Combined pituitary hormone deficiency due to gross deletions in the POU1F1 (PIT-1) and PROP1 genes.

Pituitary development depends on a complex cascade of interacting transcription factors and signaling molecules. Lesions in this cascade lead to isolated or combined pituitary hormone deficiency (CPHD). The aim of this study was to identify copy number variants (CNVs) in genes known to cause CPHD and to determine their structure. We analyzed 70 CPHD patients from 64 families. Deletions were found in three Turkish families and one family from northern Iraq. In one family we identified a 4.96 kb deletion that comprises the first two exons of POU1F1. In three families a homozygous 15.9 kb deletion including complete PROP1 was discovered. Breakpoints map within highly homologous AluY sequences. Haplotype analysis revealed a shared haplotype of 350 kb among PROP1 deletion carriers. For the first time we were able to assign the boundaries of a previously reported PROP1 deletion. This gross deletion shows strong evidence to originate from a common ancestor in patients with Kurdish descent. No CNVs within LHX3, LHX4, HESX1, GH1 and GHRHR were found. Our data prove multiplex ligation-dependent probe amplification to be a valuable tool for the detection of CNVs as cause of pituitary insufficiencies and should be considered as an analytical method particularly in Kurdish patients.

Four decades without diagnosis: Sheehan's syndrome, a retrospective analysis.

AIM: Sheehan's syndrome (SS) remains a frequent cause of hypopituitarism in undeveloped and developing countries, but due to improvements in obstetric care, it is rare in developed countries. We aimed to share the results of a retrospective study analyzing the demographic, clinical, imaging, and hormonal characteristics of a large group of patients with SS, and also increase awareness of this syndrome especially in developed countries. METHODS: The medical records of 124 patients with SS patients who were followed up in the Endocrinology Department of Dicle University between 1995 and 2015 were assessed retrospectively. RESULTS: The mean period of diagnostic delay was 20.37 ± 8.34 years on average. 5.7% of patients with SS were literate; 62% of patients delivered at home. Anemia was identified in 64.5% of SS patients. Mean blood sodium levels were 129.8 ± 11.3 mEq/L. The mean urine densities were 1013 ± 6.5. Osteoporosis and osteopenia were found in 44 (35.4%) and 71 (57.2%) patients, respectively, According to pituitary magnetic resonance imaging (MRI) analyses, 92 (74.2%) patients with SS had completely empty sella, 29 (23.3%) had partially empty sella, and 1 patient had microadenoma, and 2 had normal pituitary MRI results. CONCLUSIONS: Improved obstetric care and effective interventions for postpartum hemorrhage have limited the prevalence of SS in developed countries. However, in developing countries like Turkey, SS due to postpartum bleeding remains common. Thus, physician's awareness of the symptoms of SS is urgently required to avoid the associated morbidity and mortality.

Postprandial hyperlipidemia in overt and subclinical hypothyroidism.

BACKGROUND AND AIMS: Lipid alterations in overt hypothyroidism (OH) were well known, but its changes in subclinical hypothyroidism (SCH) and postprandial period were not clear. The aim of this study is to evaluate postprandial lipemia by oral lipid tolerance test (OLTT) in patients with OH and SCH. MATERIALS AND METHODOLOGY: Twenty-five OH and 27 SCH, totally 52 hypothyroid patients [mean age 38.3 ± 12.8 year, body mass index (BMI): 29.0 ± 5.8 kg/m(2)] and 23 BMI- and age-matched healthy controls (mean age 36.7 ± 11.9 years; BMI: 27.1 ± 6.9 kg/m(2)) were included to the study. Anthropometric measurements and HOMA-IR levels were measured. Basal and postprandial lipid profile at 2nd, 4th, 6th and 8th hours were determined by oral lipid tolerance test. RESULTS: There were not any statistical differences among three groups (control, OH and SCH) in terms of mean fasting levels of total cholesterol, LDL-cholesterol, VLDL-cholesterol, and triglyceride. On the contrary, mean triglyceride levels at postprandial 8th hour in both OH and SCH patients were higher than control subjects (p=0.017 and p=0.049, respectively). Again mean postprandial 8th hour VLDL-cholesterol levels in OH group were also higher than control subjects (p=0.05). In addition mean HOMA-IR value of SCH and OH patients was similar with control subjects (1.5 ± 1.4 in OH; 1.3 ± 0.8 in SCH; 2.2 ± 2.2 in control group). CONCLUSIONS: Although total, LDL and VLDL-cholesterol, and triglyceride levels were not different from healthy controls, triglyceride and/or VLDL-cholesterol levels apparently increased with OLTT in both OH and SCH patients. Decreased lipid clearance may be responsible for this result.

Insulin resistance in type 2 diabetes mellitus may be related to bone mineral density.

The mechanism of bone mineral density (BMD) changes in type 2 diabetes mellitus is not clear. We aimed to investigate the effect of insulin resistance in type 2 diabetics on BMD. Insulin resistance was determined using the homeostasis model assessment index (HOMA-IR). Nineteen type 2 diabetic patients with a HOMA-IR <2.7 (mean age, 51.5±9.6yr; body mass index [BMI], 27.3±5.1kg/m(2); duration of diabetes, 10.5±7.3yr) were included in Group A, and 30 BMI- and age-matched type 2 diabetic patients with a HOMA-IR ≥2.7 were included in Group B. The BMD was measured with dual-energy X-ray absorptiometry. Independent t-test was used for statistical analysis. The Group A values for mean fasting glucose and insulin levels were 160.1±77.0mg/dL and 4.79±2.89µU/L, respectively, whereas the Group B values were 195.1±58.9mg/dL (p>0.05) and 19.30±16.89µU/L (p=0.0001). Significantly higher total lumbar vertebra T-score (p=0.02) and total lumbar vertebra BMD in Group A were determined than Group B (p=0.033). The lumbar vertebra total Z-score was significantly lower in Group B (p=0.042). Marked insulin resistance may have a negative effect on BMD in type 2 diabetics, while the presence of hyperinsulinemia may be associated with the low BMD.

Assessment of bleeding disorders in Sheehan's syndrome: are bleeding disorders the underlying cause of Sheehan's syndrome?

Sheehan's syndrome (SS) is an adenopituitary insufficiency caused by hypovolemia secondary to excessive blood loss during or after childbirth. However, the mechanism of postpartum hemorrhage and ischemia is not clear. We aimed to evaluate the bleeding disorders among patients with SS, in comparison with healthy controls. In addition, we investigated underlying causes in postpartum hemorrhage that begin the event. The present study was conducted at the Dicle University School of Medicine. Forty-eight patients with SS and 50 age-matched female healthy controls were included. Biochemical and hormonal variables were measured, as was platelet function by means of closure times (PFA-100 testing using collagen plus epinephrine and collagen plus ADP), von Willebrand factor (vWF) level, prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalized ratio (INR), and coagulation factors. Although PT and INR were significantly higher in patients with SS (both P<0.01), aPTT and levels of fibrinogen, vWF, and factors II, V, VII, VIII, IX, X, XI, and XII did not differ significantly. Closure times with collagen/epinephrine and collagen/ADP also did not differ significantly between patients with SS and control patients. The nonspecific etiology and presence of excessive postpartum hemorrhage in patients with SS suggest that coagulation disorders may play a role in their predisposition to bleeding. The increased PT and INR noted might implicate bleeding diathesis as the underlying etiology, although no significant decreases were noted in factor levels. Further studies are needed to elucidate this complex mechanism of this disorder.

Analysis of thrombophilic genetic mutations in patients with Sheehan's syndrome: is thrombophilia responsible for the pathogenesis of Sheehan's syndrome?

The gene mutations of Factor V R506Q (FV-Leiden), prothrombin (FII G20210A), methylene tetrahydrofolate reductase (MTHFR) C677T and A1298C and PAI-1 4G/5G are well-established risk factors for thrombosis. We aimed to investigate the prevalence of these gene mutations and their possible impact on the development of pathogenesis in patients with Sheehan's syndrome (SS). 40 female patients with SS compared to a control group of 45 healthy women. The presence of FV-Leiden, FII G20210A, MTHFR C677T, MTHFR A1298C and PAI-1 4G/5G gene mutations were assessed by polymerase chain reaction analysis with a light cycler analyzer. An odds ratio of greater than one is considered to increase the risk of SS disease as found in Factor V Leiden, FII G20210A, MTHFR C677T, MTHFR A1298C and PAI-1 4G/5G polymorphism, as follows respectively: 1.13, 1.85, 6.00, 8.14 and 1.45. MTHFR C677T and MTHFR A1298C polymorphism were found significantly higher in SS patients than the control group (P<0.001), however FV-Leiden, FII G20210A and PAI-1 4G/5G polymorphism showed no significant difference (P>0.05). The level of plasma total homocysteine (tHcy) was significantly higher in patients with SS than in the control group (P<0.001). We suggest that the genetic mutations of FV-Leiden, FII G20210A, MTHFR C677T, MTHFR A1298C and PAI-1 4G/5G increase the risk of SS. Also, high plasma tHcy levels may be a risk factor for the development of SS.

Serum resistin and adiponectin levels in young non-obese women with polycystic ovary syndrome.

INTRODUCTION: Although polycystic ovary syndrome (PCOS) was described more than half a century ago, the underlying cause of PCOS is still unknown. The aim of our study was to evaluate whether serum resistin and adipocytokine levels alter and its changes relate with low grade inflammation in non-obese young women with PCOS. SUBJECTS AND METHODS: Newly diagnosed 31 young non-obese women with PCOS (mean age 21.8 +/- 5.4 years; body mass index (BMI): 23.8 +/- 6.6 kg/m(2)) and 25 BMI- and age-matched, regular-cycling, healthy women (mean age 24.9 +/- 5.7 years; BMI: 23.1 +/- 5.8 kg/m(2)) were included the study Anthropometric measurements were evaluated. Resistin, adiponectin, glucose, insulin, hormone profiles, Lipoprotein (Lp)(a), high sensitive C reactive protein (hs-CRP), and homocysteine levels were measured in the beginning of oral glucose tolerance test. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. RESULTS: Non-obese young women with PCOS had high adiponectin levels (28.01 +/- 6.47 ng/ml in PCOS vs. 23.89 +/- 7.70 ng/ml in control subjects, p = 0.034), whereas serum resistin levels were not significantly different compared with healthy controls (14.14 +/- 6.6 ng/ml in PCOS vs. 13.78 +/- 4.26 ng/ml in control subjects). There were no significant differences between two groups in terms of fasting insulin, Lp(a), homocysteine, and hs-CRP levels. Mean HOMA-IR value of patients with PCOS was similar with control subjects (1.93 +/- 0.73 in PCOS; 1.15 +/- 0.54 in control group). CONCLUSIONS: Resistin levels did not change in non-obese young women with PCOS whereas adiponectin level in non-obese young women with PCOS was significantly higher than control subjects, perhaps, because of no insulin resistance. Circulating resistin levels may not be candidate to play a role in pathogenesis of PCOS without insulin resistance or obesity.

The prevalence of non-classic adrenal hyperplasia among Turkish women with hyperandrogenism.

The prevalence of non-classic adrenal hyperplasia (NCAH) among Turkish women with hirsutism has not been established so far. Thus, we aimed to evaluate the prevalence of 21-hydroxylase (21-OH) deficiency by ACTH stimulation test among hirsute women. The study population consisted of 285 premenopousal women, aged 16-46 years (mean: 23.2 ± 0.3). All were hirsute and hyperandrogenic. Androgen secreting tumors of the ovaries and the adrenal glands were excluded as well as thyroid dysfunction and hyperprolactinemia. All the patients were evaluated by 0.25 mg (i.v.) ACTH stimulation test and 17-OHP responses were obtained at 30 and 60 min. The diagnosis of NCAH due to 21-OH deficiency was considered in patients with the poststimulation 17-OHP level exceed 10 ng/ml. Six (2.1%) of the patients had NCAH due to 21-OH deficiency confirmed by genotyping. The rest of the patients were polycystic ovary syndrome (n = 166, 58.2%) and idiopathic hyperandrogenemia (n = 113, 39.7%). There were no patients with idiopathic hirsutism because patients with normal serum androgen levels were excluded. This first and most extensive national study investigating NCAH prevalence among Turkish population showed that NCAH is not prevalent in this population.

Sheehan's syndrome and its impact on bone mineral density.

INTRODUCTION: Although there have been few studies investigating osteoporosis in isolated hormone deficiencies or other causes of hypopituitarism, the relationship between Sheehan's syndrome (SS) and osteoporosis has not been investigated. In the present study, we aimed to evaluate bone mineral density (BMD) in patients with SS in comparison with healthy women. METHODS: Sixty-one patients with SS and 62 matched healthy controls were included. Biochemical, hormonal assessments and BMD evaluations were carried out in patients and controls, and a subgroup analysis according to menopausal status was done (premenopausal < 50 years; postmenopausal > 50 years). RESULTS: The mean levels of serum anterior pituitary hormones were significantly lower in pre- and postmenopausal patients with SS compared with respective control groups (p < 0.0001). For both pre- and postmenopausal subjects, compared with respective controls, serum calcium and ALP levels, femur-T score, femur-Z score, spine (L1-L5)-T score, spine (L1-L5)-Z score and BMD values were lower, and phosphorus and parathyroid hormone (PTH) levels were higher in patients with SS. CONCLUSIONS: Patients with SS had low BMD. The possible mechanism responsible for osteoporosis may be hypogonadism, growth hormone deficiency and disorders of parathyroid hormone and calcium metabolism. But the contribution of each anterior pituitary hormone deficiency on bone loss should be clarified in further prospective studies.

An interesting case of pachydermoperiostosis with idiopathic myelofibrosis associated with monosomy 22.

A 24-year-old man was referred to our clinic in August 2003 with complaints of weakness, dizziness, and bilateral knee pain of 3 years' duration. Bilateral digital clubbing had been found on routine physical examination during his military service 4 years earlier. There were no cardiorespiratory or abdominal symptoms. There was no compromise in the activities of everyday life. The patient was not a chronic smoker. In the family history of the patient, his brother had been diagnosed with pachydermoperiostosis in another center 2 years earlier, but did not return to the hospital for a follow-up investigation of myelofibrosis. On physical examination, the patient showed marked drumstick clubbing of the hands (Fig. 1), and a pale general appearance. The causes of digital clubbing are shown in Table 1 (Fawcett RS, Linford S, Stulberg DL. Nail abnormalities: clues to systemic disease. Am Fam Physician 2004; 69: 1417-1424). Deep nasolabial folds were seen on the face. Skin hypertrophy, cutis verticis gyrata, and seborrhea on the face were also observed. The patient also complained of hyperhidrosis. Examination of the cardiovascular system was normal. There was bilateral swelling of the ankle and knee (Fig. 2). Hepatosplenomegaly was found on abdominal examination. Investigations showed hypochromic microcytic anemia [hemoglobin, 8.58 g/dL (normal, 12.2-18.1 g/dL); hematocrit, 28.1% (normal, 37.7-53.7%); white blood cell count, 3430/mm(3) (normal, 4600-10,200/mm(3)); neutrophils, 2470/mm(3) (normal, 2000-6900/mm(3)); lymphocytes, 820/mm(3) (normal, 600-3400/mm(3)); platelets, 162,000/mm(3) (normal, 142,000-424,000 mm(3)); mean corpuscular volume, 73.7 fL (normal, 80-97 fL)]. Anisocytosis, poikilocytosis, microcytosis, and hypochromia were observed on peripheral blood examination, and the erythrocyte sedimentation rate was 37 mm/h. The serum C-reactive protein level was 50.1 mg/L (normal, 0-5 mg/L). Biochemical parameters, including serum calcium, phosphate, alkaline phosphates and liver function tests, were found to be within the normal range. The causes of secondary hypertrophic osteoarthropathy associated with pulmonary, rheumatologic, endocrine, cardiac, and gastroenterologic disorders were excluded. Growth hormone level and thyroid function tests were normal. Antinuclear antibody, TORCH [Toxoplasma immunoglobulin M (IgM), rubella IgM, cytomegalovirus IgM, herpes simplex IgM] panel, and markers of hepatitis were negative. Serum Igs and rheumatoid factor were found to be within the normal range. There was subperiosteal new bone formation on bilateral knee X-ray (Fig. 3). Radiography of the chest, pulmonary function tests, arterial blood gas, and echocardiography were normal. Abdominal ultrasonography revealed hepatosplenomegaly. Amyloid deposition was not determined in rectal biopsy. Reticulin-type myelofibrosis was found on bone marrow biopsy (Figs 4 and 5). In the cytogenetic study, monosomy 22 was detected in four of 20 metaphase plates.

WITHDRAWN: SERUM NT-PRO TYPE BRAIN NATRIURETIC PEPTIDE LEVELS IN NEWLY DIAGNOSED ACROMEGALIC PATIENTS.

Ahead of Print article withdrawn by publisher.

The evaluation of endothelial function with flow-mediated dilatation and carotid intima media thickness in young nonobese polycystic ovary syndrome patients; existence of insulin resistance alone may not represent an adequate condition for deterioration of endothelial function.

OBJECTIVE: To evaluate endothelial function with flow-mediated dilatation (FMD) and carotid intima media thickness (IMT) in young nonobese polycystic ovary syndrome (PCOS) patients. DESIGN: Prospective case-control study. SETTING: Healthy volunteers and nonobese young PCOS patients in clinical research. PATIENT(S): Thirty-nine PCOS patients with mean age of 22.82 +/- 5.53 years and 30 body mass index- and age-matched healthy controls were evaluated. INTERVENTION(S): Insulin resistance was calculated with area under the curve, quantitative insulin sensitivity check, and the Matsuda index. Endothelial function was assessed with FMD and carotid IMT by ultrasonography. MAIN OUTCOME MEASURE(S): Antropometric, hormonal, biochemical (insulin and glucose, tumor necrosis factor-alpha, hs-c-reactive protein, and homocysteine levels, and so forth), FMD, and IMT were measured. RESULT(S): There was a significant insulin resistance in PCOS patients. Serum FSH, total and free testosterone, cortisol, androstenedione, and DHEA-S levels of PCOS patients were also higher than control subjects, but we could not find any significant difference in terms of endothelial function determined with FMD. CONCLUSION(S): Existence of insulin resistance alone may not be an adequate factor for deterioration of endothelial function and carotid IMT in young, nonobese patients with PCOS. Other factors such as duration of insulin resistance, older age, presence of obesity, and inflammatory markers may play an important role in this process.

Sheehan's syndrome as a rare cause of anaemia secondary to hypopituitarism.

Although its exact mechanism is unclear, anaemia is well recognised as a feature of hypopituitarism; and anaemia is associated with Sheehan's syndrome (SS). We aimed to evaluate the frequency and severity of anaemia and other haematological changes among patients with Sheehan's syndrome, in comparison with healthy controls. Sixty-five SS patients and 55 age-matched female healthy controls were included. Biochemical and hormonal assessments and haematological evaluations were carried out, and groups were compared. The mean number of red blood cells, as well as mean haemoglobin, iron and erythropoietin levels, total iron-binding capacity and transferrin saturation were all significantly lower in SS patients compared to controls. SS patients had significantly higher rates of anaemia (80.0% vs. 25.5%, p = 0.0001), iron deficiency (44.6% vs. 5.4%, p = 0.001), leukopenia (20.0% vs. 5.4%, p = 0.015), thrombocytopenia (9.2% vs. 0.0%, p = 0.028) and bicytopenia (21.5% vs. 1.8%, p = 0.001) compared to controls. Anaemic SS patients had normochromic-normocytic anaemia (55%) or hypochromic-microcytic anaemia (45%). Anaemia is frequently associated with Sheehan's syndrome and responds to appropriate replacement therapy. Hypopituitarism should be considered as a possible cause of anaemia, and a hormone examination should be undertaken promptly, particularly in patients with anaemia resistant to therapy and/or with a history suggestive of Sheehan's syndrome.

Levels of proinflammatory cytokines and hs-CRP in patients with homozygous familial hypercholesterolaemia.

OBJECTIVE: Homozygous familial hypercholesterolemia (FH) is an extremely rare (1/1,000,000) condition characterized by markedly increased LDL cholesterol levels and a significantly increased risk of premature coronary heart disease (CHD). We aimed to evaluate the levels of high-sensitivity C-reactive protein (hs-CRP) and proinflammatory cytokines, which are known to be associated with atherogenesis, in patients with this condition. METHOD AND RESULTS: A total of 10 patients with homozygous FH (5 women and 5 men, mean age 17.0 +/- 6.9 years, body mass index (BMI) (18.8 +/- 1.9 kg/m2) and 16 healthy controls were included. hs-CRP levels, proinflammatory cytokine levels and lipid parameters were measured and compared between patients and control subjects. Homozygous FH patients had significantly higher total cholesterol, LDL-cholesterol and Lp(a) levels and significantly lower triglyceride and HDL cholesterol levels, compared to controls (P = 0.0001, for all). Serum hs-CRP (3.7 +/- 1.3 mg/L vs. 0.6 +/- 0.6 mg/L) and IL-1beta, IL-2R, IL-6, IL-8, IL-10, TNF-alpha levels were all significantly higher in the homozygous FH group, compared to controls (P = 0.0001, for all). CONCLUSIONS: Homozygous FH patients have significantly higher levels of hs-CRP and circulating proinflammatory cytokines, which may explain their increased risk of atherosclerotic disease. hs-CRP is an important biomarker that may be helpful in the identification of asymptomatic CHD in FH patients.

Ultrastructural evaluation of the effects of cinnamon on the nervus ischiadicus in diabetic rats.

OBJECTIVE: To investigate the effects of oral cinnamon supplementation on the nervus ischiadicus at the electron microscopical level in rats. METHODS: This study was performed between 2004-2006 in Dicle University School of Medicine, Diyarbakir, Turkey in 15 adult Sprague-Dawley rats. Rats were divided into 3 groups; control (C) (n=5), diabetic without cinnamon (D) (n=5), and diabetic with cinnamon (D-C) (n=5). Diabetes was induced with intraperitoneal alloxan administration. All diabetic rats were treated with human insulin. All rats were fed with standard pellet chow. The D-C group rats were fed with standard pellet chow plus Cinnamomum cassia at the dose of 400mg/kg. All rats were sacrificed after 3 months and we obtained the nervus ischiadicus of all rats. Contrast stained thin sections evaluated by Jeol-TEM-1010 electron microscope, were not statistically different in both groups and photo samples were obtained. RESULTS: Mean blood glucose, hemoglobin A1C, and lipid profile were not statistically different in both groups. Marked detachment of myelin lamellae at Schmidt-Lanterman clefts, lysis in cristae mitochondrialis and degenerative changes, severe dispersion of organelles in neurolemma, mesoaxon region, and remarkable edema at the endoneurium were found in diabetic rats. On the contrary, mesoaxon, nucleus, nucleolus and myelin sheet were almost of normal appearance at the ultra-structural level in the D-C group. CONCLUSION: Cinnamon extracts may have beneficial effects on the development of diabetic neuropathy in alloxan induced diabetic rats.

Mutations in the amino-terminal region of proopiomelanocortin (POMC) in patients with early-onset obesity impair POMC sorting to the regulated secretory pathway.

CONTEXT: Mutations in the proopiomelanocortin (POMC) gene that impair the synthesis or structure of POMC-derived peptides predispose to human obesity. OBJECTIVE: Our objective was to identify and characterize novel mutations in the POMC gene found in patients with early-onset obesity. DESIGN AND PATIENTS: The POMC gene was screened in 500 patients with severe early-onset obesity. The biosynthesis, processing, sorting, and secretion of wild-type POMC and two newly identified POMC mutants was studied using metabolic labeling, Western blotting, and immunoassay analysis of lysates and conditioned media of transiently transfected beta-TC3 cells. RESULTS: Two novel heterozygous missense mutations in POMC (C28F and L37F) were identified in unrelated probands with early-onset obesity and their overweight or obese family members. Both mutations lie in a region of the N terminus of POMC that has been suggested to be involved in its sorting to the regulated secretory pathway. Metabolic labeling studies indicate that whereas the mutations do not reduce intracellular levels of POMC, both mutations (C28F>L37F) impair the ability of POMC to be processed to generate bioactive products. Studies of the secretion of POMC products suggest, particularly with C28F, that the impaired propeptide processing of these mutations results, at least in part, from a mistargeting of mutant POMC to the constitutive rather than the regulated secretory pathway. CONCLUSION: These mutations in patients with early-onset obesity represent a novel molecular mechanism of human POMC deficiency whereby naturally occurring mutations in its N-terminal sequence impair the ability of POMC to enter the trafficking pathway in which serial propeptide processing normally occurs.

Serum nitric oxide levels and flow-mediated dilatation in patients with Sheehan syndrome and the effect of combination therapy consisting of L-thyroxine, prednisolone, and conjugated estrogen/medroxyprogesterone acetate.

Baseline and stimulated nitric oxide (NO) levels were higher, whereas baseline arterial diameter, FMD-stimulated NO increment, and arterial dilatation ratio were lower in Sheehan syndrome (SS) patients than in control subjects. After combination therapy consisting of prednisolone, L-thyroxine, and conjugated estrogen, baseline and stimulated NO levels of SS remained as high, but FMD-stimulated NO, NO increment ratio, and arterial dilatation ratio increased with treatment.

Quinapril for treatment of hypertension in Turkey: dose titration and diuretic combination treatment strategies.

BACKGROUND AND OBJECTIVE: Recently the PatenT (Prevalence, awareness, treatment and control of hypertension in Turkey) study showed that while the prevalence of hypertension in Turkey is high, effective control of BP is infrequently achieved. This study investigated the efficacy and safety of quinapril (as monotherapy or in combination with hydrochlorothiazide [HCTZ]) for achieving BP control (target <140/90 mm Hg) in Turkish subjects with mild to moderate hypertension. METHODS: Two-hundred male and female outpatients aged 19-65 years with mild to moderate hypertension (stage I or II, Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure 7 guidelines) entered this 12-week, open-label study. All subjects received quinapril 20 mg/day for 6 weeks. If BP targets were achieved at week 6, responders were maintained on 20 mg/day; if BP targets were not achieved, non-responders were randomised to quinapril 40 mg/day or quinapril 20 mg/day + HCTZ 12.5 mg/day for the remainder of the study. RESULTS: After 6 weeks, 63% of subjects achieved BP targets, and 82% of week-6 responders who continued on quinapril 20 mg/day maintained BP targets at week 12. Of the non-responders, 50% and 52% randomised to quinapril 40 mg/day or quinapril 20 mg/day + HCTZ 12.5 mg/day, respectively, went on to achieve BP targets by week 12. Safety was not compromised with increased dosages or use of combination therapy. CONCLUSION: Quinapril was an effective and safe treatment for achieving and maintaining recommended BP targets in this sample population. These findings will provide clinicians in Turkey with valuable data on the use of quinapril for effective control and management of hypertension.

A rare embryological malformation of brain - Dandy-Walker syndrome - and its association with Kallmann's syndrome.

BACKGROUND & AIM: Dandy-Walker malformation, a rare congenital brain malformation, is described as a triad of cystic dilatation of the fourth ventricle, complete or partial agenesis of the cerebellar vermis, and an enlarged posterior fossa with elevated tentorium. We aimed to report an association of Kallmann's syndrome and Dandy-Walker malformation. CASE: A fifteen years old boy was referred to endocrinology department due to delayed puberty. Stages of male genital development according to Marshall and Tanner, was stage G1 and P1 respectively. In the LHRH test, peak LH level was 40th min.:15.3 IU/ml. Peak growth hormone with insulin tolerance test was 14.5 microg/L. Olfactory test revealed light anosmia. With these findings the patient was accepted as isolated gonadotropin deficiency (Kalmann's syndrome). In computed tomography of the brain, cerebellar vermis was found to be hypoplastic and 4th ventricle was large and in posterior fossa broad hypodens area with cerebrospinal fluid density were seen (Dandy-Walker malformation). CONCLUSION: We reported an association of Kallmann's syndrome and Dandy-Walker malformation. This is second reported case probably.