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Biomedical subjects

F Keleştimur

Publications and source records attributed to F Keleştimur.

At least 19 recordsLinked to original sources

Alternate pathway 17,20-lyase enzyme activity in the adrenals is enhanced in patients with polycystic ovary syndrome.

OBJECTIVE: To assess the activity of the enzyme cytochrome P450c17alpha in patients with polycystic ovary syndrome (PCOS). DESIGN: Prospective clinical study. SETTING: Outpatients at Erciyes University Medical School, Kayseri, Turkey. PATIENT(S): Twenty-eight women with PCOS aged 25.44 +/- 4.37 years (mean +/- SD) and 18 normal women aged 26.94 +/- 3.17 years. MAIN OUTCOME MEASURE(S): Serum levels of 11-deoxycortisol, androstenedione (A), and 17alpha-hydroxy progesterone were measured before and 30 and 60 minutes after ACTH (0.25 mg i.v.) injection. RESULT(S): There was a statistically significant correlation between basal levels of 11-deoxycortisol (4.05 +/-1.16 ng/mL) and A (3.36 +/- 0.97 ng/mL) (r = 0.539). The peak level of 11-deoxycortisol (7.82 +/- 2.36 ng/mL) was also significantly correlated with the peak level of A (6.66 +/- 1.32 ng/mL) (r = 0.570) in women with PCOS. There was no statistically significant correlation between basal A (2.33 +/- 0.50 ng/mL) and basal 11-deoxycortisol (2.71 +/- 0.59 ng/mL) or between peak A (3.38 +/- 0.50 ng/mL) and peak 11 -deoxycortisol (3.68 +/- 0.48 ng/mL) levels in control subjects. CONCLUSION(S): We believe that PCOS is characterized by enhanced activity of 17,20-lyase enzyme in an alternate pathway between 11-deoxycortisol and A in the adrenal glands.

17-alpha-Hydroxyprogesterone

Finasteride treatment for one year in 35 hirsute patients.

This study was performed to confirm the favourable therapeutic effects of finasteride in hirsute women as described by previous publications of different research groups. Our study was a non-randomized, prospective clinical trial. Thirty five patients with hirsutism were included in the study. The patients received 5 mg finasteride orally once per day over a period of 12 months. Hirsutism score, FSH, LH, E2, total T, free T, androstenedione (A), DHEAS, 17-hydroxyprogesterone (17-OHP) and sex hormone-binding globulin (SHBG) levels were determined in all the patients before treatment and every 6 months during treatment. The modified Ferriman-Gallwey score decreased from a mean of 19.06 +/- 6.12 to 11.31 +/- 4.93 during the study. Clinical improvement in the degree of hirsutism was observed in 26 of 35 patients. The percent reductions in hirsutism scores (mean% +/- SD) at 6 and at 12 months were 25.8 +/- 11.3 and 41.3 +/- 18.5, respectively. During the finasteride therapy E2 and SHBG were increased significantly while DHEAS was decreased significantly at 12 months. There were no significant changes in the values of the other hormones and no serious side effects were observed in the study. In conclusion, finasteride is a well tolerated therapeutic agent without significant side pathological laboratory findings and can be used in the treatment of hirsutism.

17-alpha-Hydroxyprogesterone

Hypothalamo-pituitary-adrenal axis and growth hormone axis in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic disease and is associated with cytokines (IL-1, IL-6, TNF-alpha) production. There is little information on hypothalamo-pituitary-adrenal (HPA) axis and growth hormone (GH) axis in the patients with RA. We have, therefore, investigated these systems in twenty patients with confirmed RA. Ten of the patients had active and 10 patients remitted RA. Serum cortisol, ACTH and GH levels were measured in the basal state and after insulin induced hypoglycaemia. Cortisol, adrenocorticotropic hormone (ACTH) and GH responses were impaired in 65%, 85% and 30% of the patients, respectively. The basal and peak hormone levels were similar between the patients with active RA and the patients in remission. These findings indicate that there is an impairment in HPA and GH axis in patients with active and remitted RA. The site of this impairment is probably hypothalamus and/or pituitary gland.

Adolescent

The treatment of insulin resistance does not improve adrenal cytochrome P450c17alpha enzyme dysregulation in polycystic ovary syndrome.

OBJECTIVE: To determine whether metformin. when given to non-diabetic women with polycystic ovary syndrome (PCOS), results in a reduction of insulin resistance and hyperinsulinemia while body weight is maintained. Also we aimed to see whether the reduction in insulin levels attenuates the activity of adrenal P450c17alpha enzyme in patients with PCOS. DESIGN: We investigated the 17-hydroxyprogesterone (17-OHP) and androstenedione responses to ACTH, insulin responses to an oral glucose tolerance test (OGTT) and glucose disposal rate in an insulin tolerance test before and after metformin therapy (500 mg, orally, twice daily, for 12 weeks). METHODS: The presence of hyperinsulinemia in 15 women with PCOS was demonstrated by an OGTT and results were compared with those of 10 healthy women. Insulin sensitivity was measured by the rate of endogenous glucose disposal after i.v. bolus injection of insulin. 17-OHP and androstenedione responses to ACTH were measured in all the women with PCOS and the normal women. RESULTS: Women with PCOS were hyperinsulinemic (102.0+/-13.0 (S.E.M.) VS 46.2+/-4.4 pmol/l) and hyperandrogenemic (free testosterone 15.3+/-1.7 vs 7.9+/-0.6 nmol/l; androstenedione 11.8+/-0.8 vs 8.2+/-0.6 nmol/l) and more hirsute (modified Ferriman-Gallwey score, 17.7+/-1.6 vs 3.0+/-0.3) than healthy women. In addition, women with PCOS had higher 17-OHP and androstenedione responses to ACTH when compared with healthy women. Metformin therapy resulted in some improvement in insulin sensitivity and reduced the basal and post-glucose load insulin levels. But 17-OHP and androstenedione responses to ACTH were unaltered in response to metformin. CONCLUSIONS: PCOS is characterized by hyperactivity of the adrenal P450c17alpha enzyme and insulin resistance. It seems that there is no direct relationship between insulin resistance and adrenal P450c17alpha enzyme dysregulation.

17-alpha-Hydroxyprogesterone

Lymphocytic hypophysitis in a patient with Graves' disease.

A case of lymphocytic hypophysitis is described in a patients with Graves' disease and diabetes mellitus. The 62-year-old man was admitted to hospital with the complaints compatible with hyperthyroidism in April 1993. His medical history, physical examination, thyroid function tests, thyroid scintigraphy and thyroid ultrasonography revealed Graves' disease. The patient had also suffered from diabetes mellitus for three years. After this, the patient's progress was not monitored for two years. The patient presented himself again in September 1995 with complaints of hypothyroidism, hypogonadism and hypoadrenalism. Hormonal investigation showed panhypopituitarism. A magnetic resonance imaging of the pituitary gland disclosed an enlarged pituitary and a thickened infundibulum. The high intensity signal of the neurohypophysis was absent. Transsphenoidal hypophysectomy was performed which revealed a grey-white, relatively avascular pituitary mass. Histology showed diffuse infiltration of the anterior pituitary by numerous lymphocytes. The neurohypophysis also showed evidence of lymphocytic infiltration. On the basis of these findings we suggest that lymphocytic hypophysitis may be associated with Graves' disease.

Diabetes Mellitus, Type 2

Comparison of cyproterone acetate plus ethinyl estradiol and finasteride in the treatment of hirsutism.

The aim of this study was to compare the clinical efficacy and safety of low dose cyproterone acetate-estrogen combination (Diane) and the 5 alpha-reductase inhibitor finasteride in the treatment of hirsutism. Fourty-two women with hirsutism were included in the study. Twenty-one patients treated with cyproterone acetate (CPA) 2 mg and ethinyl estradiol (E) 35 micrograms daily on days 5-25 of the menstrual cycle, 21 with finasteride 5 mg daily. Hirsutism score, hormone levels, multiscreen blood chemistry and side effects were evaluated at three-monthly intervals for 9 months. A significant decrease in hirsutism score as compared to baseline was observed after 9 months with either CPA + E (Diane) (mean +/- SE, 15.81 +/- 1.19 vs 8.38 +/- 1.21) or finasteride treatment (17.81 +/- 1.05 vs 10.86 +/- 0.91) (p < 0.0005). The reductions in hirsutism scores (mean% +/- SE) were 14.23 +/- 2.29 vs 19.77 +/- 2.22 (p < 0.05) at 3, 40.23 +/- 4.58 vs 29.49 +/- 2.69 (p < 0.02) at 6 and 50.99 +/- 4.13 vs 39.87 +/- 3.30 (p < 0.02) at 9 months in CPA + E and finasteride groups, respectively. No significant changes were observed in hormone levels during finasteride treatment. Serum free testosterone significantly decreased at the third month of treatment, and remained suppressed for the duration of treatment in CPA + E group. DHEAS levels also decreased significantly after 6 and 9 months of therapy with CPA + E. SHBG significantly increased during CPA + E treatment. We conclude that both drugs are effective and well tolerated, but CPA + E appears to be more effective than 5 alpha-reductase inhibitor finasteride in long-term treatment of hirsute women. Diane is also a cost-effective drug.

5-alpha Reductase Inhibitors

Comparison of Diane 35 and Diane 35 plus spironolactone in the treatment of hirsutism.

OBJECTIVE: To compare the clinical efficacy and safety of Diane 35 (cyproterone acetate [2] mg and ethinyl estradiol [35 microg]) plus spironolactone [100 mg] combination and Diane 35 alone in the treatment of hirsutism. DESIGN: Prospective clinical study. SETTING: Outpatients in Erciyes University Medical School. PATIENT(S): Fifty women with hirsutism. INTERVENTION(S): Group I patients (n = 22) were treated with Diane 35 alone and group II patients (n = 28) with Diane 35 plus spironolactone [100 mg]. MAIN OUTCOME MEASURE(S): The basal hormone levels total and free T, androstenedione, DHEAS, sex hormone-binding globulin (SHBG), and prolactin (PRL) were measured by RIA before the study. Free T, SHBG, and DHEAS were also measured at 6-month intervals for 12 months. Hirsutism was graded at 6-month intervals. RESULT(S): The basal hormone levels were similar between the groups. Hirsutism score significantly decreased at the end of the therapy in both groups. The reduction in hirsutism score in group II at 12 months was greater than in group I. But the scores before the treatment, at 6 and 12 months were similar between the groups. CONCLUSION(S): Although the actual hirsutism score and free T concentration are not significantly different between the two groups at 12 months, percentage change in the hirsutism score at 12 months was higher in the Diane 35 plus spironolactone group. Therefore, the addition of spironolactone to Diane 35 may have a synergistic effect on hirsutism score.

Adolescent

Collagenous colitis in a patient with Addison's disease: a case report.

Diarrhea is a non-specific symptom which may be associated with Addison's disease and several causes had been demonstrated in the aetiology. We describe a patient with Addison's disease who was suffering from chronic diarrhea for three months. She was diagnosed as having collagenous colitis and successfully treated with Sulphasalazine, 2 g/day. Collagenous colitis is an uncommon cause of chronic diarrhea and the association of collagenous colitis with Addison's disease has not previously been described. We think that collagenous colitis may play a role in the aetiology of diarrhea in patients with Addison's disease and therefore we suggest a full colonoscopic examination in other patients with Addison's disease and diarrhea to determine the incidence of collagenous colitis in the aetiology of diarrhea.

Addison Disease

Electrodermal activity in nonmedicated hyperthyroid patients having no depressive symptoms.

The aim of the present study was to investigate whether the alteration in hypothalamic-pituitary-thyroid axis function results in electrodermal abnormality without causing marked psychiatric manifestations or not. Electrodermal activity was recorded with the skin conductance unit and IBM-AT computer. Basal levels of electrodermal activity (EDA), as well as responsivity to repeated insignificant acoustic stimulation were studied in 24 nonmedicated hyperthyroid patients and 35 healthy controls. The outcome of psychiatric rating scores indicated that patients had low anxiety scores and normal depression scores. The basal levels of thyroid hormones were higher in patients, when compared with the control group. On the analysis of EDA, we found lower onset latency and duration of the skin conductance response and higher skin conductance level in nonmedicated patients than healthy controls. The results above provide supporting evidence that the change of hypothalamic-pituitary-thyroid axis function results in abnormal EDA, without causing marked psychiatric manifestations.

Acoustic Stimulation

A comparison between two doses of flutamide (250 mg/d and 500 mg/d) in the treatment of hirsutism.

OBJECTIVE: To compare the effects of flutamide at 250 mg/d and 500 mg/d in the treatment of hirsutism. DESIGN: Randomized, prospective clinical study. PATIENT(S): Sixty-five patients with moderate to severe hirsutism. INTERVENTION(S): Group I (n = 35) patients were treated with flutamide, 250 mg/d, and group II (n = 30) patients were treated with flutamide, 500 mg/d, for 12 months. Baseline hormone levels, body mass index, and hirsutism scores were similar between the groups. Hirsutism score, hormone levels, and multiscreen blood chemistry were measured at 3-month intervals for 12 months. RESULT(S): The modified Ferriman-Gallwey scores for hirsutism decreased significantly at months 6 and 12 from a mean +/- SEM of 17.8 +/- 0.9 to 6.0 +/- 0.6 (P < 0.001) and 17.8 +/- 0.9 to 4.8 +/- 0.7 (P < 0.001) in group I and from 17.0 +/- 0.9 to 6.6 +/- 0.7 and 17.0 +/- 0.9 to 5.2 +/- 0.7 (P < 0.001) in group II, respectively. The reductions in hirsutism scores (mean +/- SEM) were similar in group I at 6 months (64.6% +/- 2.5%) and at 12 months (71.2% +/- 2.2%) and in group II at 6 months (62.1% +/- 3.0%) and at 12 months (70.3% +/- 3.0%). The percent reductions in hirsutiam scores at 6 and at 12 months were similar within group I (64.6% +/- 2.5% and 71.2% +/- 2.2%) and group II (62.1% +/- 3.0% and 70.3% +/- 3.0%), respectively. The decreases in hirsutism scores in the first 6 months were more significant than in the last 6 months of treatment in both groups. There were no significant differences in any of the hormone levels during therapy in either group. One patient in group II was excluded from the study because of liver dysfunction. CONCLUSION(S): This study shows that two different doses of flutamide (250 mg/d and 500 mg/d) are similarly effective in reducing hair growth. Flutamide at a dose of either 250 mg/d or 500 mg/d has no further effect after 6 months. We conclude that if flutamide is administered at a dose of 250 mg/d it may represent an effective and well tolerated treatment with reduced cost for the patient.

Adult

Adrenal functions in patients with sepsis.

The basal cortisol level and cortisol response to ACTH stimulation test were assessed in patients with sepsis, the results being compared to a control group of 30 healthy persons. The study group included 49 patients with sepsis and 30 healthy subjects as a control group. The mean age in the study group was 42.6 +/- 18.7 years and 41.4 +/- 12.1 years in the control group. Fifteen of the 49 (30.6%) patients had hospital-acquired and 34 (69.4%) patients community-acquired sepsis. Etiological agent was isolated in 35 (71.4%) patients (57.1% gram negative bacteria and 34.3% gram positive bacteria, plus 8.6% polymicrobial). Fourteen of 49 (28.6%) patients died. Mean basal cortisol level was 597.1 +/- 304.6 nmol/l (range 217.8-1667.9) in the study group and 460.2 +/- 180.8 nmol/l (range 253.6-988.9) in the control group. Mean basal cortisol level in the study group was significantly higher than that of the control group (p < 0.05). Mean basal cortisol level was found to be 725.5 +/- 448.9 nmol/l in the patients who died and 545.8 +/- 210.9 nmol/l in the patients who recovered. The difference between the two groups was found to be significant (p < 0.05). ACTH stimulation test was performed in 43 of the patients and 30 healthy subjects. Cortisol response was significantly lower (mean 277.7 +/- 216.9 nmol/l) in the patients than that detected in the control group (mean 519.6 +/- 279.2) (p < 0.001). Mean cortisol response in the patients who died was 227.2 +/- 224.5 nmol/l and 302.1 +/- 212.7 nmol/l in the patients who recovered (p > 0.05). Adrenocortical insufficiency was detected in 16.3% of the patients and 42.9% of these patients died. In conclusion, sepsis is characterized by high basal cortisol level which may show a poor prognosis and a blunted cortisol response to ACTH stimulation. A small percentage of patients with sepsis may develop adrenocortical insufficiency.

Adolescent

17-Hydroxyprogesterone responses to gonadotrophin-releasing hormone agonist buserelin and adrenocorticotrophin in polycystic ovary syndrome: investigation of adrenal and ovarian cytochrome P450c17alpha dysregulation.

Abnormal regulation of cytochrome P450c17alpha causes the exaggerated secretion of ovarian androgens in polycystic ovary syndrome (PCOS). This enzyme is active in both the ovaries and adrenal glands. We examined whether there is an abnormal regulation of cytochrome P450c17alpha in the adrenal gland by investigating the relationship of 17-hydroxyprogesterone (17-OH progesterone) hyperresponsiveness to the gonadotrophin releasing hormone (GnRH) agonist, buserelin, testing with 17-OH progesterone response to adrenocorticotrophic hormone (ACTH) in PCOS. In all, 68 women with PCOS and 24 normal women were included in the study. Ultrasound, clinical and hormonal parameters were used to define PCOS. 17-OH progesterone response to ACTH was measured in all the women. In 52 of the 68 women with PCOS, 17-OH progesterone response to buserelin was measured. The mean basal 17-OH progesterone concentrations were similar in both PCOS and control groups. PCOS women had significantly higher net increment in 17-OH progesterone after ACTH administration (P<0.02). No significant correlations were found between the peak 17-OH progesterone values, the net increments in 17-OH progesterone and the area under the 17-OH progesterone-response curves after ACTH stimulation and buserelin test. Although 17-OH progesterone response to ACTH was significantly higher in the patients with PCOS than in the control subjects, the lack of relationship between 17-OH progesterone response to GnRH agonist buserelin and 17-OH progesterone response to ACTH stimulation suggests that the dysregulation of the cytochrome P450c17alpha enzyme may not play a role in adrenal androgen excess seen in PCOS.

17-alpha-Hydroxyprogesterone

Lack of relationship between 17-hydroxyprogesterone response to buserelin testing and hyperinsulinemia in polycystic ovary syndrome.

OBJECTIVE: To determine whether hyperinsulinism affects cytochrome P450c17 alpha activity by investigating the correlation between 17-hydroxyprogesterone (17-OHP) hyper-responsiveness to the gonadotropin-releasing hormone (GnRH) agonist, buserelin, and the insulin response to oral glucose in polycystic ovary syndrome (PCOS). DESIGN: Ultrasound, clinical and hormonal parameters were used to define PCOS in this prospective clinical study. We investigated the correlation between the 17-OHP response to buserelin testing and the insulin response to oral glucose in PCOS. METHODS: Twenty-eight women with PCOS and eighteen normal women were included in the study. 17-OHP response to buserelin, and insulin and C-peptide responses to oral glucose were measured. RESULTS: Twenty-five women with PCOS had an increased 17-OHP response. The PCOS patients showed significantly higher mean post-glucose load insulin and C-peptide levels than controls (P < 0.05). No significant correlations were found between basal 17-OHP and fasting insulin or fasting C-peptide, between peak 17-OHP and fasting insulin, peak insulin or peak C-peptide, between 17-OHP area under the curve (AUC) and insulin AUC or C-peptide AUC, and between percent increment in 17-OHP and insulin AUC or C-peptide AUC (P > 0.05). CONCLUSIONS: Lack of a relationship between the 17-OHP response to the GnRH agonist buserelin and hyperinsulinism suggests that hyperinsulinism may not play a role in the dysregulation of the cytochrome P450c17 alpha enzyme seen in PCOS.

17-alpha-Hydroxyprogesterone