Classic congenital or idiopathic GH deficiency occurs in about 1 in 4000 to 1 in 10,000 children. Idiopathic GH deficiency, of unidentified specific etiology, is the most common cause of both congenital and acquired GH deficiency. Less often GH deficiency is caused by anatomic defects of the pituitary gland, such as pituitary aplasia or other midline defects, with variable degrees of deficiency of other pituitary functions. Hereditary forms of GH deficiency that affect pituitary differentiation are the result of heterogeneous defects of the gene for GH, GRF, or GH receptor. Classic GH deficiencyrefers to very reduced to absent secretion of GH; numerous short children may have intermediate forms of decreased GH secretion. Acquired GH deficiency causing late-onset growth failure suggests the possibility of a tumor of the hypothalamus or pituitary causing compression of the area (see Tables 173-2 and 173-3).
Infants with congenital GH deficiency achieve a normal or near-normal birth length and weight at term, but the growth rate slows after birth, most noticeably after age 2 to 3 years. These children become progressively shorter for age and tend to have an elevated weight-to-height ratio, appearing chubby and short. Careful measurements in the first year of life may suggest the diagnosis, but most patients elude diagnosis until several years of age. A patient with classic GH deficiency has the appearance of a cherub (a chubby, immature appearance), with a high-pitched voice resulting from an immature
Karyotype Normal Normal Normal Normal 45,X or partial Normal Normal deletion of X chromosome or mosaic
Stimulated GH Low Normal for bone age Normal Possibly low, or Usually normal Low Usually normal high if patient malnourished
ACTH, Adrenocorticotropic hormone; CRH, corticotropin-releasing hormone; GH, growth hormone; GnRH, gonadotropin-releasing hormone; TRH, thyrotropin-releasing hormone; T4, thyroxine. *Possibly with GnRH, CRH, or TRH deficiency.
CBC Anemia: nutritional, chronic disease, malignancy
Leukopenia: bone marrow failure syndromes
Thrombocytopenia: malignancy, infection
ESR, CRP Inflammation of infection, inflammatory diseases, malignancy
Metabolic panel Signs of acute or chronic hepatic, renal, (electrolytes, liver adrenal dysfunction; hydration and enzymes, BUN) acid-base status
Carotene, folate, and Assess malabsorption; detect celiac prothrombin time; disease celiac antibody panel
Urinalysis with pH Signs of renal dysfunction, hydration, water and salt homeostasis; renal tubular acidosis
Cranial imaging (MRI) Assesses hypothalamic-pituitary tumors (craniopharyngioma, glioma, germinoma) or congenital midline defects
Bone age Compare with height age and evaluate height potential
IGF-1, IGF-BP3 Reflects growth hormone status or nutrition
Prolactin Elevated in hypothalamic dysfunction or destruction, suppressed in pituitary disease
BUN, Blood urea nitrogen; CBC, complete blood count; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; IGF-1, insulin-like growth factor-1; IGF-BP3, insulin-like growth factor-binding protein 3; MRI, magnetic resonance imaging.