Two cases of adrenal hyperplasia with adrenal cortical insufficiency.

The adreno-genital syndrome in infancy is associated almost invariably with bilateral adrenal hyperplasia. The characteristic syndrome is a combination of hyperfunction of the genital hormones of the suprarenal, producing precocious virilism in males and pseudohermaphroditism in females, and hypofunction of the salt-water hormones resulting in an electrolyte imbalance of the Addisonian type. Glucose metabolism is usually unaffected. The condition has been frequently reported in two or more siblings. A general review of the subject has been written by Wilkins (1948). There are numerous cases described in the literature of adrenal hyperplasia in older children or adults with sexual changes, but no symptoms of adreno-cortical insufficiency. We do not propose to discuss these further, although it would be of interest to know details of the progress in infancy of such cases. Symptoms due to Adreno-cortical Inuficiency. The classical picture is of normal progress in the first week of life. The first symptom is usually vomiting, which may start at any time between one and six weeks, and is occasionally projectile in character. Several cases are recorded of laparotomy being performed for suspected pyloric stenosis or intestinal obstruction, and our second case was treated with pylostropin at one period. Associated with the vomiting there are usually small loose stools often containing mucus, marked lethargy, pyrexia, and frequently sweating. Dehydration appears early and is disproportionately great for the degree of vomiting. The symptoms are usually insidious in onset but become suddenly and dramatically worse, usually terminating in death between six and 12 weeks in untreated cases. The clinical picture is closely similar to that of Addison's disease, except that the glucose metabolism is usually normal (Wilkins, Fleischmann, and Howard, 1940; Jacobsen, Koepf, Talbot, and Wilkins, 1949). Pigmentation of the skin sometimes occurs (Butler, Ross, and Talbot, 1939; Wilkins et al., 1940). The clinical syndrome was first brought to general notice by Dijkhuizen and Behr in 1940, and since then fairly numerous reports have been made. BiocHmical Findings. Evidence that the symptoms were associated with low serum sodium and chloride levels and high serum potassium levels was provided by Butler et al. (1939) in a case later confirned bv laparotomy, and by Thelander and Cholffin (1941 and 1946) in a child who was kept alive till 6 years of age and died in an attack of measles. Two of the four cases recorded by Zuelzer and Blum (1949) had also had biochemical investigations. Cases with similar clinical and biochemical findings, where hyperplasia of the adrenals was probable but not proved, have also been reported (Darrow, 1943-4: Jacobsen et al., 1949). The largest group of cases are those not diagnosed during life and without biochemical investigation, but where the clinical history leaves little doubt that the symptoms were due to adreno-cortical insufficiency (Allibone, Baar. and Cant, 1947; Skelton, 1945; Blackman, 1946). Cases with Adreno-cortical Insufficiecy. The sexual changes are precocious development in boys and pseudohermaphroditism in girls. We give later the reasons for thinking that these changes are probably due to hyperplasia of the reticular zone. Only one definite case has been reported in a female with normal external genitalia (Dijkhuizen and Behr. 1940). Males usually appear normal at birth, but penile enlargement and sometimes pubic hair develop within a few weeks (Thelander and Cholhfin. 1941 and 1946; Butler et al., 1939). Few investigations of the ketosteroid output have been recorded in these cases. Talbot, Albright, Saltzman. Zygmuntowitz, and Wixom (1947) in a male of 8 years found a urinary 17-ketosteroid output of about 200 mg., and an 1 1-oxycorticosterone level of 0-36. Darrow (19434) in a male of 6 months found a urinary 17-ketosteroid output of 2 5 mg. Zuelzer and Blum (1949) comment that it would be worth investigating the urinary hormones of the mother in these cases. Jacobsen et al. (1949) says