J. Endocrinol. Invest. 13: 833-837, 1990
CASE REPORT
Growth hormone therapy in a poorly growing child with hypophosphatemic rickets R. Lanes and H. E. Harrison Department of Pediatrics, Hospital de Clfnicas Caracas and the Department of Endocrinology, Hospital Central "Dr. Carlos Arvelo", Caracas, Venezuela; and Division of Pediatric Endocrinology, Johns Hopkins Children's Center, Baltimore, Maryland, USA.
ABSTRACT. We treated a 106~2 year old prepubertal male with hypophosphatemic rickets, who was growing poorly despite appropriate treatment with calcitriol and phosphate, with exogenous growth hormone (for an initial trial period of 4 months, followed by 14 months of continuous treatment at a dose of 4 IU three times weekly) even though his growth hormone testing proved to be normal. His growth rate increased significantly during treatment with synthetic growth hormone (from a basal rate of 3.9 cm/yr to 9 cm/yr during the first 4 months of therapy and from 2.7 cm/yr
to 6.0 cm/yr during next 14 months of treatment} and his predicted adult height increased as weil. Slight metabolic changes were detected in this patient during treatment, with an increase in serum phosphorus and a decrease in twenty-four hour urine calcium concentrations. It would seem reasonable to evaluate the growth hormone status of children with hypophosphatemic rickets who are growing poorly despite appropriate therapy with calcitriol and phosphate and to consider a trial period of therapy with growth hormone in some of them.
INTRODUCTION
We treated a child with hypophosphatemic rickets, who was growing poorly despite treatment with calcitriol and phosphate, with exogenous growth hormone and report the results of growth hormone testing and the effects of this therapy on his qrowth rate and mineral status. Earlier reports of growth hormone therapy in this form of rickets are very few and limited (1 0-11 ).
X-linked hypophosphatemic rickets is characterized by a renal tubular phosphate leak, inadequate mineralization of the growth plate and bone and by short stature (1 -4). Therapy with calcitriol and phosphate supplementation results in a significant improvement in calcium and phosphorus balances, as weil as in bone healing (5-8). Although the growth rates of children with hypophosphatemic rickets frequently improve with treatment, administration of calcitriol and phosphate does not uniformly restore normal growth velocity in these children (8-11 ). The growth hormone status of children with hypophosphatemic rickets has recently been studied and some of these children may be growth hormone deficient and benefit from growth hormone therapy (9).
CASE REPORT This infant was the 3,700 9 product of anormal pregnancy and was delivered by C-section due to cephalopelvic disproportion. He was breast fed 1 1/2 months and received iron fortified formula and vitamin supplementation thereafter. No abnormalities were detected until 18 months of age when bowing of the legs was noted and treated with orthopedic shoes and braces. There was no family history of skeletal deformities and no family members with unusual short stature. He was referred to a pediatric endocrinologist at 310~2 years of age who made the diagnosis of hypophospha-
Key-words: Growth hormone, hypophosphatemie riekets, growth veloeity. Correspondence: Roberto Lanes, M.D. e/o Jet Cargo INTL, M-177, P.O. Box 020010, Miami, FI. 33102, U.S.A. Reeeived January 15, 1990, aeeepted September 4, 1990.
833
R. Lanes and H.E. Harrison
Table 1 - Serum calcium, phosphorus and alkaline phosphatase and urinary calcium, phosphorus and calcium/creatinine ratio, on and off growth hormone therapy. Serum Chronological age (yr) 310~2
48~2
55~2 76~2 96~2 * 104~2 +
11 o~2 * 11 4/2 + 1111~2 *
123~2 * 131~2 * 135~2 +
Calcium (mg/dl)
Phosphorus (mg/dl)
9.6 10.2 9.8 10.2 10.3 9.6 9.9 10.6 9.5 10.1 10.0 9.7
2.6 3.1 2.9 3.7 3.7 4.3 3.9 4.9 3.6 4.8 3.7 2.7
Urine Alkaline phosphatase (lU/I) 120 135
187
171
Calcium (mg/24 hours)
Phosphorus (g/24 hours)
62.4 60
2.1 2.3
50 116 58 120 43 47 109
2.1 2.6 1.5 1.8 1-.35 1.4
Ca/Cr ratio
0.340.1 0.06 0.079
0.1
+ Off
growth hormone therapy. * Started on growth hormone therapy. - Dosage of calcitriol adjusted when urine calcium excretion exceeded normal values.
temic rickets based on radiological findings of craniosynostosis, bilateral coxavara and osteomalacia and on laboratory values of a serum calcium: 9.6 mg/dl, phosphorus: 2.6 mg/dl, normal serum electrolytes and urine negative for glucose and aminoacids; he was started on 1 gl day of phosphorus as K phosphate (neutraphos K) and 0.375 mg/ day ot dihydrotachysterol. At 48~2 years of age he was evaluated at the pediatric endocrine clinic at the Johns Hopkins Hospital presenting with short stature (height of 98.7 5th percentile), coxavara, moderate bowing cm, of the legs, medial torsion of the tibia and synostosis of the saggital suture of the skull with marked scaphocephaly; there was no evidence of increased intracranial pressure in terms of visual problems or other symptoms. Radiological studies of the knees and wrist showed excellent healing of rickets; laboratory studies 1 week off dihydrotachysterol revealed a serum calcium: 10.2 mg/dl, phosphorus: 3.1 mg/dl, alkaline phosphatase: 120 lU/I, creatinine: 0.5 mg/dl, BUN 17 mg/dl and a spot urine with a calcium/ creatinine ratio of 0.34, specific gravity of 1022, pH: 6, negative for protein and glucose. He was started on calcitriol at a dose of 0.25 J.lg I day and K phosphate was increased to 1.5 gl day. Over the next 5 years the patient was kept on calcitriol and phosphate maintaining normal serum
calcium, phosphorus and alkaline phosphatase levels (Table 1); he presented with no side effects of treatment other than occasional soft stools and abdominal cramping, but no diarrhea. The dose of calcitriol was increased to 0.5 J.lg/ day because of low urine calcium/creatinine ratio and 24-h calcium excretion (0.079 and 0.8 mg/kg). He had minimal tibial bowing and X-rays showed healing of rickets; he presented however with marked enamel dysplasia of the mandibular incisors. At a chronological age of 1 06~2 yr his bone age was 60~2 yr and his height age was 67~2 yr. Growth rate over the preceeding 2 years was 3.9 cm/yr « 5th percentile) and predicted adult height was 163 cm by the Roche-Wainer-Thissen (RWT) method for the prediction of adult stature (Table 2). Serum electrolytes, thyroxine and somatomedin C levels (SMC RIA, Nichols Institute, California) were normal (T 4: 8 J.lg/dl, SMC: 0.66 U/ml). He was given a 6-month trial of human growth hormone (Asellacrin, Serono Laboratories) at a dose of 0.06 IU/kg three times weekly with no obvious growth acceleration (3.7 cm/yr during this treatment). At 11 o~2 years of age the child was referred to a peciatric endocrinologist in Caracas, Venezuela who has followed him since. At the time serurn calcium, phosphorus and akaline phosphataselevels were 9.9 mg/dl, 3.9 mg/dl and 187 IU/I, respectively
CASE REPORT
Growth hormone therapy in a poorly growing child with hypophosphatemic rickets R. Lanes and H. E. Harrison Department of Pediatrics, Hospital de Clfnicas Caracas and the Department of Endocrinology, Hospital Central "Dr. Carlos Arvelo", Caracas, Venezuela; and Division of Pediatric Endocrinology, Johns Hopkins Children's Center, Baltimore, Maryland, USA.
ABSTRACT. We treated a 106~2 year old prepubertal male with hypophosphatemic rickets, who was growing poorly despite appropriate treatment with calcitriol and phosphate, with exogenous growth hormone (for an initial trial period of 4 months, followed by 14 months of continuous treatment at a dose of 4 IU three times weekly) even though his growth hormone testing proved to be normal. His growth rate increased significantly during treatment with synthetic growth hormone (from a basal rate of 3.9 cm/yr to 9 cm/yr during the first 4 months of therapy and from 2.7 cm/yr
to 6.0 cm/yr during next 14 months of treatment} and his predicted adult height increased as weil. Slight metabolic changes were detected in this patient during treatment, with an increase in serum phosphorus and a decrease in twenty-four hour urine calcium concentrations. It would seem reasonable to evaluate the growth hormone status of children with hypophosphatemic rickets who are growing poorly despite appropriate therapy with calcitriol and phosphate and to consider a trial period of therapy with growth hormone in some of them.
INTRODUCTION
We treated a child with hypophosphatemic rickets, who was growing poorly despite treatment with calcitriol and phosphate, with exogenous growth hormone and report the results of growth hormone testing and the effects of this therapy on his qrowth rate and mineral status. Earlier reports of growth hormone therapy in this form of rickets are very few and limited (1 0-11 ).
X-linked hypophosphatemic rickets is characterized by a renal tubular phosphate leak, inadequate mineralization of the growth plate and bone and by short stature (1 -4). Therapy with calcitriol and phosphate supplementation results in a significant improvement in calcium and phosphorus balances, as weil as in bone healing (5-8). Although the growth rates of children with hypophosphatemic rickets frequently improve with treatment, administration of calcitriol and phosphate does not uniformly restore normal growth velocity in these children (8-11 ). The growth hormone status of children with hypophosphatemic rickets has recently been studied and some of these children may be growth hormone deficient and benefit from growth hormone therapy (9).
CASE REPORT This infant was the 3,700 9 product of anormal pregnancy and was delivered by C-section due to cephalopelvic disproportion. He was breast fed 1 1/2 months and received iron fortified formula and vitamin supplementation thereafter. No abnormalities were detected until 18 months of age when bowing of the legs was noted and treated with orthopedic shoes and braces. There was no family history of skeletal deformities and no family members with unusual short stature. He was referred to a pediatric endocrinologist at 310~2 years of age who made the diagnosis of hypophospha-
Key-words: Growth hormone, hypophosphatemie riekets, growth veloeity. Correspondence: Roberto Lanes, M.D. e/o Jet Cargo INTL, M-177, P.O. Box 020010, Miami, FI. 33102, U.S.A. Reeeived January 15, 1990, aeeepted September 4, 1990.
833
R. Lanes and H.E. Harrison
Table 1 - Serum calcium, phosphorus and alkaline phosphatase and urinary calcium, phosphorus and calcium/creatinine ratio, on and off growth hormone therapy. Serum Chronological age (yr) 310~2
48~2
55~2 76~2 96~2 * 104~2 +
11 o~2 * 11 4/2 + 1111~2 *
123~2 * 131~2 * 135~2 +
Calcium (mg/dl)
Phosphorus (mg/dl)
9.6 10.2 9.8 10.2 10.3 9.6 9.9 10.6 9.5 10.1 10.0 9.7
2.6 3.1 2.9 3.7 3.7 4.3 3.9 4.9 3.6 4.8 3.7 2.7
Urine Alkaline phosphatase (lU/I) 120 135
187
171
Calcium (mg/24 hours)
Phosphorus (g/24 hours)
62.4 60
2.1 2.3
50 116 58 120 43 47 109
2.1 2.6 1.5 1.8 1-.35 1.4
Ca/Cr ratio
0.340.1 0.06 0.079
0.1
+ Off
growth hormone therapy. * Started on growth hormone therapy. - Dosage of calcitriol adjusted when urine calcium excretion exceeded normal values.
temic rickets based on radiological findings of craniosynostosis, bilateral coxavara and osteomalacia and on laboratory values of a serum calcium: 9.6 mg/dl, phosphorus: 2.6 mg/dl, normal serum electrolytes and urine negative for glucose and aminoacids; he was started on 1 gl day of phosphorus as K phosphate (neutraphos K) and 0.375 mg/ day ot dihydrotachysterol. At 48~2 years of age he was evaluated at the pediatric endocrine clinic at the Johns Hopkins Hospital presenting with short stature (height of 98.7 5th percentile), coxavara, moderate bowing cm, of the legs, medial torsion of the tibia and synostosis of the saggital suture of the skull with marked scaphocephaly; there was no evidence of increased intracranial pressure in terms of visual problems or other symptoms. Radiological studies of the knees and wrist showed excellent healing of rickets; laboratory studies 1 week off dihydrotachysterol revealed a serum calcium: 10.2 mg/dl, phosphorus: 3.1 mg/dl, alkaline phosphatase: 120 lU/I, creatinine: 0.5 mg/dl, BUN 17 mg/dl and a spot urine with a calcium/ creatinine ratio of 0.34, specific gravity of 1022, pH: 6, negative for protein and glucose. He was started on calcitriol at a dose of 0.25 J.lg I day and K phosphate was increased to 1.5 gl day. Over the next 5 years the patient was kept on calcitriol and phosphate maintaining normal serum
calcium, phosphorus and alkaline phosphatase levels (Table 1); he presented with no side effects of treatment other than occasional soft stools and abdominal cramping, but no diarrhea. The dose of calcitriol was increased to 0.5 J.lg/ day because of low urine calcium/creatinine ratio and 24-h calcium excretion (0.079 and 0.8 mg/kg). He had minimal tibial bowing and X-rays showed healing of rickets; he presented however with marked enamel dysplasia of the mandibular incisors. At a chronological age of 1 06~2 yr his bone age was 60~2 yr and his height age was 67~2 yr. Growth rate over the preceeding 2 years was 3.9 cm/yr « 5th percentile) and predicted adult height was 163 cm by the Roche-Wainer-Thissen (RWT) method for the prediction of adult stature (Table 2). Serum electrolytes, thyroxine and somatomedin C levels (SMC RIA, Nichols Institute, California) were normal (T 4: 8 J.lg/dl, SMC: 0.66 U/ml). He was given a 6-month trial of human growth hormone (Asellacrin, Serono Laboratories) at a dose of 0.06 IU/kg three times weekly with no obvious growth acceleration (3.7 cm/yr during this treatment). At 11 o~2 years of age the child was referred to a peciatric endocrinologist in Caracas, Venezuela who has followed him since. At the time serurn calcium, phosphorus and akaline phosphataselevels were 9.9 mg/dl, 3.9 mg/dl and 187 IU/I, respectively
