Effect of simvastatin use on bone mineral density in women with type 2 diabetes.

OBJECTIVE: To attempt to clarify the effect of simvastatin, a widely used statin, on the bone mineral density in women with type 2 diabetes. METHODS: We performed a cross-sectional, controlled study of 37 women with type 2 diabetes who were taking simvastatin. Each woman was matched with 2 control subjects who were closest in age, years since menopause (if applicable), and duration of diabetes on the date on which the examination was performed. We measured bone mineral density at the spine and the hip with a dual-energy xray absorptiometry scanner and compared bone density in the 2 study groups. RESULTS: The mean bone mineral density values of patients in the simvastatin group were found to be slightly increased in comparison with those of the control group, both in the lumbar vertebrae and in the femoral neck, but these differences were not statistically significant (P>0.05). CONCLUSION: In this cross-sectional study, we could not demonstrate a positive effect of long-term simvastatin treatment on bone mineral density in women with type 2 diabetes and hypercholesterolemia.

A comparison of glycemic effects of glimepiride, repaglinide, and insulin glargine in type 2 diabetes mellitus during Ramadan fasting.

Although diabetics may be exempted from Ramadan fasting, many patients still insist on this worship. Aim of the present study is to compare the effects of glimepiride, repaglinide, and insulin glargine in type 2 diabetics during Ramadan fasting on the glucose metabolism. Patients, who were willing to fast, were treated with glimepiride (n=21), repaglinide (n=18), and insulin glargine (n=10). Sixteen non-fasting control type 2 diabetics matched for age, sex, and body mass index were also included. Fasting blood glucose (FBG), post-prandial blood glucose (PBG), HbA1c, and fructosamine as well as lipid metabolism were evaluated in pre-Ramadan, post-Ramadan, and 1-month post-Ramadan time points. There was no significant change from pre-Ramadan in FBG, PBG, and HbA1c variables in fasting diabetics at post-Ramadan and 1-month post-Ramadan. However, PBG was found higher in non-fasting control diabetics at post-Ramadan and 1-month post-Ramadan (p<0.05 and p<0.001, respectively). In fructosamine levels, a significant increase was noted both in fasting group and non-fasting group at 1-month post-Ramadan (p<0.01 for all). However, no significant difference was found in the comparison of the changes in fructosamine levels between fasting group and non-fasting group. Risk of hypoglycemia did not significantly differ between fasting and non-fasting diabetics. There was no significant difference between three drug therapies regarding glucose metabolism and rate of hypoglycemia. No adverse effects on plasma lipids were noted in fasting diabetics. In this fasting sample of patients with type 2 diabetes, glimepiride, repaglinide, and insulin glargine did not produce significant changes in glucose and lipid parameters.

Papillary microcarcinomas of the thyroid gland and immunohistochemical analysis of expression of p53 protein in papillary microcarcinomas.

BACKGROUND: Thyroid papillary microcarcinoma (TPM) is defined according to WHO criteria as a thyroid tumor smaller than 1-1.5 cm. TPMs are encountered in 0.5-35.6% of autopsies or surgical specimens where carcinoma had been unsuspected. The purpose of the present study was to evaluate patients who had TPMs in terms of clinical findings, histopathological features and immunohistochemical evidence of expression of the tumor suppressor gene p53. METHODS: A total of 44 patients with TPMs less than 1.0 cm in diameter were included in the study. The patients were evaluated clinically and the tumors were evaluated in terms of their histopathological and immunohistochemical features, including expression of p53. RESULTS: The female/male ratio was 2.8/1, and the median age at time of diagnosis was 49 years (range 20-71 years). The maximum diameter of the smallest focus was 0.1 mm, and that of the largest was 10 mm microscopically. The mean diameter of all tumors was 5.7 mm. There was no correlation between tumor size and age or gender. Of the TPMs, 72% were found in the right lobe, 24% in the left lobe and 4% in the isthmus. Fine-needle aspiration biopsy provided the diagnosis of TPM in only 43.2% of the patients. All patients were treated with surgery, with 20 undergoing conservative surgery, i.e. lobectomy or isthmusectomy, and 24 undergoing total thyroidectomy. Frozen section provided the diagnosis of TPM in only 56.8% of the patients. We found lymphocytic thyroiditis in 13.6% of patients, follicular variants in 11.9%, capsular invasion in 26.8%, lymph node involvement in 11.9%, soft tissue metastases in the neck in 12.1% and multifocality in 31.7%, and none of these were related to age or gender (p > 0.05). No distant metastases were observed during approximately 10 years of follow up. We found p53 positivity in 34.5% of TPM tumors. However, p53 expression was not statistically related to age or gender. CONCLUSION: Our findings imply that TPMs may not be entirely innocent since they are associated with signs of poor prognosis such as capsular invasion, multifocal presentation, lymph node involvement and p53 positivity. Therefore, TPMs should be evaluated and followed like classical papillary cancers.

Remission criteria for the follow-up of patients with acromegaly.

OBJECTIVE: The aim was to evaluate the validity of current remission criteria in acromegaly, a random GH level of <2.5 microg/l, a glucose-suppressed GH level of <1 microg/l and a normal IGF-I level. DESIGN: In forty-one patients treated for acromegaly (23 males and 18 females, 20-69 years) and 94 healthy subjects (50 males and 44 females, 20-78 years), basal GH and IGF-I levels and nadir GH levels after 75 g oral glucose were evaluated in decade blocks; these were assayed by sensitive immunoradiometric assays. RESULTS: Basal GH levels varied widely from 0.022 to 10.4 in healthy subjects and were >2.5 microg/l in 19%. The mean post-glucose GH nadir was 0.067+/-0.009 microg/l (range 0.003-0.4 microg/l) and the upper limit of the GH nadir was 0.26 microg/l (means+2 S.D.) in healthy subjects. Thirty-five patients with acromegaly had high-for-age IGF-I levels in relation to our healthy subjects. In this group, 15 (42.9%) patients had basal GH levels of <2.5 microg/l, 14 (40%) patients had nadir GH levels of <1 microg/l, and three (8.6%) patients had GH suppression to <0.26 microg/l which was defined as normal GH suppression in our healthy subjects. Only six patients with acromegaly had normal-for-age IGF-I levels and all of these patients had basal GH levels of <2.5 microg/l and all but one had nadir GH levels of <0.26 microg/l. CONCLUSIONS: A basal or random GH level of <2.5 microg/l is not a reliable criterion for remission in acromegaly and the currently accepted normal upper limit of 1 microg/l for post-glucose GH suppression is too high. Post-glucose nadir GH levels, measured with sensitive assays, can be <1.0 microg/l in 40% and basal GH levels can be <2.5 microg/l in 43% of the active acromegalic patients. IGF-I levels appeared to correlate better with a nadir GH cut-off of 0.26 microg/l rather than 1 microg/l in the determination of disease activity.

Prevalence of subclinical Cushing's syndrome in 70 patients with adrenal incidentaloma: clinical, biochemical and surgical outcomes.

Subclinical Cushing's syndrome (SCS) is being detected with increased frequency in patients with adrenal incidentaloma. In the current study, we evaluated the prevalence of SCS in 70 patients with adrenal incidentaloma and compared the main findings on them with other patients with nonfunctional adrenal incidentaloma (NFA). Overnight 3 mg dexamethasone (DXM) suppression test to exclude cortisol hypersecretion, and high dose DXM suppression test to find out patients with SCS, were applied to all subjects. Afterwards, biochemical and clinical findings of patients with SCS were compared with the other patients with NFA. Four of the 70 patients with adrenal incidentaloma were found to have SCS, with a prevalence of 5.7%. Basal ACTH and DHEA-S levels were significantly lower (p < 0.05 and p < 0.01, respectively), and midnight cortisol and 24-hour urinary free cortisol levels were significantly higher in patients with SCS (p < 0.001 and p < 0.05, respectively). Biochemical and metabolic bone parameters were similar in patients with SCS and in patients with NFA. Hypertension, diabetes mellitus, and obesity were more common in patients with SCS. One of the patients with SCS developed adrenocortical insufficiency following unilateral adrenalectomy which lasted for about 6 months. Suppressed ACTH and DHEA-S levels, and high midnight cortisol levels may be some clues for SCS in patients with adrenal incidentaloma. Since patients with SCS frequently have risk factors for atherosclerosis such as hypertension, diabetes, and obesity, and the surgical management of SCS with adrenalectomy may offer an advantage. Patients undergoing adrenalectomy should be followed for the development of adrenal insufficiency.

Case report: patient with multiple paragangliomas treated with long acting somatostatin analogue.

Paragangliomas of the head and neck are uncommon neoplasms. They are usually benign, but tend to be locally invasive. Although surgical resection remains the definitive treatment, important issues about management arise when such lesions are inoperable. Beneficial effects of octreotide treatment have already been reported in a malign paraganglioma case. Here we report a 24 year old female with familial, bilateral, multiple paraganglioma in the head and neck region, who firstly presented with pulsatile tinnitus and hearing loss in her left ear. After embolization was performed, she underwent operation twice because of the gross tumor mass. No significant change in tumor size was determined after the operations, however there were no distant metastases. Although she experienced hypertension attacks, no hormonal overproduction was found in repeated measurements. As the tumor was unresectable, new alternative therapies were sought. Octreotide scintigraphy was positive in the tumoral tissue, so we began to treat her with somatostatin analogue octreotide. After a 16 month follow up period, an improvement of the performance status, the near normalisation of attacks and stabilization of tumor growth were achieved. However, in the last three visits, she began to experience symptoms more frequently and it had been necessary to increase the octreotide dose. She is now well and being followed up. In conclusion, the beneficial effects of octreotide treatment could be quantified by clinical, tumor and scintigraphic criteria. These data suggest that octreotide can be useful in the treatment of inoperable paragangliomas.

The prevalence of late onset congenital adrenal hyperplasia in hirsute women from Central Anatolia.

Late onset congenital adrenal hyperplasia (LO CAH) can be seen in association with polycystic ovary syndrome (PCOS) or idiopathic hirsutism (IH). The study aimed to find out the prevalence of LO CAH in Central Anatolia among hirsute women. Sixty-three patients with hirsutism were evaluated to determine the frequency of LO CAH by comparing them with their age and body mass index matched 28 healthy controls. Of those 63 hirsute women, 43 were diagnosed as PCOS, and 20 were diagnosed as IH. Following basal hormonal evaluation, all subjects underwent ACTH stimulation test and ACTH stimulated 17-hydroxyprogesterone (17-OH P), 11-desoxycortisol (11-DOC), cortisol (F), and dehydroepiandrosterone sulfate (DHEA-S) levels were determined in all subjects. ACTH stimulated 17-OH P, 11-DOC, and DHEA-S levels did not differ between groups. However, stimulated F levels were found to be higher in hirsute women (p<0.001). Six out of 63 (9.52%) patients with hirsutism met the criterion for 21 hydroxylase deficiency. We found no subject presumed to have 11-beta hydroxylase deficiency, but one subject in control group (3.57%) and two patients among PCOS subjects (4.65%) had exaggerated DHEA-S response which was suggestive of mild 3-beta hydroxysteroid dehydrogenase deficiency. In conclusion, the most frequent form of LO CAH seems to be due to 21 OH deficiency among women with PCOS and IH in Central Anatolia. Mild 3-beta HSD deficiency may also be an underlying cause for hirsutism and it may be seen without any clinical presentation. Adrenal hyperactivity is likely to be the main reason of hyperandrogenemia in women with hirsutism.

Relationship between thyroid autoimmunity and Yersinia enterocolitica antibodies.

It has previously been proposed that subclinical Yersinia enterocolitica infection may play a role in autoimmune thyroid disease (AITD). In this study, we investigated the relationship between the thyroid autoantibodies and the antibodies that produced against different serotypes of Y. enterocolitica. A total of 215 subjects were included into the study (65 newly diagnosed Graves' disease [GD], 57 Hashimoto's thyroiditis [HT], 53 nontoxic diffuse goiter [NTDG], and 40 subjects for control group [CG]). Thyroid receptor antibodies (TRAb), thyroid and agglutinating antibodies against Y. enterocolitica serotype O:3, O:5, O:8, O:9 were measured in the blood samples. The highest incidence of Y. enterocolitica antibody positivity was measured in GD (53.8% for O:3, 29.2% for O:5, 44.6% for O:8, and 40% for O:9) and followed by HT. In patients with GD, TRAb levels were also higher than in patients with HT, NTDG, and CG. There was no difference between NTDG and CG in respect to the titer levels and the positivity of both TRAb and Y. enterocolitica antibodies. There was also a weak linear correlation between TRAb level and the titer of antibodies against Y. enterocolitica antigens. It can be concluded that Y. enterocolitica infection may play a role in etiology of GD in Turkey.

Twenty-four hour 17-hydroxyprogesterone response to adrenocorticotropine in adrenal incidentalomas: augmented response after adrenalectomy in two patients.

The current study aimed to investigate the midterm (24 hour) response of 17-hydroxyprogesterone (17-OHP) and dehydroepiandrosterone sulphate (DHEA-S) to synthetic high-dose adrenocorticotropin (ACTH) in adrenal incidentalomas (Al). Seventeen patients with Al and 40 age- and sex-matched controls received synthetic ACTH (tetracosactide, 1000 microg, IM). Plasma, 17-OHP and DHEA-S were collected in basal conditions and after 1, 4, 6, 8 and 24 hours. (HPA) axis was also evaluated using circadian serum cortisol, urinary free cortisol and over-night 2 mg dexamethasone suppression. Basal plasma 17-OHP levels did not differ among the groups. However, the increment in plasma 17-OHP in patients both in terms of peak [13.76 +/- 2.52, 4.77 +/- 0.30ng/ml, mean +/- S.E.M, p < 0.001] and area under the curve [190 +/- 46, 96.75 +/- 32 ng/ml/h, p < 0.001] were significantly higher than that of the controls. Stimulated 17OH-P levels never reached 9.1 ng/ml in controls. Sixty-five (11/17) % of the patients were found to have exaggerated response. Three of the patients were found to have subclinical Cushing's syndrome and interestingly, two augmented their 17-OHP response to ACTH after unilateral adrenalectomy and normalisation of their HPA axis. Basal DHEA-S levels of the patients were significantly lower [99.21 +/- 45, 230.18 +/- 34 microg/dl, p < 0.01] and stayed persistently lower than that of the controls. Evidence of a heterozygous 21 hydroxylase deficiency, as indicated by the exaggerated 17-OHP response to ACTH, has been widely reported in Al patients. However, to our knowledge to date there is no report on augmented 17-OHP response to ACTH after adrenalectomy. Possible reasons for the augmentation were discussed.