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Guideline Summary
Guideline Title
American Association of Clinical Endocrinologists medical guidelines for clinical practice for growth hormone use in growth hormone-deficient adults and transition patients – 2009 update.
Bibliographic Source(s)
Cook DM, Yuen KC, Biller BM, Kemp SF, Vance ML, American Association of Clinical Endocrinologists. American Association of Clinical Endocrinologists medical guidelines for clinical practice for growth hormone use in growth hormone-deficient adults and transition patients - 2009 update. Endocr Pract. 2009 Sep-Oct;15 Suppl 2:1-29. [191 references] PubMed External Web Site Policy
Guideline Status

This is the current release of the guideline.

This guideline updates a previous version: American Association of Clinical Endocrinologists (AACE). American Association of Clinical Endocrinologists medical guidelines for clinical practice for growth hormone use in adults and children--2003 update. Endocr Pract 2003 Jan-Feb;9(1):64-76. [30 references]

Scope

Disease/Condition(s)

Growth hormone deficiency (GHD)

Guideline Category
Diagnosis
Evaluation
Management
Treatment
Clinical Specialty
Endocrinology
Family Practice
Internal Medicine
Pediatrics
Sports Medicine
Intended Users
Advanced Practice Nurses
Nurses
Physician Assistants
Physicians
Guideline Objective(s)
  • To provide:
    • An overview of the important principles of growth hormone (GH) therapy as a context for interpretation of subsequent evidence-based recommendations
    • An evidence-based resource for physicians who prescribe GH
    • Specific recommendations regarding the selection of appropriate patients for GH therapy
  • To summarize the current knowledge regarding the diagnosis, initiation, and maintenance of GH replacement therapy in GH-deficient adults, to offer practical recommendations for clinicians, and to describe briefly the misuse of GH in sports and aging
Target Population

Patients with biochemically proven growth hormone deficiency (GHD) in transition years and in adulthood

Interventions and Practices Considered

Diagnosis/Evaluation

  1. Insulin tolerance test (ITT)
  2. Glucagon test
  3. Growth hormone releasing hormone (GHRH) + arginine (ARG) test with body mass index (BMI) cut points
  4. ARG test alone
  5. Serum insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) concentrations

Treatment/Management

  1. Growth hormone (GH) replacement
  2. Monitoring
    • During the titration period until the maintenance dose is achieved at 6 week intervals at first and then every 6 months: serum IGF-I, fasting glucose levels, hemoglobin A1c, body mass index (BMI), waist circumference, waist-to-hip ratio, serum-free thyroxine (T4), and assessment of the hypothalamic-pituitary-adrenal axis clinically or via early morning cortisol or cosyntropin stimulation test (in patients not on glucocorticoid replacement), testosterone and fasting lipid panel, and overall clinical status
    • Cardiovascular parameters: fasting lipid profile, systolic and diastolic blood pressure, heart rate, and electrocardiogram results, and echocardiogram and carotid echo-Doppler examinations if clinically indicated
    • Osteopenia/osteoporosis: measurement of bone mineral content and bone mineral density (BMD) in GH-deficient patients before starting GH therapy and then every 2 years
    • Periodic magnetic resonance imaging in patients with pituitary tumors
    • Quality of life questionnaires
Major Outcomes Considered
  • Sensitivity and specificity of diagnostic tests
  • Safety and efficacy of growth hormone (GH) therapy

Methodology

Methods Used to Collect/Select the Evidence
Hand-searches of Published Literature (Primary Sources)
Searches of Electronic Databases
Description of Methods Used to Collect/Select the Evidence

PubMed was searched. Published papers presented during international association meetings were also reviewed. The time frame of the literature searches was 1989 to 2009.

Inclusion/Exclusion Criteria

Inclusion: English, clinical articles or reviews

Search Terms

Growth hormone, adult, growth hormone deficiency, growth hormone transition, traumatic brain injury, body composition, mortality

Number of Source Documents

Not stated

Methods Used to Assess the Quality and Strength of the Evidence
Weighting According to a Rating Scheme (Scheme Given)
Rating Scheme for the Strength of the Evidence

Levels of Scientific Substantiation in Evidence-Based Medicine*

Level Description Comments
1 Prospective, randomized, controlled trials—large Data are derived from a substantial number of trials, with adequate statistical power involving a substantial number of outcome data subjects

Large meta-analyses using raw or pooled data or incorporating quality ratings

Well-controlled trial at one or more centers

Consistent pattern of findings in the population for which the recommendation is made (generalizable data)

Compelling nonexperimental, clinically obvious evidence (for example, use of insulin in diabetic ketoacidosis); "all-or-none" indication
2 Prospective controlled trials with or without randomization—limited body of outcome data Limited number of trials, small population sites in trials

Well-conducted single-arm prospective cohort study

Limited but well-conducted meta-analyses

Inconsistent findings or results not representative for the target population

Well-conducted case-controlled study
3 Other experimental outcome data and nonexperimental data Nonrandomized, controlled trials

Uncontrolled or poorly controlled trials

Any randomized clinical trial with 1 or more major or 3 or more minor methodologic flaws

Retrospective or observational data

Case reports or case series

Conflicting data with weight of evidence unable to support a final recommendation
4 Expert opinion Inadequate data for inclusion in level 1, 2, or 3; necessitates an expert panel's synthesis of the literature and a consensus

Experience-based

Theory-driven

*Levels 1, 2, and 3 represent a given level of scientific substantiation or proof. Level 4 represents unproven claims. It is the "best evidence" based on the individual ratings of clinical reports that contributes to a final grade recommendation (see the "Rating Scheme for the Strength of the Recommendations" field).

Methods Used to Analyze the Evidence
Review of Published Meta-Analyses
Systematic Review
Description of the Methods Used to Analyze the Evidence

Current guidelines for clinical practice guidelines (CPG) in clinical medicine emphasize an evidence-based approach rather than simply expert opinion. Although a purely evidence-based approach lacks applicability to all actual clinical scenarios, its incorporation in these CPG provides objectivity.

Transparency: Levels of Scientific Substantiation and Recommendation Grades

All clinical data that are incorporated in these CPG have been evaluated in terms of levels of scientific substantiation (evidence levels [EL]; see the "Rating Scheme for the Strength of the Evidence" field). This evidence rating system is based on the original American Association of Clinical Endocrinologists (AACE) protocol published in 2004, with one minor modification; in level 2 ([EL 2]), prospective studies may be randomized or nonrandomized to allow for well-designed cohort studies. In addition, when consensus statements are cited, even if based on a synthesis of evidence as in a published "evidence-based report," evidence level 4 [EL 4] has been assigned. Every clinical reference was assigned an evidence rating, which was then inserted in brackets at the end of the citation in both the text and the reference sections. The "best evidence" rating level (BEL) corresponds to the best conclusive evidence found. The BEL accompanies the recommendation grade in the Executive Summary, where transparency is paramount. In the Executive Summary, BEL 2 ratings have been designated as "randomized," "nonrandomized," or both for additional transparency.

Methods Used to Formulate the Recommendations
Expert Consensus
Description of Methods Used to Formulate the Recommendations

The American Association of Clinical Endocrinologists (AACE) Task Force for growth hormone (GH) use was assembled to produce these clinical practice guidelines (CPG) as mandated by the AACE Board of Directors. The Chairperson and Primary Writing teams were assigned based on their credentials as experts in the field of GH therapy. Each member has extensive clinical and/or research experience in GH therapy.

Final recommendation Grades (see the "Rating Scheme for the Strength of the Recommendations" field) incorporate evidence level (EL) ratings. Hence, recommendation grades are generally based on strong "best evidence" rating level (BEL) (Grade A; BEL 1), intermediate BEL (Grade B; BEL 2), weak BEL (Grade C; BEL 3), or subjective factors when there is no clinical evidence, inconclusive clinical evidence, or contradictory clinical evidence (Grade D; BEL 4). All recommendations resulted from a consensus among the AACE primary writers and were influenced by input from reviewers. Furthermore, the correctness of the recommendation Grades and EL was subject to review at several levels.

Most of the content is based on literature reviews. In areas of uncertainty, professional judgment was applied.

Rating Scheme for the Strength of the Recommendations

Grade-Recommendation Protocol Adopted by the American Association of Clinical Endocrinologists*

Grade Description Recommendation
A ≥1 conclusive level 1 publications demonstrating benefit >> risk Action recommended for indications reflected by the published reports

Action based on strong evidence

Action can be used with other conventional therapy or as first-line therapy
B No conclusive level 1 publication

≥1 conclusive level 2 publications demonstrating benefit >> risk
Action recommended for indications reflected by the published reports

If the patient refuses or fails to respond to conventional therapy; must monitor for adverse effects, if any

Action based on intermediate evidence

Can be recommended as second-line therapy
C No conclusive level 1 or 2 publication

≥1 conclusive level 3 publications demonstrating benefit >> risk

or

No risk at all and no benefit at all
Action recommended for indications reflected by the published reports

If the patient refuses or fails to respond to conventional therapy, provided there are no significant adverse effects; "No objection" to recommending their use

or

"No objection" to continuing their use

Action based on weak evidence
D No conclusive level 1, 2, or 3 publication demonstrating benefit >> risk

Conclusive level 1, 2, or 3 publications demonstrating risk >> benefit
Not recommended

Patient is advised to discontinue use

Action not based on any evidence

*The final recommendation grades were determined by the primary writers by consensus on the basis of (1) "best evidence" ratings (see the "Rating Scheme for the Strength of the Evidence" field) and (2) subjective factors.

Cost Analysis

A formal cost analysis was not performed and published cost analyses were not reviewed.

Method of Guideline Validation
Internal Peer Review
Description of Method of Guideline Validation

The initial draft was reviewed by the Chair of the Association of Clinical Endocrinologists (AACE) Clinical Practice Guideline (CPG) Development Subcommittee. Additional AACE members reviewed the document prior to further review by the AACE publication and executive committees. Finally, the Task Force Chairperson performed a complete review of the draft prior to publication.

Recommendations

Major Recommendations

The levels of evidence (1 to 4) and the recommendation grades (A to D) are defined at the end of the "Major Recommendations" field.

Executive Summary of Recommendations

The following recommendations (labeled "R") are evidence based (Grades A, B, and C) or are based on expert opinion because of a lack of conclusive clinical evidence (Grade D). The BEL, which corresponds to the best conclusive evidence found, accompanies the recommendation grade in this Executive Summary.

R1. Growth hormone deficiency (GHD) is a well-recognized clinical syndrome in adults that is associated with significant comorbidities if untreated (Grade A; BEL 1).

R2. Growth hormone (GH) should only be prescribed to patients with clinical features suggestive of adult GHD and biochemically proven evidence of adult GHD (Grade A; BEL 1).

R3. No data are available to suggest that GH has beneficial effects in treating aging and age-related conditions and the enhancement of sporting performance; therefore, the guideline developers do not recommend the prescription of GH to patients for any reason other than the well-defined approved uses of the drug (Grade A; BEL 1).

Recommendations and Evidence Base for the Care of Transition Patients with GHD

R4. Patients with childhood-onset GHD (COGHD) previously treated with GH replacement in childhood should be retested after final height is achieved and GH therapy discontinued for at least 1 month to ascertain their GH status before considering restarting GH therapy. Exceptions include those with known mutations, those with embryopathic/congenital defects, those with irreversible hypothalamic-pituitary structural lesions, and those with evidence of panhypopituitarism (at least 3 pituitary hormone deficiencies) and serum insulin-like growth factor-I (IGF-I) levels below the age- and sex-appropriate reference range off GH therapy (Grade A; BEL 1).

R5. For childhood GH treatment of conditions other than GHD, such as Turner's syndrome and idiopathic short stature, there is no proven benefit to continuing GH treatment in adulthood; hence, there is no indication to retest these patients when final height is achieved (Grade B; BEL 2).

R6. The preferred GH stimulation test to establish the diagnosis of adult GHD in patients with childhood-onset GHD is the insulin tolerance test (ITT). Acceptable alternative stimulation tests include the growth hormone releasing hormone (GHRH)+arginine (ARG) test, the glucagon test, and, rarely, the ARG test alone (Grade A; BEL 1).

R7. In patients with hypothalamic GHD, e.g., idiopathic isolated GHD of childhood, the GHRH+ARG test may be misleading; hence, an ITT or glucagon stimulation test should be used (Grade A; BEL 1).

R8. Similar cut points for GH stimulation testing in the transition patients coming off GH therapy are applicable as for adults (Grade B; BEL 2).

R9. On restarting GH therapy, the starting dose of GH in transition patients should be approximately 50% of the dose between the pediatric doses required for growth and the adult dose (Grade C; BEL 3).

Recommendations and Evidence Base for the Diagnosis of Adult GHD

R10. Patients with irreversible hypothalamic-pituitary structural lesions and those with evidence of panhypopituitarism (at least 3 pituitary hormone deficiencies) and serum IGF-I levels below the age- and sex-appropriate reference range when off GH therapy are deemed to be GH deficient and do not require further GH stimulation testing (Grade A; BEL 1).

R11. The ITT remains the gold-standard test for diagnosing adult GHD. Acceptable alternative stimulation tests to diagnose adult GHD include the GHRH+ARG test, the glucagon test, and, rarely, the ARG test alone (Grade A; BEL 1).

R12. Appropriate GH cut points based on body mass index (BMI) should be used with the GHRH+ARG test, because body mass index has a well-validated effect on GH responses to GHRH and ARG stimulation (Grade A; BEL 1).

R13. In patients where the ITT is not desirable and when recombinant GHRH is not available, the glucagon test is a reliable alternative, but not the levodopa and clonidine tests (Grade C; BEL 3).

R14. Patients with hypothalamic GHD may demonstrate false-negative responses to the GHRH+ARG test. If the peak GH level is above the cut point in such patients, then these patients should be retested, if possible, with the ITT, glucagon test, or, rarely, the ARG test alone (using appropriate cut points) (Grade A; BEL 1).

R15. Traumatic brain injury and aneurysmal subarachnoid hemorrhage are now recognized conditions causing GHD. However, in patients with these conditions, GHD may be transient; therefore, the task force recommends GH stimulation testing to be performed at least 12 months after the event (Grade B; BEL 2).

Recommendations and Evidence Base for GH-dosing Regimens in Adults with GHD

R16. Dosing of GH replacement therapy in all patients should be individualized (Grade A; BEL 1).

R17. As GH-deficient women with an intact hypothalamic-pituitary-gonadal axis and women on oral estrogens are generally more GH resistant than men, these patients will require higher initiation and maintenance doses of GH than their male counterparts to achieve an equivalent clinical and biochemical response (Grade B; BEL 2).

R18. There are insufficient data regarding its safety to make recommendations about the use of GH during pregnancy (Grade D).

R19. The sensitivity to side effects of exogenous GH is greater in elderly GH-deficient patients; therefore, the starting dose, size of dose adjustments, and target serum IGF-I levels should be reduced when GH replacement is considered (Grade B; BEL 2).

R20. For patients with compliance issues, clinicians may consider administering GH injections on alternate days or three times per week using the same total weekly dosage (Grade C; BEL 3).

R21. There is no evidence that one GH product is more advantageous over the other, apart from differences in pen devices, dose increments and decrements, and whether or not the product requires refrigeration; therefore, the task force does not recommend the use of one commercial GH preparation over another (Grade D; BEL 4).

R22. GH dosing regimens should be individualized independent of body weight, starting with a low dose, and then gradually increasing this to the minimal dose that normalizes serum IGF-I levels without causing unacceptable side effects (Grade A; BEL 1).

R23. Initiating and maintaining GH therapy using low GH dosages (0.1–0.2 mg/day) may be more appropriate in GH-deficient patients with concurrent diabetes, obesity, and in those with previous gestational and family history of diabetes so as not to aggravate blood glucose levels (Grade A; BEL 1).

R24. After initiating GH therapy, physicians should follow up on patients at 1- to 2-month intervals, and the GH dosage should be increased in steps of 0.1 to 0.2 mg/day based on clinical response, serum IGF-I levels, side effects, and individual considerations. Longer time intervals and smaller dose increments may be needed for older patients (Grade A; BEL 1).

Recommendations and Evidence Base for Monitoring the Efficacy of GH Replacement in Adults with GHD

R25. When maintenance doses are achieved, serum IGF-I, fasting glucose levels, hemoglobin A1c, body mass index, waist circumference, waist-to-hip ratio, serum-free thyroxine (T4), and assessment of the hypothalamic-pituitary-adrenal axis clinically or via early morning cortisol or cosyntropin stimulation test (in patients not on glucocorticoid replacement), testosterone and fasting lipid panel, and overall clinical status should be performed at 6- to 12-month intervals (Grade B; BEL 2).

R26. Adults with GHD have an increased risk of cardiovascular morbidity and mortality; therefore, cardiovascular parameters to consider monitoring during follow-up include fasting lipid profile, systolic and diastolic blood pressure, heart rate, and electrocardiogram results, while more expensive and complex examinations such as echocardiogram and carotid echo-Doppler examinations should be performed only if clinically indicated (Grade C; BEL 3).

R27. Adults with GHD have an increased risk of developing osteopenia and osteoporosis; therefore, the task force recommends measurement of bone mineral content and bone mineral density (BMD) in GH-deficient patients before starting GH therapy. If the initial bone dual-energy X-ray absorptiometry (DEXA) scan is abnormal, repeat bone DEXA scans are recommended at 2- to 3-year intervals to assess the need for additional bone-treatment modalities (Grade B; BEL 2).

R28. In GH-deficient adults on GH replacement therapy with pituitary microadenomas or postsurgery residual pituitary tumor, periodic magnetic resonance imaging should be undertaken to assess the size of the tumor (Grade C; BEL 3).

R29. Adults with GHD have diminished quality of life (QOL); therefore, the task force recommends a specific questionnaire be administered to adults with GHD before they begin GH treatment; subsequently, these adults should be evaluated annually to determine whether there is a change or sustained impact of GH therapy on quality of life (Grade C; BEL 3).

R30. No data are available regarding titrating the GH dose to the ideal target serum IGF-I level; therefore, the task force recommends targeting the serum IGF-I level to the middle of the age- and sex-appropriate reference range quoted by the laboratory utilized (50th percentile or 0 standard deviation score [SDS]). This decision should be based on the circumstances of each individual patient (Grade D; BEL 4).

R31. Interaction of GH with other pituitary hormone axes may influence thyroid, glucocorticoid, and testosterone requirements that may necessitate dose adjustments of these hormones (Grade C; BEL 3).

R32. No data are available regarding the optimal length of GH replacement; therefore, the task force recommends that if patients on GH replacement report significant quality of life benefits and objective improvements in biochemistry and body composition, then GH treatment should be continued indefinitely. However, if the patient reports neither subjective nor objective benefits, then it is reasonable to consider discontinuing GH treatment altogether (Grade D; BEL 4).

Recommendations and Evidence Base for Safety of GH Replacement in Adults with GHD

R33. If diabetes mellitus is diagnosed during GH therapy, or if GH therapy is considered for patients with concurrent diabetes mellitus, adjustments in anti-diabetic medications and treatment with low-dose GH therapy may be necessary. Alternatively, it is reasonable to withhold or discontinue GH therapy and to optimize the treatment of the diabetes before reconsidering later resumption of low-dose GH replacement in these patients (Grade D; BEL 4).

R34. Growth hormone treatment is contraindicated in patients with a previous history of malignancy or in the presence of active malignancy (Grade D; BEL 4).

R35. No data are available to suggest that GH therapy is associated with causing or accelerating recurrences of pituitary-region tumors; therefore, the task force recommends continued long-term surveillance of patients with pituitary-region tumors regardless of whether or not these patients are treated with GH therapy (Grade D; BEL 4).

Definitions:

Level of Scientific Substantiation in Evidence-Based Medicine*

Level Description Comments
1 Prospective, randomized, controlled trials—large Data are derived from a substantial number of trials, with adequate statistical power involving a substantial number of outcome data subjects

Large meta-analyses using raw or pooled data or incorporating quality ratings

Well-controlled trial at one or more centers

Consistent pattern of findings in the population for which the recommendation is made (generalizable data)

Compelling nonexperimental, clinically obvious evidence (for example, use of insulin in diabetic ketoacidosis); "all-or-none" indication
2 Prospective controlled trials with or without randomization—limited body of outcome data Limited number of trials, small population sites in trials

Well-conducted single-arm prospective cohort study

Limited but well-conducted meta-analyses

Inconsistent findings or results not representative for the target population

Well-conducted case-controlled study
3 Other experimental outcome data and nonexperimental data Nonrandomized, controlled trials

Uncontrolled or poorly controlled trials

Any randomized clinical trial with 1 or more major or 3 or more minor methodologic flaws

Retrospective or observational data

Case reports or case series

Conflicting data with weight of evidence unable to support a final recommendation
4 Expert opinion Inadequate data for inclusion in level 1, 2, or 3; necessitates an expert panel's synthesis of the literature and a consensus

Experience-based

Theory-driven

*Levels 1, 2, and 3 represent a given level of scientific substantiation or proof. Level 4 represents unproven claims. It is the "best evidence" based on the individual ratings of clinical reports that contributes to a final grade recommendation (see the "Grades of Recommendations" below).

Grade-Recommendation Protocol Adopted by the American Association of Clinical Endocrinologists*

Grade Description Recommendation
A ≥1 conclusive level 1 publications demonstrating benefit >> risk Action recommended for indications reflected by the published reports

Action based on strong evidence

Action can be used with other conventional therapy or as first-line therapy
B No conclusive level 1 publication

≥1 conclusive level 2 publications demonstrating benefit >> risk
Action recommended for indications reflected by the published reports

If the patient refuses or fails to respond to conventional therapy; must monitor for adverse effects, if any

Action based on intermediate evidence

Can be recommended as second-line therapy
C No conclusive level 1 or 2 publication

≥1 conclusive level 3 publications demonstrating benefit >> risk

or

No risk at all and no benefit at all
Action recommended for indications reflected by the published reports

If the patient refuses or fails to respond to conventional therapy, provided there are no significant adverse effects; "No objection" to recommending their use

or

"No objection" to continuing their use

Action based on weak evidence
D No conclusive level 1, 2, or 3 publication demonstrating benefit >> risk

Conclusive level 1, 2, or 3 publications demonstrating risk >> benefit
Not recommended

Patient is advised to discontinue use

Action not based on any evidence

*The final recommendation grades were determined by the primary writers by consensus on the basis of (1) "best evidence" ratings (see "Levels of Scientific Substantiation" table above) and (2) subjective factors.

Clinical Algorithm(s)

Clinical algorithms are provided in the original guideline document for the diagnosis of:

  • Transition patients with possible growth hormone deficiency (GHD)
  • Adults with possible GHD

Evidence Supporting the Recommendations

Type of Evidence Supporting the Recommendations

The type of supporting evidence is identified and graded for each recommendation (see "Major Recommendations").

Benefits/Harms of Implementing the Guideline Recommendations

Potential Benefits
  • Correction of the abnormalities associated with growth hormone deficiency (GHD) (i.e., cardiovascular complications, metabolic complications, osteopenia/osteoporosis, and quality of life)
  • Prevention of the development of abnormalities consequent to long-term GHD
Potential Harms
  • Dose-related side effects of growth hormone (GH) include arthralgia and peripheral edema.
  • Sensitivity to side effects of exogenous GH is greater in elderly GH-deficient patients.
  • Although there is no evidence to date that long-term GH replacement therapy increases the risk of diabetes mellitus in adults, data from a pediatric phase 4 surveillance database reported that GH treatment in children induced a very modest increase in the incidence of type 2 diabetes mellitus. However, the effect of GH on insulin sensitivity in adults may be different from that in children.
  • It is important that hypopituitary patients with high risk of developing diabetes mellitus (obese patients or patients with previous history of gestational diabetes) are given a very low dose of GH at initiation of therapy (i.e., 0.1 to 0.2 mg/day), and that the dose of GH then is slowly increased based on the clinical response, with less emphasis on achieving serum insulin-like growth factor I (IGF-I) levels in the middle of the age- and sex-appropriate reference range quoted by the laboratory utilized. In this way, the impairment in insulin sensitivity during GH replacement therapy can potentially be minimized, if not improved in these patients. Ongoing monitoring of glucose metabolism in the form of fasting blood glucose levels and hemoglobin A1c in patients receiving long-term GH replacement is highly recommended.
  • The growth promoting effects of GH and IGF-I provide a plausible theoretical basis by which GH treatment could increase cancer risk and promote tumor regrowth/recurrence, but overall, the published data so far do not fully suggest that GH therapy is associated with causing cancer or accelerating recurrences of pituitary-region tumors.
  • Interaction of GH with other pituitary hormone axes may influence thyroid, glucocorticoid, and testosterone requirements that may necessitate dose adjustments of these hormones.
  • Patients on low doses of glucocorticoid replacement may need their doses increased upon starting GH replacement, as GH therapy can increase the metabolism of glucocorticoids and thereby potentially induce adrenal crisis.
  • Patients started on testosterone-replacement therapy may require their GH doses to be decreased as the co-administration of testosterone can potentiate GH actions and exacerbate GH-induced adverse effects.

Contraindications

Contraindications
  • Growth hormone treatment is contraindicated in patients with a previous history of malignancy or in the presence of active malignancy.

    Note: The "waiting period" until neoplasia is considered inactive following treatment is unclear. It may vary depending on tumor type, i.e., shorter for leukemia and longer for breast cancer.

  • The insulin tolerance test (ITT) is not without inherent danger of causing a seizure or unconsciousness due to neuroglycopenia, and it is contraindicated in patients with known or who are at high risk for coronary artery disease or in patients with a history of seizures.
  • The glucagon test is well tolerated with the only contraindication being in patients who are malnourished or have not eaten for more than 48 hours.

Qualifying Statements

Qualifying Statements
  • These guidelines are a working document that reflects the state of the field at the time of publication. Because rapid changes in this area are expected, periodic revisions are inevitable. Medical professionals are encouraged to use this information in conjunction with their best clinical judgment. The presented recommendations may not be appropriate in all situations. Any decision by practitioners to apply these guidelines must be made in light of local resources and individual circumstances.
  • This report consists of recommendations for indications, diagnosis, and clinical use of growth hormone (GH) in patients with biochemically proven growth hormone deficiency (GHD) in transition years and in adulthood. However, it must be emphasized that physicians should use these guidelines concurrently with their best clinical judgment for each patient.

Implementation of the Guideline

Description of Implementation Strategy

An implementation strategy was not provided.

Implementation Tools
Clinical Algorithm
For information about availability, see the Availability of Companion Documents and Patient Resources fields below.

Institute of Medicine (IOM) National Healthcare Quality Report Categories

IOM Care Need
Getting Better
Living with Illness
IOM Domain
Effectiveness
Safety

Identifying Information and Availability

Bibliographic Source(s)
Cook DM, Yuen KC, Biller BM, Kemp SF, Vance ML, American Association of Clinical Endocrinologists. American Association of Clinical Endocrinologists medical guidelines for clinical practice for growth hormone use in growth hormone-deficient adults and transition patients - 2009 update. Endocr Pract. 2009 Sep-Oct;15 Suppl 2:1-29. [191 references] PubMed External Web Site Policy
Adaptation

Not applicable: The guideline was not adapted from another source.

Date Released
2003 (revised 2009)
Guideline Developer(s)
American Association of Clinical Endocrinologists - Medical Specialty Society
Source(s) of Funding

American Association of Clinical Endocrinologists (AACE)

Guideline Committee

American Association of Clinical Endocrinologists (AACE) Task Force for Growth Hormone Use

Composition of Group That Authored the Guideline

Co-Chairpersons and Primary Writers: David M. Cook, MD, FACE; Kevin C.J. Yuen, MD

Primary Writers: Beverly M.K. Biller, MD; Stephen F. Kemp, MD, PhD, FACE; Mary Lee Vance, MD

Financial Disclosures/Conflicts of Interest

Co-Chairpersons and Primary Writers:

Dr. David M. Cook reports that he has received partial grant support from Tercica, Inc., and Indevus Pharmaceuticals and serves on the Speaker's Bureau for Eli Lilly and Company and Tercica, Inc. and Novo Nordisk A/S.

Dr. Kevin C.J. Yuen reports that he has received principal investigator salary from Pfizer Inc.

Primary Writers:

Dr. Beverly M.K. Biller reports that she has received consulting/advisory honoraria and research grant support from Novo Nordisk A/S, Pfizer Inc. and Merck Serono S.A., and consulting honoraria from Genentech, Inc.

Dr. Stephen F. Kemp reports that he has received advisory committee honoraria and principle investigator grant support from Genentech, Inc. and Pfizer Inc., and principal investigator grant support from Eli Lilly and Company and Novo Nordisk A/S.

Dr. Mary Lee Vance reports that she has received research grant support from Genentech, Inc. and Novartis AG.

AACE Reviewers:

Dr. Pauline M. Camacho reports that she has received research grant support for her role as principal investigator from the Alliance for Better Bone Health (Procter & Gamble and sanofi-aventis U.S. LLC.), Eli Lilly and Company and Novartis AG.

Dr. Daniel S. Duick reports that he has received speaker honoraria from Abbott Laboratories and Genzyme Corporation, speaker honoraria and research grant support from GlaxoSmithKline and is a stockholder and scientific consultant for Medical Technologies, Inc. (MTI).

Dr. Alan J. Garber reports that he has received Advisory Board/consultant/speaker honoraria from GlaxoSmithKline and Novo Nordisk A/S, Advisory Board/speaker honoraria from Merck & Co., Inc. and Advisory Board/consultant honoraria from Roche Diagnostics, North America.

Dr. Jeffrey R. Garber reports that he does not have any relevant financial relationships with any commercial interests.

Dr. Hossein Gharib reports that he has received research grant support from Genzyme Corporation.

Dr. Jeffrey I. Mechanick reports that he does not have any relevant financial relationships with any commercial interests.

Dr. Steven M. Petak reports that he has received speaker honoraria from Eli Lilly and Company, GlaxoSmithKline, Procter & Gamble, Novartis AG, Roche Diagnostics, North America and sanofi-aventis U.S. LLC.

Guideline Status

This is the current release of the guideline.

This guideline updates a previous version: American Association of Clinical Endocrinologists (AACE). American Association of Clinical Endocrinologists medical guidelines for clinical practice for growth hormone use in adults and children--2003 update. Endocr Pract 2003 Jan-Feb;9(1):64-76. [30 references]

Guideline Availability

Electronic copies: Available in Portable Document Format (PDF) from the American Association of Clinical Endocrinologists (AACE) Web site External Web Site Policy.

Print copies: Available from the American Association of Clinical Endocrinologists (AACE), 1000 Riverside Avenue, Suite 205, Jacksonville, FL 32204.

Availability of Companion Documents

The following is available:

Print copies: Available from the American Association of Clinical Endocrinologists (AACE), 1000 Riverside Avenue, Suite 205, Jacksonville, FL 32204.

Patient Resources

None available

NGC Status

This summary was completed by ECRI on October 1, 1998. The information was verified by the guideline developer on December 15, 1998. This summary was updated by ECRI on May 21, 2003. The updated information was verified by the guideline developer on June 27, 2003. This NGC summary was updated by ECRI Institute on August 5, 2010. The updated information was verified by the guideline developer on August 31, 2010.

Copyright Statement

All rights reserved. No part of these materials may be reproduced or retransmitted in any manner without the prior written permission of American Association of Clinical Endocrinologists (AACE)/American College of Endocrinology (ACE).

Disclaimer

NGC Disclaimer

The National Guideline Clearinghouseâ„¢ (NGC) does not develop, produce, approve, or endorse the guidelines represented on this site.

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