Hyposomatotropism (Growth Hormone Deficiency) Guidelines

Updated: Jan 24, 2019
  • Author: Sunil Kumar Sinha, MD; Chief Editor: Robert P Hoffman, MD  more...
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Guidelines

Guidelines Summary

Guidelines Summary

Guidelines on growth disorders and their treatment by the Drug and Therapeutics Committee and Ethics Committee of the Pediatric Endocrine Society [75]

  • Use growth hormone (GH) to normalize adult height (AH) and avoid extreme shortness in children and adolescents with growth hormone deficiency (GHD).
  • Suggest against routine cardiac testing, dual x-ray absorptiometry (DXA) scanning, and measurement of lipid profiles in children and adolescents treated with GH.
  • Establish a diagnosis of GHD without GH provocative testing in patients possessing all of the following 3 conditions: auxological criteria, hypothalamic-pituitary defect (such as major congenital malformation [ectopic posterior pituitary and pituitary hypoplasia with abnormal stalk], tumor, or irradiation), and deficiency of at least one additional pituitary hormone.
  • GHD due to congenital hypopituitarism should be diagnosed without formal GH provocative testing in a newborn with hypoglycemia who does not attain a serum GH concentration above 5 µg/L and has deficiency of at least one additional pituitary hormone and/or the classical imaging triad (ectopic posterior pituitary and pituitary hypoplasia with abnormal stalk).
  • Recommend against reliance on GH provocative test results as the sole diagnostic criterion of GHD.
  • Suggest sex steroid priming prior to provocative GH testing in prepubertal boys older than 11 yr and in prepubertal girls older than 10 yr with AH prognosis within -2 SD of the reference population mean in order to prevent unnecessary GH treatment of children with constitutional delay of growth and puberty.
  • Recommend against the use of spontaneous GH secretion in the diagnosis of GHD in a clinical setting.
  • Recommend an  initial GH dose of 0.16-0.24 mg/kg/wk (22-35 µg/kg/day) with individualization of subsequent dosing.
  • Suggest measurement of serum insulin-like growth factor-I (IGF-I) levels as a tool to monitor adherence and IGF-I production in response to GH dose changes. Suggest that the GH dose be lowered if serum IGF-I levels rise above the laboratory-defined normal range for the age of pubertal stage of the patient.
  • During puberty, recommend against the routine increase in GH dose to 0.7 mg/kg/wk in every child with GHD.
  • Recommend that GH treatment at pediatric doses not continue beyond attainment of a growth velocity below 2-2.5 cm/yr. The decision to discontinue pediatric dosing prior to attainment of this growth velocity should be individualized.
  • Recommend that prospective recipients of GH treatment receive anticipatory guidance regarding the potential adverse effects of intracranial hypertension, slipped capital femoral epiphysis (SCFE), and scoliosis progression.
  • Recommend monitoring of GH recipients for potential development of intracranial hypertension, SCFE, and scoliosis progression by soliciting pertinent history and performing a physical examination at every follow-up clinic visit; further testing should be pursued if indicated.
  • Recommend re-assessment of both the adrenal and thyroid axes after initiation of GH therapy in patients whose cause of GHD is associated with possible multiple pituitary hormone deficiencies (MPHD).
  • For GH initiation after completion of tumor therapy with no evidence of ongoing tumor, a standard waiting period of 12 mo to establish “successful therapy” of the primary lesion is reasonable, but can also be altered depending on individual patient circumstances.
  • Recommend that patients with multiple (≥3) pituitary hormone deficiencies regardless of etiology, or GHD with a documented causal genetic mutation or specific pituitary/hypothalamic structural defect except ectopic posterior pituitary, be diagnosed with persistent GHD.
  • Recommend re-evaluation of the somatotropic axis for persistent GHD in persons with GHD and deficiency of only one additional pituitary hormone, idiopathic isolated GHD (IGHD), IGHD with or without small pituitary/ectopic posterior pituitary, and after irradiation.
  • Suggest that measurement of the serum IGF-I concentration be the initial test of the somatotropic axis if re-evaluation of the somatotropic axis is clinically indicated.
  • Recommend GH provocative testing to evaluate the function of the somatotropic axis in the transition period if indicated by a low IGF-I level.
  • Suggest that GH treatment be offered to individuals with persistent GHD in the transition period. There is evidence of benefit; however, the specifics of the patient population that benefits, the optimal time to re-initiate treatment, and the optimal dose are not clear.
  • Because there is overlap in response between dosing groups, suggest initiating GH at a dose of 0.24 mg/kg/wk, with some patients requiring up to 0.47 mg/kg/wk.
  • Recommend the use of IGF-I therapy to increase height in patients with severe primary IGF-I deficiency (PIGFD).
  • Recommend a trial of GH therapy before initiating IGF-I for patients with unexplained IGF-I deficiency. Patients with hormone signaling defects known to be unresponsive to GH treatment can start directly on IGF-I replacement; these include patients with very low or undetectable levels of GH-binding protein (GHBP) and/or proven GH receptor (GHR) gene mutations known to be associated with Laron syndrome/GH insensitivity syndrome (GHIS), GH-neutralizing antibodies,  STAT5b gene mutations, and  IGF1 gene deletion or mutation.
  • Suggest an IGF-I dose of 80-120 µg/kg BID. Similar short-term outcomes were seen with 80 and 120 µg, but published studies had limitations, and there is no strong evidence supporting superiority of one dose over the other.

 

The Endocrine Society clinical practice guideline on the evaluation and treatment of adult growth hormone (GH) deficiency includes the following recommendations. [76]

  • Patients with childhood-onset GH deficiency who are candidates for GH therapy after adult height achievement should be retested for GH deficiency unless they have known mutations, embryopathic lesions causing multiple hormone deficits, or irreversible structural lesions/damage.
  • Adult patients with structural hypothalamic/pituitary disease, surgery or irradiation in these areas, head trauma, or evidence of other pituitary hormone deficiencies should be considered for evaluation for acquired GH deficiency.
  • Because idiopathic GH deficiency in adults is very rare, stringent criteria are necessary to make this diagnosis, and because in the absence of suggestive clinical circumstances there is a significant false-positive error rate in the response to a single GH stimulation test, it is suggested that two tests be used before making this diagnosis. The presence of a low insulin-like growth factor-1 (IGF-1) also increases the likelihood that this diagnosis is correct.
  • The insulin tolerance test (ITT) and the GH releasing hormone (GHRH)-arginine test have sufficient sensitivity and specificity to establish the diagnosis of GH deficiency, but in those with clearly established, recent (within 10 yr) hypothalamic causes of suspected GH deficiency (eg, irradiation), testing with GHRH-arginine may be misleading.
  • When GHRH is not available and performance of an ITT is either contraindicated or not practical in a given patient, the glucagon stimulation test can be used to diagnose GH deficiency.
  • Because of the irreversible nature of the cause of GH deficiency in children with structural lesions with multiple hormone deficiencies and those with proven genetic causes, a low IGF-1 level at least 1 month off GH therapy is sufficient documentation of persistent GH deficiency without additional provocative testing.
  • A normal IGF-1 level does not exclude the diagnosis of GHD but makes provocative testing mandatory to make the diagnosis of GH deficiency. However, a low IGF-1 level, in the absence of catabolic conditions such as poorly controlled diabetes, liver disease, and oral estrogen therapy, is strong evidence for significant GH deficiency and may be useful in identifying patients who may benefit from treatment and therefore require GH stimulation testing.
  • The presence of deficiencies in three or more pituitary axes strongly suggests the presence of GH deficiency, and in this context provocative testing is optional.
  • GH dosing regimens should be individualized rather than weight-based and started with low doses and be titrated according to clinical response, side effects, and IGF-1 levels.
  • During GH treatment, patients should be monitored at 1- to 2-month intervals during dose titration and semiannually thereafter with a clinical assessment and an evaluation for adverse effects, IGF-1 levels, and other parameters of GH response.