Stense Farholt

Body composition, endocrine and metabolic profiles in adults with Prader-Willi syndrome

OBJECTIVE Prader-Willi syndrome (PWS) is a complex genetic disease associated with hypothalamic-pituitary dysfunction and severe obesity. The aim of the present study was to describe the relationships between body composition, metabolic and hormonal profiles in PWS adults. METHOD Forty six adults with genetically verified PWS, 25 women and 21 men, median age 28 years were studied. Body composition was evaluated by standard anthropometric procedures and with computed tomography (CT) of the abdomen and at the mid-femur level. CT of abdomen was compared to 22 healthy, unmatched adults. Circulating lipids were measured and oral glucose tolerance test (OGTT) and hormonal screening including GH secretory capacity (GHRH/arginine test) was carried out. RESULTS Median body mass index (BMI) was 27.2 kg/m(2), with women being more obese than men. Sixteen patients had dyslipidaemia, 10 impaired glucose tolerance and seven had diabetes. Fifty percent were hypogonadal and six fulfilled BMI related criteria for growth hormone deficiency (GHD). Visceral to subcutaneous abdominal fat ratio was reduced in PWS. Visceral abdominal fat fraction correlated with both subcutaneous fat, BMI and peak GH-response. Thigh muscle volume was about half of the thigh fat volume. Beneficial effects of sex-steroid replacement on body composition were not observed. CONCLUSIONS Body fat was primarily located subcutaneously and metabolic consequences of obesity limited. The abnormal body composition similar to that in non-PWS GHD adults increases the interest of GH treatment in the prevention of obesity in adults with PWS.

One Year of Growth Hormone Treatment in Adults with Prader-Willi Syndrome Improves Body Composition: Results from a Randomized, Placebo-Controlled Study

CONTEXT Prader-Willi syndrome (PWS) is a multisymptomatic disease that shares many similarities with the GH deficiency syndrome, including altered body composition with more body fat than lean body mass. OBJECTIVE Our objective was to investigate the effect of GH on body composition in adults with PWS. DESIGN AND PATIENTS Forty-six adults with PWS were randomized to GH or placebo treatment for 12 months in a double-blind trial. MAIN OUTCOME MEASURES We evaluated change in regional body composition of the abdomen and thigh as measured by computed tomography and change in total body composition as measured by dual-energy x-ray absorptiometry. RESULTS Forty patients completed the study. Baseline median IGF-I sd score was -0.4. GH treatment increased IGF-I by 125 μg/liter (1.51 sd score), and based upon computed tomography, body composition improved with a decrease in visceral fat mass of 22.9 ml (P = 0.004), abdominal sc fat mass 70.9 ml (P = 0.003), and thigh fat mass 21.3 ml (P = 0.013), whereas thigh muscle mass increased 6.0 ml (P = 0.005). By dual-energy x-ray absorptiometry, lean body mass improved 2.25 kg (P = 0.005), and total fat mass decreased 4.20 kg (P < 0.001). No major side effects were seen. CONCLUSION Unrelated to the GH-IGF-I levels at baseline, our results showed that long-term treatment with GH effectively improved body composition and represents a safe, potential treatment option, relieving some of the negative consequences of PWS.

Growth hormone treatment for two years is safe and effective in adults with Prader-Willi syndrome.

OBJECTIVE Prader-Willi syndrome (PWS) shares similarities with the growth hormone (GH) deficiency syndrome in regards to reduced lean body mass and increased fat mass and several short-term trials with GH treatment have demonstrated beneficial effects on body composition. The aim of the present study was to evaluate the effects and safety of two years of GH therapy in adults with PWS. DESIGN Forty-three adults (24 women) with genetically verified PWS were included. Blood samples, body composition as measured by computed tomography (CT) and dual-energy x-ray absorptiometry (DXA) were performed at baseline and during two years of continued GH treatment. RESULTS Thirty-nine patients completed treatment for two years. The GH dosage averaged 0.61 mg/day (range 0.2-1.6). Based upon CT, body composition improved at two years; thigh muscle volume increased 6.7 mL (3.7 to 9.7; P<0.001) whereas abdominal subcutaneous fat volume decreased by 53.3 mL (13.8 to 92.9; P=0.01). By DXA, lean body mass improved 2.8 kg (1.9 to 3.6; P<0.001), whereas fat mass decreased by 3.0 kg (1.1 to 4.8; P=0.003). Lung function as evaluated by peak expiratory flow increased 12% (p<0.001) - indicating improved muscle function. Adverse effects were few. Fifteen out of 39 patients had diabetes (DM; n=4) or impaired glucose tolerance (IGT; n=11) prior to GH treatment. Among the 11 patients with IGT, three reverted to normal glucose tolerance, while three progressed to overt DM at two years of GH treatment. CONCLUSION The known beneficial effects of GH treatment upon body composition in PWS are maintained during two years continuous treatment. With appropriate control, GH is a safe treatment option in adults with PWS.

Normal Cortisol Response to High-Dose Synacthen and Insulin Tolerance Test in Children and Adults with Prader-Willi Syndrome

CONTEXT Prader-Willi syndrome (PWS) is a genetic disease associated with hypogonadism and partial GH insufficiency, possibly explained in part by a hypothalamic dysfunction. Partial insufficiency of the hypothalamic-pituitary-adrenal (HPA) axis has recently been suggested. OBJECTIVE The objective of the study was to further explore the HPA axis in PWS by use of routine tests. DESIGN Nonselected PWS patients were examined with a standard high-dose synacthen test or the insulin tolerance test (ITT). A random serum (s) cortisol was measured in case of acute illness. SETTING The study was conducted at university hospitals in Denmark and Sweden. PATIENTS Sixty-five PWS patients with a confirmed genetic diagnosis participated in the study. MAIN OUTCOME MEASURES A s-cortisol value above 500 nmol/liter as well as an increase of 250 nmol/liter or greater was considered a normal response. RESULTS Fifty-seven PWS patients (median age 22 yr, total range 0.5-48 yr) were examined with the high-dose synacthen test. The median s-cortisol at the time of 30 min was 699 (474-1578) nmol/liter. Only one patient had a s-cortisol level below 500 nmol/liter but an increase of 359 nmol/liter. This patient subsequently showed a normal ITT response. Two patients had increases less than 250 nmol/liter but a time of 30-min s-cortisol values of 600 nmol/liter or greater. These three patients were interpreted as normal responders. Eight patients [aged 26 (16-36) yr] examined with the ITT had a median peak s-cortisol of 668 (502-822) nmol/liter. Four children admitted for acute illnesses had s-cortisol values ranging from 680 to 1372 nmol/liter. CONCLUSION In this PWS cohort, the function of the HPA axis was normal, suggesting that clinically significant adrenal insufficiency in PWS is rare.

Two Years of Growth Hormone Treatment in Adults With Prader-Willi Syndrome Do Not Improve the Low BMD

BACKGROUND Bone mineral density (BMD) in adult patients with Prader-Willi syndrome (PWS) might be low due to high bone turnover. OBJECTIVES The objective of the study was to investigate bone mass in a group of adult PWS subjects and study the effects of GH treatment on BMD and markers of bone turnover. DESIGN Forty-six adults with genetically verified PWS were randomized to GH or placebo for 12 months, followed by open prospective GH for 24 additional months. BMD at the lumbar spine (LS) L1-4, the total hip, and the total body was assessed by dual-energy x-ray absorptiometry at baseline and every 12th month thereafter. Markers of bone turnover were measured at baseline and at the end of the controlled study. RESULTS In this cohort of adult subjects with PWS, baseline BMD was reduced in all compartments compared with the reference (Z-scores). Men had lower Z-scores BMD than women in LS and total body (P < .05). With 12 months of GH, LS-BMD was significantly reduced compared with placebo. No changes in BMD were observed with continuous GH treatment for 24 months. The bone formation markers increased with GH therapy compared with placebo, whereas the resorption marker did not change. CONCLUSIONS Adult PWS subjects, especially the men, have low bone mass that was not improved with GH treatment for 2 years. Because PWS subjects are short, BMD might be underestimated and should be adjusted for. Further studies, with adequate GH and sex hormone replacement throughout puberty and early adult life, are needed to better characterize PWS.

Occurrence of trichomoniasis in women in Denmark, 1967-1997.

Background The Neisseria Unit at Statens Serum Institut (SSI), Copenhagen, Denmark administers laboratory surveillance systems for gonorrhea and chlamydia, however, no similar system has been available for trichomoniasis. Objectives To describe changes in the occurrence of trichomoniasis in women and in the distribution according to age, and to compare these changes with those observed in women with gonorrhea or chlamydia. Study Design Data on the epidemiology of trichomoniasis were based on the annual laboratory records at the Neisseria Unit at SSI. Data on gonorrhea (1967–1997) and chlamydia (1994–1997) originated from the National Laboratory Surveillance Systems. Results During the period 1967 to 1997, the percentage of Trichomonas vaginalis–positive specimens showed a constant decrease from 19 to fewer than 2. The annual number of specimens received varied between a maximum of 31,626 in 1975 and a minimum of 3291 in 1997. The median age of women with trichomoniasis increased from 31 to 39 years as compared with a change from 21 to 24 years in women with gonorrhea (1967–1997) and a median age of 22 years in women with chlamydia (1994–1997). Conclusions A significant decline in the occurrence of trichomoniasis in women concurrent with a significant rise in the median age of women with the disorder was observed. During the periods investigated, women with trichomoniasis were significantly older than women with gonorrhea or chlamydia.

Glucose homeostasis in adults with Prader–Willi syndrome during treatment with growth hormone: Results from a 12-month prospective study ☆

OBJECTIVES To investigate glucose homeostasis in relation to body mass index (BMI) in adults with PWS before and after GH therapy. DESIGN We prospectively investigated the effects of a 12-month GH treatment on body composition and glucose homeostasis in relation to BMI in 39 adults, mean (±SD) age=28.6 (6.5) years with genetically verified PWS. We compared the results for different BMI categories (<25 kg/m²; 25-30 kg/m²; >30 kg/m²) and performed a regression analysis to detect predictors for homeostasis model of assessment-insulin resistance (HOMA-IR). RESULTS The baseline HOMA-IR was higher, with BMI of >30 kg/m². Our main findings were as follows: i) GH treatment (mean final dose, 0.6 (0.25) mg) was associated with small increases in fasting p-glucose, 2-h p-glucose by oral glucose load tolerance test, HOMA-IR and lean mass, and a reduction in fat mass. ii) Whereas the baseline HOMA-IR was associated with increased BMI (>30 kg/m²), we found no differences in HOMA-IR among the BMI categories after 12 months of GH. iii) Stepwise linear regression identified the triglyceride level as the strongest predictor of HOMA-IR at baseline, whereas an increase in VAT was the strongest predictor of the increase in HOMA-IR after therapy. CONCLUSIONS GH treatment for 12 months in adults with PWS resulted in an increase in HOMA-IR, irrespective of BMI, confirming that control of HbA1c is essential during GH treatment in PWS.

Laboratory surveillance of urogenital Chlamydia trachomatis infections in Denmark 1988 – 2007

In 1994 laboratory reporting of urogenital chlamydia was integrated in the countrywide notification system for infectious diseases. Previously (1988–1993), laboratory confirmed cases had been reported on a voluntary basis. The applied laboratory technologies changed significantly: in 1988, 48% of cases were diagnosed by culture; in 1994, 88% by enzyme immunoassays; and since 2004 more than 99% by nucleic acid amplification tests. The proportions of chlamydia-positive men diagnosed by testing urine were <1% in 1994, 10% in 2001 and 75% in 2007. From 1994 to 2002 the annual incidence rates of chlamydia per 100,000 population among women were around 350–400 and then increased to 586 in 2007. Among men the incidence rate rose from 125 in 1994 to 358 in 2007. In conclusion, the annual incidence rates of urogenital chlamydia remained high and possibly increasing during a 14-y period (1994–2007), with a high testing activity, improving technologies and countrywide information campaigns. The observed increase is likely to be associated with the introduction of more sensitive diagnostic methods and with increasing testing of men. A possible change in target groups from low- to high-prevalence could not be assessed due to lack of information about persons being tested.

Assessment of physical function in adults with Prader-Willi syndrome

Purpose. To evaluate implementation of at test battery for assessing physical function in adults with Prader-Willi syndrome (PWS). Method. Forty-three adults with PWS, 20 men and 23 women, mean age 29 ± 9 years. Body mass index (BMI) and body composition were measured. A test battery a.m. Guralnik for standing balance, 2.4 m and 10 m walk and repeated rising from a chair was scored and evaluated. Results. Mean BMI was 29.4 ± 9.1 kg/m2, body fat mass (FM) 26.0 ± 16.1 kg. The adults with PWS managed the test battery well, and high scores were achieved for standing balance and 2.4 m walk. In contrast, only 13 managed maximum score in the repeated rising from a chair and 31 to walk 10 m for 6 s or faster. Significant correlations were seen between 2.4 m walk and FM ( p = 0.041) and between 10 m walk and BMI ( p = 0.001) and FM ( p = 0.019). Conclusions. Repeated rising from a chair and 10 m walk are useful assessments in clinical practice to identify adults with PWS with reduced physical function. Reduced performance was related to higher BMI and FM emphasising the importance of efforts to keep normal body weight and body composition in adults with PWS. These measures might be useful in monitoring effects of intervention.