Iodine status among pregnant women after mandatory salt iodisation.

I is essential for thyroid hormone synthesis and neurological development. Various changes occur in thyroid hormone metabolism during pregnancy and I requirements increase significantly. The purpose of this study was to investigate I status among pregnant women in Trabzon, formerly a severely I-deficient area but shown to have become I sufficient following mandatory iodisation of table salt based on monitoring studies among school-age children (SAC) in the area. A total of 864 healthy pregnant women with a median age of 28 (25th-75th percentile 17-47) years participated in the study. None of them were using I-containing supplement. All of them were screened for use of iodised salt, obstetric history, thyroid function tests and urinary I concentrations (UIC), and thyroid ultrasonography was performed. Median UIC was 102 (25th-75th percentile=62-143) µg/l. Median UIC of the patients according to trimesters were 122 µg/l at the 1st, 97 µg/l at the 2nd and 87 µg/l at the 3rd trimester. UIC in the 1st trimester was higher compared with the 2nd and 3rd trimesters (P<0·017). Nodules were present in 17·7% of women (n 153). The rate of iodised salt usage among pregnant women was 90·7%. Our study demonstrates that, although the I status among SAC has been rectified, I deficiency (ID) is still prevalent among pregnant women. Current knowledge is in favour of I supplementation in this group. Until the effects of maternal I supplementation in mild ID have been clarified by large-scale prospective controlled trials, pregnant women living in borderline defficient and I-sufficient areas, such as Trabzon city, should receive 100-200 µg/d of I-containing supplements in addition to iodised salt.

Relative associations of polycystic ovarian syndrome vs metabolic syndrome with thyroid function, volume, nodularity and autoimmunity.

BACKGROUND: The relative associations of polycystic ovarian syndrome (PCOS) and metabolic syndrome (MS) with the risk for thyroid disease (thyroid function, volume, nodularity and autoimmunity) are unknown.We compared thyroid features and function in patients with PCOS and control subjects by the presence of MS. METHODS: We recruited 84 women with PCOS and 81 age-matched healthy controls. PCOS was defined according to the Rotterdam criteria. Thyroid ultrasound and function tests were performed in all. RESULTS: Although thyroid disease was more prevalent in women with PCOS, ovarian disease was not significantly associated with the risk for thyroid disease. Thyroid volume did not differ between women with PCOS and control subjects (13.7±8.6 vs 12.4±4.4 ml, respectively; p=0.2); however, it differed significantly between subjects with and without MS (regardless of PCOS status): 19.1±14.8 vs 12.4±4.9 ml, respectively; p=0.001). Antithyroglobulin and antithyroid peroxidase antibody levels also were significantly higher in subjects with MS, but not in participants with PCOS vs control subjects. Overall, TSH level correlated significantly with body mass index (BMI), weight, waist circumference, diastolic blood pressure, and levels of LDL cholesterol, triglycerides, and HDL cholesterol. Thyroid volume correlated significantly with age, weight, BMI, waist circumference, systolic blood pressure, 120-min postprandial glucose and HDL level. CONCLUSIONS: PCOS alone was not associated with thyroid disease in our population. However, MS and some of its components appear to be related to thyroid volume, function, and antithyroid antibody levels.

Ret proto-oncogene mutations in apparently sporadic Turkish medullary thyroid carcinoma patients: Turkmen study.

OBJECTIVE: Medullary thyroid carcinoma (MTC) frequently occurs in a sporadic form, but a substantial number of cases are hereditary and appear as part of the multiple endocrine neoplasia type 2 (MEN2) syndromes. Germline mutations in ret proto-oncogene have been shown to be the underlying cause of MEN2 syndromes. DESIGN: We carried out a multi-center study that aimed to perform mutational analysis of so called sporadic MTC patients. METHODS: Fifty-six MTC patients verified by histopathologic examination were subjected to genetic analysis. Exon 10, 11, 13, 14, 15 and 16 of the ret gene were analyzed by DNA sequencing and restriction enzyme digestion method. RESULTS: Among 56 apparently sporadic MTC patients, we identified 6 (10.7%) ret germline mutation carriers. Three individuals carried mutations at codon 634 in exon 11, one at codon 618 in exon 10, and two at codon 804 in exon 14. Identification of the predisposition gene mutation has allowed DNA-based strategy for direct mutation detection in patients with apparently sporadic MTCs. A substantial number of patients with apparently sporadic MTC carried germline mutations and 50% of their first degree relatives are expected to have or to develop MTC and/or other endocrine tumors. CONCLUSIONS: These results indicate the importance of careful genetic surveillance of any patient with apparently sporadic MTCs.

Coexistent thyroid pathologies and high rate of papillary cancer in patients with primary hyperparathyroidism: controversies about minimal invasive parathyroid surgery.

Thyroid carcinoma and benign thyroid diseases associated with primary hyperparathyroidism (PHPT) may cause difficulties in the diagnosis, localization and therapy of PHPT. In this study, we analysed coexistent thyroid pathologies in 51 patients who underwent neck exploration with a diagnosis of PHPT between 1999--2002. Five hundred thirteen patients who underwent thyroidectomy for nodular thyroid disease without a parathyroid pathology in histopathological examination served as controls. In patients with PHPT there were 43 cases (84.3%) of coexistent thyroid pathology. Nine patients (17.6 %) had coexistent papillary thyroid cancer. Nine patients (17.6 %) had lymphocytic thyroiditis, two (3.9%) had benign thyroid adenoma and 24 (47%) had nodular hyperplasia. In one patient (2%), there was intrathyroidal metastasis from a parathyroid cancer. One patient had coexistent lymphocytic thyroiditis and multifocal papillary cancer. One of the two cases with thyroid adenomas was Hürthle cell type. In the control group only 28 patients (5.5%) had thyroid malignancy (27 papillary cancer and one follicular cancer). In conclusion, the coexistent thyroid pathologies are highly prevalent in patients with PHPT and pre- and intra-operative thyroid examination should be performed to avoid overlooking important thyroid pathologies.

Urinary beta-2 microglobulin in renal dysfunction associated with hypothyroidism.

Hypothyroidism is associated with a number of functional renal disorders primarily affecting water and salt handling. In this study, we aim to investigate functional renal disorders in overt and subclinical hypothyroidism. We utilised urinary beta-2 microglobulin (beta2M) as a sensitive marker of tubular dysfunction. Urinary beta2M excretion and tests for renal functions were repeated before and after T4 replacement therapy. Forty-four patients (28 with overt disease, 16 with subclinical disease) and 31 healthy control subjects were involved in the study. There was a significant increase in urinary beta2M in both overt and subclinical hypothyroidism (p < 0.05 in both). TSH levels were correlated with beta2M excretion. Effects of hypothyroidism on renal functions were readily reversible by 3 weeks of thyroid hormone replacement therapy. Urinary beta2M was a sensitive marker of renal tubular dysfunction associated with overt and subclinical hypothyroidism.

Influence of the refinement of surgical technique and surgeon's experience on the rate of complications after total thyroidectomy for benign thyroid disease.

BACKGROUND: In recent years, many surgeons dealing with endocrine surgery have increasingly performed total thyroidectomy for benign thyroid disease. However, total excision of the thyroid in the treatment of benign lesions has been surrounded by even more controversy than its role in cancer treatment. The complication rate appears to be higher when the operation is done by inexperienced surgeons who have no special skills in endocrine surgery using proper techniques. The aim of this study is to determine whether surgeons experience and the refinement of surgical techniques are associated with postoperative recurrent laryngeal nerve (RLN) palsy or hypocalcemia after total thyroidectomy for benign thyroid disease. METHODS: A total of 68 consecutive patients who underwent total thyroidectomy for benign thyroid disease were reviewed. Twenty-six of these were from between January 1998 and June 1999 (first period) and 42 from between June 1999 and September 2000 (second period). Patients were divided into two subgroups according to different periods and different surgical techniques to identify the RLNs and the parathyroid glands. RLNs function was evaluated pre- and postoperatively by an otolaryngologist, and serum calcium levels were measured at the postoperative follow-up. RESULTS: During the first period of the study, transient hypocalcaemia was determined in 8 (31%) patients. Hypocalcaemia was clinically symptomatic in 5 (19%) patients. Transient RLN palsy developed in 4 (15%) patients. Unilateral permanent RLN palsy due to operative injury was observed in 1 (4%) patient. During the second period, we noted transient hypocalcemia in 11 (26%) patients and symptomatic hypocalcemia in 6 (4%) patients. Serum calcium levels returned to normal within 4 weeks after operation in all patients. Neither transient nor permanent RLN palsy was observed during this period. CONCLUSIONS: Complications of total thyroidectomy can be minimized with increasing experience and the refinement of surgical technique.

Clinical laboratory findings and results of therapy in 55 patients with Cushing's syndrome.

In this study, 55 patients with Cushing's syndrome (CS) (50 female, 5 male; mean age 34 +/- 12.3 yr) who attended our clinics between the years 1983 and 2000 were retrospectively evaluated for clinical and laboratory features and modalities and results of therapy, due to a few similar studies over the last ten years. Cushing's disease was diagnosed in 39 patients (71%), adrenal adenoma in 13 patients (23.6%) and adrenal carcinoma in 3 patients (5.5%). Centripedal obesity, moon face, hypertension, hirsutism and purplish stria were the most frequent findings. Loss of normal serum F circadian rhythm was found in all patients with CS. The overnight 1 mg oral dexamethasone suppression test and low-dose dexamethasone suppression test (LDDST) yielded 100% and 100% diagnostic sensitivity for CS, respectively. Sensitivity and specivity of the high-dose dexamethasone suppression test (HDDST) in distinguishing Cushing's disease was found to be 82% and 100%, respectively. All of the patients with adrenal CS were not suppressed with HDDST. Sellar CT and/or MRI accurately identified the tumor in 58% of these patients. Recurrence was observed in 3 (11%) of the 28 patients with Cushing's disease, treated by transsphenoidal adenomectomy. Recurrence was diagnosed 1.5, 3 and 6 yr after the operation in these 3 patients. One patient had residue tumor. In our case series, bilateral adrenalectomy plus pituitary irradiation achieved the highest remission rate (100%) in Cushing's disease. In 2 out of 4 patients (50%) treated by left adrenalectomy associated with pituitary irradiation, recurrence was observed. Panhypopituitarism due to tumor apoplexy was observed in one of the patients with Cushing's disease. All of the patients with adrenal CS, the tumor was accurately localized with imaging methods before the operation. The appropriate operative procedure resulted in complete remission in patients with adrenal adenoma. Consequently, Cushing's disease was the most common form of CS. The overnight 1 mg oral DST and 24-h urine free F excretion (UFC) as screening tests, 2-day LDDST as diagnostic test and 2-day HDDST as differential diagnostic test were good studies. More successful outcomes have been achieved in treatment of Cushing's disease with the development of pituitary surgery in the recent years, as well as in our case series. Surgery is also curative for adrenal adenoma patients. Survival remains poor among carcinoma patients.

Clinical characteristics and genetic screening of an extended family with MEN2A.

MEN-2A is characterized by medullary thyroid carcinoma (MTC) with pheochromocytoma and sometimes parathyroid adenoma. In affected members of the family, the risk of MTC is about 100%. Biochemical screening allows tumors to be detected early but even at this stage treatment is not always curative. Missense mutations in exon 10 and 11 of the RET proto-oncogene are associated with MEN-2A. Early detection of this mutation by DNA analysis allows the identification of the carriers of the gene. We performed genetic screening in 88 members of an extended family with MEN-2A and found 18 members positive for RET mutation (Cys634Gly). Only three of these 18 RET positive cases had a previous diagnosis of medullary cancer and/or pheochromocytoma. Up to now, 12 of the RET positive cases have undergone thyroidectomy. There was extended disease with cervical lymph node metastasis in 6 of them, bilateral medullary microcancer in 3 and c-cell hyperplasia in the remaining 3. Three of the 18 RET positive patients had also pheochromocytoma. Primary hyperparathyroidism was present in only one patient. The mean age of diagnosis of medullary cancer was between 25-50 yr and mean age of death was between 35-95 yr in affected members of the family. The family had many other affected members in other cities in Turkey and in other countries throughout the world from Australia to the Netherlands. So this family is perhaps one of the most extended families with MEN-2A.

Polyserositis as a rare component of polyglandular autoimmune syndrome type II.

Polyglandular autoimmune (PGA) syndromes (types I and II) may affect various endocrine and non-endocrine organs in the body. In the commoner PGA type II, primary adrenal insufficiency, autoimmune thyroid disease and type I diabetes mellitus are the most frequent manifestations. Serositis with pericardial or pleural involvement is not a well known component of the disease. Here, we report a 21-year-old man who first presented with a pleuropericardial effusion and Graves' disease, and who then developed type I diabetes mellitus.

Relationship Between Leptin Levels and Body Indexes in Patients with Haematologic Malignancy.

Leptin is a recently found hormone regulating body weight. In human obesity, this weight-regulating hormone level is in a positive correlation with FMI (fat mass index) and BMI (body mass index). In this study, we aimed to investigate the relation between serum leptin levels and BMI, PF (percentage fat), LMI (lean mass index), FMI and some other parameters of patients with haematologic malignant diseases. Fourty-four patients with haematologic malignant diseases and 25 healthy control group were taken into the study. In the comparison, there were no significant difference between the PF and FMI values of both groups, while the mean BMI and LMI values of the control group were significantly higher than that of the patient group. There was a positive correlation between leptin levels and BMI and FMI among parameters studied in our control group, whereas we couldn't demostrate any such correlation in patient group. We estimate that the alteration may be due to disturbances in the feed back mechanism developing in patient with haematologic malignancy.

Serum lipid and leptin concentrations in hypopituitary patients with growth hormone deficiency.

OBJECTIVE: To investigate the effects of growth hormone (GH) deficiency on serum lipid and leptin concentrations in hypopituitary patients taking conventional replacement therapy and to determine the relations between leptin and gender and anthropometric and metabolic variables. SUBJECTS: Twenty-one GH deficient adult hypopituitary patients (15 women, six men) and 21 (14 women, seven men) age, sex and body mass index (BMI) matched healthy controls. MEASUREMENTS: After an overnight fast, anthropometric parameters were measured and body composition was determined by a bioelectrical impedance analyser. Venous blood samples were obtained for the measurements of glucose, total cholesterol, high density lipoprotein (HDL) cholesterol, triglyceride, intact insulin, insulin-like growth factor 1 (IGF-1) and leptin concentrations. Serum leptin and hormones were analysed by radioimmunoassay. RESULTS: Hypopituitary patients with GH deficiency showed significantly higher triglyceride, total and low density lipoprotein (LDL) cholesterol and lower HDL cholesterol concentrations on conventional replacement therapy. The unfavourable lipid profile was particularly evident in women. Significantly higher leptin concentrations were found in patients compared with healthy controls with similar body fat content (23. 5+/-11.8 ng/ml vs 11.7+/-6.9 ng/ml, P=0.01). This difference remained significant even when leptin values were expressed in relation to fat mass percentage (0.79+/-0.40 vs. 0.42+/-0.17 ng/ml%, P<0.05) and fat mass kg (1.32+/-0.81 vs 0.66+/-0.30 ng/ml kg, P<0. 05). Significant positive correlations were observed between leptin concentrations and body fat percentage and age in the control group. In patients the sole significant relation between leptin and study parameters was the positive correlation observed between leptin and total cholesterol concentrations. Serum leptin concentrations were significantly higher in women than men in the control group, but not in the patients. No significant gender difference was observed when leptin concentrations were expressed in relation to fat mass (percentage and kg). CONCLUSION: Growth hormone deficient hypopituitary patients (particularly women) on conventional replacement therapy have a more atherogenic lipid profile. Leptin concentrations are increased in GH deficient adults even after adjustment for percentage body fat and body fat mass (kg). Although the nature of our data does not allow us to draw any conclusions on the mechanism(s) of increased leptin concentrations in GH deficiency, decreased central sensitivity to leptin and increased leptin production from per unit fat mass, or alterations in leptin clearance, might be operative.

Power Doppler sonography in the diagnosis of Graves' disease.

In addition to color and pulsed Doppler sonography findings, we aimed to describe power Doppler sonography findings in Graves' disease in this study. Twenty-three patients with Graves' disease were imaged with gray-scale, color and power Doppler sonography. Twenty normal volunteers were examined by the same equipment and the same technique as a control group. A subjective grading system was used to categorize the vascularization in pulsed Doppler sonography images from normal to markedly increased vascularization. Power Doppler sonography exhibited diffuse hypervascularity in the thyroid gland in all patients. The flow was covering about all the parenchyma. Four patients showed mild, 12 patients moderate and seven patients marked vascularity. The intensity of power Doppler flow pattern was not correlated with the severity of the disease. This study demonstrated that power Doppler sonography is a convenient, time saving, inexpensive and noninvasive method as compared with isotope scan and some other laboratory tests for confirmation of Graves' disease.

The effect of dietary treatment on erythrocyte lipid peroxidation, superoxide dismutase, glutathione peroxidase, and serum lipid peroxidation in patients with type 2 diabetes mellitus.

OBJECTIVES: The aim of the present study was to investigate the effect of dietary treatment on serum and erythrocyte lipid peroxidation and erythrocyte antioxidative enzyme activity of patients with Type 2 diabetes. DESIGN AND METHODS: A total of 30 patients with newly diagnosed as Type 2 diabetes were enrolled to the study. A total of 30 healthy subjects served as controls. Diabetic patients were given standard dietary treatment that was composed of 50% to 55% carbohydrate and 30% fat for 2 months. No diet was applied for controls. For both groups serum and erythrocyte lipid peroxidation and erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were obtained at first and at the end of 2 months. RESULTS: Diabetic patients had higher serum and erythrocyte lipid peroxidation than those of controls before dietary treatment(p < 0.05). However, there was no absolute differences in erythrocyte SOD and GSH-Px (p > 0.05). At the end of 2 months of dietary treatment, while diabetics had still higher glucose and erythrocyte lipid peroxidation than controls (p < 0.05), serum lipid peroxidation, erythrocyte SOD, and GSH-Px levels did not differ significantly from those of controls (p > 0.05). In diabetic patients, after 2 months of dietary treatment, whereas serum and erythrocyte lipid peroxidation decreased, erythrocyte SOD and GSH-Px activities showed significant increase (p < 0.05). CONCLUSIONS: Our results showed significant alteration in serum and erythrocyte lipid peroxidation and erythrocyte antioxidant enzyme status of patients with Type 2 diabetes by dietary treatment. However, whether such alterations have clinical importance for diabetic patients needs further investigation.

Low cholesterol level in patients with panic disorder: the association with major depression.

BACKGROUND: The purpose of this study was to examine whether an association exists between low cholesterol level and major depression in patients with panic disorder. METHODS: The subjects of the study were 16 patients panic disorder only, 16 panic disorder patients had also current major depressive episode, and 16 normal control subjects. An automated enzymatic colorimetric method was used for cholesterol determination. RESULTS: Panic disorder patients had higher serum cholesterol than panic disorder patients with major depression and normal controls. CONCLUSION: There is an association between low cholesterol level and the presence of major depression in patients with panic disorder. LIMITATION: Future studies with large sample are needed to confirm this finding. CLINICAL RELEVANCE: A low serum cholesterol level might serve as biological marker of major depression in patients panic disorder.