Growth Hormone (hGH)

Overview:

Pituitary function test useful in the diagnosis of hypothalamic disorder, hypopituitarism, acromegaly, and ectopic growth hormone production by neoplasm.

A single fasting growth hormone (GH) level is of limited value. Secretion of GH is episodic and pulsatile. GH has a half-life of 20 to 25 minutes. Testing for growth hormone deficiency or excess is best done as part of a dynamic test involving specific stimuli (see the online Endocrine Appendices: Growth Hormone Stimulation and Growth Hormone Suppression). Insulin-like growth factor-1 can also be useful in assessing growth hormone status.

As in the case of any diagnostic procedure, results must be interpreted in conjunction with the patient's clinical presentation and other information available to the physician.

Human growth hormone (hGH) is a polypeptide hormone secreted from the acidophil cells of the anterior pituitary gland. Secretion is episodic and is associated with exercise, the onset of deep sleep or postprandially in response to falling glucose levels. Synthesis and release are under the control of hypothalamic releasing peptides and inhibitory peptides such as somatostatin. More recently, a gastric peptide, ghrelin, has been shown to also stimulate HGH secretion. The mediator of many hGH actions in the periphery, insulin-like growth-factor I (IGF-I) exerts an inhibitory effect through negative feedback mechanisms.1 hGH in circulation consists of several molecular isoforms, with 22,000 Dalton hGH being the most abundant, followed by a 20,000 Dalton hGH variant produced by alternative splicing. Approximately 50% of circulating hGH is bound to a high affinity binding protein.2 hGH is physiologically important in two main areas. Firstly, it has an integral role in skeletal growth which is well demonstrated in either excess or deficiency in childhood. The action of hGH in part is mediated through IGF-I as well as promoting protein synthesis and the uptake of amino acids into cells. Secondly, hGH influences intermediary metabolism by stimulating lipolysis and is antagonistic to the insulin-mediated uptake of glucose.3 hGH secretion is stimulated by hypoglycemia and suppressed by hyperglycemia.

In childhood, symptoms of hGH deficiency are retarded growth and dwarfism. Etiology is often unknown and an absolute or relative deficiency usually becomes apparent at about two years of age. Diagnosis can be confirmed by demonstrating low serum hGH which does not respond to stimulation tests. hGH deficiency is a major cause of severe short stature and diagnosis at an early stage is essential for successful therapy.4 Hyposecretion in adults usually becomes apparent during the laboratory investigation of hypopituitarism.5,6

Hypersecretion, commonly due to adenoma of the acidophil cells, is characterized by two conditions depending on whether it becomes apparent before or after fusion of the bony epiphyses. In childhood, excess hGH is characterized by gigantism. Heights of eight feet may be achieved and may also be associated with hypogonadism. In adults, acromegaly results, a condition characterized by progressive thickening of bone and soft tissue. Diagnosis is usually confirmed by dynamic function testing, which demonstrates a raised serum hGH level that does not fall in response to an oral glucose load.7 In conditions where there are nutritional disturbances, such as anorexia, starvation, renal failure, and hepatic cirrhosis, increased basal hGH levels may be found.

Recombinant hGH is available for treatment of hGH deficiency in both children and adults.4-6 hGH excess is treated by surgery, irradiation therapy, or somatostatin analogues.8,9 More recently, pegvisomant, a hGH receptor antagonist, which shares structural homology to hGH and competes with hGH for binding to the hGH receptor, has been developed.10

The IDS iSYS hGH assay conforms to the recommendations outlined in the recently published consensus statement on the standardization and evaluation of growth hormone assays.11 The assay is calibrated to the WHO International Standard for Somatropin from NIBSC, code 98/574.12 The assay is 100% specific for the 22 kDalton form of hGH and has no cross-reactivity with pegvisomant.13

1. Giustina A, Veldhuis JD. Pathophysiology of the neuroregulation of growth hormone secretion in experimental animals and the human. Endocr Rev. 1998 Dec; 19(6):717-797. PubMed 2260461

2. Baumann G. Growth hormone heterogeneity: Genes, isohormones, variants, and binding proteins. Endocr Rev. 1991 Nov; 12(4):424-449. PubMed 1760996

3. Møller N, Jørgensen JO. Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects. Endocr Rev. 2009 Apr; 30(2):152-177. PubMed 19240267

4. Cohen P, Rogol AD, Deal CL, et al. Consensus statement on the diagnosis and treatment of children with idiopathic short stature: A summary of the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Paediatric Endocrinology Workshop. J Clin Endocrinol Metab. 2008 Nov; 93(11):4210-4217. PubMed 18782877

5. Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Vance ML; Endocrine Society. Evaluation and treatment of adult growth hormone deficiency: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011 Jun; 96(6):1587-1609. PubMed 21602453

6. Cook DM, Yuen KC, Biller BM, Kemp SF, Vance ML; American Association of Clinical Endocrinologists. American Association of Clinical Endocrinologists medical guidelines for clinical practice for growth hormone use in growth hormone-deficient adults and transition patients-2009 update. Endocr Pract. 2009 Sep-Oct; 15(Suppl 2):1-29. PubMed 20228036

7. Katznelson L, Atkinson JL, Cook DM, Ezzat SZ, Hamrahian AH, Miller KK. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of acromegaly-2011 update. Endocr Pract. 2011 Jul-Aug; 17(Suppl 4):1-44. PubMed 21846616

8. Clemmons DR. Clinical laboratory indices in the treatment of acromegaly. Clin Chim Acta. 2011 Feb 20; 412(5-6):403-409. PubMed 21075098

9. Melmed S, Colao A, Barkan A, et al. Guidelines for acromegaly management: An update. J Clin Endocrinol Metab. 2009 May; 94(5):1509-1517. PubMed 19208732

10. Biermasz NR, Romijn JA, Pereira AM, Roelfsema F. Current pharmacotherapy for acromegaly: A review. Expert Opin Pharmacother. 2005 Nov; 6(14):2393-2405. PubMed 16259571

11. Clemmons DR. Consensus statement on the standardization and evaluation of growth hormone and insulin-like growth factor assays. Clin Chem. 2011 Apr; 57(4):555-559. PubMed 21285256

12. Human Growth Hormone on the IDS iSYS, package insert Date, V, Immunodiagnostic Systems Inc. (IDS Inc.). Fountain Hills, Ariz.

13. Manolopoulou J, Alami Y, Petersenn S, et al. Automated 22-kD growth hormone-specific assay without interference from Pegvisomant. Clin Chem. 2012 Oct; 58(10):1446-1456. PubMed 22908135

Donaldson DL, Pan F, Hollowell JG, et al. Reliability of stimulated and spontaneous growth hormone (GH) levels for identifying the child with low GH secretion. J Clin Endocrinol Metab. 1991 Mar; 72(3):647-652. PubMed 1671784