Management and follow-up results of an incidental thyroid carcinoma in a young woman with ovarian teratoma.

Thyroid cancer in ovarian teratoma is reported to be rare and experiences are limited. A 26-year-old woman had undergone bilateral cystectomy and omentectomy for bilateral cystic adnexial masses. Pathological examination showed 1.5 cm follicular variant papillary thyroid carcinoma on the basis of unilateral mature cystic teratoma. Increased CA-125 and CA19-9 levels decreased to normal reference ranges after surgery, but postoperative magnetic resonance imaging indicated multiple abdominal cystic loci. After total thyroidectomy, high dose I-131 was administered to ablate thyroid tissue. Thereafter, levothyroxine was started to achieve subclinical hyperthyroidism. No iodine uptake was detected in post-therapeutic whole body scan (WBS) other than thyroid bed. This finding supported that tumor did not show dissemination to abdomen. No uptake on the first-year evaluation with low-dose I-131 WBS suggested the complete ablation of the thyroid gland. It is recommended that thyroid carcinoma arising from ectopic thyroid tissue in a teratoma should be managed as thyroid carcinoma in thyroid. However, direct dissemination to contiguous regions in abdomen and hematogenous dissemination to distant organs should be in mind. Radical surgery including total abdominal hysterectomy, bilateral salphingo-oopherectomy, pelvic and paraaortic lymph node excision and thyroidectomy is recommended. Fertility preserving surgery may be the surgical procedure as in the present case.

Therapeutic apheresis for severe hypertriglyceridemia in pregnancy.

INTRODUCTION: During pregnancy, a progressive increase in serum triglyceride (TG) and cholesterol levels is observed whereas TG levels mostly remain <300 mg/dl. In women with genetic forms of hypertriglyceridemia, pregnancy may cause extremely elevated TG levels leading to potentially life-threatening pancreatitis attacks and chylomicronemia syndrome. The only safe medical treatment option during pregnancy is ω-3 fatty acids, which have moderate TG lowering effects. Therapeutic apheresis could be used as primary treatment approach during pregnancy. MATERIALS AND METHODS: We reported the effect of double filtration apheresis in one pregnant women with severe hypertriglyceridemia, therapeutic plasmapheresis and double filtration methods in the other severe hypertriglyceridemic pregnant woman; a 32-year-old pregnant woman (patient 1) with a history of hypertriglyceridemia-induced acute pancreatitis during pregnancy and a 30-year-old pregnant woman with extremely high TG levels (12,000 mg/dl) leading to chylomicronemia syndrome (patient 2). Medical nutrition therapy and ω-3 fatty acids were also provided. Double filtration apheresis (patient 1) and plasmapheresis + double filtration apheresis (patient 2) were used. RESULT AND CONCLUSION: When we calculated the TG levels before and after therapeutic apheresis, maximum decrease achieved with double filtration apheresis was 46.3 % for patient 1 and 37.3 % for patient 2. However, with plasmapheresis TG level declined by 72 % in patient 2. Plasmapheresis seemed to be more efficient to decrease TG levels. Iron deficiency anemia was the main complication apart from technical difficulties by lipemic obstruction of tubing system. Healthy babies were born. Delivery led to decreases in TG levels. It is concluded that during pregnancy therapeutic apheresis is an effective method to decrease extremely high TG levels and risks of its potentially life-threatening complications.

Unchanged serum adipokine concentrations in the setting of short-term thyroidectomy-induced hypothyroidism.

OBJECTIVE: To investigate short-term effects of thyroidectomy-induced hypothyroidism on leptin, adiponectin, and resistin concentrations in association with anthropometric data. METHODS: Thirty premenopausal women with euthyroid nodular goiter-mean age, 44.0 ± 11.6 years; mean body mass index (BMI), 28.6 ± 5.9 kg/m2; 13 obese, 7 overweight, and 10 normal weight subjects-scheduled for total thyroidectomy were included in the study. Serum leptin, adiponectin, resistin, free triiodothyronine, free thyroxine, thyroid-stimulating hormone, glucose, insulin, and C-reactive protein concentrations, lipid profile, and anthropometric variables were determined in the euthyroid state (preoperatively) and the hypothyroid state (postoperatively, with a thyroid-stimulating hormone concentration >30 mIU/L). RESULTS: Body weight, BMI, waist and hip circumferences, body fat mass, and serum lipid concentrations increased significantly after thyroidectomy. No significant difference was found between preoperative and postoperative serum leptin, adiponectin, and resistin concentrations. Fat tissue mass-corrected leptin, adiponectin, and resistin concentrations did not differ significantly between euthyroid and hypothyroid periods. Thyroid hormone concentrations showed no significant correlations with adipokine levels. CONCLUSION: Serum adipokine concentrations seem not to change significantly during short-term thyroidectomy-induced hypothyroidism despite significant increases in body weight, BMI, fat mass, and lipid concentrations.

Neuroendocrine tumors presenting with thyroid gland metastasis: a case series.

INTRODUCTION: Autopsy series have shown that metastasis to the thyroid gland has occurred in up to 24% of patients who have died of cancer. Neuroendocrine tumors may metastasize to thyroid gland. CASE PRESENTATIONS: Case 1 was a 17-year-old Turkish woman who was referred from our Endocrinology Department for a thyroidectomy for treatment of neuroendocrine tumor metastasis. She was treated with a bilateral total thyroidectomy. Histopathological examination results were consistent with a neuroendocrine tumor; neoplastic cells showed strong immunoreactivity to chromogranin A and synaptophysin, but the immunohistochemical profile was inconsistent with medullary thyroid carcinoma in that the tumor was negative for calcitonin, carcinoembryonic antigen, and thyroid transcription factor-1.Case 2 was a 54-year-old Turkish woman who presented with a 3-cm nodule on her right thyroid lobe. She had undergone surgery for a right lung mass four years previously. After a right pneumonectomy, thymectomy and lymph node dissection, a typical carcinoid tumor was diagnosed. Under ultrasonographic guidance, fine needle aspiration biopsy of her right thyroid pole nodule was performed and the biopsy was compatible with a neuroendocrine tumor metastasis. She was treated with a bilateral total thyroidectomy. Histopathological examination indicated three nodular lesions, 5 cm and 0.4 cm in diameter in her right lobe and 0.1 cm in diameter in her left lobe. The tumors were consistent with a neuroendocrine phenotype, showing strong immunoreactivity to chromogranin A and synaptophysin. CONCLUSION: Thyroid nodules detected during follow-up of neuroendocrine tumor patients should be thoroughly investigated. A fine needle aspiration biopsy of the thyroid confirms the diagnosis in most cases and leads to appropriate management of those patients and may prevent unnecessary treatment approaches.

Serum adipokines and low density lipoprotein subfraction profile in hypopituitary patients with growth hormone deficiency.

The aim was to evaluate the concentrations of lipid subfractions in relation to adipokines and metabolic parameters in adult growth hormone (GH)-deficient hypopituitary patients on conventional replacement therapy. The study included 21 GH deficient-hypopituitary patients (age: 36.0 ± 15.1 years, male/female: 7/14) on conventional replacement therapy other than GH and 20 comparable controls (age: 37.3 ± 14.0 years, male/female: 6/14). Lipid subfractions (Lipoprint system), serum adipokine (leptin, adiponectin, resistin) concentrations, body composition, a surrogate marker for insulin resistance (HOMA) and conventional lipid profile were evaluated. No statistically significant difference was found with respect to HOMA, adipokine concentrations and anthropometric parameters between patients and controls except for significantly increased waist-to-hip ratio in hypopituitary group. Total and LDL cholesterol concentrations were significantly higher in the patients. LDL particle size (268.88 ± 3.16 vs. 271.31 ± 3.11 Å, P = 0.151) and small-dense LDL subfraction did not differ significantly. According to logistic regression analysis, triglyceride concentrations ≥1.69 mmol/L was the sole parameter significantly and independently predicted small (<268 Å) LDL particle size (P = 0.019) in the whole group. Increased triglyceride concentrations affect LDL particle size in GH-deficient hypopituitary patients. Small dense LDL seems not directly contribute to atherogenic potential in hypopituitarism.

Papillary thyroid carcinoma patients assessed to be at low or intermediary risk after primary treatment are at greater risk of long term recurrence if they are thyroglobulin antibody positive or do not have distinctly low thyroglobulin at initial assessment.

BACKGROUND: In papillary thyroid carcinoma (PTC), recurrences during long-term follow-up (R-LTFU) occur even in those who appear to have an excellent prognosis after initial thyroid surgery and usually, radioactive iodine (i.e., "primary treatment"). Initial studies that predict R-LTFU are not well defined. Values for serum thyroglobulin (Tg) measurements when serum thyrotropin (TSH) is >30 µU/mL, as a result of either recombinant TSH or L-thyroxine withdrawal, referred to here as stimulated Tg (STg), have been previously evaluated. The aim of the current study was to determine the parameters associated with R-LTFU in patients with PTC categorized as having low-risk disease 9 to 12 months after their primary treatment. METHODS: This was a retrospective study of 469 patients with PTC with a mean follow-up 5.8±3.9 years. Study patients had to have no uptake in the first postablative diagnostic (131)iodine whole body scan (WBS) performed 9-12 months after primary treatment, a normal cervical ultrasonography (C-US), and STg of <2 ng/mL if their test for antithyroglobulin antibody (anti-Tg) was negative. The first two criteria were required for patients with a positive anti-Tg test, and their nominal serum Tg concentrations were not analyzed. RESULTS: Twelve patients developed recurrences (2.6%) in cervical region. Greater tumor size, higher STg, and positive anti-Tg tests at initial evaluation were associated with greater R-LTFU. The recurrence rates were 1.5% (7/450) and 26% (5/19), respectively, in patients with negative and positive anti-Tg tests at initial evaluation. Recurrence-free survival was lower in the patients with initial lymph node metastases, positive anti-Tg tests, and STg of ≥0.3 ng/mL at the first postablative WBS (p=0.022, 0.001, 0.035, respectively, by log-rank test). Regression analysis in patients who were anti-Tg negative revealed that STg ≥0.3 ng/mL at this first WBS was the only parameter related to recurrence (p=0.031, odds ratio: 10.30, confidence interval: 1.23-83.3). CONCLUSION: Patients with PTC traditionally categorized as low risk during their first 9 to 12 months after primary treatment have a greater risk of R-LTFU if their postablative STg is ≥0.3 ng/mL, or they have positive anti-Tg, even at this early stage. Periodic C-US is important in these patients and should probably be more frequent in patients with PTC who have positive anti-Tg tests or STg ≥0.3 ng/mL in the first year after diagnosis.

Determinants of postoperative hypocalcemia in vitamin D-deficient Graves' patients after total thyroidectomy.

BACKGROUND: The etiology of postoperative hypocalcemia after total thyroidectomy appears to be multifactorial, that is, postoperative transient hypoparathyroidism, low 25-hydroxy vitamin D (25-OHD) concentrations, aging, and hyperthyroidism with increased bone turnover. Our aim was to evaluate the factors responsible for postoperative hypocalcemia in euthyroid vitamin D-deficient/insufficient Graves patients who underwent total thyroidectomy at our institution. METHODS: Thirty-five consecutive patients with Graves disease treated by total thyroidectomy were included in the present study. All patients were vitamin D deficient/insufficient (ie, 25-OHD concentrations of <20/<30 ng/mL, respectively). Patients were divided into 2 groups according to postoperative serum albumin corrected calcium concentrations: group 1 (n = 13) patients had postoperative serum calcium concentrations of 8 mg/dL or less; group 2 (n = 22) patients had serum calcium concentrations greater than 8 mg/dL. Bone turnover markers (deoxypiridinoline, bone-specific alkaline phosphatase) and 25-OHD were determined the day before surgery. RESULTS: In group 1 patients, disease duration was significantly longer, 25-OHD and postoperative parathyroid hormone concentrations were significantly lower, and bone turnover markers were significantly higher. Logistic regression analysis revealed that a postoperative parathyroid hormone concentration less than 10 pg/mL was the most powerful parameter to predict postoperative hypocalcemia (odds ratio, 23; 95% confidence interval, 3.3-156). CONCLUSIONS: In Graves patients with vitamin D deficiency/insufficiency, postoperative (transient) hypoparathyroidism is the most significant parameter to determine the development of postoperative hypocalcemia.

Effects of vitamin D replacement therapy on serum FGF23 concentrations in vitamin D-deficient women in short term.

OBJECTIVE: Fibroblast growth factor 23 (FGF23), a phosphatonin, inhibits renal phosphate reabsorption and suppresses 1-α hydroxylase activity. Calcitriol stimulates FGF23 synthesis in bone. We aimed to determine the effect of vitamin D replacement therapy on serum FGF23 concentrations in vitamin D-deficient women and to compare the FGF23 concentrations of vitamin D-deficient patients with healthy subjects and patients with genetically determined hypophosphatemic rachitis. DESIGN AND METHODS: The study group was composed of vitamin D-deficient females (n=18, mean age 29.1 ± 9.9 years), vitamin D-sufficient healthy females (control group; n=19, mean age 28.5 ± 5.2 years), and patients with genetically determined hypophosphatemic rachitis (n=13, mean age 26.5 ± 15.1 years). The groups were compared for serum FGF23, 1,25-dihydroxyvitamin D3 (1,25(OH)2D), calcium, phosphate, bone turnover markers, intact parathyroid hormone (PTH), and urinary excretion of calcium and phosphate. The vitamin D-deficient group was re-evaluated after a standard treatment regimen. RESULTS: Serum FGF23 concentrations were significantly lower in vitamin D-deficient patients than in vitamin D-sufficient women and hypophosphatemic rachitis group. Serum FGF23 and phosphate concentrations further decreased significantly during replacement of vitamin D (P<0.05). A significant negative correlation was evident between FGF23 and PTH before vitamin D replacement in the patients (r=-0.469, P<0.05). CONCLUSION: Decreased FGF23 concentrations, which further decline during vitamin D replacement therapy, may have favorable action on bone mineralization by counterregulatory effect on phosphate homeostasis. Lower 1,25(OH)2D concentrations at baseline and hypophosphatemia during treatment may have dominating effects on FGF23 concentrations in vitamin D deficiency, leading to decreased FGF23 concentrations at baseline and during replacement therapy.

Case report: Adrenal LH/hCG receptor overexpression and gene amplification causing pregnancy-induced Cushing's syndrome.

Transient pregnancy-induced Cushing's syndrome (CS) is extremely rare, with only several cases reported in the literature. Ectopic LH/hCG-receptors (LHCGR) in the adrenal gland have been suggested to be involved in the pathogenesis of this condition. We report the clinical, molecular, and genetic features of a patient with pregnancy-induced CS. A 29-year-old female patient developed CS during multiple pregnancies, leading to repeated miscarriage. Signs and symptoms of hypercortisolism resolved soon after delivery or abortion, only to recur in subsequent pregnancies. In the non-pregnant state, hCG stimulation testing resulted in elevated cortisol levels. Serum cortisol was not suppressible with dexamethasone. The adrenals exhibited bilateral adrenal cortical nodular hyperplasia. Quantitative RT-PCR revealed a 2-fold increase in LHCGR and progesterone receptor mRNA expression and decreased estrogen receptor-beta expression in the patient's adrenal tissue relative to normal adrenals. Higher intensity of immunostaining for LHCGR was observed, particularly within the nodular lesions, compared to controls. Quantitative PCR revealed a LHCGR-to-beta-actin ratio of 1.5 in genomic DNA from adrenal and peripheral leukocytes, suggesting the presence of a germline duplication of the LHCGR gene. LHCGR overexpression resulting from germline gene duplication may be a potential pathogenic mechanism underlying this case of pregnancy-induced CS.

Leptin concentration indexed to fat mass is increased in untreated anorexia nervosa (AN) patients.

CONTEXT: Data regarding serum adipocytokine and ghrelin concentrations in different stages of anorexia nervosa (AN) is conflicting. OBJECTIVE: Our aim is to determine serum concentrations of adiponectin (ApN), leptin and ghrelin in different stages of AN and to evaluate their relationships with study parameters. DESIGN SETTING AND PARTICIPANTS: Study group was composed of four subgroups: Group 1: patients with a recent diagnosis of AN (n = 19); group 2: weight recovered (10% increase in body weight compared with baseline) subgroup of group 1 during follow-up (n = 10); group 3: recovered patients with a previous history of AN but normal menstrual cycles and body weight currently (n = 10); group 4: control group (n = 10). Venous blood was obtained for measurements of biochemical/hormonal parameters, ApN, leptin and ghrelin. Body composition was determined by bioimpedance analysis. MAIN OUTCOME MEASURES: Changes in adipocytokine and ghrelin concentrations and relationships with anthropometric/biochemical parameters. RESULTS: Leptin: fat mass (kg) ratio was significantly higher in group 1 patients compared with group 4 (4.3 +/- 4.6 vs. 1.1 +/- 0.5 microg/l kg, P < 0.01). No significant difference was observed among ghrelin concentrations. Leptin showed significant positive correlation with body fat mass in all groups. ApN showed significant positive association with body mass index in Group 1. CONCLUSIONS: Leptin concentrations indexed to fat mass may indicate a nonphysiological higher set point of leptin per unit fat mass in treatment-naive AN patients. Correlation pattern between ApN and fat mass is modified also. Altered adipocytokine profile in AN may contribute to anorectic behaviour.

Endothelial nitric oxide synthase intron 4a/b polymorphism and early atherosclerotic changes in hypopituitary GH-deficient adult patients.

OBJECTIVE: Endothelial nitric oxide synthase (eNOS) intron 4a/b polymorphism is associated with plasma NO concentrations and coronary artery disease/hypertension in various populations. GH deficiency in adulthood predisposes to reduced NO concentrations and premature atherosclerosis. Our aim was to determine whether intron 4a/b polymorphism of eNOS gene influences endothelial function and early atherosclerotic changes in GH-deficient hypopituitary patients. DESIGN: Thirty-three hypopituitary GH-deficient patients on conventional replacement therapy other than GH and 43 age-, sex-, and body mass index (BMI)-matched controls were studied in this cross-sectional case-control study. METHODS: Early atherosclerotic changes were determined by flow-mediated dilation (FMD) of brachial artery and carotid artery intima-media thickness (IMT). eNOS4a/b polymorphism was detected by PCR. RESULTS: Hypopituitary patients had significantly higher total/low-density lipoprotein cholesterol and fat mass and lower IGF-I concentrations compared with controls. IMT was significantly higher in patients (0.777+/-0.23 vs 0.639+/-0.17 mm, P<0.01). No significant difference was observed with respect to FMD measurements. eNOS4a/b genotype frequencies were similar between patients and controls. Patients carrying 'a' allele (a/a and a/b) had significantly higher IMT compared with controls carrying 'a' allele and bb genotype (P<0.05). However, logistic regression analysis revealed that presence of hypopituitarism, age> or =45 years, and BMI> or =27.9 kg/m(2) were significant independent predictors of IMT> or =0.65 mm. CONCLUSION: No compelling data are evident to suggest that eNOS4a/b polymorphism modifies the atherosclerotic process in GH-deficient situations. A large case-control study is needed to confirm our findings.