[Adrenal insufficiency during inhaled corticosteroid treatment in a child with asthma]. / Binyrebarkinsufficiens under steroidinhalationsbehandling hos et barn med astma.

We report a 12 year-old asthmatic girl with adrenal insufficiency during inhaled corticosteroid treatment. Symptoms, investigations and treatment are discussed.

Prevalence, incidence, diagnostic delay, and mortality in Turner syndrome.

AIM: Our aim was to study prevalence, incidence, age at diagnosis, and mortality in Turner syndrome (TS) in Denmark. METHODS: Using the Danish Cytogenetic Register, we identified all cases (n = 781) of TS alive in Denmark during 1970-2001. Sixty-nine deceased women with TS were identified in the Causes of Death Register. We divided the cohort into women having the karyotype 45,X, karyotypes including an isochromosome Xq, and all other karyotypes associated with TS. We describe the number of patients diagnosed in Denmark yearly, incidence rates, and the age at diagnosis. Standardized mortality ratios (SMR) were calculated. RESULTS: A total of 349 women had a 45,X karyotype, 86 had a karyotype including an isochromosome Xq (isoXq), and 346 had another TS karyotype. Mortality was increased in TS with an SMR of 2.86 (95% confidence interval, 2.18-3.55). SMR was increased for coronary diseases, congenital malformations, endocrine diseases, and other causes. The mortality was increased for all types of karyotypes in comparison with the general population but was highest among females with 45,X and isoXq. There was a steady increase in prevalence, but incidence was unchanged. Age at diagnosis was mainly distributed in three periods: less than 1 yr of age (14.9%), during adolescence (10-17 yr) (33.2%), and during adulthood (38.5%), with a median age at diagnosis of 15.1 yr, decreasing during the study period (P < 0.01). CONCLUSIONS: Patients with TS and especially the karyotypes 45,X and isoXq have a higher mortality compared with the background population. TS was diagnosed with a considerable diagnostic delay. Prevalence is increasing, but incidence of TS was stable.

Effect of growth hormone and 17beta-oestradiol treatment on metabolism and body composition in girls with Turner syndrome.

OBJECTIVE: Girls with Turner syndrome (TS) receive GH treatment during childhood, and in adolescence this treatment may be combined with oestradiol. We have studied the effects of this combined treatment on metabolism and body composition. MATERIAL AND METHODS: We performed a double-blind, placebo-controlled, randomized, crossover study. All girls with TS (n = 8, 16 +/- 2 years) were treated with placebo + placebo, GH + placebo or GH + 17beta-oestradiol for 2 months, and were studied at the end of each period. Controls (n = 10, 14 +/- 2 years) were studied once without treatment. Twenty-four-hour sampling of oestradiol, growth factors, insulin, glucose, lipolytic and gluconeogenic precursors was performed, followed by an oral glucose tolerance test (OGTT) and assessment of body composition and mineral content. RESULTS: GH induced insulin resistance, which was not aggravated further by concomitant oestradiol treatment. The 24-h integrated serum 17beta-oestradiol was reduced compared to controls (0.58 +/- 0.32 vs. 2.81 +/- 2.78 nmol/l/24 h, P = 0.032), but increased during GH + oestrogen (E2) treatment without reaching control levels, while GH + placebo caused a further reduction (anova, P = 0.008). Total fat mass was increased in girls with TS compared with controls (P = 0.009), while lean body mass (P = 0.02) and bone mineral content (P = 0.04) was decreased, with specific regional characteristics in body composition. CONCLUSION: GH treatment induces insulin resistance and changes in body composition in TS, which is not further compromised by concomitant oestradiol treatment. Body composition is changed in TS, with specific regional changes, in comparison with controls. Integrated 24-h oestradiol is low in TS, and is only partially restored during treatment with standard doses of 17beta-oestradiol.

The effects of GH and hormone replacement therapy on serum concentrations of mannan-binding lectin, surfactant protein D and vitamin D binding protein in Turner syndrome.

OBJECTIVE: Studies in animals and humans indicate that growth hormone (GH) and insulin-like growth factor-I (IGF-I) modulate immune function. Recently, it was reported that GH therapy increased the level of mannan-binding lectin (MBL) in normal patients, and that treatment of acromegalics with pegvisomant decreased the levels of MBL. The effect on MBL was thought to be due to a specific action of GH, since IGF-I treatment did not affect MBL. Whether it is advantageous or not to have high or low levels of MBL is not known. Likewise, it is not clear how the modifications induced by GH affect immune function. In the present study we examined whether GH or hormone replacement therapy (HRT) in Turner syndrome (TS) influence the serum concentrations of MBL and two other proteins partaking in the innate immune defence, surfactant protein D (SP-D) and vitamin D binding protein (DBP). DESIGN: Study 1: a double-blind crossover study of 12 healthy TS adolescents examined during treatment with either placebo or GH for 2 months, and compared with a control group. Study 2: triple-blind crossover study of 9 healthy TS adolescents randomized to treatment with placebo, GH or GH+17beta-estradiol. Study 3: 60 adult TS patients (55 received HRT) compared with 59 age-matched controls. Study 4: 27 patients with TS were examined before and during sex hormone replacement with 17beta-estradiol and norethisterone and compared with age-matched controls (n=24). METHODS: Measurement of MBL, SP-D, DBP, and other inflammation markers. RESULTS: Study 1: the levels of MBL (P=0.002) and SP-D (P=0.012) increased during GH treatment, whereas no changes were observed in comparison with controls. DBP was unchanged by GH, but was significantly higher in TS compared with controls (P=0.017). Study 2: treatment with GH increased MBL (P=0.045) and SP-D (P=0.05) concentrations in TS, while treatment with GH+17beta-estradiol did not increase levels further. DBP was unchanged by treatment. Study 3: levels of MBL, SP-D, and DBP were similar in adult TS and control subjects. Study 4: DBP levels decreased in response to HRT, while MBL and SPD levels were unchanged. Levels of all three plasma proteins were similar to controls. CONCLUSION: We show that treatment with GH significantly increases MBL and SP-D concentrations in TS, while HRT marginally decreases DBP. Whether the present findings, suggesting a link between the endocrine and the immune system, have clinical consequences needs to be studied further.

Short-term growth hormone treatment in girls with Turner syndrome decreases fat mass and insulin sensitivity: a randomized, double-blind, placebo-controlled, crossover study.

BACKGROUND: Most girls with Turner syndrome (TS) receive growth hormone (GH) treatment during childhood and adolescence, but controlled data on the effects on body composition and glucose metabolism are lacking. OBJECTIVE: To study the effects of GH treatment on insulin sensitivity, glucose metabolism, bone turnover, and body composition. METHODS: A randomized, placebo-controlled, crossover study was conducted with girls with TS. All girls with TS were treated with GH 0.1 IU/kg/d subcutaneously at bedtime or with placebo for 2 months and studied at the end of each period. Control subjects were studied once without treatment. Twelve girls with TS, aged 9.5 to 14.8 years (median: 12.9 years) and 16 age-matched control subjects (10.3-16.0 years; median: 12.1 years) were studied. Twenty-four-hour sampling of blood was performed; GH, insulin-like growth factor I (IGF-I), IGF binding proteins (IGFBPs), insulin, glucose, and lipolytic and gluconeogenic precursors were assayed, followed by an oral glucose tolerance test. Body composition was evaluated by dual-energy x-ray absorptiometry scanning and body mass index (BMI). Fasting bone markers were measured. RESULTS: Height was reduced in TS as compared with control subjects. In the placebo situation, 24-hour integrated GH as well as IGF-I was significantly reduced in girls with TS compared with control subjects. Controlling for differences in lean body mass (LBM; or fat mass [FM]) and sexual development did not explain the difference in 24-hour integrated GH. Differences in sexual development, BMI, FM, insulin sensitivity, and IGFBP-3 could explain the difference in IGF-I between TS and control subjects. Carbohydrate metabolism in TS was comparable with control subjects. GH treatment induced insulin resistance, with increments in fasting glucose and insulin, as well as 24-hour insulin. Circulating levels of lipid and gluconeogenic substrates were comparable in TS and control subjects and unchanged in response to treatment. Bone markers increased in response to GH. Total FM was increased in girls with TS, accounted for by an increased FM in the arms and trunk, whereas LBM was decreased. Especially LBM in the legs was decreased. Overall, bone mineral content was diminished. Treatment with GH reduced FM in TS, especially in the arms and legs, and likewise increased total LBM, primarily in the trunk. CONCLUSION: This study documented evidence of impaired GH secretion and action, disproportionate body composition, but a normal carbohydrate metabolism in girls with TS. Short-term GH administration was associated with favorable changes in body composition but also with relative impairment of glucose tolerance and insulin sensitivity. We recommend that glucose metabolism be monitored carefully during long-term GH treatment in these patients.

Inhibin A and B in adolescents and young adults with Turner's syndrome and no sign of spontaneous puberty.

BACKGROUND: The aim of this study was to assess levels of inhibin A and B, FSH and LH in Turner's syndrome (TS) without signs of spontaneous ovarian activity. METHODS: Twenty-four girls with TS (median age, 14.7 years) without signs of spontaneous ovarian function were included in the study. Sixty prepubertal girls (PPG) (10.3 years) that had not yet experienced menarche (all Tanner stage 1), and 34 pubertal girls (PG) (13.8 years) (Tanner stage 3-4), who were regularly menstruating, served as controls. The levels of inhibin A and B, FSH, LH, and pubertal stage were determined. RESULTS: Inhibin A was not detected in females with TS, or in almost all PPG (59 of 60) (P = not significant), and inhibin B in TS females, while most PPG produced inhibin B (53 of 60, P < 0.0005). FSH and LH were elevated in TS, but with overlapping values. In follow-up samples in TS, three of twenty-four females showed detectable levels of inhibin A and/or B. In one of these, 6 serial samples were available. At 20 years this patient had a high level of LH and FSH, which declined, and concurrently inhibin A and inhibin B rose, only later to decrease, when FSH and LH started to rise again. In comparison with PG baseline levels of inhibin A and B were lower in TS, with inhibin A detectable in 23 of 34, and inhibin B detectable in 32 of 34 PG. Levels of FSH and LH were also different, although with overlapping values. CONCLUSION: The result raises the possibility that functional or partly functional ovaries are present in some females with TS, without apparent menstrual cycling.