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.

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.

The prevalence of Vitamin D deficiency and effects of ultraviolet light on Vitamin D levels in elderly Turkish population.

Vitamin D deficiency is commonly found in the elderly and is associated with osteoporosis and hip fractures. In this study, Vitamin D status of 138 female and 87 male subjects living in old age homes (OAH) and 171 female and 24 male subjects living in own homes (OH) from Central Anatolia were assessed. A questionnaire was applied to collect information about wearing features and degree of sunlight exposure and benefiting from ultraviolet index calculated (BFUI). We have found Vitamin D deficiency in 33.4% among our subjects. Also, 40.1% of subjects living in OAH (54.1% of females and 18.4% of males) and 24.4% of subjects living in OH (27.9% of females and 4.2% of males) were Vitamin D deficient. Vitamin D deficiency was significantly higher in subjects living in OAH than subjects living in OH (P = 0.001) and also higher in females than males (40.7% versus 15.3%, P < 0.001). Subjects with Vitamin D deficiency were older (P < 0.001), BFUI was lower (P < 0.001) and parathyroid hormone (PTH) was higher (P < 0.001) than those having normal level of 25(OH)D. There was a significant negative correlation between 25(OH)D levels and age (P < 0.001, r = -0.248) PTH and 25(OH)D (P = 0.004, r = -0.340), and positive correlation between 25(OH)D and BFUI (P < 0.001, r = 0.340). Vitamin D deficiency is very common in Turkish elderly subjects especially living in OAH and there is a significant low exposure to sunlight among them. Simply by asking clothing habits and exposure to sunlight, we can able to identify risk of Vitamin D insufficiency in elderly subjects.

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.

Suppressive therapy with levothyroxine for euthyroid diffuse and nodular goiter.

In this study, 35 patients with euthyroid diffuse goiter and 35 patients with euthyroid nodular goiter were treated with Levothyroxine (L-T4) for six months. The aim was to evaluate the efficacy of treatment on thyroid and nodule volumes and to evaluate the correlation between volume changes and thyroglobulin levels. Serum thyroid hormones, TSH, thyroglobulin, thyroid and nodule volumes were measured at the initial visit and after 6 months. Radioactive iodine uptakes of the thyroid gland were evaluated before treatment. The mean decrease of thyroid volume at six months was about 20% (20.4 +/- 8.8 ml vs. 16 +/- 7.9 ml, P<0.001) in patients with diffuse goiter. All patients with diffuse goiter showed some decrement in their goiter sizes. Thyroid nodules, in response to thyroid hormone treatment, showed a variable behavior. A reduction of 50% or more in volume was detected in 31% (11/35) of the patients. 54% of the patients (19/35) showed a 10-49% decrease in nodule volume. Five of the patients were found to be insensitive to the therapy. Their nodule volumes either increased or did not change during therapy. Free T4 and free T3 levels increased and TSH levels decreased with L-T4 treatment in all patient groups. Patients with higher TSH levels (within normal limits) showed more volume reduction in the diffuse goiter group. No uniform correlation was found between volume changes and thyroglobulin levels in either of the patient groups. In conclusion, suppressive thyroxine treatment is effective in reducing the size of the goiter, and nodules and thyroglobulin levels cannot be taken as an indicator of the efficacy of L-T4 therapy.

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.

Adrenal function during tuberculous infection and effects of antituberculosis treatment on endogenous and exogenous steroids.

SETTING: To date, few studies have been published on the frequency of adrenal disorder during active tuberculosis and whether rifampicin treatment has an adverse effect on adrenal function. OBJECTIVE: We evaluated endogenous and exogenous steroid metabolism in patients with active tuberculosis before and during treatment to observe whether the functions were affected by tuberculosis and rifampicin. DESIGN: Basal hormone levels and Synacthen stimulation test were obtained in 22 patients with active tuberculosis before and 20-30 days after antituberculosis treatment including rifampicin. Exogenous steroid metabolism was assessed by 1 mg overnight dexamethasone suppression test before and during antituberculosis treatment. RESULTS AND CONCLUSION: No significant differences were found on basal plasma cortisol or adrenocorticotropic hormone levels, but significant decrements were found on basal dehydroepiandrosterone sulfate (P < 0.05) and urinary free cortisol levels (P < 0.01) before and after commencing antituberculosis treatment. After Synacthen stimulation, only one patient had insufficient increment in plasma cortisol levels. This patient was diagnosed as a case of Addison's disease. Although nine patients (42%) showed sufficient suppression of cortisol secretion on the dexamethasone test before treatment, none had sufficient suppression with dexamethasone after antituberculosis treatment. We found less mean maximum adrenal cortisol responsiveness to Synacthen stimulation during the course of antituberculosis treatment (P < 0.01). Although impairment of adrenal function is a rare condition in active tuberculosis, rifampicin may have a significant effect on steroid metabolism.

A potential risk for osteomalacia due to sociocultural lifestyle in Turkish women.

Osteomalacia is a metabolic bone disease caused by deficiency of vitamin D or its active metabolites. Because poor sunlight exposure is one of the most common causes of osteomalacia, the disease seems to be rare in countries with adequate sunlight. We report nine Turkish female patients with osteomalacia with ages between 21 and 50 years. Osteomalacia was diagnosed on the basis of a history of bone aches or pains, muscle weakness, low or low normal serum calcium and urinary calcium, decreased concentrations of serum inorganic phosphorus and 25- hydroxyvitamin D and increased serum intact PTH and alkaline phosphatase levels. Radiographically, pseudo-fractures were present in seven of the patients. The patients' symptoms and signs were relieved with the treatment with vitamin D analogues and calcium. Their hypovitaminosis D are suggested to be caused by excessive clothing in the outdoors due to sociocultural and religious reasons. Excessive clothing may be a risk factor for osteomalacia in young to middle-aged and otherwise healthy women even in countries with adequate sunlight.

Omeprazole: calcitonin stimulation test for the diagnosis follow-up and family screening in medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) occurs sporadically but may also be inherited as part of the multiple endocrine neoplasia (MEN) type 2 syndrome. Screening of the patients and first degree relatives annually with basal and provocative tests for serum immunoreactive calcitonin (CT) levels is essential and enables potentially curative disease. Pentagastrin and calcium are the usual provocative agents used worldwide. We used endogenous gastrin (GT) release achieved by omeprazole, 20 mg b.i.d., to stimulate CT in 9 MTC, in 3 MEN 2A family members, and in 50 healthy control subjects. A steady and significant increase both in GT and CT levels was achieved in 9 MTC patients and 3 of the 14 family members tested, whereas in healthy controls the CT increase stimulated by GT was insignificant. Preliminary results showed that this new, safe, cheap, and outpatient-basis test can be used in MTC diagnosis, follow-up, and screening.

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.

Adrenal myelolipoma: case report with a review of the literature.

A 40 year old woman who was pre-operatively diagnosed as possibly having adrenal myelolipoma is reported. Adrenal myelolipomas are rare, non-functional benign tumours comprising varying amounts of fat and haematopoietic elements. Albeit possibly coincidental, there is a frequent association with obesity, hypertension, and/or diabetes mellitus. A growing number of patients are being diagnosed during ultrasonographic or computerized tomographic scanning for unrelated problems.

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.

Normal growth and pubertal development during bromocriptine therapy in two patients with prolactinoma.

The cases of two boys, a 14 years 10 months old and an 18-year-old, with delayed puberty are presented. The first patient also had a short stature. Both patients had a pituitary adenoma, as shown by computed tomography, with high prolactin levels. After bromocriptine therapy was started, there was a spontaneous progression of normal puberty. The first patient used a synthetic growth hormone together with bromocriptine, however, even after the growth hormone was stopped progression in puberty and gain in height continued. The favorable response obtained in these patients implies that bromocriptine can be an effective therapy for adolescent patients with prolactinoma.

The use of antiandrogen flutamide in the treatment of hirsutism.

In this study the efficacy of flutamide, an antiandrogen which does not have a steroid structure, or progestational and estrogenic activities, on hirsutism and hormone levels in polycystic ovary syndrome (PCOS) and idiopathic hirsutism (IH) was investigated. Ten patients with PCOS and nine patients with IH between 19 and 36 years of age were selected for the study. They were given a 500 mg daily dose of flutamide and were followed up for clinical and hormonal effects at the second, sixth, eighth and twelfth months of the treatment. The severity of hirsutism was assessed according to the Ferriman-Gallwey's score. There was a slight decrease to below the pre-treatment level in serum LH at the end of the eighth month (P < 0.05) and there was also a persistent decrease in progesterone (P) after the second month of the treatment (P < 0.05). No other significant change was observed in ovarian or adrenal androgens. Clinical examinations revealed that after six months of the therapy the dose of flutamide had caused a significant alleviation of hirsutism and this continued during the following months.

Sodium ipodate in the treatment of toxic diffuse goiter. Short-term and long-term effects on thyrotoxicosis.

Iodinated radiocontrast medication has been successful in the treatment of thyrotoxicosis when used for short periods up to 21 days, but experience with long-term use is lacking. In the first part of this study, a group of seven patients each taking 1.5 g. sodium ipodate daily was observed for 21 days and compared to a similar group of seven thyrotoxic patients taking 400 mg. propylthiouracil (PTU) daily. Sodium ipodate brought about a more significant decrease in serum total T3 and T4 levels, and more prominent increase in reverse T3 levels in the first ten days of the treatment. In the second part, a group of seven patients with thyrotoxicosis were given sodium ipodate, 1.5 g, daily for 20 days and 0.75 g. thereafter and were compared to a similar group of seven patients who took PTU, 300 mg. daily for the first 20 days and 150 mg. daily afterwards. Serum thyroid hormone levels decreased in both groups at the end of the first month of treatment, but rose again, along with worsening of symptoms, in five patients on ipodate treatment. Therefore, sodium ipodate, an iodinated radiocontrast agent is unable to control thyrotoxicosis for longer than a month.

Biologically ineffective gonadotropin secretion: two cases.

Symptoms of gonadal insufficiency, in the presence of high serum levels of gonadotropins, generally indicate primary gonadal failure. An exception to this generalization is the secretion of ineffective gonadotropic hormone secretion by the pituitary. One such case was reported in 1979. However rare it may be, this disorder should still be taken into consideration when evaluating hypogonadal patients. In fact, it may not be so rare as it is supposed. In this report, two such cases are presented. They both show signs of gonadal insufficiency in the presence of high serum gonadotropin concentrations, but responding normally to exogenously administered chorionic gonadotropin.

The differentiation between constitutional delayed puberty and hypogonadotropic hypogonadism: experience with three newly devised methods.

There is no known method that is wholly successful in differentiating between hypogonadotropic hypogonadism and constitutional delayed puberty at an early stage. We present here the results we have got with three recently suggested methods in patients with delayed and absent puberty. These methods are te LHRH test before and after 36 hour pulsatile LHRH treatment, the prolactin response to TRH, and the prolactin response to metoclopramide.