1 of 2 endocrinology fellows (inexperienced physicians). RESULTS: Of the 1,320 nodules, 713 biopsy specimens were obtained by the experienced physician and 607 were obtained by the inexperienced physicians. Nodule size was significantly larger in the endocrinologist's group of patients than in the fellows' group of patients (17 mm versus 14 mm, respectively; P<.001). The inadequacy rate of the US-FNAC procedures performed by the experienced physician (22 of 713 thyroid nodules or 3.1%) was significantly lower than for those performed by the inexperienced physicians (102 of 607 thyroid nodules or 16.8%) (P<.001). CONCLUSION: We conclude that, with increasing operator experience, the number of inadequate cytologic specimens generated by US-FNAC procedures is substantially reduced. This limits both direct and indirect costs and also minimizes the risks of possibly unnecessary surgical procedures.

Metabolic syndrome and its components are associated with increased thyroid volume and nodule prevalence in a mild-to-moderate iodine-deficient area.

OBJECTIVE: Metabolic syndrome (MetS) is a cluster of metabolic abnormalities with insulin resistance (IR) as a major component. It has been recently questioned whether MetS and its related components are associated with functional and morphological alterations of the thyroid gland. The aim of our study is to examine thyroid volume and nodule prevalence in a case-control study of patients with MetS in a mild-to-moderate iodine-deficient area. DESIGN: Two hundred and seventy-eight patients with MetS were randomly matched for age, gender, and smoking habits with 261 subjects without MetS. Serum TSH, free tri-iodothyronine and thyroxine, and the level of IR, which was estimated by the homeostasis model assessment for IR, as well as other MetS parameters were evaluated. Thyroid ultrasonography was performed in all subjects. All subjects with thyroid nodules >1 cm were offered to undergo thyroid fine needle aspiration biopsy. RESULTS: TSH was significantly positively correlated with the presence of MetS diagnosis. There was no association between free thyroid hormone levels and MetS and its related components. Mean thyroid volume was significantly higher in patients with MetS than in controls (17.5 + or - 5.5 vs 12.2 + or - 4.2 ml, P<0.0001). Also the percentage of patients with thyroid nodules was significantly higher in patients with MetS (50.4 vs 14.6%, P<0.0001). Subjects were also divided into two groups according to the presence of IR. The group of subjects with IR had increased thyroid volume and nodule formation. The odds ratio for the development of thyroid nodule in the presence of IR was 3.2. TSH as well as all MetS components were found to be independent predictors for thyroid volume increase. IR but not TSH was found to be correlated with thyroid nodule formation. Thyroid cancer was diagnosed in 3 out of 38 patients with MetS who agreed to have a biopsy (7.9%). None of the subjects in the control group was diagnosed to have thyroid cancer. CONCLUSIONS: The results suggest that patients with MetS have significantly increased thyroid volume and nodule prevalence. Multivariate regression analysis model demonstrated that the presence of IR contributed substantially to this increased risk. Our data provide the first evidence that IR is an independent risk factor for nodule formation in an iodine-deficient environment.

Evaluation of brain natriuretic peptide levels in hyperthyroidism and hypothyroidism.

BACKGROUND: Brain natriuretic peptide (BNP) is secreted from the ventricular myocardium in response to volume expansion and pressure overload. Serum BNP levels are also affected by thyroid function status, which was mostly related to a direct stimulatory effect of thyroid hormones on the secretion of BNP. Although the diagnostic value of BNP in heart failure is undisputed, its value in the presence of the thyroid dysfunction has been recently questioned. The aim of this study was to evaluate the influence of thyroid dysfunction on BNP levels. METHODS: Evaluation of 18 overt and 47 subclinical hyperthyroid patients together with 39 subclinical and 13 overt hypothyroid patients was carried out in a cross-sectional study. Thirty-three age-, sex- and body mass index (BMI)-matched control subjects were also included. RESULTS: BNP levels were more than five times higher in hyperthyroid than euthyroid control subjects (P < 0.001). BNP levels were also higher in subclinical hyperthyroidism than euthyroid control subjects (P = 0.09). Correlation analysis revealed that free T4 and free T3 concentrations were associated with high serum BNP levels. The BNP level in patients with subclinical or overt hypothyroidism was similar to that of the controls. CONCLUSION: The current study provides additional insight into the diagnostic value of BNP in the presence of coexistent thyroid dysfunction and demonstrates important independent effects of thyroid hormones upon BNP plasma concentrations.

Effects of raloxifene on platelet functions in patients with postmenopausal osteoporosis.

Many studies have addressed the effects of estrogenic compounds on platelet function. Raloxifene is a selective estrogen receptor modulator (SERM), which is currently used for the treatment of postmenopausal osteoporosis. At present, there are no clinical data about the effects of raloxifene on platelet function. The purpose of this study was to determine if raloxifene at therapeutic doses affects platelet function in patients with postmenopausal osteoporosis. The effects of raloxifene on platelet function were investigated using a commercial platelet function analyzer (PFA-100) with collagen epinephrine and collagen adenosine 5'-diphosphate (ADP) cartridges. We studied platelet function of 30 patients with postmenopausal osteoporosis before and 15 days after initiation of raloxifene 60 mg/daily. Closure times did not differ significantly between samples obtained before (117.8 +/- 20.5 s) and after raloxifene therapy (106.5 +/- 25.4 s) in collagen/epinephrine cartridges (P > 0.05). There was also no statistically significant difference in mean closure times with collagen/ADP cartridges at baseline (86.2 +/- 18.5 s) and after raloxifene therapy (84.4 +/- 13.8 s) (P > 0.05). Platelet counts (278.3 +/- 72.9 vs. 262.4 +/- 56.7 109/L, P > 0.05) and mean platelet volumes (8.9 +/- 1 vs. 9.1 +/- 1 fL, P > 0.05) were not different before and after raloxifene therapy. Although estrogen related compounds do affect platelet function, there is suggestive data in our study that raloxifene in therapeutic dose exhibit no effect on platelet function in patients with postmenopausal osteoporosis.