Effect of glucocorticoid therapy on bones in children with congenital adrenal hyperplasia: A Sri Lankan experience

Abstract

Introduction: Congenital adrenal hyperplasia (CAH) requires lifelong glucocorticoid therapy (GCT). Long- term use of GCT is known to adversely affect bone metabolism. Vitamin D synthesis in the skin can be impaired by the hyperpigmentation seen in CAH patients. Objectives: To describe the effects of glucocorticoid therapy and vitamin D status on the bones in children with CAH. Method: Children with CAH followed up in the University Unit at the Lady Ridgeway Hospital, Colombo were studied. Mean values of the daily dose of hydrocortisone received, serum calcium, intact parathormone (iPTH) and 25-hydroxy vitamin D levels were compared with the duration of therapy categorized into 3 groups. Skin pigmentation was graded using the Fitzpatrick scale and was described with the biochemical parameters according to vitamin D status (sufficiency >50nmol/L). Results: Thirty eight children were studied. Mean daily dose of hydrocortisone of children treated for less than 4 years (n=6), 4 to 7 years (n=6) and more than 7 years (n=26) were 14.0, 13.4, and 14.0 mg/m2/day respectively (recommended dose 10-15 mg/m2/day). Mean serum calcium levels (2.53, 2.41, 2.28mmol/L) and iPTH levels (3.59, 4.46, 6.30pmol/L) were in the normal range and vitamin D levels (47.55, 47.97, 44.44nmol/L) were in the insufficient range. The differences between the groups were not significant. However, the difference seen in alkaline phosphatase (ALP) was significant (p=0.026). There was also an apparent inverse association of ALP with the total average daily dose of glucocorticoids (R2=0.077, F=3.0, p=0.092). Vitamin D deficiency (≤37.5nmol/L) was seen in 8 (21.1%) patients. Degree of pigmentation and biochemical parameters assessed were not significant according to vitamin D status. Conclusions: Serum ALP levels show an inverse relationship with the duration of glucocorticoid therapy indicating possible adverse outcome on bones. The apparent inverse relationship of total average daily dose of glucocorticoids with ALP failed to reach statistical significance. No relationship was found with vitamin D status and other parameters assessed.