Growth Hormone Deficiency Workup

  • Author: Mohsen S Eledrisi, MD, FACP, FACE; Chief Editor: George T Griffing, MD   more...
 
Updated: Dec 2, 2011
 

Laboratory Studies

Evaluation for GHD should be considered if the following conditions exist:

  • A child with a standing height of more than 3 standard deviation below the mean for chronological age, sex, and ethnic background
  • A child with a height velocity below the fifth to tenth percentile for age, with no clear etiology
  • A child with a standing height that is 2 SD to 3 SD below the mean for chronologic age, and with growth deceleration (growth velocity less than the twenty-fifth percentile) that cannot otherwise be explained
  • Hypothalamic-pituitary dysfunction (eg, microphallus, septo-optic dysplasia, intracranial tumor, history of cranial irradiation) with decelerating growth
  • Deficits in other hypothalamic-pituitary hormones, either congenital or acquired
  • Adults with manifestations suggestive of GHD

Local laboratory assays and their cutoffs should be kept in mind when performing tests for GHD.[14]

In newborns, a serum growth hormone level of less than 20 ng/mL is highly suggestive of GHD. After the newborn period, random serum growth hormone levels are of little value because of the pulsatile nature of growth hormone secretion. Measurement of growth hormone secretion through the night or for 24 hours is cumbersome, costly, and impractical.

Growth hormone stimulation (provocative) tests play a critical role in the diagnosis of GHD. The most frequently used tests include the insulin tolerance test (ITT); arginine; GHRH, with or without arginine; levodopa (L-dopa); glucagon, with or without a beta blocker, such as propranolol; and clonidine.[15, 16]

Most endocrinologists use a cutoff serum growth hormone concentration of more than 10 mcg/L in children and of more than 3 mcg/L (some authorities use 5 mcg/L) in adults to define normal response on provocative tests.[14]

  • The Growth Hormone Research Society has recommended the ITT as the standard test for the diagnosis of GHD in adults.
  • In an ITT, insulin is administered intravenously to produce a nadir in the plasma glucose level of less than 40 mg/dL (2.2 mmol/L); serum (or blood) glucose and serum growth hormone levels are measured at times 0, 15, 30, 60, 90, and 120 minutes after administering insulin. An experienced staff under the direct supervision of a physician should perform the test. GHD is diagnosed when the growth hormone level is less than 5.1 mcg/L.[15]
  • An ITT is contraindicated in patients with cardiovascular disease, cerebrovascular disease, or seizure disorders, or in patients older than 65 years.
  • The GHRH-arginine test is used by many centers as an alternative to the ITT. When the GHRH-arginine test is employed, a GHD is diagnosed when the growth hormone level is less than 4.1 mcg/L.[15, 11]
  • In patients with a GHD of hypothalamic origin (as a result, for example, of irradiation), GHRH can give falsely normal testing. In such patients, arginine without GHRH should be used

Some clinicians require that these criteria occur on 2 provocative tests because of the high frequency of false-negative results for each single test.

  • Levels of insulinlike growth factor 1 (IGF-1) or IGF–binding protein 3 (IGFBP-3) can provide presumptive evidence of reduced growth hormone secretion, but normal levels do not exclude the possibility of GHD.[15]
  • Patients who have a deficiency of 3 or more pituitary hormones and an IGF-1 level of < 84 ng/ml can be considered to have GHD and may not require provocative testing. However, some insurance bodies require the results of a growth hormone stimulation test before providing reimbursement for GH therapy.

Patients with GHD may have an increase in total cholesterol, low-density lipoprotein (LDL) cholesterol, and apolipoprotein B, as well as in triglyceride levels. The high-density lipoprotein (HDL) cholesterol level may be low.[7]

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Imaging Studies

  • Magnetic resonance imaging (MRI) of the hypothalamic-pituitary region to define the anatomy of this region and to identify tumors or congenital anomalies
  • Bone age radiographs to assess chronologic age in children
  • Bone mineral densitometry to look for reduced bone mineral density
  • Cardiac echocardiogram to look for reduced ejection fraction at rest and during exercise
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Other Tests

  • Increased type-1 plasminogen activator inhibitor (PAI-1) activity
  • Increased fibrinogen levels
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Histologic Findings

Histologic findings vary by the etiologic factor that causes GHD, such as a pituitary tumor in adults (usually an adenoma) or a congenital anomaly in children (see Causes).

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Contributor Information and Disclosures
Author

Mohsen S Eledrisi, MD, FACP, FACE  Consultant, Department of Internal Medicine, Division of Endocrinology and Metabolism, King Abdulaziz National Guard Medical Center, Saudi Arabia

Mohsen S Eledrisi, MD, FACP, FACE is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, American Medical Association, and Endocrine Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Steven R Gambert, MD  Professor of Medicine, Johns Hopkins University School of Medicine; Director of Geriatric Medicine, University of Maryland Medical Center and R. Adams Cowley Shock Trauma Center

Steven R Gambert, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physician Executives, American College of Physicians, American Geriatrics Society, Association of Professors of Medicine, Endocrine Society, and Gerontological Society of America

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Don S Schalch, MD  Professor Emeritus, Department of Internal Medicine, Division of Endocrinology, University of Wisconsin Hospitals and Clinics

Don S Schalch, MD is a member of the following medical societies: American Diabetes Association, American Federation for Medical Research, Central Society for Clinical Research, and Endocrine Society

Disclosure: Nothing to disclose.

Mark Cooper, MBBS, PhD, FRACP  Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD  Professor of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Additional Contributors

Ali A Al-Qarni, MD, Consulting Endocrinologist, King Abdulaziz National Guard Hospital, Saudi Arabia, contributed to this article.

References

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