Definitions for the quality of the evidence (+OOO, ++OO, +++O, and ++++); the strength of the recommendation (1 or 2); and the difference between a "recommendation" and a "suggestion" are provided at the end of the "Major Recommendations" field.
Definition of Growth Hormone Deficiency (GHD) in Adults
The Task Force recommends that patients with childhood-onset GHD who are candidates for growth hormone (GH) therapy after achievement of adult height be retested for GHD as adults unless they have known mutations, embryopathic lesions causing multiple hormone deficits, or irreversible structural lesions/damage (1|++++).
The Task Force recommends that adult patients with structural hypothalamic/pituitary disease, surgery or irradiation in these areas, head trauma, or evidence of other pituitary hormone deficiencies be considered for evaluation for acquired GHD (1|++++).
Idiopathic GHD in adults is very rare, and stringent criteria are necessary to make this diagnosis. 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, the Task Force suggests the use of two tests before making this diagnosis. The presence of a low insulin-like growth factor I (IGF-I) also increases the likelihood that this diagnosis is correct (2|+OOO).
Diagnosis of GHD
The Task Force recommends that the insulin tolerance test (ITT) and the growth-hormone-releasing hormone (GHRH)-arginine test have sufficient sensitivity and specificity to establish the diagnosis of GHD. However, in those with clearly established recent (within 10 years) hypothalamic causes of suspected GHD, e.g. irradiation, testing with growth-hormone-releasing hormone-arginine may be misleading (1|++++).
The Task Force suggests that when GHRH is not available and performance of an insulin tolerance test (ITT) is either contraindicated or not practical in a given patient, the glucagon stimulation test can be used to diagnose GHD (2|++OO).
The Task Force recommends that because of the irreversible nature of the cause of the GHD in children with structural lesions with multiple hormone deficiencies and those with proven genetic causes, a low IGF-I level at least 1 month off GH therapy is sufficient documentation of persistent GHD without additional provocative testing (1|+++O).
The Task Force recommends that a normal IGF-I level does not exclude the diagnosis of GHD but makes provocative testing mandatory to making the diagnosis of GHD (1|++++). However, a low IGF-I level, in the absence of catabolic conditions such as poorly controlled diabetes, liver disease, and oral estrogen therapy, is strong evidence for significant GHD and may be useful in identifying patients who may benefit from treatment and therefore require GH stimulation testing (1|++OO).
The Task Force recommends that the presence of deficiencies in three or more pituitary axes strongly suggests the presence of GHD, and in this context, provocative testing is optional (1|+++O).
Consequences of GHD and Benefits of Treatment with GH
The Task Force recommends that GH therapy of GH-deficient adults offers significant clinical benefits in body composition and exercise capacity (1|+++O).
The Task Force suggests that GH therapy of GH-deficient adults offers significant clinical benefits in skeletal integrity (2|++OO).
The Task Force recommends after documentation of persistent GHD that GH therapy be continued after completion of adult height to obtain full skeletal/muscle maturation during the transition period (1|++OO).
The Task Force suggests that GH therapy of GH-deficient adults improves several cardiovascular surrogate outcomes, including endothelial function, inflammatory cardiovascular biomarkers, lipoprotein metabolism, carotid intima-media thickness (IMT), and aspects of myocardial function, but tends to increase insulin resistance (2|++OO).
The Task Force suggests that, although mortality is increased in patients with hypopituitarism and GHD has been implicated in this, GH has not yet been shown to improve mortality (2|+OOO).
The Task Force suggests that GH therapy of GH-deficient adults improves the quality of life of most patients (2|++OO).
Side Effects and Risks Associated with GH Therapy
The Task Force recommends that treatment is contraindicated in the presence of an active malignancy (1|+OOO).
The Task Force recommends that GH treatment in patients with diabetes mellitus may require adjustments in antidiabetic medications (1|+++O).
The Task Force suggests that thyroid and adrenal function be monitored during GH therapy of adults with GHD (2|++OO).
The Task Force recommends that GH-dosing regimens be individualized rather than weight-based and start with low doses and be titrated according to clinical response, side effects, and IGF-I levels (1|++++).
The Task Force recommends that GH dosing take gender, estrogen status, and age into consideration (1|++++).
The Task Force suggests that during GH treatment, patients 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-I levels, and other parameters of GH response (2|++OO).
Quality of Evidence
+OOO Denotes very low quality evidence
++OO Denotes low quality evidence
+++O Denotes moderate quality evidence
++++ Denotes high quality evidence
Strength of Recommendation
1 - Indicates a strong recommendation and is associated with the phrase "The Task Force recommends."
2 - Denotes a weak recommendation and is associated with the phrase "The Task Force suggests."