Consensus Guidelines for Adult Growth Hormone Deficiency 2007

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Ten years after the Growth Hormone (GH) Research Society drafted its “Consensus Guidelines for the Diagnosis and Treatment of Adults with Growth Hormone Deficiency (GHD)”, a second international workshop was convened (Sydney, Australia) with 30 delegates to create an updated set of guidelines in 2007. Diagnosis of adult GHD was expanded in patient scope since the first document. Testing should be reserved for patients with evidence of hypothalamic-pituitary disease and with intention to treat. This includes patients with signs and symptoms of hypothalamic-pituitary disease (endocrine, structural, or genetic causes), patients who had received cranial irradiation or tumor treatment, and a new group, patients who had sustained traumatic brain injury or subarachnoid hemorrhage. Of note, the degree of pituitary dysfunction does not correlate with the severity of brain injury, and GH testing should be deferred for at least 12 months after injury due to the rate of endogenous GH axis recovery.

Another new patient group discussed is the GHD patient during the transition period, that newly recognized life stage between cessation of statural growth (ie, epiphyseal closure) and acquisition of complete somatic maturation (ie, full development of lean body mass and bone mineralization). Apart from patients with known genetic causes of GHD/hypopituitarism and patients with multiple pituitary hormone deficiencies (who should continue GH treatment without the need for further testing), patients with childhood onset GHD should undergo reevaluation of their GH function after at least one month off GH treatment for assessment of potential treatment during the transition period. A second reevaluation may be considered at the end of the transition period (about age 25) for those with isolated idiopathic GHD or discordant testing (low insulin-like growth factor [IGF]-I but normal stimulated GH peak) at the start of transition. Adult GH treatment is not indicated for patients with non-GHD pediatric indications, such as those born small for gestational age or Turner syndrome.

Adult GH treatment aims to “…correct the metabolic, functional, and psychological abnormalities associated with adult GHD.” Dosing should be based on age and gender, not body weight, and escalated to response in a gradual and individualized fashion. Recommended monitoring of response includes:

Anthropometry (including weight, height, BMI and waist circumference): at least yearly
Quantified body composition and bone mineral density (DEXA): at baseline and every 2 years thereafter
Serum marker for GH dose titration (serum IGF-I): at least yearly and no sooner than 6 weeks after a dose change
Cardiovascular risk factors (blood pressure, fat mass, cholesterol panel): yearly, with similar goals as the general population
Fasting serum glucose: yearly
Quality of life (careful history, not disease-specific quality of life questionnaires)

Although GH treatment is indicated for adult patients with proven GHD, GH supplementation is not recommended for the physiologic age-related decline in GH/IGF secretion. Lower doses are called for in the elderly, to reduce the incidence of side effects and maintain age-dependent normal levels of IGF-I.

Ho KKY on behalf of the 2007 GH Deficiency Consensus Workshop Participants. Consensus guidelines for the diagnosis and treatment of adults with GH deficiency II: a statement of the GH Research Society in association with the European Society for Pediatric Endocrinology, Lawson Wilkins Society, European Society of Endocrinology, Japan Endocrine Society, and Endocrine Society of Australia. Eur J Endocrinol. 2007;157:695-700.

First Editor’s Comment

The reader is encouraged to go through the entire original document, as the guidelines were too extensive to summarize here; this abstract highlights the newer recommendations. Also covered are the dosing recommendations, interactions with other hormone deficiencies, and treatment safety issues.
More than the advances, what struck me were the persistent unknowns of the field. Ten years after the first set of guidelines, we remain prey to suboptimal diagnostic testing. The lack of standardization of the GH and IGF-I assays was lamented in the consensus statement, as was the need for better age- and gender-related normative data. There was an entire section devoted to the various GH stimulation tests, their respective indications and limitations, and the multiple cut-off levels which also need better substantiating normative data. It is not surprising that the authors concluded, “…partial GHD is not adequately defined.” Unless we can accurately distinguish normal from abnormal hormone levels, how can clinical care and research in the growth field advance effectively?

Adda Grimberg, MD

Second Editor’s Comment

The reader is encouraged to review the article in its entirety. However it may be worth noting a few more pertinent points in addition to those elaborated above. The consensus of experts stated that one stimulation test was sufficient for the diagnosis of adult GHD. They endorsed the use of an insulin or a glucagon tolerance test, and did not recommend clonidine, L-DOPA or arginine. GH releasing hormone (GHRH) + arginine or GHRH + GH-releasing peptide (GHRP) have also been validated, though GHD of hypothalamic origin may be missed, particularly in patients treated with cranial irradiation, then insulin or glucagon tolerance test may be necessary. The peak GH level for diagnosis was <3 mcg/L after insulin, higher levels may be acceptable following GHRH in individuals with a BMI of <25 kg/m2. Measurements of circulating IGF-I levels constitute a good screen, though a normal level may not rule out GHD. Sex steroid, glucocorticosteroid and thyroid replacement should be optimized before testing or initiating GH treatment. The efficacy of treatment should be monitored and objective parameters determined, ie, body composition. Where available, DEXA should be utilized to quantitate body composition changes. IGF-I levels are indicted for titration of the GH dosages. Disease-specific quality of life questionnaires that assess the problems need to be validated.

Fima Lifshitz, MD

Reference - (linked to )

Genetics of height variation. Growth Genet Horm. 2007;23:2.

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Last Updated: 04/30/2008