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Biomedical subjects

Claus Hagen

Publications and source records attributed to Claus Hagen.

16 recordsLinked to original sources
PubMed2006

Effect of pioglitazone on glucose metabolism and luteinizing hormone secretion in women with polycystic ovary syndrome.

OBJECTIVE: To thoroughly examine the mechanisms for insulin resistance in polycystic ovary syndrome (PCOS) and to evaluate the effects of pioglitazone treatment on insulin resistance, beta-cell function, LH secretion, and glucose metabolism. DESIGN: Randomized, blinded, placebo-controlled study. SETTING: Outpatient clinic, at a university hospital in Denmark. PATIENT(S): Thirty obese women with PCOS and 14 weight-matched healthy females. INTERVENTION(S): Sixteen weeks of blinded treatment with pioglitazone (30 mg/d) or placebo. MAIN OUTCOME MEASURE(S): Fasting blood samples, 24-hour 20-minute integrated blood sampling (LH, insulin, and C-peptide), euglycemic hyperinsulinemic clamps including 3-(3)H glucose, and indirect calorimetry were performed before and after the intervention period. RESULT(S): Patients with PCOS had significantly lower insulin sensitivity compared with controls, including significantly decreased insulin-stimulated oxidative and nonoxidative glucose metabolism. Pioglitazone treatment resulted in significantly lower levels of fasting insulin and significantly higher insulin sensitivity, increased insulin-stimulated glucose oxidation, and increased insulin-stimulated inhibition of lipid oxidation. During 24-hour blood sampling, significantly lower area under-the-curve insulin and lower median insulin levels were observed. Secretion profiles of LH and E(2) and T levels did not change significantly. CONCLUSION(S): Insulin resistance in PCOS was characterized by hyperinsulinemia, impaired insulin-stimulated oxidative and nonoxidative glucose metabolism, which was partly reversed by pioglitazone treatment.

Adult↗
PubMed2006

Evaluation of metabolic risk markers in polycystic ovary syndrome (PCOS). Adiponectin, ghrelin, leptin and body composition in hirsute PCOS patients and controls.

OBJECTIVE: Polycystic ovary syndrome (PCOS) patients are abdominally obese and are at increased risk of developing the metabolic syndrome. Low adiponectin and ghrelin levels in PCOS patients could be caused by insulin resistance as well as high testosterone levels. DESIGN: Adiponectin and ghrelin levels were evaluated in 51 hirsute PCOS patients referred to the outpatient clinic of an academic, tertiary care medical centre and in 63 weight-matched female controls. Relationships between adiponectin, ghrelin, leptin, body composition, testosterone and insulin were examined. METHODS: Measurements of body composition including waist-hip-ratio (WHR), body mass index (BMI) and whole body dual-energy X-ray absorptiometry scan measures of body fat mass. Measurements of fasting levels of adiponectin, ghrelin, leptin, androgen status, oestradiol, lipid variables and insulin during follicular phase. RESULTS: Adiponectin levels were significantly decreased in obese PCOS patients compared with weight-matched controls (geometric mean (-2 to 2 s.d.) 5.3 (2.5-11.1) vs 7.3 (3.0-17.4) mg/l, P<0.05). Mean ghrelin was significantly lower in hirsute PCOS patients than in controls (0.6 (0.3 to 1.4) vs 0.8 (0.4 to 1.7) microg/l, P<0.001) and this remained significant after subdividing subjects according to waist circumference and BMI. During multiple regression analysis, testosterone correlated positively with adiponectin and negatively with ghrelin independent of BMI, WHR and total fat mass. CONCLUSION: Obese hirsute PCOS patients demonstrated significantly lower adiponectin levels than weight-matched controls suggesting a very high risk for the metabolic syndrome. Furthermore, ghrelin levels were decreased in hirsute PCOS patients and showed a significant, negative correlation with testosterone independent of body composition.

Absorptiometry, Photon↗
PubMed2005

MTHFR c.677C>T polymorphism as an independent predictor of peak bone mass in Danish men--results from the Odense Androgen Study.

The MTHFR c.677C>T polymorphism has been shown to have significant effects on skeletal health in middle-aged to elderly women and men. Despite an accumulating amount of data on MTHFR genetics and the association between homocysteine levels and fracture, it remains unknown if MTHFR c.677C>T genotype affects bone mineral accretion in youth or bone loss in adulthood. The purpose of this cross-sectional study was to examine the effects of this common allelic polymorphism on peak bone mass and bone turnover. We performed MTHFR genotyping in 780 healthy Danish men, aged 20 to 29 years, participating in the Odense Androgen Study. BMD at the spine, hip and whole-body was measured using a Hologic QDR-4500 densitometer. Genotype frequencies were compatible with Hardy-Weinberg equilibrium. Spine BMD was significantly associated with genotype, with a decrease in BMD of 0.20 SD for each copy of the T-allele. Effects were independent of age, BMI, smoking and serum levels of vitamin D and IGF-I. Associations with BMD of the hip and whole body were short of statistical significance. MTHFR genotype showed no association with the bone turnover markers 1-CTP, bone specific alkaline phosphatase or osteocalcin. In conclusion, significant skeletal effects of this common polymorphism were present at the lumbar spine in men at the age of 25 years.

Absorptiometry, Photon↗
PubMed2005

Pioglitazone treatment increases spontaneous growth hormone (GH) secretion and stimulated GH levels in polycystic ovary syndrome.

BACKGROUND: Low GH levels, probably due to insulin resistance and increased abdominal fat mass, are well described in polycystic ovary syndrome (PCOS). GH acts as an important ovarian cogonadotropin, and GH disturbances may be an additional pathogenic factor in PCOS. Decreased abdominal fat mass and improved insulin sensitivity during pioglitazone treatment may affect GH secretion. OBJECTIVE: The objective of the study was to investigate the effect of pioglitazone on GH levels in PCOS. DESIGN: Thirty insulin-resistant PCOS patients were randomized to either 16 wk pioglitazone (30 mg/d) or placebo treatment. Before and after intervention, levels of fasting insulin, GH, total IGF-I, free IGF-I, IGF binding protein-1, IGF-II, free fatty acids, testosterone, and SHBG were measured. Patients underwent whole-body dual x-ray absorptiometry scans, pyridostigmine-GHRH tests, and 24-h 20-min integrated blood sampling for measurement of GH. RESULTS: Peak GH and area under the curve for GH in pyridostigmine-GHRH tests and 24-h mean GH concentrations and pulsatile GH secretion significantly increased after pioglitazone treatment. No significant changes were observed in GH pulse frequency, pulse duration, approximate entropy levels, or basal GH release. Levels of IGF binding protein-1 significantly increased, whereas no significant differences were measured in total IGF-I and free IGF-I. Pioglitazone treatment significantly decreased fasting insulin and homeostasis model assessment levels. No significant changes were observed in Ferriman Gallwey score or androgen levels. CONCLUSION: Pioglitazone treatment significantly increased GHRH-stimulated GH levels and 24-h pulsatile GH secretion, probably directly or indirectly due to improved insulin sensitivity.

Absorptiometry, Photon↗
PubMed2005

Cotreatment of acromegaly with a somatostatin analog and a growth hormone receptor antagonist.

CONTEXT: Pegvisomant is a GH receptor antagonist that blocks the peripheral actions of GH in acromegaly. Pegvisomant, in contrast to somatostatin (SMS) analogs, does not suppress the activity of the GH-producing adenoma. OBJECTIVE: We assessed the effects of cotreatment with pegvisomant and SMS in acromegaly on GH secretion, IGF-I levels, and glucose tolerance. DESIGN, PATIENTS, AND INTERVENTIONS: Eleven patients with persistent disease despite previous therapy underwent the following fixed treatment algorithm: 1) on SMS therapy, 2) off therapy for 2 months, 3) 6-wk treatment with 10 mg/d pegvisomant, 4) 6-wk treatment with 15 mg/d pegvisomant, and 5) 3-month treatment with 15 mg pegvisomant plus SMS. Blood was sampled in the fasting state and during an oral glucose tolerance test. RESULTS: Total serum IGF-I levels (micrograms per liter) decreased after pegvisomant, but the lowest levels were obtained with cotreatment [458 +/- 67 (SMS), 562 +/- 78 (active), 376 +/- 51 (10 mg), 269 (15 mg), 195 +/- 24 (combined) (P < 0.0001)]. Free and bioactive IGF-I changed in a similar pattern. Steady-state pegvisomant levels (micrograms per liter) were obtained, but SMS cotreatment increased pegvisomant levels by 20% (P = 0.02) [2631 +/- 616 (10 mg), 6536 +/- 1413 (15 mg), 8030 +/- 1914 (combined)]. Pegvisomant increased endogenous GH levels (micrograms per liter), which was countered by SMS cotreatment [5.1 +/- 1.3 (SMS), 8.9 +/- 2.9 (active), 14.6 +/- 4.9 (10 mg), 19.7 +/- 6.5 (15 mg), 11.8 +/- 2.8 (combined) (P < 0.01)]. Plasma glucose levels (millimoles per liter) were highest during SMS and lowest during pegvisomant 15 mg [2-h oral glucose tolerance test: 10.3 +/- 0.7 (SMS), 8.9 +/- 0.7 (active), 7.2 +/- 0.7 (10 mg), 6.5 +/- 0.5 (15 mg), 8.0 +/- 0.8 (combined) (P = 0.02)]. CONCLUSIONS: Dual blockade of the GH axis with pegvisomant and a SMS analog is feasible in acromegaly.

Acromegaly↗
PubMed2005

Higher bone mineral density in Caucasian, hirsute patients of reproductive age. Positive correlation of testosterone levels with bone mineral density in hirsutism.

OBJECTIVE: The mechanisms leading to higher bone mineral density (BMD) in hirsute patients than in healthy controls have seldom been examined. We compared the metabolic, hormonal and bone metabolic parameters in hirsute patients and female controls and correlated BMD and bone metabolic parameters with testosterone, oestradiol and metabolic parameters. PATIENTS: Fifty-one Caucasian, reproductive-aged, hirsute patients referred to the outpatient clinic of an academic tertiary-care medical centre and 63 healthy, female Caucasian controls matched for season, weight and age. MEASUREMENTS: BMD (hip, neck, lumbar and total BMD), bone metabolic parameters (osteocalcin, alkaline phosphatase, PTH, ionized calcium, phosphate and 25-hydroxyvitamin D (25OHD)) and endocrine profiles (androgen status, oestradiol and insulin) were evaluated during follicular phase. Oestradiol measurement was repeated during cycle days 8-12. RESULTS: Lumbar and neck BMD levels were significantly higher in hirsute patients than in controls: (mean +/- SD): lumbar BMD 1.10 +/- 0.12 vs. 1.06 +/- 0.10 g/cm2 and neck BMD 0.91 +/- 0.11 vs. 0.87 +/- 0.12 g/cm2, P < 0.05. Fasting insulin and free testosterone levels were significantly higher in hirsute patients than in controls. Free testosterone correlated positively with neck and hip BMD levels in hirsute patients. During multiple regression analysis, testosterone, oestradiol and waist/hip ratio (WHR) were found to have positive effects on BMD levels independent of body mass index (BMI). 25OHD levels were significantly lower in hirsute patients [42 (13-131)] than in controls [72 (27-196)] nmol/l (geometric mean +/- 2SD), P < 0.001]. CONCLUSION: Hirsute patients demonstrated significantly higher bone mineral density levels than controls, which could be explained by hyperinsulinaemia and higher testosterone levels in hirsute patients compared with controls. The pathogenesis for significantly lower 25-hydroxyvitamin D levels in hirsute patients compared with controls needs to be evaluated in future studies.

Adult↗
PubMed2004

Prevalence of endocrine diseases and abnormal glucose tolerance tests in 340 Caucasian premenopausal women with hirsutism as the referral diagnosis.

OBJECTIVE: To perform an audit on the examination of hirsute patients and to establish a rational routine examination program in an outpatient endocrine clinic. DESIGN: Systematic, retrospective audit. SETTING: Academic tertiary-care medical center. PATIENT(S): Three hundred forty women with hirsutism as the referral diagnosis. INTERVENTION(S): Hormone analyses and ACTH tests during cycle days 2-8, 2 hours of oral glucose tolerance test (OGTT), and vaginal ultrasound. MAIN OUTCOME MEASURE(S): End diagnosis, fasting, 30-, 60-, and 120-minute oral glucose-stimulated levels of insulin and capillary blood glucose. RESULT(S): Two hundred one patients were diagnosed as having idiopathic hirsutism (IH) and 134 as having polycystic ovary syndrome (PCOS). End diagnosis: prolactinoma: n = 1, Cushing's syndrome: n = 1, androgen-producing ovarian tumor: n = 1, late-onset 21-hydroxylase defects: n = 2. During OGTT, 4.9% (13 of 263) had previously undiagnosed diabetes; no significant difference in diabetes prevalence was found between idiopathic hirsutism and PCOS. For 50.8%, fasting insulin values were in the upper quartile for a reference population. CONCLUSION(S): Initial evaluation of hirsute patients with irregular menses should include serum (s)-17alpha-hydroxyprogesterone, s-prolactin, s-Testosterone (T), and s-sex hormone-binding globulin. Further evaluation is needed in patients with markedly elevated s-T or with clinical Cushing's syndrome. Hirsute patients have a high risk of diabetes, although this could be due to the high number of overweight patients among this population.

Adrenal Hyperplasia, Congenital↗
PubMed2003

Low levels of the 150-kD insulin-like growth factor binding protein 3 ternary complex in patients with anorexia nervosa: effect of partial weight recovery.

BACKGROUND/AIM: In healthy adults, serum insulin-like growth factor I (IGF), IGF-binding protein 3 (IGFBP-3), and acid-labile subunit (ALS) form a 150-kD ternary complex under the control of growth hormone (GH). Circulating IGF-I half-life, bioavailability, and endocrine actions depend on the ternary complex formation. Despite GH hypersecretion, serum IGF-I, IGFBP-3, and ALS levels have all been reported to be low in patients with anorexia nervosa (AN), while the degree of ternary complex formation in AN is unknown. METHODS: Serum ALS and 150-kD ternary complex formation were measured in 6 women with AN at the time of diagnosis and after partial weight recovery and in 6 healthy age-matched women serving as controls. RESULTS: Patients with AN had low levels of ALS and IGFBP-3 contained in the 150-kD ternary complex and in the non-150-kD fraction. Following partial weight recovery, the 150-kD IGFBP-3 ternary complex was fully normalized, despite only partial normalization of serum GH and IGF-I levels. Patients with AN did not present with IGFBP-3 proteolysis different from controls. CONCLUSION: The present data indicate a pivotal role of the nutritional status in the regulation of each of the three components of the 150-kDa ternary IGFBP-3 complex and in the formation of the complex itself.

Adult↗
PubMed2003

Development of acromegaly in patients with prolactinomas.

OBJECTIVES: Patients with prolactinomas and patients with acromegaly often have heterogenous adenomas. In this study we have focused on patients with prolactinomas who developed acromegaly and acromegalic patients with hyperprolactinaemia. Our hypothesis is that some patients with hyperprolactinaemia may develop clinical acromegaly. METHODS: We have included patients examined at department M, Odense University Hospital between 1996 and 2001. Seventy-eight patients with prolactinomas, 65 females and 13 males, with a median age (range) of 30 Years (14-74) and 47 Years (20-66), respectively, were included in the study. RESULTS: In females and males the median prolactin (PRL) levels were 90 microg/l (27-4700; normal values (NV) <or=23) and 1075 microg/l (24-6500; NV <or=14), respectively. The PRL levels were significantly higher in males compared with females (P<0.002). Fifty-nine patients with acromegaly, 24 females and 35 males, with a median age (range) of 45 Years (24-70) and 53 Years (19-70), respectively, were included. Seven of the 24 females had hyperprolactinaemia, with PRL levels of 90 microg/l (27-494). Thirteen of the 35 males had hyperprolactinaemia with PRL levels of 47 microg/l (17-251). Three females with prolactinomas developed acromegaly clinically and biochemically. These patients had a normal low GH level and/or a normal IGF-I level at first diagnosis. CONCLUSIONS: Our findings suggest that there is a common group of patients with a pituitary adenoma who secrete PRL and GH unsynchronously. Some of these patients have clinical acromegaly at diagnosis and some patients diagnosed as prolactinomas will develop acromegaly. We suggest an annual IGF-I measurement as a screening test.

Acromegaly↗
PubMed2002

Fractures in patients with anorexia nervosa, bulimia nervosa, and other eating disorders--a nationwide register study.

OBJECTIVE: To study fracture risk in patients with anorexia nervosa (AN), bulimia nervosa (BN), or eating disorders not otherwise specified (EDNOS). METHOD: Cohort study including all Danes diagnosed with AN (n = 2,149), BN (n = 1,294), or EDNOS (n = 942) between 1977 and 1998. Each patient was compared with three randomly drawn age- and gender-matched control subjects. RESULTS: Fracture risk was increased in AN after diagnosis compared to controls (incidence rate ratio: 1.98, 95% CI: 1.60-2.44), but not before. The increased fracture risk persisted more than 10 years after diagnosis. A significant increase in fracture risk was found before diagnosis in BN (1.31, 95% CI: 1.04-1.64), with a trend towards an increase after diagnosis (1.44, 95% CI: 0.93-2.22). EDNOS patients had a significant increase in fracture risk before (1.39, 95% CI: 1.06-1.81) and after diagnosis (1.77, 95% CI: 1.25-2.51). DISCUSSION: The increased fracture risk many years after diagnosis indicates permanent skeletal damage.

Adult↗
PubMed2002

Fracture risk is increased in patients with GH deficiency or untreated prolactinomas--a case-control study.

OBJECTIVE: The pituitary secretes many hormones of significance to bone turnover and thus skeletal integrity. The aim of this study was to examine fracture risk in patients with pituitary disorders with special reference to GH deficiency and hyperprolactinaemia. DESIGN: Case-control study. MEASUREMENTS: Fracture occurrence. PATIENTS: A self-administered questionnaire was issued to 537 consecutive patients with pituitary disorders excluding Cushing's disease. A total of 426 (79%) returned the questionnaire and 422 of these could be analysed. Each respondent was compared to three age- and gender-matched control respondents to the same questionnaire drawn randomly from the background population. RESULTS: The patients had a mean age of 51.4 +/- 14.8 years. One hundred and eight patients had acromegaly, 86 had prolactinomas, 136 had non-functioning pituitary adenomas (NFPA), 23 had craniopharyngiomas, and 73 had other types of pituitary disorders. For the total group the fracture risk was not elevated either before or after confirmed diagnosis compared to controls. However, among the patients with prolactinomas, the fracture risk was significantly increased before (relative risk, RR = 1.6, 95% CI: 1.1--2.3) but not after diagnosis. In patients with NFPA, fracture risk was borderline significantly elevated following diagnosis (RR = 1.6, 95% CI: 1.0--2.6). Patients with subnormal stimulated peak GH values suggestive of GH deficiency had a significantly higher risk of fractures after diagnosis than patients who had normal stimulated peak GH values (odds ratio, OR = 4.90, 95% CI: 1.10--21.88). CONCLUSIONS: Untreated prolactinomas were associated with a significant increase in fracture risk. Growth hormone deficiency was also associated with a higher fracture risk.

Adenoma↗
PubMed2002

Increased risk of osteoporotic fractures in patients with Cushing's syndrome.

OBJECTIVE: To evaluate if fracture risk was increased in patients with Cushing's syndrome due to the increased endogenous cortisol production. DESIGN: Cohort. METHODS: A self-administered questionnaire was mailed to 125 patients with Cushing's syndrome diagnosed between 1985 and 1999 in Denmark. The response of each patient was compared with that of three age- and gender-matched control subjects randomly drawn among respondents to the same questionnaire from the background population. RESULTS: One hundred and four patients (83%) responded. The median age of the patients was 48 years (range 19-85 years). Sixty-eight had pituitary disease, 28 had adrenal disease, four had had both pituitary and adrenal surgery while four had not undergone surgery at the time of the study. The median time from diagnosis to surgery was 0.2 (range 0-3) years. Eighty-six percent were cured following surgery. There was an increased fracture risk within the last 2 years prior to diagnosis (incidence rate ratio 6.0, 95% confidence intervals (CI): 2.1-17.2). More than 2 years prior to diagnosis and following diagnosis there was no difference in fracture risk between patients and controls. The patients had more low-energy fractures than the controls (relative risk 5.4, 95% CI: 1.4-20.1). There was no difference in fracture risk between patients with adrenal or pituitary disease. CONCLUSIONS: Patients with Cushing's syndrome had an increased fracture risk in a narrow time interval before diagnosis, while no increase in fracture risk could be demonstrated after diagnosis and treatment.

Adrenal Glands↗
PubMedDate not supplied

Patients with eating disorders. A high-risk group for fractures.

PURPOSE: To analyze fracture risk and bone mineral density in patients with eating disorders (anorexia nervosa, bulimia nervosa, and other eating disorders). DESIGN: Clinical overview. FINDINGS: Bone mineral density is decreased and fracture risk increased in patients with anorexia nervosa. In patients with bulimia nervosa, bone mineral is only marginally decreased and fracture risk marginally increased. In patients with other eating disorders (eating disorders not otherwise specified), bone mineral density is decreased and fracture risk increased. CONCLUSIONS: Fracture risk is increased in patients with eating disorders. An eating disorder should be suspected in severely underweight young individuals (primarily girls) presenting with fractures, especially low-energy fractures.

Age Distribution↗