Disorders of Growth and Development: Clinical Perspectives
A 9-year-old boy presented with complaint of growth failure since 2 years of age. He was a product of non-consanguineous marriage and was delivered at full-term by normal vaginal delivery. His birth weight was 3.3 kg and he had normal Apgar score. However, data of his birth length was not available. He had history of prolonged physiological jaundice, that lasted for 3 weeks and required phototherapy for its resolution. There was no history of any episode of hypoglycemia. His developmental milestones were normal, except delay in walking which was due to congenital dislocation of his left hip. The growth velocity data available, showed his height at 1 year of age was 65 cm, at second year 75 cm, and later at the age of 9 year it was 96 cm with annual growth velocity of approximately 3 cm/year from third year of age onward. He has good scholastic performance and now is studying in fourth standard. There was no history of any systemic illness, chronic diarrhea, drug intake (e.g., steroid), head injury, meningitis/encephalitis, headache, and visual defects. He had no history of fatigue, lethargy, irritability, somnolence, or constipation. His both parents were short and were <3rd percentile. He has one sibling with normal history of growth and development. On examination, his height was 96 cm (−7 SDS, height age 3 years, target height 164 cm), upper and lower segment ratio 1.2, arm span 92 cm, weight 21.2 kg (weight age 6 years), and BMI 23 kg/m2 (>95th percentile). He had cherubic face with frontal bossing, depressed nasal bridge, midfacial hypoplasia, low-set ears, and poor dentition with crowded teeth. He had no goiter. His blood pressure was 90/60 mmHg. He had bilateral palpable testes with testicular volume of 1 ml and stretch penile length of 2 cm with Tanner staging of A-, P1. He had bilateral palpable testes with testicular volume of 1 ml and stretched penile length of 2 cm, and he had bilateral lipomastia. Systemic examination was unremarkable except shortening of his left lower limb with restriction of movement at the left hip joint. On investigations, his hemoglobin was 10 g/dl with normal total and differential leukocyte counts. Renal and liver function tests, electrolytes (K+ and HCO3−), calcium profile, and IgA tTG were normal. Hormonal profile showed serum T4 6.7 μg/dl (N 4.8–12.7), TSH 4.6 μIU/ml (N 0.27–4.2), 0800 h cortisol 140 nmol/L (N 171–536), LH <0.1 mIU/ml (N 1.7–8.6), FSH 0.52 mIU/ml (N 1.5–12.4), testosterone <0.08 nmol/L (N 9.9–27.8), prolactin 5.07 ng/ml (N 4–15.2), and IGF1 50 ng/ml (N 58–401). GH response to insulin-induced hypoglycemia and clonidine stimulation test, after priming with estrogen, were performed and showed subnormal peak GH response to both these stimuli (<0.03 ng/ml for both). Peak cortisol response to insulin-induced hypoglycemia was also suboptimal (150 nmol/L). His bone age was 7 years. CEMRI sella showed small pituitary with normal midline stalk and eutopic posterior pituitary bright spot. X-ray pelvis showed dislocation of left hip joint. With this profile, a diagnosis of multiple pituitary hormone deficiency (GH and ACTH) was considered, and patient was initiated with rhGH at doses of 0.3 mg/kg/week and hydrocortisone 2.5 mg twice a day. With this treatment, the growth velocity during first year was 11 cm and during second year was 14 cm, and after 2 years of initiation of rhGH therapy, the height increased from 96 to 121 cm. His weight increased from 21 to 41 kg, possibly due to immobilization during his surgery for hip dislocation. After 3 months of initiation of rhGH, the serum T4 level declined to 5.2 μg/dl and he was initiated with 50 μg/day of L-thyroxine. Serum IGF1 levels were 378 ng/ml (N 70–458) and 251 ng/ml (N 82–516) after first and second years of therapy, respectively. No adverse event was noted during the course of therapy (Fig. 1.1).