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Growth Hormone Deficiency

Growth Hormone Deficiency is a topic covered in the 5-Minute Clinical Consult.

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Basics

Description

  • Insufficient production of growth hormone (GH) in adults or children caused by problems arising in the pituitary gland and/or hypothalamus
  • GH is produced by somatotroph cells of the anterior pituitary gland, which is stimulated by growth hormone–releasing hormone (GHRH) and inhibited by somatostatin from the hypothalamus.
  • GH, also called somatotropin, is a polypeptide hormone that stimulates growth and cell reproduction.
  • Hypopituitarism is a deficiency in at least one pituitary hormone, including GH.
  • Panhypopituitarism is a deficiency in all the hormones produced in the pituitary gland.
  • System(s) affected: endocrine, musculoskeletal, cardiovascular, psychological
  • Synonym(s) and keywords: hypopituitarism; familial short stature; short height; growth pattern; pituitary dwarfism; acquired GHD; isolated GHD; congenital GHD; panhypopituitarism

Epidemiology

Incidence
  • Most common cause of GHD in children is idiopathic.
  • Most common cause of GHD in adults is a pituitary adenoma or treatment of the adenoma with surgery or radiotherapy:
    • 76% of patients with GHD had a pituitary tumor.
    • 13% had an extrapituitary tumor.
    • 8% idiopathic cause
    • 1% had sarcoidosis.
    • 0.5% had Sheehan syndrome.

Prevalence
  • In children, isolated GHD is reported to affect 1 in 4,000.
  • Adult-onset idiopathic GHD is extremely rare.

Etiology and Pathophysiology

  • GHD is caused by a genetic or acquired absence or decline in production of GH.
  • Hypothalamus secretes GHRH, which stimulates the pituitary to secrete GH.
  • Somatostatin is secreted by the hypothalamus to inhibit GH secretion.
  • When GH pulses are secreted into the blood, then insulin-like growth factor (IGF)-1 is released from the liver.
  • GHD may result from disruption of the GH axis—in the higher brain, the hypothalamus, or the pituitary gland (1)[C].
  • Congenital
    • Genetic (see “Genetics”)
    • Structural brain defects
      • Agenesis of corpus callosum
      • Septo-optic dysplasia
      • Empty sella syndrome
      • Encephalocele
      • Hydrocephalus
      • Arachnoid cyst
    • Associated midline facial defects
      • Single central incisor
      • Cleft lip/palate
  • Acquired
    • Trauma
    • CNS infection
    • Tumors of hypothalamus or pituitary
      • Pituitary adenoma
      • Craniopharyngioma
      • Rathke cleft cyst
      • Glioma/astrocytoma
      • Germinoma
      • Metastatic tumor
    • Infiltrative/granulomatous disease
      • Sarcoidosis
      • Tuberculosis
      • Langerhans cell histiocytosis
      • Hypophysitis
    • Cranial irradiation
    • Idiopathic
    • Pituitary infarction
    • Surgical
    • Hemochromatosis (rare)

Genetics

A variety of congenital genetic causes of GHD:

  • Transcription factor defects (POU1F1/PIT-1, PROP-1, LHX3/4, HESX-1, SOX-3, and PITX-2)
  • GHRH-receptor gene defects
  • GH secretagogue (GHS) receptor gene defects
  • GH receptor/postreceptor defects
  • Prader-Willi syndrome
  • Deletion and mutation of GH-1

Commonly Associated Conditions

  • Pituitary adenoma (particularly macroadenoma)
  • Sarcoidosis
  • Sheehan syndrome

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Citation

Stephens, Mark B., et al., editors. "Growth Hormone Deficiency." 5-Minute Clinical Consult, 27th ed., Wolters Kluwer, 2019. Medicine Central, im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/117502/all/Growth_Hormone_Deficiency.
Growth Hormone Deficiency. In: Stephens MB, Golding J, Baldor RA, et al, eds. 5-Minute Clinical Consult. 27th ed. Wolters Kluwer; 2019. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/117502/all/Growth_Hormone_Deficiency. Accessed August 21, 2019.
Growth Hormone Deficiency. (2019). In Stephens, M. B., Golding, J., Baldor, R. A., & Domino, F. J. (Eds.), 5-Minute Clinical Consult. Available from https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/117502/all/Growth_Hormone_Deficiency
Growth Hormone Deficiency [Internet]. In: Stephens MB, Golding J, Baldor RA, Domino FJ, editors. 5-Minute Clinical Consult. Wolters Kluwer; 2019. [cited 2019 August 21]. Available from: https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/117502/all/Growth_Hormone_Deficiency.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - Growth Hormone Deficiency ID - 117502 ED - Stephens,Mark B, ED - Golding,Jeremy, ED - Baldor,Robert A, ED - Domino,Frank J, BT - 5-Minute Clinical Consult, Updating UR - https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/117502/all/Growth_Hormone_Deficiency PB - Wolters Kluwer ET - 27 DB - Medicine Central DP - Unbound Medicine ER -