Hypopituitarism in first cousins.

There is still much difficulty in elucidating the aetiological causes of dwarfism as it presents itself in children. After Erdheim in 1916 attributed dwarfism to a lack of pituitary secretion, it was for many years a common habit to implicate a pituitary deficiency in alJ dwarfs whatever their clinical features. A reaction to this unscientific approach was to be expected, and it has been so extreme in some quarters (Horstmann, 1950) that a pituitary origin for any type of dwarfism has been denied. Such a reaction is only possible if one contends that the enormous body of experimental work demonstrating the presence of an anterior pituitary growth hormone has no application to man, if one ignores the clinical pictures of dwarfism associated with destruction of the anterior pituitary, if one forgets the few reports of post-mortem examination in dwarfs which have demonstrated a deficiency of eosinophil cells in the anterior pituitary (Hewer, 1944), if one overlooks the clinical pictures of gigantism and acromegaly, and if one prefers not to remember that the absence of most hormones in the body is represented by a specific clinical syndrome. This aetiological nihilism, therefore, entails a denial of established fact which is too complete for most observers; but a moderate conservatism demands that some evidence of hypopituitarism should be forthcoming in any case of dwarfism before a diagnosis of pituitary dwarfism is made. In the attempt to establish the aetiology of dwarfism in the individual child, all the systemic causes of infantilism and all the bone diseases which can produce short stature must be excluded. There are then two questions which urgently require an answer, Is this child suffering from hypothyroidism ? Is there organic disease in the region of the pituitary ? The clinical picture of cretinism is well recognized, but continued observation may be necessary to establish the diagnosis of juvenile myxoedema. If an arrest of growth can be shown not to be due to disease or malnutrition, then hypothyroidism should be suspected, and the signs of diminished vitality, cold extremities, slow pulse, electrocardiographic abnormalities, raised blood cholesterol level, and low basal metabolic rate must be looked for. Gross destruction of the pituitary by tumour, by xanthomatosis or by inflammation is rare in children, and a craniopharyngioma as a cause of dwarfism is very uncommon. When these infrequent causes are excluded, there remains a large group of children in whom a cause for their dwarfism has still to be sought, and among them will be examples of pituitary dwarfism. The separation of the cases of pituitary dwarfism due to the absence of the growth hormone would be simple if it were possible to assay the level of growth hormone in the blood or to determine the quantity of its metabolized products in the urine. However, no such investigations are as yet possible, and to determine whether dwarfism is related to a deficiency of the growth hormone, it is necessary to depend on a clinical picture of pituitary dwarfism, and to look for evidence of the absence of the other pituitary hormones. The gonadotropic hormones are excreted in small quantities before puberty. Until the age of puberty arrives, and the average time of onset may extend from 10 to 15 years of age in girls and 11 to 16 years in boys, it is not possible to support a diagnosis of pituitary dwarfism by the absence of gonadotropic hormones whether directly or indirectly. The remaining two pituitary hormones are the thyrotropic and the adrenocorticotropic hormones. It is rarely possible to demonstrate any evidence of thyroid underaction in the absence of frank cretinism or myxoedema. Evidence of defective adrenocortical function should be sought in disturbances of carbohydrate metabolism, as in hypoglycaemia which may be due to a deficiency of the gluconeogenetic hormones of the adrenal cortex; in a disturbance of serum electrolytes together with