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Chapter: Paediatrics: Growth and puberty

Paediatrics: Growth hormone deficiency

GH is secreted from the somatomammotropic cells of the anterior pituitary gland in a pulsatile pattern.

Growth hormone deficiency


Physiology: secretion


GH is secreted from the somatomammotropic cells of the anterior pitu-itary gland in a pulsatile pattern. Secretion is diurnal and largely noctur-nal and is controlled by a rhythmically changing equilibrium between two hormones secreted by the hypothalamus: GH releasing hormone (GHRH) and GH-inhibiting hormone (or somatostatin). GHRH induces GH syn-thesis and secretion whenever somatostatin is low. Different factors act at the level of the hypothalamus to regulate GH hormone secretion. GH secretion is regulated by negative feedback by circulating insulin-like growth factor-I (IGF-I) at the pituitary and hypothalamus, and by short loop-feedback by GH on the hypothalamus.


Causes of growth hormone deficiency


These may be primary (or congenital) or secondary (acquired) in origin. In clinical practice the most frequent cause of GH deficiency is s to cranial radiotherapy.


Clinical features


Presentation depends on the age of onset of GH deficiency.


GH deficiency in infancy


May present with hypoglycaemia. Co-existing deficiencies in the adrenal, thyroid, and gonadal axes may cause prolonged jaundice and micropenis. Size at birth and growth during the 1st year of life may be normal as growth during this period is not GH-dependent.


GH deficiency in childhood


Typically presents with slow growth rate and short stature. Other charac-teristics include increased subcutaneous fat, truncal obesity, and decreased

muscle mass. Children with congenital GH deficiency develop relative hypoplasia of the mid-facial bones, frontal bone protrusion, and delayed dental eruption. Delayed closure of the anterior fontanelle may also be observed.






·Baseline/random serum IGF-I and IGFBP-3: GH-dependent and may be low in GH deficiency, but normal levels do not exclude GH deficiency.

·GH provocation tests.


All tests should be performed in the morning after an overnight fast and serial blood samples are collected. The insulin tolerance test (ITT) is con-sidered the gold-standard test. GH provocation test should only be per-formed in those centres with experience and with appropriate technical and laboratory support.



Assessment commonly used in children/adolescents


Pharmacological stimulation tests

·  Insulin tolerance test (gold standard; children aged ≥5yrs)


·  Glucagon stimulation tests


·  Clonidine test


·  Arginine test


Physiological tests


·  Exercise


·  Overnight or 24hr GH serum profiles


·  Random serum IGF-1 and/or IGFBP3 level




·  Bone age

MRI scan of brain (hypothalamic/pituitary structures)



NICE criteria for diagnosis of GH deficiency1


·  GHD is primarily a clinical diagnosis supported by auxological, biochemical, and radiological findings. Confirmation of the diagnosis is usually by GH provocation testing


·  Two such tests should be used in children with suspected isolated GH deficiency together with evaluation of other aspects of pituitary function


Definition of a normal GH response remains arbitrary as there is a continuous spectrum of GH secretory ability in childhood—peak GH concentrations <20mIU/L (7microgram/L) have traditionally been used to support the diagnosis


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