larynx. Unless severe hypoglycemia occurs or dysraphism (midline defects) of the head includes a central nervous system (CNS) defect that affects mentation, the patient has normal intellectual growth and age-appropriate speech. Male neonates with isolated GH deficiency with or without gonadotropin deficiency may have a microphallus (a stretched penile length of <2 cm [normal is 3 to 5 cm]) and fasting hypoglycemia. Patients who lack the adrenocorticotropic hormone (ACTH, stimulates cortisol) in addition to GH may have more profound hypoglycemia because cortisol also stimulates gluconeogenesis.
A very rare cause of growth failure is GH resistance or GH insensitivity, caused by abnormal number or function of GH receptors or by a postreceptor defect. Patients with the autosomal recessive Laron syndrome, involving mutations of the GH receptor, have a prominent forehead, hypoplastic nasal bridge, delayed dentition, sparse hair, blue sclerae, delayed bone maturation and osteoporosis, progressive adiposity, hypercholesterolemia, and low blood glucose. They have elevated serum GH concentrations, although serum IGF-1 and IGF-BP3 concentrations are low. Malnutrition, medications (corticosteroids), or severe liver disease may cause acquired GH resistance because serum GH is elevated and IGF-1 is decreased.
If family or other medical history does not provide a likelydiagnosis, screening tests should include a metabolic panelto evaluate kidney and liver function, a complete bloodcount (CBC) to rule out anemia, a celiac panel to rule outceliac disease, and carotene and folate levels to reflect nutrition and rule out malabsorption. A urinalysis aids in theevaluation of renal function. Urinary pH and serum bicarbonate can assess for renal tubular acidosis. In a girl without another explanation for short stature, a karyotype mayrule out Turner syndrome. A bone age will establish skeletal maturation.
If chronic disease or familial short stature are ruled out and routine laboratory testing is normal (Table 173-4), two GH stimulatory tests are commonly performed (see Table 170-2). GH testing should be offered to a patient who is short (<5th percentile and usually >3.5 SDs below the mean), growing poorly (<5th percentile growth rate for age), or whose height projection, based on bone age, is considerably below the target height when corrected for family height.
Classic GH-deficient patients do not show an increase in serum GH levels after stimulation. Some patients release GH in response to secretagogue testing but cannot release GH spontaneously during the day or night. Measuring serum IGF-1 and IGF-BP3 is suggested but not consistently helpful in establishing a diagnosis of GH deficiency. Tests for GH secretion are insensitive, not very specific, and fairly variable. In equivocal cases, an operational definition of GH deficiency might be that patients grow significantly faster when administered a normal dose of GH than before treatment.
GH deficiency is treated with biosynthetic recombinant DNA–derived GH. Dosage is titrated to the growth rate. Treatment with GH carries the risk of an increased incidence of slipped capital femoral epiphysis, especially in rapidly growing adolescents, and of pseudotumor cerebri.