Cold stress and congenital adrenal hyperplasia heterozygotes

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is common in certain regions of the world characterised by cold winters. The persistence of this potentially lethal recessively inherited disease suggests that an evolutionary advantage is conferred upon the partially affected heterozygotes. Profound hypothermia following acute cold exposure in normal subjects carries a considerable mortality especially from cardiac arrhythmias and dehydration. A hypothesis is proposed to suggest that the incomplete block at the 21-hydroxylase step of steroid biosynthesis decreases stress-induced steroid responses, especially in the younger heterozygote and clinically non-salt-losing homozygote; glucocorticoid and mineralocorticoid insufficiency reduces the severity of cold-induced water diuresis; prevention of severe dehydration contributes towards the ability to survive profound hypothermia. Studies into the salt and water metabolism of the congenital adrenal hyperplasia heterozygote at various ages as well as examination of antidiuretic hormone and steroid hormone interactions upon the renal tubule in cold-exposed normal individuals are merited.