ENDOCRINE GLAND DISORDERS CAUSING SHORT STATURE

The two main endocrine gland disorders which cause short stature are growth hormone deficiency and thyroid deficiency.

Growth hormone deficiency

by Child Growth Foundation

The deficiency does not affect intra-uterine growth, at least to an extent measurable by birthweight, but from the first year of life onwards growth is slower than normal and occasionally growth failure commences from birth. Most cases of growth hormone deficiency are called "idiopathic", meaning "of unknown origin". Idiopathic growth hormone deficiency occurs, it seems in about 1 in 5000 births in the UK population at present.

There is evidently a hereditary predisposition, at least in some cases. About 3% of cases have brothers or sisters with the disorder. In a very few families one of the parents is affected. The deficiency is two to three times more common in boys than in girls, for reasons quite unknown.

These children are simply small with normal skeletal proportions, facial appearance and intelligence. They tend to be fat (this reduces during growth hormone treatment) and they often have a delayed bone age. The diagnosis is confirmed by lck of growth hormone production in response to a stimulation test, which requires a morning in hospital.

The deficiency may be of growth hormone only, although other pituitary hormones may also be affected. The most commonly associated deficiencies are those of the thyroid-stimulating hormone, (TSH), and of the gonadotrophins - follicle-stimulating hormone (FSH) and leutinising hormone (LH). The adrenal-stimulating hormone (ACTH) is much less frequently involved, but any deficiency is extremely important to detect.

The treatment of growth hormone deficiency has been a major success of paediatrics since the first patient was given human growth hormone by Raben in 1958 in Boston, USA, although since October 1985, biosynthetic growth hormone has replaced the pituitary derived hormone in the UK. Provided treatment is started at a reasonably early age (at least before age 6 years) the results are nearly always excellent (even at later stages results are sometimes spectacular, but not invariably).

Catch-up growth occurs following initial treatment and thereafter a normal growth rate is usually maintained. If TSH lack is also present, thyroxine is given, and if gonadotrophin declares itself at the time of puberty (which is usually late in growth hormone deficient children), the sex hormones have also to be given and the treatment can initiate sexual maturation. Very occasionally antibodies develop to the injected hormone and cancel out the effects of treament but this is rare with more modern biosynthetic human growth hormones; otherwise side-effects are practically unknown.

Oncology survivors

Other causes of growth hormone deficiency are associated with tumours of the central nervous system which destroy the part of the brain controlling the pituitary gland, the pituitary itself, or both.

Some tumours are benign, ie not cancerous, and the one which is by far the most common, craniopharyngioma, is not technically a brain tumour at all, but part of a piece of mouth epithelium pinched off and left behind during development.

Craniopharyngiomas can be identified by taking a skull x-ray or by computer-assisted tomography of the brain. They are usually surgically removable. Occasionally, they recur, but are removable again. The child with a tumour in the brain occasionally comes to the physician with the sole complaint of short stature, but much more usually the symptoms are neurological eg headaches, nausea, affected vision.

Treatment will involve radiotherapy and surgical removal of the tumour, after which the child may suffer from any combination of pituitary hormone deficiencies. Most, though not all, have growth hormone deficiency. They are treated with growth hormone, often in conjunction with thyroxine, cortisol, (hydrocortisone) and, at the time of puberty, gonadotrophins or sex hormones. In addition such children may need replacement of the posterior pituitary hormone, vasopressin, in order to restore a natural fluid balance.

Hypothyroidism

Lack of thyroid gland secretion also stops normal growth occurring, as all cells need a certain level of thyroid hormone in them in order to function properly. Hypothyroidism may start in utero, in which case the brain is affected and diagnosis and treatment directly after birth is a matter of urgency. The condition can be diagnosed by measuring the levels of thyroid hormone in the blood and recently, in some areas, this has been instituted as a routine screening test for all new-borns.

Short stature is more usually caused by the type of hypothyroidism which occurs during childhood, often subtley. The catch-up growth during thyroid hormone replacement treatment is marked but, unfortunately, never complete.

Premature sexual maturation (including precocious puberty)

Rarely there is a disease of the gonads, adrenal or other glands, leading to premature sexual maturation; in such cases the child grows at a faster rate than normal and develops secondary sexual characteristics (such as pubic hair, penile enlargement or breast development) at an early age.

It is important to distinguish this from precocious puberty, whereby normal puberty occurs but at an age earlier than 8 years in a girl and 9 years in a boy. The child may be very large for his or her age but as growth stops early, the final result may be short stature. Premature sexual maturation always requires investigation and assessment by a growth specialist. Treatment will depend on the underlying cause.

Cushing's Syndrome

This is rare condition where the adrenal glands (situated just above the kidneys) oversecrete hormones - both corticosteroids (primarily cortisol) and androgens (male hormones). The effect of excess corticosteroids is obesity and growth arrest, whereas that of androgen excess is early pubic hair, excess male hair growth, greasy hair and acne. The diagnosis is confirmed by measurments of steroid hormones in the blood and urine.

The syndrome is caused either by over function of the pituitary gland (which controls the adrenal gland through the release of the hormone (ACTH) or over function of the adrenal gland itself. It is often difficult to separate the two causes and it can therefore take a considerable amount of time before investigations are complete and a full diagnosis is made.