Problems that emerge in persons with<unk>  CAH can be divided into: # mineralocorticoid deficiency, # glucocorticoid deficiency, # sex steroid deficiency, and # damage to gonads caused by<unk>  accumulation. Mineralocorticoid deficiency Most infants born with<unk>  CAH have had genitalia female enough that no disease was suspected at birth. Because the adrenal zona glomerulosa is undifferentiated and inactive before delivery, it is undamaged at birth and can make aldosterone for a while, so the eventual salt-wasting crisis develops more gradually and variably than with severe 21-hydroxylase-deficient CAH. Most come to medical attention between 2 weeks and 3 months of age, when after a period of poor weight gain and vomiting, they were found to be dehydrated, with severe hyponatremia, hyperkalemia, and metabolic acidosis ("Addisonian or adrenal crisis"). Renin but not aldosterone is elevated. Many infants born with this condition died before a method for diagnosis was recognized for proper treatment to begin. In some cases, the condition is more mild with signs and symptoms of mineralocorticoid and glucocorticoid deficiency appearing after months or even years (late onset). Glucocorticoid deficiency Insufficiency of cortisol synthesis has several consequences. Elevated ACTH is accompanied by and contributes to marked hyperpigmentation even in the newborn period. An inadequate cortisol response to stress undoubtedly hastens the deterioration as dehydration develops, can cause hypoglycemia, and contributes to the high mortality rate in infancy. Sex steroid deficiency and gonadal damage In development Prenatal production of DHEA by the fetal adrenal glands is impaired, resulting in abnormally low maternal estriol levels by the middle of pregnancy. The effects of impaired progesterone production from placental cells that originate from the affected baby (trophoblasts) in the case of<unk>  CAH due to P450scc deficiency are still unclear, but are thought to result in miscarriage when the deficit in the enzyme's activity are severe enough. The results of reduced or absent testosterone output by fetal Leydig cells in the male is detailed below. Female patients Genetic XX females with<unk>  CAH are born with normal external and internal pelvic anatomy. They come to medical attention when they develop a salt-wasting adrenal crisis or other signs of progressive adrenal insufficiency. With glucocorticoid and mineralocorticoid replacement, these girls will reach the age of puberty. Because the ovaries are relatively inactive in fetal life and childhood, they sustain little damage from<unk>  accumulation during childhood. In the case of<unk>  CAH due to StAR deficiency, when rising gonadotropin levels initiate puberty, despite the inefficiency of sex steroid synthesis, the ovaries will usually make enough estradiol to produce breast development, and in some cases even menarche, with menses continuing for some years. Ovarian and adrenal androgen production is minimal and produces little pubic or other body hair. However insufficient estradiol and progesterone are produced to induce maturation of an egg and ovulation. Although prepubertal ovaries are inactive enough that no<unk>  accumulates to cause damage, once they have begun to produce estrogen,<unk>  damage begins to accrue and the ability to produce estrogen, as well as ovulate, is slowly degraded. Cysts also form in the ovaries. Women with<unk>  CAH have been infertile presumably due to anovulation. Male patients The genitalia of XY fetuses with<unk>  CAH are severely undervirilized due to impairment of steroid hormone synthesis. The fetal testes make AMH, which prevents a uterus and inner vagina from forming, but since the Leydig cells fail to make testosterone during development even in response to hCG, the testes are usually remain in the abdomen or lodge in the inguinal canals (undescended testes) and are nonfunctional. Consequently, XY patients do not undergo puberty and remain infertile. In addition to the testes remaining inside, formation of the penis, also dependent on testosterone, is compromised. Hence, the external genitalia in most of infants resemble that of normal females (though the vagina is a short, blind pouch), or is slightly ambiguous (more female than male). Nearly all reported XY cases have been assumed to be girls and raised as such. Late onset forms of the disease Milder cases of<unk>  CAH have been described that arise from less severe mutations that compromise but do not eliminate the ability of StAR to instigate steroid production. In these cases, mineralocorticoid deficiency emerges up to several years after birth. Sex steroid production may be sufficient to allow for normal sexual development as well and even fertility. These nonclassic forms of the disorder are sometimes diagnosed as familial glucocorticoid deficiency type 3.
Lipoid congenital adrenal hyperplasia
Late onset congenital adrenal hyperplasia
Congenital adrenal hyperplasia
Primary pigmented nodular adrenocortical disease
Persistent adrenarche syndrome
X-linked adrenal hypoplasia congenita
Congenital iodine deficiency syndrome
Kallmann syndrome