Guideline sources The following summarized guidelines for the evaluation and management of adult growth hormone deficiency (AGHD) are prepared by our editorial team based on guidelines from the Endocrine Society (ES 2020; 2011) and the American College of Endocrinology (ACE/AACE 2019). 1 2 3 Guidelines 1. Screening and diagnosis Indications for testing: As per AACE 2019 guidelines: Consider screening patients with TBI, subarachnoid hemorrhage, ischemic stroke, and CNS infections for adult GH deficiency. C Obtain GH stimulation testing only after at least 12 months following TBI or subarachnoid hemorrhage, as GH deficiency in these conditions may be transient. C Obtain GH-stimulation tests only based on the appropriate clinical context of each individual patient with a history suggestive of a reasonable clinical suspicion of GH deficiency and with the intent to initiate recombinant human GH replacement if the diagnosis is confirmed. B As per ES 2011 guidelines: https://web.pathway.md/diseases/recfUiFwgJnBHDweg 1/5 6/23/23, 2:11 AM Adult growth hormone deficiency Pathway Consider testing for acquired GH deficiency in adult patients with structural hypothalamic/pituitary disease, surgery or irradiation in these areas, head trauma, or evidence of other pituitary hormone deficiencies. B Retest for GH deficiency in patients with childhood-onset GH deficiency being candidates for GH therapy after adult height achievement unless they have known mutations, embryopathic lesions causing multiple hormone deficits or irreversible structural lesions/damage. A Diagnosis: As per AACE 2019 guidelines, recognize that adults can be diagnosed with GH deficiency in childhood (childhood-onset GH deficiency) and adulthood (adult-onset GH deficiency). B Show 4 more As per ES 2011 guidelines, recognize that idiopathic GH deficiency in adults is very rare and stringent criteria are necessary to make this diagnosis. Consider obtaining two tests before making 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. Recognize that the presence of a low IGF-1 also increases the likelihood that this diagnosis is correct. B 2. Diagnostic investigations Provocative testing: As per AACE 2019 guidelines, do not obtain random serum GH and IGF-1 levels alone for the diagnosis of adult GH deficiency. Obtain GH stimulation tests to confirm the diagnosis with the exception of certain subpopulations such as patients with: organic hypothalamic-pituitary disease (such as suprasellar mass with previous surgery and cranial irradiation) having multiple ( 3) pituitary hormone deficiencies and low serum IGF-1 levels (< - 2.0 SDS) genetic defects affecting the hypothalamic-pituitary axes hypothalamic-pituitary structural brain defects. D Show 6 more As per ES 2011 guidelines, obtain insulin tolerance test and GH-releasing hormone-arginine test to establish the diagnosis of GH deficiency. Recognize that GH-releasing hormone-arginine testing may be misleading in patients with clearly established, recent (within 10 years) hypothalamic causes of suspected GH deficiency such as irradiation. A Show 5 more Brain magnetic resonance imaging: obtain baseline MRI in patients with any post-surgical tumor remnant in the hypothalamic-pituitary region before initiating recombinant human GH therapy, and obtain periodic MRI during therapy. B Lipid profile: Assess lipid profile at diagnosis to screen for dyslipidemia in adult patients with GH deficiency. B https://web.pathway.md/diseases/recfUiFwgJnBHDweg 2/5 6/23/23, 2:11 AM Adult growth hormone deficiency Pathway Consider obtaining lipid profile and initiating treatment for dyslipidemia and other cardiovascular risk factors in adult patients with GH deficiency associated with hypopituitarism. C Assessment of quality of life: consider assessing baseline quality of life using specific Quality of Life in Adult GH Deficiency Assessment questionnaires before initiating recombinant human GH treatment and at 12-month intervals to determine whether there is a change or sustained impact of recombinant human GH therapy on quality of life. C 3. Medical management Growth hormone therapy, indications: As per ES 2020 guidelines, do not use GH replacement solely to lower LDL-C to reduce cardiovascular risk in adult patients with GH deficiency. D As per ES 2011 guidelines, initiate GH therapy in patients with adult GH deficiency to provide significant clinical benefits in body composition, exercise capacity B and skeletal integrity. B Show 3 more Growth hormone therapy, dosing and duration: As per AACE/ACE 2019 guidelines, insufficient evidence to recommend one commercial recombinant human GH product over another. I Show 8 more As per ES 2011 guidelines, individualize GH dosing regimens taking into account gender, estrogen status and age, starting with low doses and titrating according to clinical response, side effects and IGF-1 levels. A Growth hormone therapy, monitoring: As per AACE/ACE 2019 guidelines, recognize that treatment-related side effects are mainly related to fluid retention effects and are typically seen during initiation and dose escalation of recombinant human GH and generally respond to dose reductions or cessation of therapy. Initiate lower doses of recombinant human GH in patients with obesity and in older patients generally being more susceptible to the side effects of recombinant human GH replacement. A Show 5 more As per ES 2011 guidelines: Consider monitoring thyroid and adrenal function during GH therapy. C Monitor patients at 1- to 2-month intervals during dose titration and semi-annually thereafter with a clinical assessment and an evaluation for adverse effects, IGF-1 levels and other parameters of GH response. B 4. Specific circumstances Pregnant patients: do not use recombinant human GH during pregnancy. D Patients with diabetes mellitus: https://web.pathway.md/diseases/recfUiFwgJnBHDweg 3/5 6/23/23, 2:11 AM Adult growth hormone deficiency Pathway As per AACE 2019 guidelines: Consider using low doses of recombinant human GH and adding and/or adjusting antidiabetic medications in patients developing diabetes mellitus during recombinant human GH therapy or if recombinant human GH therapy is considered in patients with concurrent diabetes mellitus. B Consider initiating or increasing the doses of antidiabetic therapy or discontinuing recombinant human GH therapy and optimizing treatment of diabetes mellitus first before considering resuming recombinant human GH therapy in patients experiencing worsening of preexisting diabetes mellitus while on recombinant human GH therapy. B As per ES 2011 guidelines, consider adjusting antidiabetic medications in patients with diabetes mellitus and adult GH deficiency receiving GH therapy. B Patients with malignancy: do not use recombinant human GH therapy in patients with a history of active malignancy (other than basal-cell or squamous-cell skin cancers) and active proliferative or severe nonproliferative diabetic retinopathy. D Show 3 more 5. Follow-up and surveillance Pediactric transition to adult care: retest for GH deficiency with GH stimulation tests after at least 1 month following discontinuation of recombinant human GH therapy in transition patients with idiopathic isolated GH deficiency with low-normal (between 0 to -2 SDS) or low (< -2 SDS) serum IGF-1 levels, after longitudinal growth is completed. B Show 10 more Monitoring for comorbidities: Monitor cardiovascular parameters, including fasting lipids, systolic and diastolic BP, and HR, at 6- to 12-month intervals in patients with adult GH deficiency. Consider obtaining more detailed examinations, such as ECG, echocardiogram, and carotid echo-Doppler, if clinically indicated. B Consider measuring bone mineral content and bone mineral density in patients with GH deficiency before starting recombinant human GH therapy. Obtain repeated bone DEXA at 2- to 3-year intervals to assess the need for additional bone-treatment modalities if the initial bone DEXA is abnormal. C 6. Quality improvement Laboratory quality control: adopt laboratory standards set by the National Institute for Biological Standards and Control, including reporting serum GH levels in mass units without reliance on conversion factors. B Show 6 more Growth hormone in sports: https://web.pathway.md/diseases/recfUiFwgJnBHDweg 4/5 6/23/23, 2:11 AM Adult growth hormone deficiency Pathway Recognize that detection of recombinant human GH abuse is difficult because GH is a naturally occurring substance with a short half-life after SC and IV injection, is released in a pulsatile fashion and the levels increase after exercise. Do not obtain drug testing with urine sampling as it is not accurate and reliable, whereas repeated blood sampling over 24 hours is neither practical nor feasible in the sports setting. A Do not prescribe recombinant human GH for sports or anti-aging purposes under any circumstances, recognizing that the off-label distribution or marketing of GH for the enhancement of athletic performance or to treat aging or aging-related conditions is illegal in the United States. D References 1. Mark E Molitch, David R Clemmons, Saul Malozowski et al. Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011 Jun;96 6 1587 609. Open 2. Kevin C J Yuen, Beverly M K Biller, Sally Radovick et al. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY GUIDELINES FOR MANAGEMENT OF GROWTH HORMONE DEFICIENCY IN ADULTS AND PATIENTS TRANSITIONING FROM PEDIATRIC TO ADULT CARE. Endocr Pract. 2019 Nov;25 11 1191 1232. Open 3. Connie B Newman, Michael J Blaha, Jeffrey B Boord et al. Lipid Management in Patients with Endocrine Disorders: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2020 Dec 1;105 12):dgaa674. Open 4. Sklar CA, Antal Z, Chemaitilly W et al. Hypothalamic-Pituitary and Growth Disorders in Survivors of Childhood Cancer: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018 Aug 1;103 8 2761 2784. Open https://web.pathway.md/diseases/recfUiFwgJnBHDweg 5/5