Physiology and control of growth hormone
GH is the pituitary factor responsible for stimulation of body growth in humans. Its secretion is stimulated by GHRH, released into the portal system from the hypothalamus; it is also under inhibitory control by GHRIH (somatostatin). GH stimulates the hepatic production of an intermediate (IGF-1, previously known as somatomedin C) that actually stimulates growth. Plasma levels of IGF-l, however, reflect local growth activity poorly, partly as there are multiple IGF-binding proteins (IGFBP). The metabolic actions of the system are:
• Increasing collagen and protein synthesis
• Promoting retention of calcium, phosphorus and nitrogen, necessary substrates for anabolism
• Opposing the action of insulin GH release is intermittent and mainly nocturnal, especially during REM sleep. The frequency and size of GH pulses increase during the growth spurt of adolescence and decline thereafter. Acute stress and exercise both stimulate GH release while, in the normal subject, hyperglycaemia suppresses it.
Factors other than GH involved in linear growth in the human are:
GENETIC. Children of two short parents will probably be short.
NUTRITIONAL. Adequate nutrients must be available; impaired growth can result from inadequate dietary intake or small-bowel disease (e.g. coeliac disease).
GENERAL HEALTH. Any serious systemic disease in childhood is likely to reduce growth (e.g. renal failure).
INTRAUTERINE GROWTH RETARDATION. These infants often grow poorly in the long term, while infants with simple prematurity usually catch up.
EMOTIONAL DEPRIVATION AND PSYCHOLOGICAL FACTORS. These can impair growth by complex, poorly understood mechanisms, possibly involving temporarily decreased GH secretion. The relevant aspects of history and examination in the assessment of problems.
Assessment of growth
Charts showing ranges of height and weight for normal British children are available (Fig. 16.17); other national data are available. Height must be measured very carefully, ideally at the same time of day on the same instrument by the same observer. In general, there are three overlapping phases of growth: infantile (0-2 years), which appears largely substrate (food) dependent; childhood (age 2 years to puberty), which is largely GH dependent; and the adolescent ‘growth spurt’, dependent on GH and sex hormones.
More important than current height is height velocity, which requires at least two measurements some months apart and, ideally, multiple serial measurements. This is a rate of current growth (em per year), while attained height is largely dependent upon previous growth. Standard deviation scores (SDS) based on the degree of deviation from age-sex norms are widely used by experts-these and growth velocities are far more sensitive than simple charts in assessing growth. The approximate future height of a child (‘midparental height’) can be simply predicted from the parental heights. For a boy, this is [(Maternal height +13 ern (5 inches) + Paternal height)/2] and for a girl [(Paternal height -13 em (5 inches) + Maternal height)/2].
Thus, with a father of 5 ft 10 inches and mother of 5 ft 1 inch, the predicted heights are 5 ft 8 inches for a son and 5 ft 3 inches for a daughter.
Rate of growth (home/school records, e.g. heights on kitchen door)
Comparison with peers at school and siblings
Change in appearance (old photos)
Change in shoe/glove/hat size or frequency of ‘growing out’
Age of appearance of pubic hair, breasts, menarche
Evidence of systemic disease
Body habitus, Size, relative weight, proportions (span versus height)
Skin thickness, Interdental separation
Grading of secondary sexual characteristics
GROWTH FAILURE-SHORT STATURE
When children or their parents complain of short stature particular attention should focus on:
• Intrauterine growth retardation, weight and gestation at birth
• Possible systemic disorder-any system but especially small-bowel disease
• Evidence of skeletal, chromosomal or other congenital abnormalities
• Endocrine status-particularly primary hypothyroidism
• Dietary intake and use of drugs, especially steroids for asthma
• Emotional, psychological, family and school problems
School, general practitioner, clinic and home records of height and weight should be obtained if possible to allow growth-velocity calculation. If unavailable, such data must be obtained prospectively. A child with normal growth velocity is unlikely to have significant endocrine disease. However, low growth velocity without apparent systemic cause requires further investigation. Sudden cessation of growth suggests major physical disease; if no gastrointestinal, respiratory, renal or skeletal abnormality is apparent, then a cerebral tumour or hypothyroidism are lilceliest. Consistently slow-growing children require full endocrine assessment.
Features of the commoner causes of growth failure are given in Table 16.21. Where constitutional delay is clearly shown and symptoms require intervention then very low dose sex steroids in 3-6 month courses will usually induce acceleration of growth.
Systemic disease having been excluded, the following should be undertaleen:
THYROID FUNCTION TESTS: serum TSH and T4 to exclude hypothyroidism.
GH STATUS: basal levels are of little value, though urinary GH measurements may prove to be of some value in screening. Overnight repeated sampling is optimal but the GH response to Bovril, exercise, clonidine, arginine and insulin are all used; a normal peale response is >20 mU litre “. The ‘gold standard’ test has been the insulin tolerance test (lIT), but this should only be performed in specialist centres for safety reasons. ASSESSMENT OF BONE AGE: non-dominant hand and wrist X-rays allow assessment of bone age by comparison with standard charts (Tanner, Greulich and Pyle).
SYSTEMIC ILLNESS should be treated.
PRIMARY HYPOTHYROIDISM: replace with thyroxine 0.05-0.2 mg daily.
GH INSUFFICIENCY: human GH (collected from pituitaries) was previously used but was withdrawn as cases of Creutzfeld-Iakob disease were reported. It has been superseded by very expensive recombinant GH, which is given as nightly injection in doses of 10- 20 U m? of body surface area. Treatment should be supervised in expert centres.
The place of GH treatment in so-called ‘short normal’ children has still not been adequately defined. In Turner’s syndrome large doses of GH are needed combined with oxandrolone, a growth-stimulating synthetic sex steroid.
GROWTH HORMONE EXCESSGIGANTISM AND ACROMEGALY GH stimulates skeletal and soft-tissue growth. GH excess therefore produces gigantism in children (if acquired before epiphyseal fusion) but acromegaly in adults .