Mehtap Cakir

Musculoskeletal manifestations in patients with thyroid disease

objective Thyroid dysfunction may cause musculoskeletal symptoms. We have evaluated the prevalence of adhesive capsulitis, Dupuytrens contracture, trigger finger, limited joint mobility and carpal tunnel syndrome in a series of patients with various thyroid diseases and differing levels of function.

Comparison of Efficacy of Sibutramine or Orlistat Versus Their Combination in Obese Women

Objective: Sibutramine and orlistat are currently used for weight loss. We aimed to investigate the effect of orlistat and sibutramine combination therapy in treatment of obese women. Subjects and Design: Study population consisted of 89 obese women who had a body mass index ≥ 30 kg/m2, were normotensive, and had normal glucose tolerance. All patients were placed on a diet which contained fat approximately 30% of total calorie intake and the diet was designed to cause an energy deficit of approximately 2.51–3.56 megajoule/day. At the first month of diet (baseline), all patients were randomly divided into three therapy groups: Diet + Orlistat (group 1; n = 30 patients), Diet + Sibutramine (group 2; n = 29 patients), Diet + Orlistat + Sibutramine (group 3; n = 30 patients). Body weight, body fat distribution and serum lipid levels were evaluated baseline and after six months in all subjects. Results: Mean weight loss was 5.5 ± 4.9 kg (p = 0.024) in group 1, 10.1 ± 3.6 kg (p < 0.001) in group 2, 10.8 ± 6.6 kg (p < 0.001) in group 3 after the six months. Weight loss was significantly greater in group 2 (p = 0.003) and group 3 (p = 0.002) when compared with group 1. Percentage of mean weight loss was 5.5 ± 3.1% in group 1, 10.2 ± 4.8% in group 2, 10.6 ± 5.7% in group 3. Percentage of weight loss was higher in group 2 (p = 0.01) and group 3 (p = 0.009) when compared with group 1. Weight loss and percentage of weight loss were not different between group 2 and group 3. Conclusion: These three regimens had different results on weight loss in obese women. Combination drug therapy and sibutramine therapy were both more effective than orlistat therapy alone. However, no significant difference was noted between combination drug therapy and sibutramine treatment groups.

Clinical importance of vascular endothelial growth factor (VEGF) for papillary thyroid carcinomas

Vascular endothelial growth factor (VEGF) is a major regulator of angiogenesis and may be produced by some cancer cells. Several recent reports have documented that increased expression of VEGF is associated with risk of recurrence or decreased recurrence‐free survival in papillary thyroid cancers (PTC). The aims of this study were to determine whether immunohistochemical expression of VEGF is related to local and distant recurrence of PTC and to evaluate the relationship between hypervascularization and VEGF expression in papillary thyroid carcinomas. VEGF expression was examined immunohistochemically in 48 papillary carcinomas. Ten normal thyroids were used as controls. Patients were followed for 61.7 (range 24–143) months. Twelve of the patients had local and distant recurrences. VEGF immunostaining, blinded for clinicopathological data, was evaluated semiquantitatively by two pathologists. The difference between the recurrent (n:12) and nonrecurrent (n:36) carcinomas was statistically significant (p:0.001). VEGF expression was also stronger in papillary thyroid carcinomas than in normal thyroid tissues. The mean microvascular densities were significantly higher than in normal thyroid tissues. These data indicate that VEGF staining is strongly associated with increased frequency of local and distant recurrence in PTC and that the immunohistochemical profile of the expression may be used as a marker for predicting which tumors have metastatic potential.

Incidental Thyroid Carcinoma in Thyrotoxic Patients Treated by Surgery

Background and Aims: Thyroid malignancy detected incidentally in patients who are operated for thyrotoxicosis has been reported at different rates. The aim of this study was to investigate the rate of incidental thyroid carcinoma in thyrotoxic patients managed with surgery in our institution. Methods: Of the 375 thyrotoxic patients who had thyroid surgery between the years of 1997–2004, 70.7% were females and 29.3% were males. Among thyrotoxic patients 65.3% (n = 245) had toxic multinodular goiter (TMG), 16.8% (n = 63) had toxic adenoma (TA) and 17.9% (n = 67) had Graves’ disease. Results: Twenty-six (6.9%) of all thyrotoxic patients had thyroid carcinoma. Eighteen (7.3%) of TMG, 4 (6.3%) of TA and 4 (6%) of Graves’ disease patients had thyroid carcinoma. Histologic examination revealed 18 papillary (9 microscopic), 5 follicular, 2 hurthle cell and 1 anaplastic carcinoma. Conclusion: In our study, incidental thyroid carcinoma was found in 6.9% of subjects with thyrotoxicosis. Papillary thyroid microcarcinomas constituted 34.6% (26/9) of these newly diagnosed thyroid carcinomas. The incidence of thyroid carcinoma was not higher in subjects with Graves’ disease compared to TMG and TA. The rate of incidental thyroid carcinoma in subjects with thyrotoxicosis treated with surgery was similar to previous studies reported from different countries.

A case of Costello with parathyroid adenoma and hyperprolactinemia

A 23‐year‐old female with Costello syndrome is presented. She had mental retardation, macrocephalia, “coarse” facial features, deep palmar and plantar creases, hyperkeratosis in palms and soles, hyperpigmentation, curly hair, and cutis laxa, which are among the diagnostic features of the syndrome, and a history of hyperprolactinemia since the age of 16. Her present complaint was weakness and widespread bone‐pain. In routine biochemistry, she had an elevated calcium level of 11.1 (8.6–10.2) mg/dl and her DEXA evaluation was consistent with osteoporosis (vertebra and femur T score <−2.5). High PTH levels, 103 (8–78) pg/ml, suggested presence of a parathyroid adenoma. Tc‐MIBI scintigraphy revealed two focuses of pathological uptake, one located inferior to left lobe of thyroid and the other in the superior left lobe of thyroid gland. After parathyroid adenomectomy, her serum calcium and PTH levels returned to normal values. This is the first case of parathyroid adenoma and hyperprolactinemia in the literature, reported in a patient with Costello syndrome.

Medullary thyroid carcinoma, follicular variant

We report here a 48-yr-old woman presenting with a solitary thyroid nodule in the left lobe of the thyroid. The aspiration cytology of the nodule was reported as follicular neoplasia and she underwent surgery. Frozen section was suspicious for medullary thyroid carcinoma and a total thyroidectomy was performed. The pathology report revealed medullary thyroid carcinoma, follicular variant. Immunohistochemical analysis was negative for thyroglobulin and positive for calcitonin. A few patients with this variant have been reported in the literature, mainly diagnosed by immunohistochemical features of the tumor. In light of the limited information we have obtained from the literature, it is reasonable to emphasize that these cases should be distinguished from the mixed medullary-follicular thyroid carcinomas and medullary carcinomas with entrapped follicles. Immunohistochemical examination with calcitonin and thyroglobulin is also essential.

Coexistence of THRB and TBG Gene Mutations in a Turkish Family

OBJECTIVE Resistance to thyroid hormone is a syndrome characterized by high serum free T4 levels and unsuppressed serum TSH concentration. Thyroxine-binding globulin complete deficiency manifests with low serum total T4 and T3 levels and normal serum TSH concentration. Our objective is to describe a family with the coexistence of resistance to thyroid hormone and thyroxine-binding globulin complete deficiency. METHODS We conducted clinical studies and genetic analyses. RESULTS The proband presented with mental retardation, hearing loss, and recurrent upper respiratory tract infections accompanied by high serum levels of TSH, T3, T4, and high thyroglobulin antibody titers. His elder sister presented with normal TSH and T3 and high serum T4 levels. Both patients were found to be heterozygous for the mutation P453A in the thyroid hormone receptor beta (THRB) gene. One of the probands brothers had low serum total T3 and T4 and normal TSH concentrations, without any clinical manifestations. He was hemizygous for the mutation P50fs51X in the TBG gene. The probands mother showed slightly elevated TSH, normal total T3 and T4, and elevated titers of thyroperoxidase antibodies and thyroglobulin antibodies. She was heterozygous for both THRB and TBG genes mutations. CONCLUSIONS To our knowledge, this is the first report of the coexistence of THRB and TBG gene mutations in the same individual (mother of the proband), whereas other affected family members had only 1 of the 2 genes mutated. The case illustrates the difficulty that might be encountered in the interpretation of thyroid function tests when different genetic defects affecting thyroid function coexist.

Reproducibility of Fasting and OGTT-derived Insulin Resistance Indices in Normoglycemic Women

RESUME To determine the reproducibility of fasting and oral glucose tolerance test (OGTT) -derived insulin-resistance (IR) indices in obese and nonobese women. Twenty-one obese (BMI 37.7±6.3 kg/m2 ) and 14 nonobese (BMI 21.5±1.0 kg/m2 ) age-matched, healthy, premenopausal women were included in the study. An OGTT was performed twice, with a 1-week interval between tests. IR was calculated from both fasting and post-load glucose and insulin values, using some of the more well-known indices. When the 2 groups were evaluated separately, all indices were found to be reproducible in obese subjects, but some indices were not reproducible in nonobese healthy controls. When results were analyzed in the study population as a whole, all indices were reproducible.

Leptin Response to Oral Glucose Tolerance Test in Obese and Nonobese Premenopausal Women

The objective of this study was to investigate the serum leptin response to oral glucose stimulation in a group of obese and nonobese normotensive, normolipidemic, and glucose-tolerant premenopausal women. Twenty-one obese (BMI: 37.7 ± 6.3 kg/m2) and 14 nonbese (BMI: 21.5 ± 1.0 kg/m2) age-matched, healthy premenopausal women were included in the study. Serum glucose, insulin, and leptin levels were measured at 30 min intervals during the 120 min of an oral glucose tolerance test (OGTT). Mean serum glucose, insulin, and leptin levels were significantly higher in the obese group compared to nonobese subjects during OGTT. Except for a 120 min decrement noted in obese women, no changes occurred in serum leptin levels during oral glucose stimulation in both groups. As a conclusion, absence of a significant elevation in serum leptin levels during OGTT in our obese subjects compared to nonobese subjects may be related to their normal metabolic variables despite being abdominally obese and insulin resistant.

Cortisol Levels During an Oral Glucose Tolerance Test in Lean and Obese Women

Because of the similarities between Cushing’s syndrome and insulin resistance syndrome, cortisol metabolism in obesity has been investigated in numerous studies. Our study investigates serum glucose, insulin, and cortisol response to oral glucose stimulation in a group of obese and lean normotensive, normolipidemic, and glucose-tolerant premenopausal women. Twenty-one obese [body mass index (BMI) 37.7 ± 6.3 kg/m2) and 14 lean (BMI: 21.5 ± 1.0 kg/m2) age-matched healthy premenopausal women were included in the study. Serum glucose, insulin, and cortisol levels were measured at 30-minute intervals during 120 minutes of oral glucose tolerance testing (OGTT). Mean serum glucose and insulin levels were significantly higher in the obese group compared with lean subjects, and cortisol levels were similar during OGTT. There was not a significant difference for cortisol area under the curve (AUC) during OGTT between the two groups. No correlation between cortisol AUC, insulin AUC, and glucose AUC was noted for both groups. During OGTT, a decrease in cortisol levels was observed in both groups. The decrement occurred at 30 minutes of the OGTT in the obese group and at 60 minutes of the OGTT in the lean group. At 90 and 120 minutes of the OGTT, serum cortisol levels were similar to basal levels in both the obese group and the lean group. Previous studies reported altered hypotalamic-pituitary-adrenal axis activity, altered levels of urinary cortisol excretion, and increased metabolic clearance of cortisol in obesity. In our study in obese women, the only detected difference from lean subjects was a quicker suppression and recovery in serum cortisol levels after glucose administration.