ABSTRACT: Background and objectiveTo evaluate the clinical and biochemical profile and growth hormone receptor polymorphism of children presenting with short stature to a tertiary care centre. This would thus be directing resources to patients with GH deficiency who would respond best to it.Materials and methodsThis was an observational study on short stature children presenting to a tertiary care hospital over a period of 3 years. All children enrolled underwent extensive baseline work up to investigate for causes of short stature like endocrine causes, malnutrition, chronic diseases, celiac disease, syndromic association, skeletal dysplasia, familial short stature, constitutional short stature and idiopathic short stature. In children with pathological short, serum growth hormone (GH), IGF-1 and IGFBP-3 levels were estimated using two different pharmacological stimuli. GH value of less than 10 mg/L was considered to be GH deficient. Children with GH deficiency were subjected to analysis of the GHD3 exon deletion status. For the genotyping of GHR exon 3 locus, the frequency of GHR transcript variants with retention (GHRfl) or exclusion (GHRd3) of exon 3 was tested by the multiplex PCR assay. This was performed with primers G1, G2, and G3 with a well-defined protocol.ResultsA total of 473 children with a median age of 3.65 years (range, 2-18 years) were enrolled. Twenty three percent of the children each were diagnosed as growth hormone deficient and idiopathic short stature. Celiac disease also contributed significantly in 18% of cases. The other causes seen were skeletal dysplasia (7%), syndromic (12%) and malnutrition (2%). Amongst children with endocrine disorders, 40% children had hypothyroidism, panhypopituitarism was seen in 10% children and 50% had Laron’s syndrome. In children with chronic disorders, 72% were diagnosed with thalassemia, 21% with chronic kidney disease and one child had renal tubular acidosis. Constitutional and familial short statures were seen in 6% and 2% children respectively. Amongst patients with GHD, 60.7% had wild type (GHRfl/fl), 19.2% were heterozygous (GHRfl/GHRd3) and 20.1% were homozygous (GHRd3/d3), whereas for idiopathic short stature they were 67.5%, 14.5% and 18% respectively.ConclusionsThe diagnosis could be attained in 85% of cases. Growth hormone deficiency and celiac disease contribute significantly even though majority is normal variants. Also, genotyping done would help in prediction of response to recombinant GH therapy in a resource constraint resulting in appropriation of finances which could be utilized for a higher priority area.
