Growth Hormone Physiology and Disorders

Growth hormone, secreted by the anterior pituitary under opposing hypothalamic control, regulates linear growth in childhood and metabolism throughout life, acting largely through insulin-like growth factor 1. Its disorders span deficiency, which impairs growth and adult metabolism, and excess, which causes acromegaly or, in childhood, gigantism.

Definition

Growth hormone (somatotropin) is an anterior pituitary peptide hormone that promotes growth and regulates carbohydrate, lipid, and protein metabolism, principally by stimulating hepatic and peripheral production of insulin-like growth factor 1.

Scope

This topic covers the regulation, action, and feedback control of growth hormone and the clinical consequences of too little or too much of it. It treats the physiology and the disorder concepts as a reference and does not provide diagnostic cut-offs, stimulation-test protocols, or treatment regimens.

Core questions

• How is growth hormone secretion regulated by the hypothalamus and by feedback?
• How does growth hormone act through insulin-like growth factor 1?
• What clinical pictures result from growth hormone deficiency versus excess?

Key concepts

• Growth hormone-releasing hormone and somatostatin
• Insulin-like growth factor 1 (IGF-1)
• Pulsatile growth hormone secretion
• Growth hormone deficiency
• Acromegaly and gigantism
• Negative feedback by IGF-1

Mechanisms

Growth hormone secretion is driven by hypothalamic growth hormone-releasing hormone and restrained by somatostatin, producing a pulsatile pattern that is further modulated by ghrelin, sleep, exercise, and nutritional state; insulin-like growth factor 1 generated in response to growth hormone feeds back to suppress further secretion (Giustina & Veldhuis, 1998). Most growth-promoting and many metabolic effects are mediated by insulin-like growth factor 1. Deficiency, from pituitary disease or hypothalamic dysfunction, impairs growth in children and alters body composition and metabolism in adults (Molitch et al., 2011), whereas autonomous excess from a somatotroph adenoma raises insulin-like growth factor 1 and causes acromegaly in adults or gigantism before growth plates fuse (Katznelson et al., 2014).

Clinical relevance

Growth hormone disorders are recognised by their effects on growth, body composition, and metabolism, and they intersect with pituitary tumour disease and hypopituitarism. This topic explains the underlying physiology and the disorder concepts; it is a reference and does not give individualised testing or treatment guidance.

Epidemiology

Adult growth hormone deficiency most often follows pituitary or hypothalamic disease or its treatment, while acromegaly is an uncommon disorder almost always caused by a growth hormone-secreting pituitary adenoma. Detailed rates are addressed in the cited guidelines (Molitch et al., 2011; Katznelson et al., 2014).

History

The role of the pituitary in growth was inferred from early observations of gigantism and dwarfism, and the characterisation of growth hormone and later of insulin-like growth factor 1 clarified how the hormone acts. The dual hypothalamic control by growth hormone-releasing hormone and somatostatin and the feedback role of insulin-like growth factor 1 established the regulatory model now used clinically (Giustina & Veldhuis, 1998).

Key figures

• Andrea Giustina
• Johannes Veldhuis
• Mark Molitch
• Laurence Katznelson

Seminal works

• giustina-veldhuis-1998
• katznelson-2014
• molitch-2011

Frequently asked questions

How does growth hormone make the body grow?

Growth hormone acts largely by stimulating the liver and other tissues to produce insulin-like growth factor 1, which in turn promotes the growth of bone and other tissues; growth hormone also has direct metabolic effects on fat, carbohydrate, and protein handling.

What is the difference between acromegaly and gigantism?

Both result from growth hormone excess, usually from a pituitary tumour. Gigantism occurs when the excess begins in childhood before the growth plates close, causing very tall stature, whereas acromegaly occurs in adults after the plates have fused, causing enlargement of the hands, feet, and facial features rather than height.