Endocrinology · Pediatric Endocrinology
The facts most likely to be tested
Growth hormone deficiency presents clinically as short stature with a height velocity below the 3rd percentile or more than 2 standard deviations below the mean for age and sex.
The initial screening laboratory evaluation for suspected growth hormone deficiency includes measuring insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) levels.
A definitive diagnosis of growth hormone deficiency requires failure to achieve an adequate peak serum concentration during growth hormone stimulation testing using agents like arginine or clonidine.
Patients with growth hormone deficiency typically exhibit a delayed bone age on radiographic skeletal survey of the left hand and wrist.
The gold standard treatment for pediatric growth hormone deficiency is daily subcutaneous injections of recombinant human growth hormone (rhGH).
Growth hormone deficiency is frequently associated with midline defects, such as cleft lip or palate, or sept-optic dysplasia (de Morsier syndrome).
Untreated growth hormone deficiency often results in delayed puberty and increased adiposity due to the metabolic effects of growth hormone on lipid and glucose homeostasis.
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A 6-year-old boy is brought to the clinic by his parents due to concerns about his height compared to his peers. Physical examination reveals a height below the 3rd percentile for his age, while his weight is at the 50th percentile, resulting in a truncal obesity appearance. His bone age is determined to be 4 years on a wrist radiograph. He has no history of chronic illness, and his thyroid function tests are within normal limits. His IGF-1 levels are significantly low for his age.
What is the most appropriate next step in the management of this patient?
Growth hormone stimulation testing
The patient's clinical presentation of short stature, delayed bone age, and low IGF-1 levels warrants confirmation of growth hormone deficiency via stimulation testing before initiating rhGH therapy.
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High yield triage
Etiology / Epidemiology
Often idiopathic or secondary to pituitary tumors or craniopharyngioma. Congenital forms involve GH-releasing hormone or GH gene mutations.
Clinical Manifestations
Presents as proportional short stature with delayed bone age and cherubic facies. Look for midline defects like cleft palate.
Diagnosis
Screen with IGF-1 levels; confirm with GH stimulation test (e.g., arginine or insulin). Failure to rise above 10 ng/mL is diagnostic.
Treatment
Daily subcutaneous recombinant human growth hormone. Contraindicated in active malignancy or closed epiphyses.
Prognosis
Early intervention maximizes final adult height. Monitor for slipped capital femoral epiphysis and scoliosis.
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Epidemiology & Etiology
Most cases are idiopathic, but structural causes include pituitary hypoplasia or damage from craniopharyngioma. Genetic causes include Pit-1 mutations affecting multiple pituitary hormones. Consider radiation therapy history as a major risk factor for acquired deficiency.
Pertinent Anatomy
The anterior pituitary (adenohypophysis) secretes GH under the influence of the hypothalamus. Disruption of the pituitary stalk prevents hypothalamic signaling, leading to panhypopituitarism.
Pathophysiology
GH deficiency leads to decreased IGF-1 production in the liver, impairing chondrocyte proliferation at the epiphyseal plates. This results in reduced linear bone growth and delayed skeletal maturation. Metabolic effects include hypoglycemia due to loss of GH-mediated glucose counter-regulation.
Clinical Manifestations
Patients exhibit proportional short stature (height < 3rd percentile) and delayed bone age on X-ray. Classic features include cherubic facies (immature face), truncal obesity, and a high-pitched voice. Red flags include hypoglycemia in neonates or midline defects like cleft palate or optic nerve hypoplasia.
Diagnosis
Initial screening requires IGF-1 and IGFBP-3 levels, which are low in GH deficiency. The GH stimulation test (using arginine, glucagon, or insulin) is the gold standard for confirmation. A peak GH level < 10 ng/mL confirms the diagnosis.
Treatment
Management involves daily subcutaneous injections of recombinant human growth hormone. Therapy continues until epiphyseal closure is achieved. Contraindications include active malignancy, proliferative retinopathy, and closed epiphyses due to risk of acromegaly.
Prognosis
Early diagnosis is critical to achieve normal adult height. Patients require monitoring for slipped capital femoral epiphysis (SCFE), scoliosis, and pseudotumor cerebri during rapid growth phases.
Differential Diagnosis
Hypothyroidism: elevated TSH with delayed bone age
Turner Syndrome: 45,X karyotype in females
Constitutional growth delay: normal growth velocity with delayed bone age
Achondroplasia: disproportionate short stature with rhizomelia
Cushing Syndrome: growth failure with weight gain and striae