Fas ligand (FasL, Apo-1L/CD95L) expression and clinical outcome in papillary microcarcinoma and papillary thyroid carcinomas with diameter smaller than 1.5 centimeters.

CONTEXT: The presence and the importance of FasL (FasL, APO-1L/CD95L) in papillary microcarcinoma lesions which are smaller than 1.5 cm of the thyroid is unclear. OBJECTIVE: It was aimed to investigate FasL expression in papillary microcarcinoma (PMC) of the thyroid. DESIGN: FasL immunoreactivity was evaluated in PMC lesions. Paraffin sections of thyroid specimens obtained from 59 papillary thyroid carcinoma consecutive patients were stained using antibody to FasL. Fas ligand expression and the relation and comparison with clinical and pathological findings in PMC were determined. RESULTS: There were 39 females (66.1%) and 20 males (33.9%) aged 23-74 years (51.9±11.8 yrs), and 20 patients with tumor size ≤5 mm, 24 patients with 6-10 mm and 15 patients with 10-15 mm. The mean of the intensity and the percentage of FasL immunoreactivity were significantly higher in lesions of PMC than peripheral thyroid tissue (29.5±37.9% and 1.42±1.25 vs. 2.1±5.4% and 0.46±0.95, respectively; p<0.001). Fas ligand immunoreaction were not different according to tumor size, the presence of tumor capsule and tumor invasion, invasion of thyroid capsule, peripheral tissue and vascular structures and multicentricity (p>0.05). However, FasL positivity, staining and intensity were high in patients above 45 years, in oncocytic and tall cell variants, in TNM stage pT4A (p<0.05). CONCLUSIONS: This study showed that FasL expression (positivity, staining and intensity) was high and increased in PMC of the thyroid tissue, and above 45 years, in tall cell and oncocytic variants, and in advanced tumor.

Investigation of early atherosclerotic changes in acromegalic patients.

BACKGROUND: Functional and morphological changes of endothelium were risk factors for mortality attributed to atherosclerosis. Studies investigating early atherosclerotic alterations and the effect of the treatment of acromegaly on these alterations gave conflicting results. OBJECTIVE: Surrogate markers of early atherosclerotic changes, i.e. brachial artery flow-mediated dilation (FMD) and carotid artery intima-media-thickness (IMT) in active and inactive acromegalic patients were compared with control subjects matched to patients for age, sex and cardiovascular risk factors to find out the direct effects of growth hormone (GH)/insulin-like growth factor-1 excess. METHODS: In 14 active acromegalics and their 14 matched controls, 14 inactive acromegalics and their 14 matched controls, carotid artery IMT and FMD of brachial artery were measured. Inactive acromegalics were in remission for at least 1 year. RESULTS: Active acromegalics had higher IMT than matched controls and inactive acromegalics (0.85 +/- 0.20 mm, 0.64 +/- 1.77 mm, 0.66 +/- 0.20 mm respectively; p < 0.005, p < 0.05) and IMT of inactive acromegalics was not different from their matched controls (0.61 +/- 0.12 mm). FMD was significantly lower in active acromegalics than in matched controls and inactive acromegalics (2.910 +/- 2.00 mm, 6.5 +/- 2.81 mm, 5.68 +/- 2.9 mm respectively; p < 0.005, p < 0.05). FMD of inactive acromegalics was not significantly different from their matched controls (7.96 +/- 3.12 mm). A significant inverse relationship was found between GH and FMD in active acromegalics (r = -0.659, p = 0.010). CONCLUSION: In active acromegalics, early atherosclerotic changes are not only attributed to the high prevalence of risk factors, but also to the abnormal GH secretion itself.

Thyroid hormone receptor beta gene mutation (P453A) in a family producing resistance to thyroid hormone.

BACKGROUND: Resistance to thyroid hormone (RTH) is a dominantly inherited syndrome characterized by decreased responsiveness of target tissues to thyroid hormone. Two members of a Turkish family, a mother and son, had thyroid function tests suggestive of resistance to thyroid hormone (RTH). METHODS: The clinical presentation was, however, different. The mother (proposita) had palpitation, weakness, tiredness, nervousness, dry mouth and was misdiagnosed as having multinodular toxic goiter which was treated with antithyroid drugs and partial thyroidectomy. Her younger son had attention deficit hyperactivity disorder and primary encopresis, but normal intellectual quotient. Both had elevated serum iodothyronine levels with nonsuppressed thyrotropin. RESULTS: A mutation in one allele of the thyroid hormone receptor beta gene (P453A) was identified, providing a genetic confirmation for the diagnosis of RTH. CONCLUSION: Mutational analysis of the TRss gene allows definitive diagnosis of RTH, potentially avoiding the need for protracted and expensive pituitary function testing.

The presence of erythropoietin receptor in parathyroid cells.

CONTEXT: Effects of erythropoietin on parathyroid cell function has not been studied before. OBJECTIVE: We aimed to demonstrate whether erythropoietin receptor present in parathyroid cells. DESIGN: The specimens of normal parathyroid gland, parathyroid adenoma and hyperplasia were retrieved from our pathology archives. The sections were stained immunohistochemically. Quantitative gene expression study was performed for erythropoietin and erythropoietin receptor. RESULTS: Erythropoietin receptors were detected by immunohistochemical staining and by its gene expression. Its density was higher in normal parathyroid, followed by parathyroid adenoma and hyperplasia. CONCLUSION: Erythropoietin receptor is present in normal parathyroid, parathyroid adenoma, and hyperplasia.

Severe osteomalacia in a patient with idiopathic chronic pancreatitis.

We report a 30-year-old woman who was confined to a wheelchair because of severe myopathy. She was first seen by a neurologist because of a convulsive syndrome of unknown etiology when she was nine. She was started on anticonvulsive drugs but the drug was stopped when her serum calcium level was found to be very low. She had a history from childhood of steatorrhea and abdominal pain after a fatty meal and became vegetarian at age five years. She worked in a hospital as a nurse and at home her living room received no direct sunlight. As a result of these conditions osteomalacia progressed. We believe an awareness of chronic pancreatitis (CP) during childhood could have prevented the consequences of the disease in this case.

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.

Relationship of bone turnover parameters, endogenous hormones and vit D deficiency to hip fracture in elderly postmenopausal women.

Hip fracture is one of the severest consequences of osteoporosis affecting elderly women, but abnormalities of bone turnover responsible for bone loss have not been clearly defined. This study evaluated the relationship of bone turnover parameters to hip fracture in postmenopausal elderly women. We also investigated the effects of endogenous hormones and vitamin D deficiency on osteoporotic hip fracture. The subjects were 21 osteoporotic patients with hip fracture (study group) and 20 healthy postmenopausal women (control group). We measured osteocalcin levels, total and bone alkaline phosphatase (T-ALP and B-ALP), calcitonin, intact parathyroid hormone (iPTH), serum 25 hydroxyvitamin D (25OHD), urinary free deoxypyridinoline (D-pyr) and cross-linked N-telopeptides of type 1 collagen (NTx) levels. Serum T-ALP and B-ALP levels in the study group were lower than those of the control group. The mean serum 25OHD levels in the study group were not significantly different from the control group, but in five cases the mean serum iPTH level was increased. The mean urinary NTx levels were significantly increased in the study group compared with the control group (p<0.05). There was no significant increase in urinary free D-pyr between the two groups. There was significant correlation between serum T-ALP levels and B-ALP levels and between serum iPTH levels and B-ALP levels. The mean serum SHBG level in the study group was higher than in the control group (p<0.05). These data suggest that postmenopausal hip fracture patients have biochemical evidence of decreased bone formation and increased bone resorption compared with postmenopausal healthy subjects. We suggest these abnormalities play a role in the decrease of bone mass and the consequent increase in bone fragility that characterises osteoporotic hip fracture.

Association of Fallot Tetralogy with Carney's complex.

The Carney complex is an inherited, autosomal disease of multicentric tumors in many organs. Some components of Carney's complex are cardiac myxoma, spotty pigmentation, and endocrine overactivity. Primary pigmented nodular adrenocortical dysplasia (PPNAD) is an exceedingly rare cause of Cushing's syndrome in infants, children, and young adults. PPNAD occurs sporadically or as part of a familial syndrome called Carney's complex. Up to our knowledge, the association of Fallot Tetralogy with Carney's complex has not been previously reported. We presented, a 20-year-old woman, who had been operated for Fallot Tetralogy at the age of 3 years, had Carney's complex, i.e. left atrial myxoma, two facial spotty pigmented areas, and PPNAD.

Prolactin response to TRH in patients with panic disorder.

The effects of TRH administration (400 microg, i.v.) on the release of prolactin were examined in 15 patients who met DSM-III-R criteria for panic disorder and 15 normal control subjects. Four hundred micrograms TRH was given via IV route. Blood samples were taken before TRH administration (baseline values) and at 15, 30 and 60 min. The results demonstrate that prolactin responses to TRH did not differ between panic disorder patients and normal control subjects. When only women were evaluated, the findings indicate that women with PD tend to show excessive prolactin responses to TRH. The findings are discussed in view of findings from earlier reports.

Sunlight exposure and vitamin D deficiency in Turkish women.

Vitamin D is an essential steroid involved in bone metabolism, cell growth, differentiation, and regulation of the minerals in the body. The main sources of this vital vitamin are adequate diet and photosynthesis in the skin. The aim of this study was to investigate the efficiency of vitamin D synthesis in 48 premenopausal women (14-44 years) in relation to three different types of dressing in summer. Women in the first group (Group I) dressed in a style which exposed the usual areas of the skin to sunlight; women in the second group (Group II wore traditional clothing with the skin of the hands and face uncovered, while the third group (Group III) dressed in traditional Islamic style, covering the whole body including hands and face. Serum 25OHD levels of Group I, Group II, and Group III were 56+/-41.3 nmol/l, 31.9+/-24.4 nmol/l, 9+/-5.7 nmol/l, respectively (Group I vs Group III, p<0.001; Group II vs Group III, p<0,03; Group I vs Group II, p>0.05). Vitamin D levels were low in 44 percent of the Group I and 60% of the Group II, which suggested that sun exposure of skin areas of hands and face may partially provide vitamin D synthesis, but may not be enough to eliminate vitamin D deficiency. All the patients in group III had vitamin D levels below normal. This study emphasizes the necessity of vitamin D fortification of food even in a sunny country where some people may not be exposed to sunlight because of inappropriate clothing or an indoor-life.

Anaplastic thyroid cancer with transient thyrotoxicosis: case report and literature review.

A 55-year-old woman with anaplastic thyroid carcinoma presented with hyperthyroidism and neck swelling, hoarseness, and cervical lymphadenopathy. On physical examination, she was found to be clinically hyperthyroid with an enlarged, nontender multinodular goitre. Her serum thyroid hormone levels confirmed hyperthyroidism and technetium-99m pertechnetate scan failed to visualize the thyroid gland. Open biopsy showed an invasion of the thyroid gland by anaplastic thyroid carcinoma. The thyrotoxic phase lasted 60 days with predominantly increased thyroxine level and triiodothyronine/thyroxine (T3/T4) ratio decreased below 15. The thyrotoxic period was followed by subclinical hyperthyroidism and hypothyroidism which continued until she died of lung metastasis.

Disappointing results with Tc-99m tetrofosmin for detecting medullary thyroid carcinoma metastases comparison with Tc-99m VDMSA and TI-201.

PURPOSE: This prospective study assessed the detectability of metastatic lesions by Tc-99m tetrofosmin in medullary thyroid carcinoma and to compare the results with Tc-99m penta dimercapto succinic acid (VDMSA) and TI-201. METHODS: A prospective study was performed on 24 patients (10 men, 14 women; ages 23 to 76 years) with medullary thyroid carcinoma after total thyroidectomy. Five cases were sporadic and 19 were familial. After the injection of 740 MBq (20 mCi) tetrofosmin, 740 MBq (20 mCi) VDMSA and 74 MBq (20 mCi) TI-201, whole-body scans and 5-minute static images of the head, neck, chest, abdomen and pelvis were obtained. All scintigraphic studies were compared with calcitonin levels, radiologic findings, histopathologic results, and clinical follow-up. RESULTS: Thirty-four metastatic sites were detected in 12 patients on the basis clinical, radiologic, and histopathologic findings. Patients were divided into three groups according to the calcitonin levels and scintigraphic findings. Group 1 consisted of patients with elevated calcitonin levels and positive scintigraphic findings. Among 34 metastatic sites, 30 could be detected with VDMSA. Only 21 and 20 metastatic sites could be visualized with TI-201 and tetrofosmin, respectively. All 30 lesions showed intense VDMSA uptake but only faint or no uptake with TI-201 and tetrofosmin. Patients in group 2 were accepted to have micrometastases. In this group, calcitonin was minimally elevated, and the results of all three scintigraphs were negative. Group 3 included patients with true-negative results. All patients had normal calcitonin levels and negative results of scintigraphic studies. CONCLUSIONS: Tetrofosmin has no role in the detection of medullary thyroid carcinoma metastases. These results show that VDMSA is clearly superior to TI-201 and tetrofosmin in the follow-up of patients with medullary thyroid carcinoma.

Determination of medullary thyroid carcinoma metastases by 201Tl, 99Tcm(V)DMSA, 99Tcm-MIBI and 99Tcm-tetrofosmin.

Medullary carcinoma of the thyroid (MCT) is malignancy derived from the parafollicular cells (or C-cells) of the thyroid. It is usually sporadic, although it is familial in some cases. Several scintigraphic procedures can provide information regarding the primary and metastatic foci of the tumour. We performed whole-body scanning to establish the pathology of MCT using 201Tl, 99Tcm(V)DMSA and 99Tcm-MIBI in 14 patients, and found average sensitivities of 73%, 82% and 81%, respectively. Moreover, we also scanned three patients with 99Tcm-tetrofosmin and identified two of four pathological foci as well as residual thyroid tissue. The sensitivities of 201Tl, 99Tcm(V)DMSA and 99Tcm-MIBI were 100%, 100% and 85% in identifying lymphadenopathies; 40%, 50% and 71% for soft tissue foci; 100% and 100% for foci in pulmonary parenchyma; and 100%, 66% and 100% for recurrences in thyroid gland. Although 99Tcm(V)DMSA identified all bony metastases in three patients (100%), 99Tcm-MIBI detected only two of three foci (66%) and 201Tl none. 201Tl, 99Tcm-MIBI and 99Tcm-tetrofosmin accumulated in residual thyroid tissue, but 99Tcm(V)DMSA did not, as expected. We conclude that these agents were complementary, since they had different sensitivities in different tissues. The tumour-seeking properties of tetrofosmin are to be evaluated in a larger series.

Thyrotropin stimulating hormone response to thyrotropin releasing hormone in patients with panic disorder.

OBJECTIVE: The aim of this study is to assess thyrotropin stimulating hormone (TSH) response to thyrotropin releasing hormone (TRH) in patients with panic disorder (PD). METHOD: The effects of TRH administration on the release of TSH were examined in 15 patients who met DSM-III-R criteria for PD and compared their test results with those of 15 normal control subjects. Blood samples were taken before TRH administration (baseline values) and at 15, 30 and 60 min. RESULTS: delta max TSH values were lower in the panic disorder patients than in the control subjects. Using the criterion of delta max TSH < or = 7 mlU/l, nine of the 15 panic disorder patients and four of the 15 control subjects had a blunted TSH response to TRH. CONCLUSIONS: These results confirm the findings from earlier reports that patients with PD show blunted TSH response to TRH which is similar to that seen in depressed patients.

Thallium-201, technetium-99m-tetrofosmin and iodine-131 in detecting differentiated thyroid carcinoma metastases.

UNLABELLED: The purpose of this study was to asses the detectability of differentiated thyroid carcinoma (DTC) metastases by 99mTc-tetrofosmin and to compare the results of 99mTc-tetrofosmin with 131I and 201Tl. The reliability of 201Tl and 99mTc-tetrofosmin scanning during suppression therapy also has been studied. METHODS: A prospective study was performed on 41 patients (30 females, 11 males) with DTC (30 papillary, 11 follicular) who had undergone total thyroidectomy and received an average dose of 117 mCi (4329 MBq) of radioiodine for ablation of postsurgical residual thyroid tissue. All patients (n = 41) had 201Tl, 99mTc-tetrofosmin or 131I whole-body imaging after discontinuation of thyroid hormone replacement (thyroxine-off group). Eight of 14 patients with distant metastases also were imaged when they were on thyroxine therapy both with 201Tl and 99mTc-tetrofosmin (thyroxine on-and-off group). Radiologic studies (chest radiography, CT and MRI), serum thyroglobulin assays and histopathologic examinations were performed to clarify the presence of metastases with positive uptake on any of three radionuclide studies. RESULTS: In 26 of 41 patients all three scans were negative. These patients also clinically didn't show any evidence of metastases. Fourteen patients were considered to have distant metastases on the basis of clinical, radiologic and histopathologic findings. The sensitivities of 201Tl, 99mTc-tetrofosmin and 131I in diagnosing distant metastases were comparable (0.85, 0.85 and 0.78, respectively). Iodine-131 was much more sensitive than 201Tl and 99mTc-tetrofosmin for demonstrating residual thyroid tissue after surgery (1.00, 0.33 and 0.33, respectively). The only false-positive case involved radioiodine uptake in a tuberculoma. Thyroxine-on images of 8 patients with distant metastases showed no difference from their thyroxine-off images regarding the site, number and uptake of metastases. CONCLUSION: Technetium-99m-tetrofosmin and 201Tl imaging are highly sensitive for detecting differentiated thyroid carcinoma metastases and do not require prior withdrawal of thyroid hormone suppressive therapy.

Scintigraphic varieties in Hashimoto's thyroiditis and comparison with ultrasonography.

The scintigraphic findings in Hashimoto's thyroiditis are highly variable and can mimic any thyroid abnormality. In this study, we compared the scintigraphic findings with ultrasonography in 48 patients with Hashimoto's thyroiditis. Thyroid scintigrams revealed diffuse hyperplasia in 12 patients, multinodular goiter in 20 patients and a solitary nodule in 16 patients (toxic adenoma, n = 1; hypoactive nodule, n = 4; hyperactive nodule with no suppression, n = 3; normoactive nodule, n = 8). Ultrasonography revealed diffuse hyperplasia in 19 patients, multinodular goiter in 20 patients and a solitary nodule in 9 patients. The thyroid scan and ultrasonography revealed the same findings of diffuse hyperplasia in 12 patients and multinodular goiter in 20 patients. Of the 16 patients with a solitary nodule on scintigraphy, only 9 showed the same finding on ultrasonography, with the other 7 showing diffuse hyperplasia. The difference in nodularity between thyroid scanning (74.9%) and sonography (60.4%) has been attributed to pseudonodularity in Hashimoto's thyroiditis. In conclusion, our results confirmed that Hashimoto's thyroiditis can mimic any thyroid abnormality, including diffuse hyperplasia, nodular goiter and multinodular goiter on scintigraphy. Therefore, scintigraphy, ultrasonography and serum thyroid hormone estimation alone may not be helpful for the final diagnosis of Hashimoto's disease. To eliminate unnecessary surgical intervention, all patients should be evaluated by means of physical examination and thyroid autoantibodies, in addition to a thyroid scan, ultrasonography, serum thyroid hormones and fine-needle aspiration biopsy when necessary.

Propylthiouracil-induced cutaneous vasculitis.

Cutaneous reactions to propylthiouracil and methimazole occur in 3%-5% of adults. Generalized maculopapular and papular purpuric eruptions are perhaps the most common thionamide-induced reactions. We report 3 patients who developed cutaneous vasculitis which is a rare and serious side-effect during antithyroid drug therapy. The observation of cutaneous vasculitis during administration of propylthiouracil suggested that clinical awareness of this complication should be of considerable importance.

Steroid cell tumor of the ovary as a rare cause of virilization.

BACKGROUND: Virilization is associated with either ovarian causes, including polycystic ovary syndrome, hyperthecosis, and ovarian tumor, or with adrenal causes, including tumors and congenital adrenal hyperplasia. In establishing the diagnosis, levels of dehydroepiandresterone sulfate, testosterone, and 17 alpha-hydroxyprogesterone (17-OHP), with their response to dexamethasone treatment, should be assessed; and, where indicated, computerized tomography, ultrasound, and selective venous catheterization should be undertaken. CASE REPORT AND RESULTS: A 21-year-old woman presented with a 17-year history of early accelerated linear growth and virilization. During this time, a putative diagnosis of nonclassic congenital adrenal hyperplasia had been made, and she had been treated with glucocorticoids, with no regression in virilization, for 8 years. On presentation to our group, the failure of low- and high-dose dexamethasone suppression tests to decrease blood levels of testosterone and 17-OHP, combined with a relatively low blood level of corticotropin, led us to investigate an androgen-secreting tumor of ovarian origin. When ultrasonography and computerized tomography of the ovaries and adrenal glands displayed no abnormality, selective venous catheterization was performed, revealing an abnormal ovarian-peripheral gradient for testosterone, 17-OHP, estradiol, and androstenedione in the right ovarian vein. On exploratory laparotomy, a neoplasm adjacent to the right ovary was resected and was found to be a steroid cell tumor of the ovary not otherwise specified, one of the rarest tumors causing virilization in children. Symptomatic resolution followed tumor removal. CONCLUSION: Selective ovarian and adrenal venous catheterization for hormone assays is an efficient method of identification and localization of an androgen source in virilizing syndromes when noninvasive methods fail.

Cyproheptadine treatment in Cushing's disease.

Cyproheptadine, a nonselective 5-hydroxytryptamine receptor blocking agent, reduces ACTH and beta-endorphin secretion from the ACTH-producing tumors. A 35-year-old female suffering from Cushing's disease due to microadenoma of the pituitary gland has been followed since the age of 15. Subtotal adrenalectomy followed by total adrenalectomy, pituitary irradiation, and transsphenoidal hypophysectomy, combined with second radiotherapy of the pituitary, were unsuccessful in achieving remission of the disease. Remission was achieved with cyproheptadine up to a dosage of 24 mg/day. Every attempt to discontinue cyproheptadine treatment was accompanied by recurrence of the disease. This is the first case of Cushing's disease in which cyproheptadine treatment has been the only efficacious therapy for a period of 11 yr. Cyproheptadine may be an alternative long-term therapy for Cushing's disease when other methods of treatment fail.