Clinical Scenario:
A 7-year-old girl is evaluated for progressive growth failure. Her height has fallen from the 25th percentile to below the 3rd percentile over the past 2 years, and her current height velocity is 3 cm/year. Her bone age is approximately 4 years. She has normal body proportions and no dysmorphic features. Thyroid function tests and a morning cortisol level are normal. Which of the following is the most appropriate next investigation?
A. Serum IGF-1 and IGFBP-3
B. Karyotype
C. Growth hormone stimulation test
D. MRI of the brain
E. Skeletal survey
Correct answer & Explanation:
Answer: A. Serum IGF-1 and IGFBP-3
Discussion: Growth hormone deficiency
This child has progressive growth deceleration, markedly reduced height velocity, and delayed bone age, raising suspicion for an endocrine disorder, particularly growth hormone deficiency (GHD).
Serum IGF-1 and IGFBP-3 are appropriate screening investigations of the GH–IGF-1 axis. If the clinical picture and screening results support possible GHD, GH stimulation testing may subsequently be required to establish the diagnosis.
A GH stimulation test is not the preferred initial investigation because GH secretion is pulsatile, making a random GH level unreliable, and stimulation testing is more invasive and should be interpreted in the context of the clinical and biochemical evaluation.
MRI of the hypothalamic-pituitary region is generally considered after GHD has been established or is strongly suspected, particularly when there are features suggesting an intracranial lesion or other pituitary hormone abnormalities.
Karyotyping should be considered in a girl with unexplained short stature when Turner syndrome is suspected, especially when characteristic phenotypic features or other clinical clues are present. This child has no such features.
A skeletal survey is not routinely indicated in a child with proportionate short stature and no clinical evidence of skeletal dysplasia.
Key exam point:
Poor height velocity + delayed bone age → consider endocrine disease. When GHD is suspected, IGF-1 and IGFBP-3 are useful screening tests; GH stimulation testing is a subsequent diagnostic test, not the first investigation.
