Growth hormone deficiency and excess

The mark goes to the candidate who reasons along three axes at once. The first is the child in front of you and the growth chart: a trajectory crossing centiles, a height far from the mid-parental target, or a growth velocity that is abnormal for age and sex. The second is the axis physiology: pulsatile growth hormone from the somatotrophs acting through hepatic and local IGF-1, with IGF-1 in turn feeding back to suppress growth hormone release. The third is the whole child: a growth hormone deficiency that is often part of multiple pituitary hormone deficiency and a midline malformation, and a growth hormone excess that is often a pituitary adenoma with mass effect on the optic chiasm and the rest of the pituitary. Treatment is lifelong and multidisciplinary, and the transition from paediatric to adult endocrine care is a high-risk moment that the candidate must own. [1] [10]

Overview & Definition

Growth hormone deficiency is the state in which the anterior pituitary somatotrophs fail to secrete enough growth hormone to sustain normal linear growth and metabolic homeostasis, producing short stature with a delayed bone age and, in early and severe forms, fasting hypoglycaemia and central adiposity. Growth hormone excess is the sustained over-secretion of growth hormone, almost always from a pituitary somatotropinoma, producing pathological linear growth while the growth plates are open — pituitary gigantism — and acral overgrowth with soft-tissue swelling and visceromegaly once the plates fuse, the paediatric counterpart of adult acromegaly. Both sit at the centre of the somatotrope axis, the neuroendocrine loop that runs from the hypothalamus through the pituitary and liver to the growth plate. [1] [10]

The axis is built around insulin-like growth factor 1. Growth hormone releasing hormone from hypothalamic neurones stimulates the somatotrophs to release growth hormone in pulsatile fashion, peaking at night and rising through puberty under the influence of sex steroids. Growth hormone acts on the liver to generate circulating (endocrine) IGF-1 and on cartilage and other tissues to generate local (paracrine) IGF-1, and IGF-1 then drives chondrocyte proliferation and linear growth at the growth plate while feeding back negatively on the hypothalamus and pituitary to restrain further growth hormone release. Insulin-like growth factor binding protein 3 is the principal carrier of IGF-1 in the circulation and is co-regulated by growth hormone, so a low IGF-1 with a low IGFBP-3 is the biochemical signature of growth hormone deficiency. [1] [3]