Growth Hormone Deficiency in Adults Workup

Updated: Jun 17, 2022
  • Author: Mohsen S Eledrisi, MD, FACP, FACE; Chief Editor: George T Griffing, MD  more...
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Workup

Approach Considerations

Evaluation for growth hormone (GH) deficiency is recommended in patients with hypothalamic-pituitary disease, surgery or radiation therapy in these areas, head trauma, or the presence of other pituitary hormone deficiencies. [15] 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—unless they have known mutations, embryopathic lesions causing multiple hormone deficits, or irreversible structural lesions/damage. [15, 18] 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. [15]

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.

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Laboratory Studies

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

GH deficiency is suspected 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. The use of stimulation tests is generally required to confirm the diagnosis of GH deficiency. [15] The presence of deficiency of three or more pituitary hormones in the context of organic hypothalamic-pituitary disease strongly suggests GH deficiency; in this setting, stimulation testing is not needed [12, 19] or is optional. [15]

The insulin tolerance test (ITT), the combination of GH-releasing hormone (GHRH) and arginine (GHRH-arginine test), glucagon stimulation test, or macimorelin test can be used as stimulation tests for the diagnosis of GH deficiency. [9, 12, 15, 20]

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

ITT

In the ITT, regular 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 to 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 the peak GH level is ≤5.1 mcg/L. [12]

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.

The ITT should be avoided in patients with cardiovascular disease, cerebrovascular disease, or seizure disorders. Because of these safety concerns and laboriousness, the ITT is less frequently used.

GHRH-arginine test

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.

In patients with GH deficiency of hypothalamic origin (eg radiation therapy), GHRH can stimulate the pituitary and, therefore, the GHRH-arginine test can yield falsely normal results. [21] In such cases, using alternative stimulation tests is recommended.

Because body mass index (BMI) can influence the GH response, the following criteria have been used to establish the diagnosis of GH deficiency when using the GHRH-arginine test [12, 15, 18] :

  • BMI of < 25 kg/m 2: Peak GH level ≤11.0 mcg/L
  • BMI of 25 to 29.9 kg/m 2: Peak GH level ≤8.0 mcg/L
  • BMI of ≥30 kg/m 2: Peak GH level ≤4.0 mcg/L

Glucagon stimulation test

If GHRH is not available, the GHRH-arginine test is expected to give inaccurate results, or performing the ITT is either contraindicated or not practical, the glucagon stimulation test [9, 12, 15, 18, 20] or the macimorelin test [18, 22, 23, 24] can be used to diagnose GH deficiency. 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 increasingly used. [9, 15]

The glucagon stimulation test has become the most commonly used diagnostic test for the diagnosis of GH deficiency because of its availability, reproducibility, safety, and lack of influence by sex and hypothalamic cause of GH deficiency. The test is carried out by administering intramuscular glucagon at a dose of 1 mg (1.5 mg for patients who weigh >90 kg); serum GH levels are measured just before the injection and every 30 minutes for 4 hours.

The following criteria are recommended by the American Association of Clinical Endocrinologists to establish a diagnosis of GH deficiency using the glucagon stimulation test [18, 25] :

  • BMI of < 25 kg/m 2: Peak serum GH level ≤3.0 mcg/L
  • BMI of 25 to 29.9 kg/m 2: Peak serum GH level ≤3.0 mcg/L
  • BMI of ≥30 kg/m 2: Peak serum GH level ≤1.0 mcg/L

Macimorelin test

In 2017, the US Food and Drug Administration (FDA) approved macimorelin, an oral ghrelin agonist that stimulates GH, for the diagnosis of adults with GH deficiency. [22] Approval was based on comparative test results between macimorelin and ITT in adult patients with GH deficiency and healthy control subjects.

The macimorelin test has an accuracy comparable to that of the ITT. [26] The test is performed by administering macimorelin as an oral solution at a dose of 0.5 mg/kg body weight. Serum GH levels are measured just before and at 30, 45, 60, and 90 minutes after the administration of macimorelin. GH deficiency is diagnosed if the peak GH level is ≤2.8 mcg/L. [18]

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