Growth Hormone Deficiency in Adults Workup

Updated: Jun 26, 2018
  • Author: Mohsen S Eledrisi, MD, FACP, FACE; Chief Editor: George T Griffing, MD  more...
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Approach Considerations

Evaluation for growth hormone (GH) deficiency is recommended in patients with hypothalamic-pituitary disease, surgery or irradiation in these areas, head trauma, or the presence of other pituitary hormone deficiencies. [7]  For patients with childhood-onset GH deficiency, retesting for GH deficiency is indicated after achievement of adult height to determine the need to continue therapy. In these patients, discontinuing GH therapy for at least 1 month is recommended before retesting. Patients with congenital or irreversible hypothalamic-pituitary structural abnormalities do not require retesting for GH deficiency. [7]

Magnetic resonance imaging (MRI) of the hypothalamic-pituitary region may be used to define the anatomy of this region for the presence of tumors or structural abnormalities.

Dual-energy x-ray absorptiometry (DXA) may be used to assess bone mineral density.


Laboratory Studies

Random serum growth hormone (GH) levels are of little value because of the pulsatile nature of GH secretion.

GH deficiency is diagnosed by a low level of serum insulin-like growth factor-1 (IGF-1), but a normal IGF-1 level does not exclude the possibility of GH deficiency and requires the use of stimulation tests. [7] The presence of deficiency of three or more pituitary axes makes GH deficiency more likely; in this setting, provocative testing is optional. [7]

Either the insulin tolerance test (ITT) or the combination of GH-releasing hormone (GHRH) and arginine (GHRH-arginine test) can be used as stimulation tests for the diagnosis of GH deficiency. [5, 7, 10]

If GHRH is not available and performance of an ITT is either contraindicated or not practical in a given patient, the glucagon stimulation test can be used. [5, 7, 10]  Because GHRH is not widely available (the only US commercial formulation was discontinued in 2008) and because of safety concerns over the use of ITT, the glucagon stimulation test is being increasingly used. [5, 7]

In December 2017, the FDA approved macimorelin, an oral ghrelin agonist, for the diagnosis of adults with GH deficiency (AGHD). [11] Approval was based on comparative test results between macimorelin and ITT results in adult patients with different pretest probability of GH deficiency and healthy control subjects. Agreement between ITT and macimorelin was 89% for a positive diagnosis and 100% for a negative diagnosis in patients with a high likelihood of AGHD. The maximally stimulated serum GH level below 2.8 ng/mL (ie, at the 30-, 45-, 60- and 90-minute time points) following macimorelin administration confirms the presence of adult GH deficiency. [12]  A GH cut-off of 5.1 ng/mL for the ITT and macimorelin test appears to have a 92% sensitivity and 96% specificity for both tests. [13]

Patients should have adequate replacement of other deficient pituitary hormones before being tested for GH secretion. All stimulation tests are done after an overnight fast and involve measuring serum GH levels.

In the ITT, insulin is administered intravenously at a dose of 0.1 unit/kg (time 0) to produce a lowering in plasma glucose level to less than 40 mg/dL (2.2 mmol/L). Glucose levels are monitored by capillary samples every 15 minutes and until symptoms of hypoglycemia develop. A repeated dose of insulin can be administered if hypoglycemia does not develop by 30-60 minutes. Serum glucose and serum GH levels are measured at 0, 15, 30, 60, 90, and 120 minutes after administering insulin. GH deficiency is diagnosed if peak GH level is less than 5.1 mcg/L. [5] Patients usually develop symptoms of hypoglycemia, including sweating, palpitations, and, rarely, convulsions and loss of consciousness. Therefore, the test should be undertaken by an experienced staff under the direct supervision of a physician. It should be avoided in patients with cardiovascular disease, cerebrovascular disease, or seizure disorders.

In the glucagon stimulation test, glucagon is administered intramuscularly at a dose of 1 mg (1.5 mg for patients who weigh >90 kg); GH levels are measured just before the injection and every 30 minutes for 4 hours. The American Association of Clinical Endocrinologists initially recommended to use a peak GH level of less than 3.1 mcg/ L to diagnose GH deficiency [14] ; this was later proposed to be revised to a cut-point of less than 1 mcg/L, [15] whereas the Endocrine Society recommends a cut-point of between 2.5 and 3 mcg/L. [7]

In the GHRH-arginine test, GHRH is administered intravenously at a dose of 1 mcg/kg body weight (time 0), followed by an intravenous infusion of 0.5 g/kg body weight (maximum 30 g) of arginine over 30 minutes. Serum GH is measured at -30, 0, 30, 60, 90, and 120 minutes.

Because body mass index (BMI) can influence the GH response, the following criteria are used to establish the diagnosis of GH deficiency when using the GHRH-arginine test [7] :

  • Peak GH level < 11.1 mcg/L in patients with BMI < 25 kg/m 2
  • Peak GH level < 8.1 mcg/L in patients with BMI of 25 to < 30 kg/m 2
  • Peak GH level < 4.1 mcg/L in patients with BMI of ≥30 kg/m 2

In patients with GH deficiency of hypothalamic origin (eg, irradiation), GHRH can stimulate the pituitary and therefore yields falsely normal results. [7]  In such cases, using alternative stimulation tests is recommended.