Nuri Kamel

Iodine status and goiter prevalence in Turkey before mandatory iodization

Endemic goiter is an important public health problem in Turkey. Legislation for mandatory iodization of household salt was passed in July 1999. Current study is aimed at ascertaining the goiter prevalence and iodine nutrition in school-age children (SAC) living in known endemic areas of Turkey. Sonographic thyroid volumes (STV) and urinary iodine concentrations (UIC) of 5,948 SAC from 20 cities were measured between 1997–1999. STV of 31.8% of the SAC examined stayed above the upper-normal limits for the same age and gender recommended by the World Health Organization (WHO). Goiter prevalence ranged between 5 to 56% and median UIC ranged between 14 to 78 μg/l, indicating severe to moderate iodine deficiency (ID) in 14 and mild ID in 6 of the cities surveyed. Neither of the cities was found to have sufficient median UIC levels. The current study shows that endemic goiter is an important public health problem and iodine nutrition is inadequate nationwide. It also provides reliable scientific evidence and shows the need for a controlled and effective iodine supplementation program nationwide. Mandatory iodization of household salt seems to be the essential measure taken for the moment, additional measures may be needed in the near future.

Is it useful to routinely biopsy hot nodules in iodine deficient areas

Incidence of nodular thyroid disease as well as that of functioning thyroid nodules (FTN) increases dramatically in iodine deficient (ID) areas. Cancer is extremely rare in FTN; thus, some do not routinely biopsy and treat them with radioactive iodine (RAI) straight away or follow-up. The outcome of 296 patients followed or treated at our institution for solitary or multiple FTN were retrospectively evaluated. Hospital records of 224 female, 72 male patients, with a mean ±SD age of 54.9±12.4 yr and followed for 22 (0–156) months were examined. 175 patients had solitary, 121 had multiple hot or warm nodules. 230 (77.7%) of the patients received RAI treatment. 402 fine needle aspiration biopsies (FNABs) were performed on 260 patients and on 343 FTN (381 benign and 21 suspicious diagnoses). Eleven of the patients were operated for suspicious FNAB results and 10 were followed-up. Only one nodule turned out to be malignant. Malignancy is extremely rare in functioning thyroid nodules (0.34%) and some of malignant cases could be predicted by their suspicious clinical features. Routine practice of treating FTN with RAI therapy is reasonable in clinically low-risk patients. FNAB is reserved for cases with suspicious clinical features, resulting in fewer surgeries and reduced cost.

Endemic goiter, thiocyanate overload, and selenium status in school-age children.

Iodine deficiency (ID) and related disorders are still major, yet unresolved health concerns. Recently, in a systematic survey of schoolage children (SAC), we reported severe to moderate ID, in Ankara and three cities from Black Sea region of Turkey. The current study attempted to evaluate selenium (Se) status, thiocyanate (SCN−) overload, and their possible contribution to the goiter endemics and thyroid hormone profile observed in these cities. Thyroid ultrasonography was performed and serum Se, SCN−, thyroid hormones, sensitive TSH (sTSH) levels, and urinary iodine concentrations (UICs) were determined from 251 SAC (9–11 yr old).Thyroid volumes (TVs) exceeding recommended upper normal limits and median UIC indicated goitre endemics and moderate to severe ID in the areas studied. Mean serum SCN− concentrations were found to be greater than the controls from the literature. The UIC/SCN− ratio was found to be lowest in Bayburt and Trabzon denoting that SCN− overload may contribute to the goiter endemics. Serum Se concentrations represent a marginal deficiency in the four areas studied. No significant correlations between serum Se concentrations and the other parameters studied (i.e., TV, SCN−, thyroid hormones, sTSH, UIC) was detected.In conclusion, this study showed that selenium is also marginally deficient in the iodine-deficient endemic areas studied, but this has little or no impact on the thyroid hormone profile and the goiter endemics. SCN− overload may contribute to the endemics, especially for the areas where iodine is severely deficient. An effective iodine supplementation program will not only resolve the goiter endemics but also the consequence of SCN− overload as well in the endemic goiter areas studied.

Effects of alendronate sodium therapy on carotid intima media thickness in postmenopausal women with osteoporosis.

Osteoporosis and cardiovascular disease are major health problems that lead to morbidity and mortality. Bisphosphonates are among the drugs used most frequently worldwide to treat osteoporosis, especially in older women. B-mode ultrasonography has recently become a valuable tool for early diagnosis of atherosclerotic disease because of its ability to measure carotid artery intima media thickness (CIMT). The purpose of the present study was to investigate whether alendronate sodium therapy has an effect on CIMT in postmenopausal women with osteoporosis. A total of 71 postmenopausal women with osteoporosis were evaluated before and after they began taking alendronate sodium; follow-up was provided for an average of 13±2 mo. Osteoporosis was diagnosed with the use of dual-energy x-ray absorptiometry, and therapy with alendronate sodium was begun at a dose of 70 mg/wk. For CIMT, B-mode ultrasonography was performed on the right and left middle and distal main carotid arteries. Before alendronate sodium therapy was initiated, the average CIMT value was 0.734±0.121 mm; after therapy, the average CIMT was 0.712±0.111 mm. This difference was not confirmed to be statistically significant. Treatment of osteoporosis does not seem to have an effect on CIMT, which is an early marker of atherosclerosis.

Impact of first trimester and postpartum period thyroid autoantibodies on abortus incidence in Turkish pregnant women.

Objective.Abortus is a common problem and is observed approximately in one third of all pregnancies. In this study, we aimed to evaluate in euthyroid pregnant population the effect of thyroid autoantibodies of both first trimester and postpartum period on abortus incidence. Design and method.Euthyroid 128 pregnant women were included in the study. All pregnants were required having a history of maximum one abortus without any previous endocrinological, immunological disorders. Thyroid autoimmunity was defined as having serum levels of either antithyroidperoxidase or antithyroglobulin antibodies higher than 34 and 115 IU/ml, respectively. Results and conclusions.One hundred of 128 pregnant women (78.1%) had no thyroid autoantibodies, whereas 28 pregnant women (21.9%) had positivity for one of thyroid autoantibodies. One hundred pregnant women (78.1%) gave healthy births, whereas 28 (21.9%) had abortus. Abortus incidence was 28.6% in autoantibody positive group, whereas it was 20% in autoantibody negative group. Serum anti-Tg levels both in first trimester and both in postpartum period were higher in pregnants abortus group when compared with healthy births group. Although, we found no correlation between abortus incidence and thyroid autoantibodies presence, first trimester serum levels of anti-Tg levels may have correlated with abortus incidence and may be an indicator of a closer follow-up. In sight of this study, it can be concluded that autoimmunity against thyroid may continue after termination of pregnancy and this was the first study evaluating the postpartum antibodies levels which may be helpful in subsequent pregnancies.

Multiple endocrine neoplasia type 2A/localized cutaneous lichen amyloidosis associated with malignant pheochromocytoma and ganglioneuroma

We hereby present a rare variant of multiple endocrine neoplasia type 2A (MEN2A) associated with a rare skin disease primary cutaneous lichen amyloidosis and discrete malignant pheochromocytoma in both adrenal glands and pancreatic tail, and interestingly accompanied ganglioneuroma located in retroperitoneum in a 34-yr-old female. The presence of composite tumor of pheochromocytoma and ganglioneuroma arising in the adrenal glands has been described previously in MEN2A and in sporadic cases. The patient displayed classical signs and symptoms of catecholamine excess. Biochemical screening proved pheochromocytoma. Computed tomography revealed multiple mass lesions in both adrenal glands. It also showed a large heterogeneous mass that clearly discriminated from right adrenal gland in retroperitoneal location. After surgical exploration, both adrenal glands and the suspicious mass in pancreatic tail were removed successfully together with subtotal resection of the retroperitoneal tumor. Histopathologic examinations confirmed the presence of pheochromocytoma in both adrenal glands as well as pancreatic lesion. A retroperitoneal ganglioneuroma was also present. Symptomatic and biochemical evidence of pheochromocytoma subsided after the operation. Further evaluation for medullary thyroid carcinoma and primary hyperparathy-roidism confirmed MEN2A. Mutation analysis of the ret proto-oncogene revealed a missense point mutation at position 634 in exon 11, which gives rise to the substitution of a cysteine codon with a tyrosine residue.

Papillary microcarcinomas of the thyroid gland and immunohistochemical analysis of expression of p53 protein in papillary microcarcinomas

BackgroundThyroid papillary microcarcinoma (TPM) is defined according to WHO criteria as a thyroid tumor smaller than 1–1.5 cm. TPMs are encountered in 0.5–35.6 % of autopsies or surgical specimens where carcinoma had been unsuspected. The purpose of the present study was to evaluate patients who had TPMs in terms of clinical findings, histopathological features and immunohistochemical evidence of expression of the tumor suppressor gene p53.MethodsA total of 44 patients with TPMs less than 1.0 cm in diameter were included in the study. The patients were evaluated clinically and the tumors were evaluated in terms of their histopathological and immunohistochemical features, including expression of p53.ResultsThe female/male ratio was 2.8/1, and the median age at time of diagnosis was 49 years (range 20–71 years). The maximum diameter of the smallest focus was 0.1 mm, and that of the largest was 10 mm microscopically. The mean diameter of all tumors was 5.7 mm. There was no correlation between tumor size and age or gender. Of the TPMs, 72 % were found in the right lobe, 24 % in the left lobe and 4 % in the isthmus. Fine-needle aspiration biopsy provided the diagnosis of TPM in only 43.2 % of the patients. All patients were treated with surgery, with 20 undergoing conservative surgery, i.e. lobectomy or isthmusectomy, and 24 undergoing total thyroidectomy. Frozen section provided the diagnosis of TPM in only 56.8 % of the patients. We found lymphocytic thyroiditis in 13.6% of patients, follicular variants in 11.9%, capsular invasion in 26.8%, lymph node involvement in 11.9%, soft tissue metastases in the neck in 12.1% and multifocality in 31.7 %, and none of these were related to age or gender (p > 0.05). No distant metastases were observed during approximately 10 years of follow up. We found p53 positivity in 34.5 % of TPM tumors. However, p53 expression was not statistically related to age or gender.ConclusionOur findings imply that TPMs may not be entirely innocent since they are associated with signs of poor prognosis such as capsular invasion, multifocal presentation, lymph node involvement and p53 positivity. Therefore, TPMs should be evaluated and followed like classical papillary cancers.

Effect of simvastatin use on bone mineral density in women with type 2 diabetes.

OBJECTIVE To attempt to clarify the effect of simvastatin, a widely used statin, on the bone mineral density in women with type 2 diabetes. METHODS We performed a cross-sectional, controlled study of 37 women with type 2 diabetes who were taking simvastatin. Each woman was matched with 2 control subjects who were closest in age, years since menopause (if applicable), and duration of diabetes on the date on which the examination was performed. We measured bone mineral density at the spine and the hip with a dual-energy xray absorptiometry scanner and compared bone density in the 2 study groups. RESULTS The mean bone mineral density values of patients in the simvastatin group were found to be slightly increased in comparison with those of the control group, both in the lumbar vertebrae and in the femoral neck, but these differences were not statistically significant (P>0.05). CONCLUSION In this cross-sectional study, we could not demonstrate a positive effect of long-term simvastatin treatment on bone mineral density in women with type 2 diabetes and hypercholesterolemia.

Effect of radioiodine therapy on thyroid nodule size and function in patients with toxic adenomas.

BackgroundAutonomously functioning toxic adenomas are a common cause of hyperthyroidism. Although 131I seems to be a good therapeutic option with little postablative hypothyroidism for these patients, only a small number of recent studies have objectively evaluated changes in nodule size by ultrasonography following radioiodine therapy. MethodsWe prospectively followed 39 patients with a mean age of 51.2 (35–75) years for 12 months and the patients who remained toxic thereafter, until euthyroidism was provided. Thyroid function tests, sonographic volumes were determined initially and 3, 6 and 12 months after treatment. Radioiodine doses of 3.7 MBq·g−1 thyroid tissue corrected to a 100% 24 h 131I uptake were given. Thirty patients received a single dose, two required two doses and three required three to five doses of 131I due to persistent thyrotoxicosis. Sonographic volumes of the diffuse parts of the glands decreased significantly by 18% from a mean±SD value of 50±27.6 ml to 41±27.4 ml by the end of the 12 months. A significant decrease (8.3%, P=0.002) was achieved in the first three months. Toxic adenomas decreased in size more efficiently (54%) from a mean of 26±24 ml to 12±10 ml during 12 months, but also most significantly (28.8%, P=0.003) in the first 3 months of the follow-up. Thirty of the patients (76.9%) became euthyroid at the end of 12 months of follow-up. Four patients (10.3%) became overtly hypothyroid during the follow-up. ConclusionSingle or multiple doses of radioiodine can successfully treat toxic adenomas with a low rate of hypothyroidism and considerable nodule-volume reduction.

Somatotropin adenoma and resistance to thyroid hormone

Resistance to thyroid hormone (RTH) is a rare disease characterized by non-suppressed TSH in spite of high free thyroid hormone levels. Up to date, in the literature, there are more than 600 RTH cases, but co-incidental hypophyseal adenoma was reported in only 1 case. In the literature, despite reported cases with thyrotropinoma accompanying RTH, we could not find a case with somatotropinoma accompanying RTH. Here, we report a 34-yr-old male patient, who was admitted to the hospital with complaints of dyspnea, chest pain, and palpitation in 2003. His α-subunit value was normal and the α-subunit/TSH molar ratio was <1. His response to TRH stimulation test was normal. His TSH level was suppressed in the T3 suppression test. Hypophyseal magnetic resonance imaging showed a 6-mm hypophyseal microadenoma. Levels of all anterior hypophyseal hormones, including GH and IGF-I, were normal. Oral glucose tolerance test (OGTT)-GH suppression test was normal. The patient was followed with the diagnosis of RTH and incidental hypophyseal adenoma. After 3 yr, because of high levels of IGF-I: 901 ng/ml (68–324), the OGTT-GH suppression test was reported and no suppression was detected. Thus, the patient was referred to surgery with the pre-diagnosis of RTH and acromegaly. Immunohistochemistry was showed as strong GH staining with low Ki 67 index while TSH and other anterior hypophyseal hormones stainings were negative. Post-operative thyroid hormones were still high.