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Adult growth hormone deficiency

Definition
AGHD is a condition characterized by the inadequate production of GH in adults.
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Pathophysiology
The pathophysiology of AGHD often involves dysfunction in the hypothalamus or pituitary gland, which are responsible for the production and release of GH. The most common causes are isolated idiopathic GH deficiency and hypothalamic-pituitary tumors and/or their treatment regimens.
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Epidemiology
The incidence of AGHD is estimated at around 2-3 per 100,000 person-years.
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Disease course
Clinically, AGHD manifests with a range of symptoms including neuropsychiatric-cognitive, cardiovascular, neuromuscular, metabolic, and skeletal abnormalities. Most of these can be reversed with GH therapy.
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Prognosis and risk of recurrence
AGHD is associated with increased mortality. The prognosis can be improved with early diagnosis and appropriate treatment.
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Key sources
The following summarized guidelines for the evaluation and management of adult growth hormone deficiency 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).
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Guidelines

1.Screening and diagnosis

Indications for testing
As per AACE 2019 guidelines:
Consider screening patients with traumatic brain injury, subarachnoid hemorrhage, ischemic stroke, and CNS infections for AGHD.
C
Obtain GH stimulation testing only after at least 12 months following traumatic brain injury 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
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  • Diagnosis

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 AGHD. 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
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  • Brain MRI

  • Lipid profile

  • Assessment of QoL

3.Medical management

Growth hormone therapy, indications, ES: do not use GH replacement solely to lower LDL-C to reduce cardiovascular risk in adult patients with GH deficiency.
D

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  • GH therapy (dosing and duration)

  • GH therapy (monitoring)

4.Specific circumstances

Pregnant patients: do not use recombinant human GH during pregnancy.
D

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  • Patients with diabetes mellitus

  • Patients with malignancy

5.Follow-up and surveillance

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
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  • Monitoring for comorbidities

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
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  • GH in sports