Delayed Puberty in Girls With Cystic Fibrosis Despite Good  Clinical Status

Johannesson, Marie; Gottlieb, Claes; Hjelte, Lena

doi:10.1542/peds.99.1.29

Cited by 113 publications

(88 citation statements)

References 37 publications

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“…It appears that the testosterone deficiency in male CF patients was too moderate to induce gross effects on muscle mass -at least identifiable on the basis of cross-sectional data -while BMD might already be affected. This finding is compatible with a previous study reporting that the manifestation of delayed puberty in girls with CF was independent of their nutritional status (48). Furthermore, it supports the view that different threshold levels -although undefined yet -of circulating serum testosterone for target effects on bone and muscle might exist (45,49).…”

Section: Discussionsupporting

confidence: 92%

Sex steroids and body composition in men with cystic fibrosis

Leifke¹,

Friemert²,

Heilmann

et al. 2003

European Journal of Endocrinology

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Objective: Delayed sexual maturation and low body weight is common in cystic fibrosis (CF). Concomitant data on sex hormones and concomitant body composition are lacking in men with CF. Design: Cross-sectional study. Subjects and methods: Serum levels of testosterone, 17b-oestradiol (E 2 ), 25-hydroxyvitamin D (25(OH)D), sex hormone-binding globulin (SHBG) and LH were measured by RIA and total and regional lean body mass (LBM), fat body mass (FBM), bone mineral content and bone mineral density (BMD) were assessed by dual-energy X-ray absorptiometry, in men with CF (n ¼ 40; age 24:7^5:4 years) and age-matched healthy controls ðn ¼ 28; age 25:7^3:7Þ: Only men without acute disease exacerbation or systemic glucocorticoid treatment were included. Results: Mean levels of hormonal serum parameters differed significantly between healthy controls ðtestosterone ¼ 20:2^5:5 nmol=l; E 2 ¼ 95:0^20:2 pmol=l; 25ðOHÞD ¼ 62:8^28:3 nmol=lÞ and patients ðtestosterone ¼ 15:9^4:1 nmol=l; E 2 ¼ 60:7^19:4 pmol=l; 25ðOHÞD ¼ 39:5^17:8 nmol=l; P , 0:001Þ while no difference was found for SHBG or LH. Eleven (for E 2 , 19 of 40, for 25(OH)D, 20 of 40) out of 40 patients had serum testosterone levels 2 S.D. below the mean of normal. Men with CF showed a relative shift from FBM to LBM and a different body fat distribution compared with healthy controls ðP , 0:01Þ: Testosterone was not correlated with weight, total or regional LBM or FBM, but significantly with BMD ðr ¼ 0:32; P , 0:05Þ independently from body height and 25(OH)D levels. E 2 was correlated with regional and total FBM ðr ¼ 0:48; P , 0:05Þ: In a multiple regression analysis of the joint effect of testosterone and body components on E 2 , a testosteroneindependent effect was found for FBM. Conclusions: CF patients with stable disease have moderately reduced serum testosterone levels. This might already imply detrimental effects on bone. The change in LBM of patients appears to have no direct association with sex hormone levels while low FBM might cause reduced net conversion of serum testosterone to E 2 with possible effects on FBM distribution.

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Section: Discussionsupporting

confidence: 92%

Sex steroids and body composition in men with cystic fibrosis

Leifke¹,

Friemert²,

Heilmann

et al. 2003

European Journal of Endocrinology

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“…In the absence of a pancreatic or intestinal origin for the reduced growth, absence of Cftr from the endocrine system may provide an alternative explanation. The various endocrine abnormalities observed in CF patients have been attributed to malnutrition or lung infections, but patients with good clinical and nutritional status still display endocrine abnormalities (23,24). Among these abnormalities is a reduction in insulin-like growth factor I (IGF-I), an important endocrine player in somatic growth, that has been reported in both humans and mice with CF (2,19,28,45,51).…”

Section: Discussionmentioning

confidence: 99%

Cystic fibrosis growth retardation is not correlated with loss of Cftr in the intestinal epithelium

Hodges¹,

Grady²,

Mishra³

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

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Maldigestion due to exocrine pancreatic insufficiency leads to intestinal malabsorption and consequent malnutrition, a mechanism proposed to cause growth retardation associated with cystic fibrosis (CF). However, although enzyme replacement therapy combined with increased caloric intake improves weight gain, the effect on stature is not significant, suggesting that growth retardation has a more complex etiology. Mouse models of CF support this, since these animals do not experience exocrine pancreatic insufficiency yet are growth impaired. Cftr absence from the intestinal epithelium has been suggested as a primary source of growth retardation in CF mice, a concept we directly tested by generating mouse models with Cftr selectively inactivated or restored in intestinal epithelium. The relationship between growth and functional characteristics of the intestines, including transepithelial electrophysiology, incidence of intestinal obstruction, and histopathology, were assessed. Absence of Cftr exclusively from intestinal epithelium resulted in loss of cAMP-stimulated short-circuit current, goblet cell hyperplasia, and occurrence of intestinal obstructions but only slight and transient impaired growth. In contrast, specifically restoring Cftr to the intestinal epithelium resulted in restoration of ion transport and completely protected against obstruction and histopathological anomalies, but growth was indistinguishable from CF mice. These results indicate that absence of Cftr in the intestinal epithelium is an important contributor to the intestinal obstruction phenotype in CF but does not correlate with the observed growth reduction in CF.

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“…However, with increasing age CF patients often develop a catabolic condition with decline in body mass index (BMI), chronic pulmonary infection and impaired glucose metabolism (3). A delay in sexual maturation followed by a delay in the pubertal increment in several anabolic hormones such as sex hormones and growth hormone (GH) may also contribute to an increased catabolism (4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

Normal spontaneous and stimulated GH levels despite decreased IGF-I concentrations in cystic fibrosis patients

Laursen¹,

Lanng

Rasmussen

et al. 1999

European Journal of Endocrinology

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Objective: The aim of the present study was to investigate whether patients with cystic fibrosis (CF) are GH resistant with increased GH release and decreased concentrations of IGF-I as a result of malabsorption, increased catabolism and impaired glucose tolerance. Design: Twenty CF patients were included, ten with normal glucose tolerance (five male, five female, median age 25.5 years (range 20-31)) and ten with diabetes mellitus (five male, five female, median age 25.3 years (range 17-45). Twenty healthy individuals served as controls (ten male, ten female, median age 28.4 years (range 18-36)). Methods: GH status was evaluated by 12 h spontaneous GH release during the night time, argininestimulated GH release and the basal concentrations of IGF-I and insulin-like growth factor-binding protein-3 (IGFBP-3). Twelve hour spontaneous GH profiles were estimated using a constant blood withdrawal technique with sampling every 30 min and the Pulsar method was used for the analysis of profiles. Results: No significant differences were found in spontaneous and stimulated GH release in CF patients compared with healthy controls, whereas IGF-I and IGFBP-3 were significantly decreased in CF patients compared with healthy controls. The combination of reduced IGF-I and IGFBP-3 with normal GH release points to a relative GH resistance or a disturbance in the pituitary axis in patients with CF. The spontaneous GH release, the stimulated GH release and the basal concentrations of IGF-I and IGFBP-3 were not significantly different in diabetic CF patients compared with CF patients with normal glucose tolerance and the presence of diabetes mellitus was not consistent with increased GH resistance in CF patients. Conclusion: CF patients with normal glucose tolerance and diabetic CF patients had normal GH release and decreased concentrations of IGF-I indicating a relative GH resistance.

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Delayed Puberty in Girls With Cystic Fibrosis Despite Good Clinical Status

Abstract: Pubertal delay still existed among the CF patients despite good clinical status. The patients homozygous for deltaF508 and those with pathological OGTT showed the most delayed puberty.

Cited by 113 publications

References 37 publications

Sex steroids and body composition in men with cystic fibrosis

Sex steroids and body composition in men with cystic fibrosis

Cystic fibrosis growth retardation is not correlated with loss of Cftr in the intestinal epithelium

Normal spontaneous and stimulated GH levels despite decreased IGF-I concentrations in cystic fibrosis patients

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