Utility of baseline serum phosphorus levels for predicting remission in acromegaly patients.

PURPOSE: High GH and IGF I levels increase tubular phosphate reabsorption in patients with acromegaly. We aimed to investigate the utility of serum phosphorus levels as an indicator for predicting chance of remission in acromegaly patients. DESIGN: Fifty-one patients (n: 51; F: 24, M: 27) with diagnosis of acromegaly were included in the study. Plasma IGF-1, Phosphorus (P) and nadir GH levels on oral glucose tolerance test (OGTT) at the time of diagnosis were analysed retrospectively. Patients were classified into two groups according to their plasma P levels; P ≤ 4.5 mg/dl (Group-1, n: 23, 45.1%), P > 4.5 mg/dl (Group-2, n: 28, 54.9%). Two groups were compared according to remission status; remission (n: 27) and non-remission (n: 24). Remission was defined with absence of clinical symptoms, normal plasma IGF-1 (adjusted for age and gender) and GH levels (<1 mcg/dl) at least 3 months after initial treatment. RESULTS: Serum P levels decreased significantly after treatment in both groups (p < 0.001). There was a significant correlation between baseline phosphorus levels and remission rates, nadir GH in OGTT, pituitary adenoma size and Ki-67 scores (p = 0.001, r: -0.51; p = 0.01, r: 0.44; p = 0.001, r: 0.52; p = 0.02, r: 0.71, respectively). Mean baseline P levels were significantly higher in patients with non-remission (4.8 vs 4.2, P < 0.001). Logistic regression analysis did not reveal an independent effect on remission with any of these risk factors. CONCLUSION: High serum P levels may be an indicator for a low likelihood of onset of remission in acromegaly patients. Further studies with wider spectrum are needed to make specific suggestions.

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.

Brown tumour of the maxilla and mandible: a rare complication of tertiary hyperparathyroidism.

Hyperparathyroidism is nowadays diagnosed early and asymptomatically with the improvements in routine biochemical tests and radiological procedures. The late bony complications of the disease have therefore started to decline rapidly. Brown tumours are one of the bony complications of hyperparathyroidism. The mandible is the predominantly affected site in the maxillofacial area. Maxillary involvement is rare. Here, an extremely rare case of a 19-year-old male patient with brown tumours in his maxilla and mandible associated with tertiary hyperparathyroidism is presented. A thorough diagnostic work-up was carried out and treatment options for both hyperparathyroidism and brown tumours were discussed. The importance of different radiological evaluation methods and the consultation between the oral and maxillofacial surgeons, general practitioner dentists, endocrinologists and radiologists are emphasised.

Impact of total versus subtotal thyroidectomy on calcium metabolism and bone mineral density in premenopausal women.

OBJECTIVE: This study aimed to compare the impact of total versus subtotal thyroidectomy on calcium metabolism and bone mineral density in euthyroid, premenopausal women. SUBJECTS: The study included 24 premenopausal women who had undergone total (n = 10) or subtotal (n = 14) thyroidectomy and who were receiving nonsuppressive doses of thyroxine. The median post-operative period was four years. We determined, in all patients, the following parameters associated with calcium metabolism: total serum calcium, inorganic phosphate, intact parathormone, calcitonin and alkaline phosphatase. The bone mineral density of the spine and hip were measured using a Hologic QDR 4500C bone densitometer and were compared with controls matched for age and peak bone mineral density (using the t-test). RESULTS: The measured calcium metabolism parameters were normal in all patients, and none had osteoporosis. There was no significant difference in the bone mineral density measurements for the spine and hip, comparing patients who had undergone total versus subtotal thyroidectomy (using the t-test). CONCLUSION: The impact of total thyroidectomy on bone mineral metabolism is not significantly different from that of subtotal thyroidectomy, in premenopausal women with normal thyroid-stimulating hormone values.

Hypoglycemia due to ectopic release of insulin from a paraganglioma.

Insulin-secreting pancreatic tumors and insulin-like growth hormone-secreting non-islet cell tumors can cause hypoglycemia. However, insulin-releasing paraganglioma or pheochromocytoma has almost never been reported. A 67-year-old female patient was admitted to our hospital because of headache, palpitation, perspiration, faintness, frequent sense of hunger and absent-mindedness. These intermittent symptoms had begun approximately a year before admission. On physical examination, she had high blood pressure of 150/90 mm Hg. Hormonal studies demonstrated increased urinary norepinephrine levels, and hyperinsulinemic hypoglycemia was confirmed while the patient was symptomatic. Abdominal MRI revealed a retroperitoneal mass measuring 4.5 cm in the pancreatic region. She was treated with an alpha-blocking agent to control blood pressure preceding the removal of the mass. Histopathological diagnosis was paraganglioma, and immunohistochemically insulin staining in the neoplastic cells was demonstrated. Her blood pressure normalized and hypoglycemia relieved after the operation. The patient did not have recurrence of hypoglycemia after a year of follow-up. Paraganglioma is a rare tumor of the neural crest, and co-secretion of insulin and catecholamines has been reported only by a single case report in the literature. The present patient is another case with this co-secretion.

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.

Concomitant association of thyroid sarcoidosis and Graves' disease.

OBJECTIVE: Graves' disease (GD) with sarcoid involvement of the thyroid gland has rarely been reported. METHOD: We report a case of GD with thyroid sarcoidosis in a 28-year-old woman. Thyroid function was assessed by triiodothyronine (T(3)), thyroxine (T(4)), thyroid-stimulating hormone (TSH) and TSH receptor antibodies (TSH-R Ab). Thyroid scintigraphy, ultrasound and fine-needle aspiration biopsy were performed. The patient underwent surgery. RESULT: The patient had a nodular goiter. Serum T(3), T(4) and TSH-R Ab levels were elevated with suppressed TSH level. Scintigraphy showed diffuse activity as seen in GD, and ultrasound revealed that parenchyma was heterogenous. Sarcoidosis was discovered on routine chest X-ray. Although no sarcoid involvement was found on specimen, the thyroid gland showed non-caseating granulomas on histology. CONCLUSION: Since sarcoid involvement of the thyroid gland can cause hypofunction, we report the uncommon infiltration of sarcoidosis with hyperthyroidism.

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.

Leukemia in a patient treated with growth hormone.

It is well known that growth hormone (GH) therapy is associated with increased risk of development of malignant tumors, especially leukemia. In the case presented, growth hormone treatment was initiated in a 25-year-old patient with hypopituitarism. After 4 months of therapy with thrice a week injections of rhGH, acute myelogenous leukemia developed. It was thought that no clearcut evidence existed to establish a relationship between the growth hormone treatment and development of acute leukemia.

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.

Fatty acid composition of 19 species of fish from the Black Sea and the Marmara Sea.

Evidence suggests that differences in fatty acid composition among various fish species may be due to differences in diet or to environmental factors such as temperature, salinity, and depth at which the fish are caught. The beneficial effects of a diet containing fish on cardiovascular or other diseases have been associated with their high content of eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3) acids. In this study we analyzed the fatty acid composition of the flesh of 18 different species of marine fish and of cultured rainbow trout. The fish were obtained from the Black and the Marmara Seas, both of which have unique biological and ecological systems as well as eutrophication and pollution. The contents of 20:5n-3 and 22:6n-3 in the marine fish ranged from 4.2 to 13.3 wt% of total fatty acids, and from 6.6 to 40.8 wt%, respectively. The most important differences from other studies on oceanic fish were the tendencies toward higher percentages of 16:0 and 22:6n-3. The n-3 series of polyunsaturated fatty acids were present as 32.4+/-1.9% of the total fatty acids. The present study suggests that mature and immature Pomatomus saltator as well as Engraulis encrasicolus, Mullus surmuletus, Sardina pilchardus, Mugil cephalus, and Sarda sarda may be preferred for the Turkish diet as a result of their high 20:5n-3 and 22:6n-3 contents. The cultured rainbow trout Oncorhynchus mykiss is not as good a source of n-3 fatty acids as are the marine fish.

The value of DNA content in predicting the prognosis of thyroid carcinoma in an endemic iodine deficiency region.

DNA content of tumour was found to correlate with various prognostic factors and survival, especially in well differentiated thyroid carcinoma. The aim of this investigation was to evaluate the correlation between the DNA ploidy and the prognosis as well as the survival in thyroid carcinoma in our country, being an endemic iodine deficiency region. DNA flowcytometry was performed on paraffin embedded archival tissue blocs of 74 patients with thyroid carcinoma (70 well differentiated, 3 anaplastic and Hurthle cell carcinoma) and 12 patients with multinodular goitre. DNA ploidy was defined as diploidy or aneuploidy. Aneuploidy was detected in 5 (6.8%) patients with thyroid carcinoma (3 anaplastic, 1 papillary and 1 Hurthle cell carcinoma). Aneuploidy was significantly more frequent in patients with anaplastic carcinoma (n: 3/3, 100%) compared to well differentiated thyroid carcinoma (n: 1/70, 1.4%) (p < 0.0001). Aneuploid DNA content significantly correlated with advanced age (p < 0.01), large tumour size (p < 0.001), and low survival (p < 0.01). Mean survival period of patients with anaplastic carcinoma in whom aneuploidy was frequently encountered, was shorter compared to patients with diploid well differentiated tumours (p < 0.01). In conclusion, although anaplastic and follicular carcinoma are more frequently diagnosed in endemic areas, the rate on aneuploidy was found to be lower in thyroid carcinoma in our country compared to data reported to nonendemic areas. As the prognostic predictive value of DNA ploidy is reliable in well differentiated thyroid carcinoma, DNA measurement of FNA biopsy may influence the extent of surgery. Thyroid carcinoma, other than well differentiated types, require radical operations independent of the DNA content. However, adjunctive treatment methods may be used earlier postoperatively according to quantitative DNA measurement.

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.

Multiple vascular leiomyomas involving bilateral adrenal glands, spleen, and epicardium, associated with bilateral testicular microlithiasis and empty sella turcica.

Leiomyomas can arise from any tissue having smooth muscle as one of its constituents, especially gastrointestinal and genitourinary systems, less frequently in the skin, and rarely in deep soft tissue. An unusual case of multiple vascular leiomyomas involving bilateral adrenal glands, spleen, and epicardium, associated with bilateral testicular microlithiasis, and empty sella turcica is reported in a 15-year-old boy. The adrenal masses were incidentally discovered by ultrasonography. These three findings, taken individually are rare, and the constellation of the three, to the best of our knowledge, is the first recorded example. Furthermore, bilateral involvement of the adrenal glands with leiomyomas is, by itself, very uncommon. The tumors considered benign were surgically removed. Orchiectomy wasn't performed. The boy is well after 1.5-year follow-up under cortisone, 9alpha-fludrocortisone, and testosterone therapy.

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.