Growth Hormone Deficiency in Adults

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The somatotroph cells of the anterior pituitary gland produce growth hormone (GH), which is stimulated by GH-releasing hormone (GHRH) and inhibited by somatostatin, both of which are produced by the hypothalamus.

GH deficiency in adults usually manifests as reduced physical performance and impaired psychological well-being. It results in alterations in the physiology of different systems of the body, manifesting as altered lipid metabolism, increased subcutaneous and visceral fat, decreased muscle mass, decreased bone density, low exercise performance, and reduced quality of life. ^[1]

Adult GH deficiency can be a transition from childhood-onset GH deficiency or it can be acquired during adulthood. The majority of cases are caused by pituitary tumors or by their treatment with surgery, radiation therapy, or both. Traumatic brain injury is another important cause. ^{[2, 3, 4]}

The goals of GH therapy in adults are to improve conditioning, strength, body composition, and quality of life, as well as reduce the burden of associated medical conditions such as cardiovascular disease and decreased bone mineral density.

Patients should be educated about the technique of subcutaneous injection of GH.

For patient education resources, see Thyroid and Metabolism Center as well as Growth Hormone Deficiency, Growth Hormone Deficiency Medications, and Growth Hormone Deficiency FAQs.

The main cause of growth hormone (GH) deficiency is a pituitary tumor or the consequences of treatment of the tumor, including surgery and/or radiation therapy. Traumatic brain injury is increasingly recognized as an important cause of GH deficiency, both during the acute stage of the injury and during the rehabilitation stage. ^{[2, 3, 4]}

Causes of GH deficiency can be divided into three categories: congenital, acquired, and idiopathic. ^[5]

Congenital conditions are caused by genetic abnormalities or structural brain defects. Genetic abnormalities include transcription factor defects (PIT-1, PROP-1, LHX3/4, HESX-1, PITX-2), GH-releasing hormone (GHRH) receptor gene defects, GH gene defects, and GH-receptor or post-receptor defects. Structural defects include agenesis of the corpus callosum, septo-optic dysplasia, empty sella syndrome, encephalocele, hydrocephalus, and arachnoid cyst. GH deficiency can occur in association with midline facial defects such as single central incisor, cleft lip, and cleft palate.

Acquired conditions of GH deficiency include tumors of the pituitary gland or the hypothalamus and metastatic disease; surgery or radiation therapy of the pituitary or hypothalamus; infiltrative diseases such as sarcoidosis, tuberculosis, histiocytosis X, hemochromatosis, and lymphocytic hypophysitis; infarction of the pituitary or hypothalamus (which can be spontaneous or result from Sheehan syndrome); and head trauma.

In some cases, no clear etiology can be determined.

An estimated 6,000 adults are diagnosed with growth hormone (GH) deficiency every year in the United States. ^[2] Adult GH deficiency has been estimated to affect 1 in 100,000 people annually, whereas its incidence is approximately 2 cases per 100,000 population when childhood-onset GH deficiency patients are considered. About 15%-20% of the cases represent the transition of childhood GH deficiency into adulthood. ^[6]

The age of presentation of acquired GH deficiency in adults often coincides with the discovery of pituitary tumors, usually between the fourth and fifth decades of life.

Brod M, Hojbjerre L, Adalsteinsson JE, Rasmussen MH. Assessing the impact of growth hormone deficiency and treatment in adults: development of a new disease-specific measure. J Clin Endocrinol Metab. 2014 Apr. 99 (4):1204-12. [Medline]. [Full Text].

Tanriverdi F, Schneider HJ, Aimaretti G, Masel BE, Casanueva FF, Kelestimur F. Pituitary dysfunction after traumatic brain injury: a clinical and pathophysiological approach. Endocr Rev. 2015 Jun. 36 (3):305-42. [Medline]. [Full Text].

Tanriverdi F, Kelestimur F. Neuroendocrine disturbances after brain damage: an important and often undiagnosed disorder. J Clin Med. 2015 Apr 28. 4 (5):847-57. [Medline]. [Full Text].

Guaraldi F, Grottoli S, Arvat E, Ghigo E. Hypothalamic-pituitary autoimmunity and traumatic brain injury. J Clin Med. 2015 May 19. 4 (5):1025-35. [Medline]. [Full Text].

Melmed S. Idiopathic adult growth hormone deficiency. J Clin Endocrinol Metab. 2013 Jun. 98 (6):2187-97. [Medline]. [Full Text].

[Guideline] Allen DB, Backeljauw P, Bidlingmaier M, et al. GH safety workshop position paper: a critical appraisal of recombinant human GH therapy in children and adults. Eur J Endocrinol. 2016 Feb. 174 (2):P1-9. [Medline]. [Full Text].

[Guideline] 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):1587-609. [Medline]. [Full Text].

Stochholm K, Gravholt CH, Laursen T, et al. Incidence of GH deficiency – a nationwide study. Eur J Endocrinol. 2006 Jul. 155 (1):61-71. [Medline].

Mo D, Blum WF, Rosilio M, Webb SM, Qi R, Strasburger CJ. Ten-year change in quality of life in adults on growth hormone replacement for growth hormone deficiency: an analysis of the hypopituitary control and complications study. J Clin Endocrinol Metab. 2014 Dec. 99 (12):4581-8. [Medline].

Biller BM, Samuels MH, Zagar A, et al. Sensitivity and specificity of six tests for the diagnosis of adult GH deficiency. J Clin Endocrinol Metab. 2002 May. 87 (5):2067-79. [Medline].

US Food and Drug Administration. NDA approval [letter]. NDA 205598. Available at https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2017/205598Orig1s000ltr.pdf. December 20, 2017; Accessed: January 8, 2018.

Macrilen (macimorelin) [package insert]. Goettingen, Germany: Aeterna Zentaris GmbH. Revised January 2018. Available at [Full Text].

Garcia JM, Biller BMK, Korbonits M, et al. Macimorelin as a diagnostic test for adult growth hormone deficiency. J Clin Endocrinol Metab. 2018 May 31. [Medline].

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. [Medline].

[Guideline] Yuen KC, Tritos NA, Samson SL, Hoffman AR, Katznelson L. American Association of Clinical Endocrinologists and American College of Endocrinology Disease state clinical review: update on growth hormone stimulation testing and proposed revised cut-point for the glucagon stimulation test in the diagnosis of adult growth hormone deficiency. Endocr Pract. 2016 Oct. 22 (10):1235-44. [Medline]. [Full Text].

Hoffman AR, Strasburger CJ, Zagar A, Blum WF, Kehely A, Hartman ML, et al. Efficacy and tolerability of an individualized dosing regimen for adult growth hormone replacement therapy in comparison with fixed body weight-based dosing. J Clin Endocrinol Metab. 2004 Jul. 89 (7):3224-33. [Medline].

Arnold JR, Arnold DF, Marland A, Karavitaki N, Wass JA. GH replacement in patients with non-functioning pituitary adenoma (NFA) treated solely by surgery is not associated with increased risk of tumour recurrence. Clin Endocrinol (Oxf). 2009 Mar. 70 (3):435-8. [Medline].

Buchfelder M, Kann PH, Wuster C, et al. Influence of GH substitution therapy in deficient adults on the recurrence rate of hormonally inactive pituitary adenomas: a case control study. Eur J Endocrinol. 2007 Aug. 157 (2):149-56. [Medline].

Karavitaki N, Warner JT, Marland A, et al. GH replacement does not increase the risk of recurrence in patients with craniopharyngioma. Clin Endocrinol (Oxf). 2006 May. 64 (5):556-60. [Medline].

Jenkins PJ, Mukherjee A, Shalet SM. Does growth hormone cause cancer?. Clin Endocrinol (Oxf). 2006 Feb. 64 (2):115-21. [Medline].

Poidvin A, Carel JC, Ecosse E, Levy D, Michon J, Coste J. Increased risk of bone tumors after growth hormone treatment in childhood: A population-based cohort study in France. Cancer Med. 2018 Jun 14. [Medline].

Holmes SJ, Shalet SM. Which adults develop side-effects of growth hormone replacement?. Clin Endocrinol (Oxf). 1995 Aug. 43 (2):143-9. [Medline].

Maison P, Griffin S, Nicoue-Beglah M, Haddad N, Balkau B, Chanson P. Impact of growth hormone (GH) treatment on cardiovascular risk factors in GH-deficient adults: a meta-analysis of blinded, randomized, placebo-controlled trials. J Clin Endocrinol Metab. 2004 May. 89 (5):2192-9. [Medline].

Losa M, Scavini M, Gatti E, et al. Long-term effects of growth hormone replacement therapy on thyroid function in adults with growth hormone deficiency. Thyroid. 2008 Dec. 18 (12):1249-54. [Medline].

Giavoli C, Libe R, Corbetta S, et al. Effect of recombinant human growth hormone (GH) replacement on the hypothalamic-pituitary-adrenal axis in adult GH-deficient patients. J Clin Endocrinol Metab. 2004 Nov. 89 (11):5397-401. [Medline].

Giannoulis MG, Sonksen PH, Umpleby M, et al. The effects of growth hormone and/or testosterone in healthy elderly men: a randomized controlled trial. J Clin Endocrinol Metab. 2006 Feb. 91 (2):477-84. [Medline].

Cook DM, Ludlam WH, Cook MB. Route of estrogen administration helps to determine growth hormone (GH) replacement dose in GH-deficient adults. J Clin Endocrinol Metab. 1999 Nov. 84 (11):3956-60. [Medline].

Chikani V, Cuneo RC, Hickman I, Ho KK. Growth hormone (GH) enhances anaerobic capacity: impact on physical function and quality of life in adults with GH deficiency. Clin Endocrinol (Oxf). 2016 Oct. 85 (4):660-8. [Medline].

van Bunderen CC, van Varsseveld NC, Erfurth EM, Ket JC, Drent ML. Efficacy and safety of growth hormone treatment in adults with growth hormone deficiency: a systematic review of studies on morbidity. Clin Endocrinol (Oxf). 2014 Jul. 81 (1):1-14. [Medline].

Rosilio M, Blum WF, Edwards DJ, et al. Long-term improvement of quality of life during growth hormone (GH) replacement therapy in adults with GH deficiency, as measured by questions on life satisfaction-hypopituitarism (QLS-H). J Clin Endocrinol Metab. 2004 Apr. 89 (4):1684-93. [Medline].

Cuneo RC, Salomon F, McGauley GA, Sonksen PH. The growth hormone deficiency syndrome in adults. Clin Endocrinol (Oxf). 1992 Nov. 37 (5):387-97. [Medline].

De Boer H, Blok GJ, Voerman HJ, De Vries PM, van der Veen EA. Body composition in adult growth hormone-deficient men, assessed by anthropometry and bioimpedance analysis. J Clin Endocrinol Metab. 1992 Sep. 75 (3):833-7. [Medline].

Gazzaruso C, Gola M, Karamouzis I, Giubbini R, Giustina A. Cardiovascular risk in adult patients with growth hormone (GH) deficiency and following substitution with GH–an update. J Clin Endocrinol Metab. 2014 Jan. 99 (1):18-29. [Medline].

Svensson J, Bengtsson BA, Rosen T, Oden A, Johannsson G. Malignant disease and cardiovascular morbidity in hypopituitary adults with or without growth hormone replacement therapy. J Clin Endocrinol Metab. 2004 Jul. 89 (7):3306-12. [Medline].

Rosen T, Bengtsson BA. Premature mortality due to cardiovascular disease in hypopituitarism. Lancet. 1990 Aug 4. 336 (8710):285-8. [Medline].

Jorgensen JOL, Juul A. Therapy of endocrine disease: growth hormone replacement therapy in adults: 30 years of personal clinical experience. Eur J Endocrinol. 2018 Jul. 179 (1):R47-56. [Medline].

Verhelst J, Mattsson AF, Camacho-Hubner C, Luger A, Abs R. The prevalence of the metabolic syndrome and associated cardiovascular complications in adult-onset GHD during GH replacement: a KIMS analysis. Endocr Connect. 2018 May. 7 (5):653-62. [Medline].

McCallum RW, Petrie JR, Dominiczak AF, Connell JM. Growth hormone deficiency and vascular risk. Clin Endocrinol (Oxf). 2002 Jul. 57 (1):11-24. [Medline].

Colao A, Di Somma C, Rota F, et al. Short-term effects of growth hormone (GH) treatment or deprivation on cardiovascular risk parameters and intima-media thickness at carotid arteries in patients with severe GH deficiency. J Clin Endocrinol Metab. 2005 Apr. 90 (4):2056-62. [Medline].

Cannavo S, Marini F, Curto L, et al. High prevalence of coronary calcifications and increased risk for coronary heart disease in adults with growth hormone deficiency. J Endocrinol Invest. 2011 Jan. 34 (1):32-7. [Medline].

Colao A, Di Somma C, Spiezia S, et al. Growth hormone treatment on atherosclerosis: results of a 5-year open, prospective, controlled study in male patients with severe growth hormone deficiency. J Clin Endocrinol Metab. 2008 Sep. 93 (9):3416-24. [Medline].

Maison P, Chanson P. Cardiac effects of growth hormone in adults with growth hormone deficiency: a meta-analysis. Circulation. 2003 Nov 25. 108 (21):2648-52. [Medline].

Wuster C, Abs R, Bengtsson BA, et al, for the KIMS Study Group and the KIMS International Board, Pharmacia Upjohn International Metabolic Database. The influence of growth hormone deficiency, growth hormone replacement therapy, and other aspects of hypopituitarism on fracture rate and bone mineral density. J Bone Miner Res. 2001 Feb. 16 (2):398-405. [Medline].

Appelman-Dijkstra NM, Claessen KM, Hamdy NA, Pereira AM, Biermasz NR. Effects of up to 15 years of recombinant human GH (rhGH) replacement on bone metabolism in adults with growth hormone deficiency (GHD): the Leiden Cohort Study. Clin Endocrinol (Oxf). 2014 Nov. 81 (5):727-35. [Medline].

Snyder PJ, Biller BM, Zagar A, et al. Effect of growth hormone replacement on BMD in adult-onset growth hormone deficiency. J Bone Miner Res. 2007 May. 22 (5):762-70. [Medline].

Bex M, Abs R, Maiter D, Beckers A, Lamberigts G, Bouillon R. The effects of growth hormone replacement therapy on bone metabolism in adult-onset growth hormone deficiency: a 2-year open randomized controlled multicenter trial. J Bone Miner Res. 2002 Jun. 17 (6):1081-94. [Medline].

Pappachan JM, Raskauskiene D, Kutty VR, Clayton RN. Excess mortality associated with hypopituitarism in adults: a meta-analysis of observational studies. J Clin Endocrinol Metab. 2015 Apr. 100 (4):1405-11. [Medline].

Thilmany S, Mchirgui L, Brunelle C, Beauloye V, Maiter D, Alexopoulou O. Correlation between the responses to growth hormone (GH) treatment during childhood and adulthood in a monocentric cohort of GH-deficient patients. Horm Metab Res. 2018 Jun. 50 (6):462-8. [Medline].

Sherlock M, Ayuk J, Tomlinson JW, et al. Mortality in patients with pituitary disease. Endocr Rev. 2010 Jun. 31 (3):301-42. [Medline].

Bates AS, Van’t Hoff W, Jones PJ, Clayton RN. The effect of hypopituitarism on life expectancy. J Clin Endocrinol Metab. 1996 Mar. 81 (3):1169-72. [Medline].

Rosen T, Wiren L, Wilhelmsen L, Wiklund I, Bengtsson BA. Decreased psychological well-being in adult patients with growth hormone deficiency. Clin Endocrinol (Oxf). 1994 Jan. 40 (1):111-6. [Medline].

Hartman ML, Crowe BJ, Biller BM, et al, for the HyposCCS Advisory Board, US HypoCCS Study Group. Which patients do not require a GH stimulation test for the diagnosis of adult GH deficiency?. J Clin Endocrinol Metab. 2002 Feb. 87 (2):477-85. [Medline].

Darzy KH, Aimaretti G, Wieringa G, Gattamaneni HR, Ghigo E, Shalet SM. The usefulness of the combined growth hormone (GH)-releasing hormone and arginine stimulation test in the diagnosis of radiation-induced GH deficiency is dependent on the post-irradiation time interval. J Clin Endocrinol Metab. 2003 Jan. 88 (1):95-102. [Medline].

Mavromati M, Kuhn E, Agostini H, et al. Classification of patients with GH disorders may vary according to the IGF-I assay. J Clin Endocrinol Metab. 2017 Aug 1. 102 (8):2844-52. [Medline].

[Guideline] Fleseriu M, Hashim IA, Karavitaki N, et al. Hormonal replacement in hypopituitarism in adults: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2016 Nov. 101 (11):3888-921. [Medline]. [Full Text].

Brod M, Beck JF, Hojbjerre L, et al. Assessing the impact of growth hormone deficiency (GHD) in adults: interpreting change of the treatment-related impact measure-adult growth hormone deficiency (TRIM-AGHD). Pharmacoecon Open. 2018 May 23. [Medline].

Ramos-Levi AM, Marazuela M. Treatment of adult growth hormone deficiency with human recombinant growth hormone: an update on current evidence and critical review of advantages and pitfalls. Endocrine. 2018 May. 60 (2):203-18. [Medline].

Johannsson G, Feldt-Rasmussen U, Hakonsson IH, et al, for the REAL 2 Study Group. Safety and convenience of once-weekly somapacitan in adult GH deficiency: a 26-week randomized, controlled trial. Eur J Endocrinol. 2018 May. 178 (5):491-9. [Medline].

Mohsen S Eledrisi, MD, FACP, FACE Senior Consultant, Department of Medicine/Endocrinology, Hamad Medical Corporation, Qatar

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

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: Received salary from Medscape for employment. for: Medscape.

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 and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

George T Griffing, MD Professor Emeritus 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, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

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 Association for Physician Leadership, American College of Physicians, American Geriatrics Society, Endocrine Society, Gerontological Society of America, Association of Professors of Medicine

Disclosure: Nothing to disclose.

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

Growth Hormone Deficiency in Adults

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