: J Pediatr Endocrinol Metab 2001 July; 14 Suppl Factors determining final height in congenital adrenal hyperplasia. New MI Department of pediatrics, New York-Presbyterian Hospital and the Weill Medical College of Cornell University, NY 10021, USA. minew@mail.med.cornell.edu Congenital adrenal hyperplasia (CAH) is a family of adrenal disorders whereby cortisol biosynthesis is impaired or abolished. In most cases, CAH is caused by a deficiency of the enzyme 21-hydroxylase causing a massive build up of adrenal precursors. In addition to prenatal virilisation of genetic females and postnatal virilisation of both males and females, shot stature is characteristic of the disorder. The inadequate final height in CAH patients is often attributed to over treatment with glucocorticoid replacement and poor growth hormone alone and in combination with gonaotropin releasing hormone analogue in children with CAH and poor predicted final height was found to decrease height deficit after one and two years of treatment. I note here that she ‘knows’ what causes the poor growth, but recommends the dosing regime that Sandra is using presently for Jackson---that being twice daily ---which is in effect over treating him. Here is another abstract on bone loss: PEDIATRICS Vol. 100 No. 4 October 1997, pp. 671-674 Bone Mineral Density in Prepubertal and in Adolescent and Young Adult Patients With the Salt-wasting Form of Congenital Adrenal Hyperplasia Received Dec 26, 1996; accepted Feb 26, 1997. Miquel Gussinyé*, Antonio Carrascosa*, Neus Potau , Manuel Enrubia*, Enric Vicens-Calvet*, Lourdes Ibáñez*, and Diego Yeste* From the * Adolescent and Endocrine Unit, and Adolescent, Endocrine, and Hormonal Units, Department of Pediatrics, Children's Hospital Vall d' Hebron, Autonomous University, Barcelona, Spain. Objective: To evaluate bone mineral density (BMD) in prepubertal and in adolescent and young adult patients with the salt-wasting form of congenital adrenal hyperplasia (CAH). Design. A relationship between bone mineral content and risk for osteoporotic fractures has been observed in adulthood. Infancy, childhood, and adolescence are critical periods for skeletal mineralization; thus, chronic diseases may impair bone mass peaking, particularly if children and adolescents are overexposed to glucocorticoids, as may occur in patients with CAH. Lumbar L2-L4 BMD values were measured by dual x-ray absorptiometry and compared with those of 471 age- and sex-matched controls. Patients. Thirty-three patients with the salt-wasting form of CAH were studied. Sixteen (10 girls and 6 boys; age range, 1.5 to 8.3 years) were prepubertal and 17 (13 women and 4 men; age range, 17.1 to 28.2 years) were adolescent and young adults who had reached final height and had presented normal pubertal development and normal gonadal function thereafter. The average doses of hydrocortisone (mg/m2 body surface/day) received from diagnosis in the neonatal period to BMD evaluation were 21.2 ± 2.2 and 22.3 ± 2.6, respectively. Results. Mean BMD Z score values were 0.16 ± 1.01 in prepubertal patients and 0.06 ± 1.02 in adolescent and young adult patients with no statistically significant differences with age- and sex-matched controls. Mean height Z score values were 0.03 ± 1.13 in prepubertal patients and 1.13 ± 0.62 in adolescent and young adult patients with significant differences between the latter and their respective age- and sex-matched controls. Conclusion. Long-term glucocorticoid therapy does not impair bone mass peaking in CAH patients with normal gonadal function, even though their adult height values are low. Key words: salt-wasting form of congenital adrenal hyperplasia, skeletal mineralization, bone mass peaking, bone mineral density, gonadal function, adult height. This article has been cited by other articles: · White, P. C., Speiser, P. W. (2000). Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency. Endocr Rev 21: 245-291 [Abstract] [Full Text] · Zborowski, J. V., Cauley, J. A., Talbott, E. O., Guzick, D. S., Winters, S. J. (2000). Bone Mineral Density, Androgens, and the Polycystic Ovary: The Complex and Controversial Issue of Androgenic Influence in Female Bone. J Clin Endocrinol Metab 85: 3496-3506 [Full Text] Here is one on Growth Hormone in children with Turners Syndrome due to the same reason where bone loss is concerned as CAH kids : Turner Syndrome and Osteoporosis: Mechanisms and Prognosis Received Feb 6, 1998; accepted Mar 20, 1998. Karen Rubin From the Department of Pediatric Endocrinology and Diabetes, Connecticut Children's Medical Center, Hartford, Connecticut, and the Department of Pediatrics, University of Connecticut School of Medicine, Farmington, Connecticut. Despite only limited reports of a greater number of fractures during childhood or adulthood, osteoporosis historically has been described as a feature in Turner syndrome, because of the frequent observation of radiographic osteopenia and the coarse trabecular pattern of the carpal bones on radiographs. The pathogenesis of the skeletal demineralization remains unclear, but the data support the concept of an intrinsic bone defect that is then exacerbated by a number of hormonal factors, including the growth-regulating hormones, the gonadal steroids, and possibly the calcium-regulating hormones. The advent of more refined methods, such as single- and dual-photon absorptiometry and dual energy x-ray absorptiometry, has led to improved insights into bone mineral density (BMD) status in Turner syndrome (TS). A major limitation of these projection methods is that they report areal and not true volumetric BMD, resulting in an underestimation of the true BMD in smaller subjects. In assessing BMD in TS, various methods have been used to eliminate the confounding effect of bone size. Some consistent patterns do emerge in persons with TS who are not treated with long-term growth hormone (GH) or estrogen therapy. A significant deficit in cortical bone commonly appears in childhood and usually is associated with a low bone-turnover state. Significant osteopenia at predominantly trabecular sites develops during mid- to late adolescence and persists into adulthood, when it is associated with increased bone turnover. Preliminary BMD data on patients after long-term GH therapy show an absence of osteopenia. With respect to the impact of long-term estrogen therapy, the BMD deficit in adults with TS who have been treated adequately with estrogen, but who have not been treated with GH, is less than it is in those who have been insufficiently treated or not treated at all with estrogen. The available data indicate that long-term GH treatment during the prepubertal and early to midpubertal years optimizes BMD and improves the prognosis for adequate peak bone mass being achieved after a puberty that, most often, has been induced with exogenous estrogen. Long-term treatment with estrogen and progestin that is initiated during mid- to late adolescence and is continued throughout adulthood appears necessary for a normal peak bone mass to be achieved and the BMD to be preserved well beyond the time of peak bone mass. Additional measures to prevent osteoporosis must be used, such as ensuring adequate calcium intake and ample weight-bearing activities, focusing on preventing injuries and avoiding overtreatment with thyroid hormones. Long-term surveillance with measurement of BMD and of bone turnover in a large TS population into their later adult years is necessary before it can be concluded that the osteopenia observed in TS is a nonprogressive asymptomatic bone defect of no clinical consequences. Key words: Turner syndrome, osteoporosis, osteopenia, growth hormone, estrogen therapy, peak bone mass, bone mineral density. This article has been cited by other articles: · Soyka, L. A., Fairfield, W. P., Klibanski, A. (2000). Hormonal Determinants and Disorders of Peak Bone Mass in Children. J Clin Endocrinol Metab 85: 3951-3963 [Full Text] HERE IS A STUDY DONE ON SHORT CHILDREN Do short children secrete insufficient growth hormone? Z Zadik, SA Chalew, S Raiti and AA Kowarski The 24-hour integrated concentration of growth hormone from 46 children of normal stature was compared with that of 90 short children. Nineteen of the short children had classic growth hormone deficiency by standard pharmacologic growth hormone stimulation tests. Seventy-one children had normal growth hormone responses to stimulation. The mean integrated concentration of growth hormone for children with normal stature (6.6 +/- 1.9 ng/mL) was greater than the mean value for those with normal stimulated growth hormone (3.8 +/- 2.3 ng/mL) and greater than the mean value for those with growth hormone deficiency (1.6 +/- 0.6 ng/mL); differences between groups were all statistically significant (P less than .0001). Forty-five percent of children with normal stimulated growth hormone responses had integrated concentration of growth hormone within the range of values for the group with growth hormone deficiency; this finding may provide the explanation for their poor growth. Thus, patients with normal growth hormone responses have a spectrum of spontaneous growth hormone secretion ranging from normal to impaired. Recent reports indicate that children with normal growth hormone responses who have very low integrated concentration of growth hormone may have the potential to improve their growth with growth hormone therapy. Therefore, use of the integrated concentration of growth hormone may be a more effective method than standard pharmacologic stimulation tests for determining which short children are potentially able to respond to growth hormone therapy. Volume 76, Issue 3, pp. 355-360, 09/01/1985 Copyright © 1985 by The American Academy of Pediatrics This article has been cited by other articles: · (1999). Somatostatin Infusion Withdrawal: Studies in Normal Children and in Children with Growth Hormone Deficiency. J Clin Endocrinol Metab 84: 4426-4430 [Abstract] [Full Text] · Aimaretti, G., Baffoni, C., Bellone, S., Di Vito, L., Corneli, G., Arvat, E., Benso, L., Camanni, F., Ghigo, E. (2000). Retesting Young Adults with Childhood-Onset Growth Hormone (GH) Deficiency with GH-Releasing-Hormone-Plus-Arginine Test. J Clin Endocrinol Metab 85: 3693-3699 [Abstract] [Full Text] · Shalet, S. M., Toogood, A., Rahim, A., Brennan, B. M. D. (1998). The Diagnosis of Growth Hormone Deficiency in Children and Adults. Endocr Rev 19: 203-223 [Abstract] [Full Text] GROWTH HORMONE LEVELS DURING SLEEP AND GROWTH HORMONE DEFICIENT CHILDREN LE Underwood, K Azumi, SJ Voina and JJ Van Wyk Department of Pediatrics, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27514. ABSTRACT. Plasma growth hormone levels were determined from samples drawn at 15-minute intervals during the first 2 hours of spontaneous, nocturnal sleep in 16 normal children, one nongrowth hormone deficient dwarf, and three children with hypopituitarism. Depth of sleep was assessed by continuous EEG monitoring. Daytime growth hormone responses to insulin-induced hypoglycemia were also assessed in most of these children and in a larger group of normal and hypopituitary children. In the normal children and in the nongrowth hormone deficient dwarf, increases in plasma growth hormone after the onset of fire slow wave pattern on EEG were equivalent to those seen after insulin-induced hypoglycemia. No significant changes in growth hormone levels were seen in the hypopituitary patients. Interpretation of growth hormone levels in blood specimens obtained by serial sampling after the onset of deep sleep appears to be as reliable a method of assessing pituitary function as the levels resulting from insulin-induced hypoglycemia. Although growth hormone analysis of a single sample taken about 1 hour after the onset of deep sleep should exclude the diagnosis of growth hormone deficiency in as main 70% of the nongrowth hormone deficient individuals, a positive diagnosis of hyposomatotropism must be based on either serial sampling during deep sleep or challenge with insulin and/or arginine. *************** I will come back to this later and post some more abstracts when I have time to look for them. Basically , to summarize, it seems like our kids could grow perfectly ok as long as most Endocrinologists all got their heads together on this and dosed the kids how they need to be and should their growth be poor, tune the meds more to allow for growth. This has basically made me feel that three monthly monritoing is imperative to success of good control of these kids and taking an great interest not just in the CAH aspect of it but all the other factors that it effects in them and working around those issues such as growth. I did find an article that actually stated that bone loss can be reversed with growth hormone. I also am sure I saw one specifically about CAH. The one by Maria New was on the Pub Med site on Saturday and I printed it off. When I went to cut and paste today is had been removed for some reason---I could not find it so I had to type it up from my printed copy. I will try to find it when I have more time. For now, I thought I would post these for folks to study. Regards Val