Etiological study of short stature in children and role of insulin like growth factor-1 and insulin like growth factor binding protein-3 as screening markers for growth hormone deficiency.

OBJECTIVE: To determine aetiological factors in children with short stature, and to evaluate the role of insulin like growth factor-1 and insulin like growth factor binding protein-3 as screening markers for growth hormone deficiency. METHODS: The cross-sectional study was conducted at the Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from August 2020 to July 2021, and comprised children with short stature. Evaluation protocol included complete history and examination, baseline laboratory investigations, X-ray for bone age and karyotyping. Growth hormone status was assessed using growth hormone stimulation tests, and serum insulin like growth factor-1 and insulin like growth factor binding protein-3 levels were also assessed. Data was analysed using SPSS 25. RESULTS: Of the 649 children, 422(65.9%) were boys and 227(34.9%) were girls. The overall median age was 11 years (interquartile range: 11 years). Of the total, 116(17.9%) children had growth hormone deficiency. Familial short stature was present in 130(20%) children and constitutional delay in growth and puberty in 104(16.1%). There was no significant difference in levels of serum insulin like growth factor-1 and insulin like growth factor binding protein-3 in children who had growth hormone deficiency and those who had other causes of short stature (p>0.05). CONCLUSIONS: Physiological variants of short stature were found to be more common in the population followed by growth hormone deficiency. Serum insulin like growth factor-1 and insulin like growth factor binding protein-3 levels alone should not be used to screen children with short stature for growth hormone deficiency.

Diagnosis of GH Deficiency Without GH Stimulation Tests.

Growth hormone deficiency (GHD) is the most commonly affected pituitary hormone in childhood with a prevalence of 1 in 4000-10000 live births. GH stimulation testing (GHST) is commonly used in the diagnostic workup of GHD. However, GHD can be diagnosed in some clinical conditions without the need of GHST. The diagnosis of GHD in newborns does not require stimulation testing. Likewise infants/children with delayed growth and/or short stature associated with neuroradiological abnormalities and one or more additional pituitary hormone deficiencies may not need GHST. This review summarizes the current evidence on the diagnosis of GHD without stimulation tests.

The Boy:Girl Ratio of Children Diagnosed with Growth Hormone Deficiency-Induced Short Stature Is Associated with the Boy:Girl Ratio of Children Visiting Short Stature Clinics.

BACKGROUND: About twice as many boys as girls undergo growth hormone (GH) therapy in GH deficiency (GHD). However, this sex difference may not correctly reflect a real incidence. OBJECTIVES: We analyzed the evidence of a selection bias whereby more boys seek treatment at short stature clinics. SUBJECTS AND METHODS: The present study included 3,902 children who visited 17 short stature clinics with a height SD score of -2 SD or less. The percentage of children who underwent the GH stimulation test was compared between boys and girls, as was the percentage of children ultimately diagnosed with GHD. RESULTS: The children comprised 2,390 boys (61.3%) and 1,512 girls (38.7%), with a boy:girl ratio of 1.58:1. The percentage of children who underwent the GH stimulation test did not differ between boys (45.7%) and girls (49.8%). Among the children who underwent the GH stimulation test, the percentage diagnosed with GHD did not differ significantly between boys (22.0%) and girls (20.1%). The boy:girl ratio of children diagnosed with GHD was 1.59:1. CONCLUSIONS: The boy:girl ratio of children with short stature (1.58:1) did not differ significantly from that of children diagnosed with GHD (1.59:1). These results indicate that the predominance of boys in GHD does not reflect a real incidence, but rather a selection bias whereby a higher proportion of boys with short stature seek treatment at clinics. This difference arises because parents are more concerned about boys' height, and because boys reach adult height at an older age.

Provocative growth hormone testing in children: how did we get here and where do we go now?

OBJECTIVES: Provocative growth hormone (GH) tests are widely used for diagnosing pediatric GH deficiency (GHD). A thorough understanding of the evidence behind commonly used interpretations and the limitations of these tests is important for improving clinical practice. CONTENT: To place current practice into a historical context, the supporting evidence behind the use of provocative GH tests is presented. By reviewing GH measurement techniques and examining the early data supporting the most common tests and later studies that compared provocative agents to establish reference ranges, the low sensitivity and specificity of these tests become readily apparent. Studies that assess the effects of patient factors, such as obesity and sex steroids, on GH testing further bring the appropriateness of commonly used cutoffs for diagnosing GHD into question. SUMMARY AND OUTLOOK: Despite the widely recognized poor performance of provocative GH tests in distinguishing GH sufficiency from deficiency, limited progress has been made in improving them. New diagnostic modalities are needed, but until they become available, clinicians can improve the clinical application of provocative GH tests by taking into account the multiple factors that influence their results.