Recombinant human thyrotropin versus thyroid hormone withdrawal in differentiated thyroid carcinoma follow-up: a single center experience.

Introduction: Our goal was to evaluate and compare the diagnostic utility of thyroid hormone withdrawal (THW) and recombinant thyroid-stimulating hormone (rhTSH) methods in detecting recurrence/persistence (R/PD) of differentiated thyroid carcinoma (DTC). Methods: The study included 413 patients with DTC who underwent total thyroidectomy and had remnant ablation. DxWBS, s-Tg levels, R/PD were evaluated retrospectively. A s-Tg level≥2 ng/mL was considered as "positive s-Tg". Results: DxWBS and s-Tg levels were evaluated with rhTSH in 116 and THW in 297 subjects, respectively. The sensitivity and specificity of "positive s-Tg" for R/PD in THW group were 77.3% and 92.7%, with 90.3% accuracy, respectively. The sensitivity and specificity of "positive s-Tg" for R/PD in rhTSH group were 58.8% and 100% with 93.9 % accuracy, respectively. An uptake outside thyroid bed at WBS showed a sensitivity of 17.1%, specificity of 100% for R/PD with 89.4% accuracy in THW group. An uptake outside thyroid bed at WBS showed a sensitivity of 7.7%, specificity of 100% for R/PD with 88.8% accuracy in rhTSH group. Conclusion: Method of TSH stimulation did not influence the reliability of DxWBS. The "positive s-Tg level" had a higher sensitivity with THW when compared to rhTSH in detecting R/PD.

Type 2 diabetes mellitus in a patient with malignant insulinoma manifesting following surgery.

BACKGROUND: Insulinomas, although they are rare, are the most common of pancreatic islet cell tumours. The incidence is estimated at only four per million person-years and only 5-12% of reported cases are malignant. Distinction between malignant and benign tumours can only be made by the presence of metastasis, as there are no specific morphologic, biochemical or genetic features distinguishing them. Most patients with malignant insulinoma have lymph node or liver metastases and, rarely, bone involvement. The coincidence of insulinoma and diabetes mellitus is an extremely rare condition and reported only in a few cases. CASE REPORT: We report a 45-year-old woman who was diagnosed with insulinoma on the basis of clinical and laboratory findings and endoscopic examination. Histopathological diagnosis revealed well-differentiated endocrine carcinoma of the pancreas with lymph node metastases. The case was accepted as malignant insulinoma and the patient underwent surgery. Interestingly, hyperglycaemia occurred after the removal of the insulinoma, with the requirement for insulin in the post-operative 3 weeks, which was changed to oral anti-diabetic agents as a permanent treatment. The patient is still being treated with oral anti-diabetic agents. We think that the patient might have had diabetes mellitus, because of insulin resistance that developed with a high-caloric intake stimulated by hypoglycaemia, and which had been masked for many years, but manifested overtly after removal of the tumour. CONCLUSIONS: Although this is a rare condition, clinicians should bear in mind that insulinomas may exist together with diabetes mellitus, and it is important to have this suspicion when considering the perioperative approach and for the prevention of morbidities.

Clinical trial: insulin-sensitizing agents may reduce consequences of insulin resistance in individuals with non-alcoholic steatohepatitis.

BACKGROUND: Currently, although only a few therapies normalize the liver test abnormalities with/without improving the liver histology, no pharmacologic therapy has proved to be effective for the treatment of non-alcoholic steatohepatitis. AIM: To investigate the role of insulin sensitizers in the treatment of individuals with non-alcoholic steatohepatitis (NASH). METHODS: A total of 74 individuals with NASH (male/female, 44/30; mean age, 47.2 +/- 9.0 years) were enrolled. Participants were divided into two distinct groups: group 1 (n = 25) participants were administered a conventional diet and exercise programme while those in group 2 (n = 49) were administered the diet and exercise programme plus insulin sensitizers. RESULTS: With respect to baseline metabolic, biochemical and histological parameters, no significant differences were observed between the two groups (P > 0.05). Insulin sensitizers significantly improved metabolic parameters (homeostasis model assessment-insulin resistance score, P < 0.05), serum aminotransferase levels [aspartate aminotransferase (AST): 45.9 +/- 24.2 to 33.3 +/- 17.7 IU/L, P < 0.01; alanine aminotransferase (ALT): 78.2 +/- 46.3 to 47.3 +/- 34.5 IU/L, P < 0.001] and histological features (median non-alcoholic fatty liver disease activity score: 5.0-3.0, P = 0.01), while diet and exercise improved serum aminotransferase levels (AST: 39.3 +/- 11.1 to 30.0 +/- 8.6 IU/L, P < 0.01; ALT: 66.9 +/- 28.9 to 42.0 +/- 16.2 IU/L, P < 0.001) at the end of the 48 weeks when compared to baseline. Insulin sensitizers improved the high-sensitivity C-reactive protein levels (P < 0.01). No serious adverse effects of insulin sensitizers were observed. CONCLUSION: Insulin sensitizers can lead to improvement in metabolic, biochemical and histological abnormalities of NASH as a result of improved insulin sensitivity.

Effect of very low LDL-cholesterol on cortisol synthesis.

BACKGROUND: Cardiovascular disease is the most common cause of mortality around the world. The relationship between coronary artery disease and serum LDL-cholesterol levels has become obvious in recent years and statin treatment has been used more commonly. However, influence of intensive statin treatment on steroidal hormonal functions has remained unclear. In this paper, we evaluated the effect of very low LDL levels (<70 mg/dl) on serum cortisol concentrations, which is mainly synthesized from cholesterol. SUBJECTS AND METHODS: Forty-one patients with serum LDL-cholesterol levels below 70 mg/dl were included in the study. The control group consisted of 38 healthy people. Adrenal axis was evaluated by means of cortisol response to 1 microg ACTH test. RESULTS: The mean age of patients was 52.45+/-10.74 yr. Of 41 patients, 19 (46.9%) were female. There were statistically significant differences between the study and control group according to their serum cholesterol and LDL levels. Main serum LDL levels were 58+/-11.4 mg/dl and 131+/-25.8 mg/dl in the study and control group, respectively. There were no statistically significant differences in response to 1 microg ACTH stimulation test at basal, 30 min and 60 min among both study and control group. Atorvastatin treatment was generally well tolerated. CONCLUSIONS: Our data reflect that having serum LDL-cholesterol levels below 70 mg/dl did not affect the adrenal axis function in terms of cortisol.

The effect of short-term glycemic regulation with gliclazide and metformin on postprandial lipemia.

AIM: Exaggerated postprandial lipemia is now accepted as an independent risk factor in atherogenesis in type 2 diabetes mellitus. We investigated if better glycemic control improves fasting and postprandial lipid profile in type 2 diabetic patients in the short-term. METHODS: Thirty-two type 2 diabetic patients were studied before and after desired glycemic regulation with gliclazide and metformin. Basal levels of glucose, total cholesterol, high density lipoprotein, low density lipoprotein, triglyceride, insulin, and C-peptide were evaluated at fasting state. Afterwards, patients were given a standard 400-kcal mixed meal as a breakfast, contaning 35 % fat. At the 2nd and the 4th hours after the breakfast, postprandial glucose, triglyceride, insulin, and C-peptide levels were determined again. RESULTS: Significant decrease was observed in total cholesterol levels after better glycemic regulation (p<0.05). Besides, triglyceride levels decreased significantly from 175.36+/-17.85 mg/dl to 138.73+/-14.93 mg/dl at fasting state (p<0.05), from 197.26+/-20.85 mg/dl to 154.15+/-14.61 mg/dl at the 2nd hour after mixed meal (p<0.05), and from 209.63+/-28.54 mg/dl to 155.63+/-15.68 mg/dl (p<0.05) at the 4th hour after the mixed meal, when better glycemic profile was provided. Area under curve for triglyceride levels decreased significantly with the better glycemic regulation (p<0.01). CONCLUSIONS: Improved glycemic regulation can lower the raised fasting and postprandial triglyceride levels which are important atherosclerotic risk factors in diabetic patients even in short-term. Since this improvement in triglyceride levels comes early, diabetic patients can be evaluated for fasting and postprandial triglyceride levels in the first month of therapy.

Role of ovary and adrenal glands in hyperandrogenemia in patients with polycystic ovary syndrome.

Ovary is the main source of the hyperandrogenism in polycystic ovary syndrome (PCOS). Adrenal glands may also be involved in the pathogenesis of the development of PCOS. To investigate this possibility and to find out if buserelin test is able to distinguish PCOS patients from the patients with idiopathic hirsutism (IH), ACTH and buserelin tests were performed in 29 women with PCOS, 21 women with IH, and 20 control subjects (CS). We also aimed to determine the role of dysregulation of 17 hydroxylase in the development of PCOS. Basal and stimulated dehydroepiandrosterone sulfate (DHEA-S) and stimulated cortisol (F) levels after ACTH administration were significantly higher in PCOS group than in IH and CS groups (p<0.0001 and p<0.05, respectively). PCOS patients also possessed significantly higher basal and stimulated 17-hydroxyprogesterone (17-OH P) levels, including the peak levels (p<0.02), during buserelin testing when compared with IH patients and CS. There was no significant correlation between the ACTH-stimulated and the buserelin-stimulated peak 17-OH P values. In conclusion, significantly higher basal and ACTH-stimulated levels of F and DHEA-S in PCOS compared with controls and patients with IH, reflect that adrenal hyperactivity also plays a role in hyperandrogenemia seen in PCOS. Because of the lack of the correlation between ACTH-stimulated and buserelin-stimulated 17-OH P levels, it is hard to say that adrenal hyperactivity seen in PCOS is the result of the dysregulation of cytochrome P450c17-alpha enzyme. Our results suggest that buserelin test which is an GnRH analogue could distinguish at least some of the patients with PCOS from the other patients presenting with the common symptoms of hyperandrogenemia.

Increased insulin-like growth factor-I levels in women with polycystic ovary syndrome, and beneficial effects of metformin therapy.

We aimed to investigate whether metformin would reverse the endocrinopathy of polycystic ovary syndrome (PCOS), allowing resumption of cyclic ovulation and regular menses, and whether metformin causes any change in the serum concentration of insulin-like growth factor-I (IGF-I) in patients with PCOS. Fifty-eight women with PCOS participated in the study and received metformin at a dose of 850 mg three times a day (total 2550 mg) for 16 weeks. Serum concentrations of luteinizing hormone, follicle stimulating hormone, estradiol, free testosterone, total testosterone, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate, fasting insulin, IGF-I, sex hormone binding globulin and insulin-like growth factor binding protein-1 (IGFBP-1) were evaluated before and after metformin treatment. Patients were divided into two groups as responders and non-responders according to the achievement of regular menstrual periods. The mean IGF-I levels decreased significantly on metformin therapy. After 16 weeks of metformin treatment, 55.17% of PCOS patients achieved regular menses. Only the change in serum levels of progesterone and IGF-I on metformin were statistically significant between responders and non-responders; metformin-induced decremental change in IGF-I levels were greater in responders. In conclusion, we observed that elevated IGF-I levels may have a crucial role in many consequences of PCOS in addition to hyperinsulinemia. By decreasing insulin and IGF-I levels, metformin therapy offers additional beneficial effects in resumption of regular menses. Thus, in PCOS patients with elevated levels of IGF-I, metformin may be considered as an appropriate agent to be used for the regulation of menstrual cycles.

I-131 therapy for thyroglobulin positive patients without anatomical evidence of persistent disease.

OBJECTIVE: the aim of this retrospective study was to evaluate the diagnostic relevance of I-131 whole body scan (WBS) performed after second empirical therapeutic doses of iodine-131 (I-131) in thyroglobulin (Tg)-positive thyroid cancer patients without evidence of local and distant metastasis. We also evaluated the efficacy of second empirical therapeutic doses of I-131 in these patients. METHODS: we retrospectively compared the results of diagnostic I-131 WBS and post-therapy scans of second therapeutic doses of I-131 in 38 patients with detectable Tg while off T4 therapy (TSH>25 mlU/ml). All patients underwent a near-total or total thyroidectomy and I-131 ablation with 75-125 mCi. All of the reported subjects had no prior evidence for detectable disease before second high dose empirical I-131 therapy. RESULTS: there was almost complete concordance in uptake between diagnostic I-131 WBS and final scans carried out after second I-131 therapy in 22 out of 38 patients. Whereas abnormal foci of new uptake was detected in all of the remaining 16 patients, seven of them were found to have negative diagnostic WBS results. Distant metastases were observed in 3 of 16 subjects and mediastinal uptake was found in 2 of 16 patients in post-therapy scan. During the subsequent follow-up, extending from 8-46 months, 6 out of 16 patients showed normalization of serum Tg levels while off T4. Serum Tg levels were normalized in 3 out of 7 patients who had negative WBS results, increased in one and unchanged in the remaining 3. None of the patients with distant metastases had normalization of Tg levels. Totally, 6 out of 38 showed normalization of Tg levels while off T4 therapy. CONCLUSION: the empirical therapeutic doses of 1-131 may help in localization of the disease in Tg positive patients without anatomical evidence of persistent disease, but the effect of I-131 therapy on long-term survival is not obvious.

Plasma leptin concentrations in patients with Graves' disease with or without ophthalmopathy.

BACKGROUND: Recent studies have demonstrated that human preadipocyte fibroblasts in orbital connective tissues from patients with Graves' ophthalmopathy differentiate into cells resembling adipocytes and acquire expression of leptin and functional thyroid stimulating hormone receptors. These finding imply that leptin may play a role in the pathogenesis of Graves' ophthalmopathy. However, little is known about plasma leptin concentration in patients with Graves' disease with or without ophthalmopathy. MATERIAL AND METHODS: To investigate this relationship; 28 patients with active Graves' ophthalmopathy (19 female and 9 male, mean age: 32.7+/-10.5 years, mean BMI: 24.8+/-3.7 kg/m2) and 10 patients without ophthalmopathy (6 female and 4 male, mean age: 24.6+/-5.6, mean BMI: 23.02+/-2.4 kg/m2) all with untreated Graves' disease were included in the study at first diagnosis in our endocrinology out-patient clinic. Sex-, BMI- and age-matched twenty healthy subjects (13 female, 7 male, mean age: 31.9+/-10.0, mean BMI: 24.2+/-3.0 kg/m2) were selected as a control group. Plasma leptin levels were measured by a RIA method with a sensitivity of 0.5 ng/ml. RESULTS: Results showed any significant differences neither between patients and controls (7.97+/-5.2 ng/ml vs. 7.83+/-3.7 ng/ml) nor between patients with or without Graves' ophthalmopathy (8.29+/-5.0 ng/ml vs. 7.06+/-5.8 ng/ml) (both P>0.05). Moreover, no correlation was found between plasma leptin levels and ophthalmopathy index score, or proptosis. CONCLUSIONS: Although effects of local leptin production in the orbit cannot be excluded, our data suggest that circulating plasma leptin does not have a significant direct influence on ophthalmopathy index score or pathophysiology of Graves' ophthalmopathy.

Effect of octreotide treatment on Graves' ophthalmopathy.

In this study, nine patients with Graves' ophthalmopathy with positive clinical activity score (CAS), who were either unresponsive or not suitable for glucocorticoid treatment, were given 100 microg of octreotide three times daily, subcutaneously, for three months. The mean age was 49+/-13 years. All patients were under either propylthiouracil or methimazole therapy and were euthyroid for at least one month prior to the start of the octreotide treatment. The mean degree of proptosis as measured with the Hertel exophthalmometer decreased slightly after the treatment (22.0+/-3.0 vs 19.6+/-2.4 for the right eye and 22.2+/-1.9 vs 20.2+/-2.2 for the left eye; p<0.05). The mean activity score decreased from 3.2+/-0.8 to 1.7+/-1.1 (p<0.005) and the mean score of eye signs according to the NOSPECS classification showed improvement with octreotide therapy (3.2+/-0.7 vs. 2.2+/-1.4; p<0.05). Seven patients responded favorably to octreotide treatment. In the remaining two no improvement was observed. Four of the responders could be followed up for 20 months after the treatment and all maintained the favorable state of eye findings obtained with octreotide. We conclude that octreotide seems to be a safe and effective drug in Graves' ophthalmopathy, especially in improving soft tissue involvement, and can be used in patients who are unresponsive to glucocorticoid treatment or who cannot use these drugs for some reason.

Degree of thyrotropin suppression in differentiated thyroid cancer without recurrence or metastases.

Forty-eight patients with differentiated thyroid cancer (DTC), who had no evidence of tumor recurrence or metastases on studies such as radioiodine scanning, neck ultrasonography, and with thyrotropin (TSH) and thyroglobulin (Tg) levels less than 1 mU/L and 5 ng/mL, respectively, were included in the study. The mean age was 43 +/- 12 years (range 15-65) and all were receiving levothyroxine (LT4) treatment with a mean dose of 184 +/- 46 microg daily. Patients were divided into two groups; group A included patients that had baseline TSH levels of 0.4 mU/L or more, and group B patients had baseline TSH levels of less than 0.4 mU/L. LT4 doses for all patients were increased, and serum TSH and Tg measurements were reevaluated after 2 months of dose increments. The mean TSH of group A (patients with baseline TSH levels > or = 0.4 mU/L) decreased from 0.67 +/- 0.28 mU/L to 0.16 +/- 0.08 mU/L (p < 0.001), but mean serum Tg level showed no change after dose increments (2.92 +/- 1.36 ng/mL vs. 3.59 +/- 0.93 ng/mL at the second month; p > 0.05). Similar results were also observed in group B (patients with baseline TSH levels < 0.4 mU/L). Mean TSH level decreased from 0.26 +/- 0.07 mU/L to 0.1 +/- 0.05 mU/L (p = 0.006), but no decrease occurred in mean Tg level (3.0 +/- 1.16 ng/mL vs. 3.3 +/- 1.03 ng/mL; p > 0.05). The patients' data were reevaluated according to second-month TSH levels. Patients with a TSH level between 0.11 to 0.4 mU/L were set as "final TSH > 0.1 group," and patients with a TSH level equal or less than 0.1 mU/L were set as "final TSH < or = 0.1 group," and baseline and second-month Tg levels were assessed. The mean second month Tg levels did not differ in these two patient groups (3.7 +/- 0.74 ng/mL for final TSH > 0.1 group vs. 3.3 +/- 1.2 ng/mL for final TSH < or = 0.1 group; p > 0.05). No difference could be found between initial and second-month Tg levels in both groups (2.8 +/- 1.4 ng/mL vs. 3.7 +/- 0.74 ng/mL in final TSH > 0.1 group and 3.11 +/- 1.1 ng/mL vs. 3.3 +/- 1.2 in final TSH < or = 0.1 group; p > 0.05). In conclusion, these results indicate that serum Tg levels cannot be suppressed by maximal TSH suppression in tumor-free DTC patients. The suppression of TSH to less than 0.1 mU/L seems not to be necessary in most patients who have no evidence of active disease.

Lymphocytic infundibuloneurohypophysitis presenting as diabetes insipidus in a man.

We report a patient with diabetes insipidus, whose sella magnetic resonance imaging revealed a normal hypophysis with a focal nodular thickening of the infundibulum and lack of hyper-intense signal of the normal neurohypophysis. The histopathologic examination of the lesion showed a lymphoplasmacytic, predominantly lymphocytic, infiltration. A diagnosis of lymphocytic infundibuloneurohypophysitis was made, by the exclusion of other infiltrative, granulomatous diseases.

Melperone treatment in an organic delusional syndrome induced by hyperprolactinemia: a case report.

A young female with organic delusional syndrome induced by hyperprolactinemia was admitted to the Psychiatry Clinic of Ankara Social Security Hospital. The most striking characteristic of her history was either worsening of the endocrinologic clinical outcome under conventional neuroleptic treatment or worsening of clinical psychiatric outcome under bromocriptine therapy. A new atypical neuroleptic, melperone, suggested to minimally affect plasma prolactin levels, was started. Her psychotic complaints significantly subsided and she was devoid of any symptomatological change regarding her endocrinological status. These results were discussed.

Furosemide and dDAVP for the treatment of pseudohypoaldosteronism type II.

A 27-year-old Turkish male presented with fatigue, long lasting hypertension, hyperkalemia, hyperchloremic metabolic acidosis and normal glomerular filtration rate. His brother also showed hyperkalemia with no other features of the disease. Plasma renin levels were low and serum aldosterone levels were inappropriately low-normal to his hyperkalemia. Plasma cortisol levels were normal. Plasma renin aldosterone levels responded appropriately to postural changes, salt restriction and saline infusion. Fludrocortisone was ineffective in his hyperkalemia. The conditions were consistent with Type II pseudohypoaldosteronism (PHA). Furosemide and sodium bicarbonate were effective to control his hyperchloremia, metabolic acidosis and hypertension but partly effective for his hyperkalemia. dDAVP alone did not control the situation and hypertension and metabolic derangement reoccurred. Adding dDAVP to furosemide and sodium bicarbonate successfully controlled hyperkalemia, hyperchloremic acidosis and hypertension. The patient stayed normotensive with normal metabolic and biochemical parameters after 6 months with furosemide and dADVP although sodium bicarbonate had been discontinued after the first month of therapy. dDAVP is a useful adjunct to furosemide and non chloride anions which altogether successfully reverse the metabolic derangement in Type II PHA.

Obesity and left ventricular diastolic dysfunction.

To assess the influence of obesity on left ventricular function, 20 obese women (mean body mass index (BMI) 33.8 +/- 3.1 kg/m2 and mean age 31.1 +/- 2.4 years) without evidence of heart disease were evaluated by echocardiography. Obese subjects had greater left ventricular mass index (103 +/- 22 g/m2, 76 +/- 18 g/m2; P < 0.0001) and augmented fractional shortening (39 +/- 2.6%, 36 +/- 0.1%; P < 0.0001) than normals. Isovolumic relaxation time was prolonged in the obese group (92 +/- 11 ms) as compared with the control group (76 +/- 11 ms; P < 0.0001). The ratio of peak early and atrial filling velocities was significantly lower (1.2 +/- 0.4, 1.9 +/- 0.6; P < 0.0001) and atrial contribution was higher (39 +/- 9, 25 +/- 5; P < 0.0001) in obese subjects than in normals. Shortened deceleration time was measured in obese subjects (142 +/- 30, 179 +/- 20 ms; P < 0.0001). In conclusion, obesity causes relaxation and early filling abnormalities and diastolic filling is compensated by augmented atrial contribution. Diastolic dysfunction is an early indicator of cardiac involvement in obesity.

The characteristics of nine patients with adrenal incidentalomas.

With the widening use of computerized tomography, the incidentaloma, an adenoma found incidentally in the adrenal, in computerized tomograms obtained for problems not necessarily related to the adrenal, has emerged as a recent clinical entity. Nine cases with such tumors are presented, here, along with a brief review of the related medical literature. Endocrine and other studies have shown that two of these nine patients had hormone secreting adrenal tumors, two pheochromocytomas. Surgical resection of the tumor was performed in six of the cases and aspiration biopsy was done in four with three completely benign cytological examination results (Class I or II) and one Class III result. The tumor with the class III result turned out to be a benign pheochromocytoma. CT estimates of the tumor size were 25 mm to 80 mm in the whole group and 30 to 80 mm in the patients who were operated on. Operation and histopathologic examination revealed three cortical adenomas, two pheochromocytomas, and one myelolipoma. Although no malignant tumors were found, the percentage of functioning adrenal neoplasms is rather high (22.2%) in this group of nine incidentalomas. Cases of adrenal incidentaloma therefore require a thorough endocrine evaluation along with other examinations which allow the clinician to follow tumor size.