GROWTH HORMONE DEFICIENCY

TABLE 22.4: Diagnostic criteria for GH deficiency

• Short stature (Height lt;3 SD)

• Poor growth velocity (lt;25^th centile)

• Delayed bone age (but more than height age)

• Peak growth hormone levels lt; 7 ng/ml

• Low IGF-1 or IGFBP-3 levels[†††††††]

• Resumption of growth on GH therapy

*IGFBP: Insulin Like Growth Factor Binding Protein

midfacial hypoplasia, micropenis/hypoplastic labia and small hands/feet, (c) delayed bone age, but more than height age, (d) normal intelligence, and (e) delayed onset of puberty.

Mid-line defects, e.g. septum pellucidum, optic nerve hypoplasia and cleft palate may be seen, particularly in genetic forms. Delayed skeletal maturation permits linear growth to continue well beyond the usual age of completion and partly compensate for poor growth velocity in early life.

Diagnosis must be suspected on the basis of short stature with delayed bone age and needs to be confirmed by GH assays (Table 22.4).

Considering diurnal variations, random GH levels are unreliable. IGF-1 and IGF binding proteins-(IGFBP-3) are useful screening tests but affected by malnutrition and systemic disorders. Provocation or stimulation tests after administration of clonidine, insulin, L-dopa, arginine or glucagon etc. are necessary for confirmation. While no single test is foolproof, peak GH levels of lt;7 ng/ml on two different provocation tests are highly suggestive of GH deficiency.

GH levels are elevated or normal in qualitative/ receptor defects. Low IGF1 and IGFBP-3 levels with normal/high GH levels suggest GH-nonresponsiveness, e.g. Laron syndrome.

Relevant investigations with neuroimaging studies are also indicated to exclude secondary causes of hypopituitarism.

D/D of GH deficiency includes other causes of short stature (Ch 3.3) and MPHD (abnormal TSH and ACTH levels).

Management: Availability of recombinant growth hormone preparations has improved outcome of GH deficiency and treatment should be started as soon as possible as daily night injections (25-50 #956;g#8725;kg, subcutaneously). Higher doses may be used during puberty. Therapy should continue till the bone age exceeds 14 years in girls and 16 years in boys or growth velocity falls to lt;2 cm/year or desired height is achieved, whichever is earlier.

Maximum response is seen in first year of therapy, which may decrease in later years due to normalization of growth or development of antibodies. Pseudotumor cerebri is significant but rare complication of GH therapy. Rare side-effects include fluid retention, impaired glucose tolerance, worsening of scoliosis and slipped capital femoral epiphysis. Very rarely, there is increased risk of malignancy in some predisposed genetic conditions.

GH therapy is currently also recommended to enhance growth in many other non-GH deficiency short statures, e.g. chronic renal disease, intrauterine growth retardation, Turner syndrome, Noonan syndrome, Prader-Wili syndrome, and idiopathic short stature. Recombinant IGF1 is also available for treatment of IGHD due to hypothalamic causes and IGF1 deficiency.

22.2.3 HYPERPITUITARISM

22.2.4