Infertility observed in adult males with congenital adrenal hyperplasia (CAH) has been associated with testicular adrenal rest tumors (TART) that may originate during childhood. TART in prepubertal males with classic CAH could be found during childhood (20%). Martinez-Aguayo et al. reported differences in markers of gonadal function in a subgroup of patients, especially in those with inadequate control.

Most XY children are so undervirilized that they are raised as girls. The testes are uniformly nonfunctional and undescended; they are removed when the diagnosis is made due to the risk of cancer development in these tissues.

Nearly all mammals display sex-dimorphic reproductive and sexual behavior (e.g., lordosis and mounting in rodents). Much research has made it clear that prenatal and early postnatal androgens play a role in the differentiation of most mammalian brains. Experimental manipulation of androgen levels in utero or shortly after birth can alter adult reproductive behavior.

Girls and women with CAH constitute the majority of genetic females with normal internal reproductive hormones who have been exposed to male levels of testosterone throughout their prenatal lives. Milder degrees of continuing androgen exposure continue throughout childhood and adolescence as a consequence of the imperfections of current glucocorticoid treatment for CAH. The psychosexual development of these girls and women has been analyzed as evidence of the role of androgens in human sex-dimorphic behaviors.

Girls with CAH have repeatedly been reported to spend more time with "sex-atypical" toys and "rough-and-tumble" play than unaffected sisters. These differences continue into adolescent, as expressed in social behaviors, leisure activities, and career interests. Interest in babies and becoming mothers is significantly lower by most measures.

Cognitive effects are less clear, and reports have been contradictory. Two studies reported spatial abilities above the average for sisters and for girls in general. Other evidence in males with and without androgen deficiencies suggests that androgens may play a role in these aptitudes.

However, gender identity of girls and women with CAH is nearly always unequivocally female. Sexual orientation is more mixed, though the majority are heterosexual. In one study, 27% of women with CAH were rated as bisexual in their orientations. Abnormalities of body image due to the effects of the disease likely play a role in the sexual development of these women, and one cannot conclude that the androgens are the major determinant of their sexuality.

Lipoid CAH is quite rare in European and North American populations. Most cases occur in Japan and Korea (where the incidence is 1 in 300,000 births) and Palestinian Arabs. Despite autosomal inheritance, there has been an unexplained preponderance of genetic females in reported cases.

The incidence varies geographically. In the United States, congenital adrenal hyperplasia is particularly common in Native Americans and Yupik Eskimos (incidence ). Among American Caucasians, the incidence is approximately ).

Hypertension and mineralocorticoid excess is treated with glucocorticoid replacement, as in other forms of CAH.

Most genetic females with both forms of the deficiency will need replacement estrogen to induce puberty. Most will also need periodic progestin to regularize menses. Fertility is usually reduced because egg maturation and ovulation is poorly supported by the reduced intra-ovarian steroid production.

The most difficult management decisions are posed by the more ambiguous genetic (XY) males. Most who are severely undervirilized, looking more female than male, are raised as females with surgical removal of the nonfunctional testes. If raised as males, a brief course of testosterone can be given in infancy to induce growth of the penis. Surgery may be able to repair the hypospadias. The testes should be salvaged by orchiopexy if possible. Testosterone must be replaced in order for puberty to occur and continued throughout adult life.

Further variability is introduced by the degree of enzyme inefficiency produced by the specific alleles each patient has. Some alleles result in more severe degrees of enzyme inefficiency. In general, severe degrees of inefficiency produce changes in the fetus and problems in prenatal or perinatal life. Milder degrees of inefficiency are usually associated with excessive or deficient sex hormone effects in childhood or adolescence, while the mildest forms of CAH interfere with ovulation and fertility in adults.

Because 11β-hydroxylase activity is not necessary in the production of sex steroids (androgens and estrogens), the hyperplastic adrenal cortex produces excessive amounts of DHEA, androstenedione, and especially testosterone.

These androgens produce effects that are similar to those of 21-hydroxylase deficient CAH. In the severe forms, XX (genetically female) fetuses can be markedly virilized, with ambiguous genitalia that look more male than female, though internal female organs, including ovaries and uterus develop normally.

XY fetuses (genetic males) typically show no abnormal features related to androgen excess. A megalopenis (>22 cm/8.7in) is usually present in male patients.

In milder mutations, androgen effects in both sexes appear in mid-childhood as early pubic hair, overgrowth, and accelerated bone age. Although "nonclassic" forms causing hirsutism and menstrual irregularities and appropriate steroid elevations have been reported, most have not had verifiable mutations and mild 11β-hydroxylase deficient CAH is currently considered a very rare cause of hirsutism and infertility.

All of the issues related to virilization, neonatal assignment, advantages and disadvantages of genital surgery, childhood and adult virilization, gender identity and sexual orientation are similar to those of 21-hydroxylase CAH and elaborated in more detail in Congenital adrenal hyperplasia.

As with other forms of CAH, the primary therapy of 11β-hydroxylase deficient CAH is lifelong glucocorticoid replacement in sufficient doses to prevent adrenal insufficiency and suppress excess mineralocorticoid and androgen production.

Salt-wasting in infancy responds to intravenous saline, dextrose, and high dose hydrocortisone, but prolonged fludrocortisone replacement is usually not necessary. The hypertension is ameliorated by glucocorticoid suppression of DOC.

Long term glucocorticoid replacement issues are similar to those of 21-hydroxylase CAH, and involve careful balance between doses sufficient to suppress androgens while avoiding suppression of growth. Because the enzyme defect does not affect sex steroid synthesis, gonadal function at puberty and long-term fertility should be normal if adrenal androgen production is controlled. See congenital adrenal hyperplasia for a more detailed discussion of androgen suppression and fertility potential in adolescent and adult women.

All causes in this category are genetic, and generally very rare. These include mutations to the "SF1" transcription factor, congenital adrenal hypoplasia due to "DAX-1" gene mutations and mutations to the ACTH receptor gene (or related genes, such as in the Triple A or Allgrove syndrome). "DAX-1" mutations may cluster in a syndrome with glycerol kinase deficiency with a number of other symptoms when "DAX-1" is deleted together with a number of other genes.

The sex steroid consequences of severe 3β-HSD CAH are unique among the congenital adrenal hyperplasias: it is the only form of CAH that can produce ambiguity in both sexes. As with 21-hydroxylase deficient CAH, the degree of severity can determine the magnitude of over- or undervirilization.

In an XX (genetically female) fetus, elevated amounts of DHEA can produce moderate virilization by conversion in the liver to testosterone. Virilization of genetic females is partial, often mild, and rarely raises assignment questions. The issues surrounding corrective surgery of the virilized female genitalia are the same as for moderate 21-hydroxylase deficiency but surgery is rarely considered desirable.

The extent to which mild 3β-HSD CAH can cause early appearance of pubic hair and other aspects of hyperandrogenism in later childhood or adolescence is unsettled. Early reports about 20 years ago suggesting that mild forms of 3β-HSD CAH comprised significant proportions of girls with premature pubic hair or older women with hirsutism have not been confirmed and it now appears that premature pubarche in childhood and hirsutism after adolescence are not common manifestations of 3β-HSD CAH.

Undervirilization of genetic males with 3β-HSD CAH occurs because synthesis of testosterone is impaired in both adrenals and testes. Although DHEA is elevated, it is a weak androgen and too little testosterone is produced in the liver to offset the deficiency of testicular testosterone. The degree of undervirilization is more variable, from mild to severe. Management issues are those of an undervirilized male with normal sensitivity to testosterone.

If the infant boy is only mildly undervirilized, the hypospadias can be surgically repaired, testes brought into the scrotum, and testosterone supplied at puberty.

Management decisions are more difficult for a moderately or severely undervirilized genetic male whose testes are in the abdomen and whose genitalia look at least as much female as male. Male sex can assigned and major reconstructive surgery done to close the midline of the perineum and move the testes into a constructed scrotum. Female sex can be assigned and the testes removed and vagina enlarged surgically. A recently advocated third choice would be to assign either sex and defer surgery to adolescence. Each approach carries its own disadvantages and risks. Children and their families are different enough that none of the courses is appropriate for all.

Congenital adrenal hyperplasia due to 17α-hydroxylase deficiency is an uncommon form of congenital adrenal hyperplasia resulting from a defect in the gene CYP17A1, which encodes for the enzyme 17α-hydroxylase. It produces decreased synthesis of both cortisol and sex steroids, with resulting increase in mineralocorticoid production. Thus, common symptoms include mild hypocortisolism, ambiguous genitalia in genetic males or failure of the ovaries to function at puberty in genetic females, and hypokalemic hypertension (respectively). However, partial (incomplete) deficiency is notable for having inconsistent symptoms between patients, and affected genetic (XX) females may be wholly asymptomatic except for infertility.

Some of the childhood management issues are similar those of 21-hydroxylase deficiency:

- Replacing mineralocorticoid with fludrocortisone

- Suppressing DHEA and replacing cortisol with glucocorticoid

- Providing extra glucocorticoid for stress

- Close monitoring and perhaps other adjunctive measures to optimize growth

- Deciding whether surgical repair of virilized female genitalia is warranted

However, unlike 21-hydroxylase CAH, children with 3β-HSD CAH may be unable to produce adequate amounts of testosterone (boys) or estradiol (girls) to effect normal pubertal changes. Replacement testosterone or estrogen and progesterone can be initiated at adolescence and continued throughout adult life. Fertility may be impaired by the difficulty of providing appropriate sex hormone levels in the gonads even though the basic anatomy is present.

Because hyperandrogenism can appear as a symptom of numerous different genetic and medical conditions, it is difficult to make a general statement on whether hyperandrogenic symptoms can be passed from parent to offspring. However, a collection of the conditions with hyperandrogenic symptoms, including polycystic ovary syndrome, have been observed as hereditary in certain cases. One potential cause of polycystic ovary syndrome is maternal hyperandrogenism, where the hormonal irregularities of the mother can affect the development of the child during gestation, resulting in the passing of polycystic ovary syndrome from mother to child.

Treatment of HH is usually with hormone replacement therapy, consisting of androgen and estrogen administration in males and females, respectively.

Outcomes are typically good when treated. Most can expect to live relatively normal lives. Someone with the disease should be observant of symptoms of an "Addison's crisis" while the body is strained, as in rigorous exercise or being sick, the latter often needing emergency treatment with intravenous injections to treat the crisis.

Individuals with Addison's disease have more than a doubled mortality rate. Furthermore, individuals with Addison's disease and diabetes mellitus have an almost 4 time increase in mortality compared to individuals with only diabetes.

To form cortisol, the adrenal gland requires cholesterol, which is then converted biochemically into steroid hormones. Interruptions in the delivery of cholesterol include Smith-Lemli-Opitz syndrome and abetalipoproteinemia.

Of the synthesis problems, congenital adrenal hyperplasia is the most common (in various forms: 21-hydroxylase, 17α-hydroxylase, 11β-hydroxylase and 3β-hydroxysteroid dehydrogenase), lipoid CAH due to deficiency of StAR and mitochondrial DNA mutations. Some medications interfere with steroid synthesis enzymes (e.g. ketoconazole), while others accelerate the normal breakdown of hormones by the liver (e.g. rifampicin, phenytoin).

Iatrogenic Cushing's syndrome (caused by treatment with corticosteroids) is the most common form of Cushing's syndrome. Cushing's disease is rare; a Danish study found an incidence of less than one case per million people per year. However, asymptomatic microadenomas (less than 10 mm in size) of the pituitary are found in about one in six individuals.

People with Cushing's syndrome have increased morbidity and mortality as compared to the general population. The most common cause of mortality in Cushing's syndrome is cardiovascular events. People with Cushing's syndrome have nearly 4 times increased cardiovascular mortality as compared to the general population.

The frequency rate of Addison's disease in the human population is sometimes estimated at roughly one in 100,000. Some put the number closer to 40–144 cases per million population (1/25,000–1/7,000). Addison's can affect persons of any age, sex, or ethnicity, but it typically presents in adults between 30 and 50 years of age. Research has shown no significant predispositions based on ethnicity.

Symptoms generally considered hyperandrogenic can also manifest as results of consuming certain drugs. This can happen according to one of five major mechanisms, namely the direct introduction of androgens to the body, the binding of the drug to androgen receptors and subsequent participation in androgenic action (as is the case with anabolic-androgenic steroids), the reduction of sex hormone-binding globulin plasma concentration that leads to a resulting increase in free testosterone, the interference with and alteration of the hypothalamic–pituitary–ovarian (HPO) axis, or the increase in release of adrenal androgens.

Adrenal gland disorders (or diseases) are conditions that interfere with the normal functioning of the adrenal glands. Adrenal disorders may cause hyperfunction or hypofunction, and may be congenital or acquired.

The adrenal gland produces hormones that affects growth, development and stress, and also helps to regulate kidney function. There are two parts of the adrenal glands, the adrenal cortex and the adrenal medulla. The adrenal cortex produces mineralocorticoids, which regulate salt and water balance within the body, glucocorticoids (including cortisol) which have a wide number of roles within the body, and androgens, hormones with testosterone-like function. The adrenal medulla produces epinephrine (adrenaline) and norepinephrine (noradrenaline). Disorders of the adrenal gland may affect the production of one or more of these hormones.

There are a multitude of different etiologies of HH. Congenital causes include the following:

- Chromosomal abnormalities (resulting in gonadal dysgenesis) - Turner's syndrome, Klinefelter's syndrome, Swyer's syndrome, XX gonadal dysgenesis, and mosaicism.

- Defects in the enzymes involved in the gonadal biosynthesis of the sex hormones - 17α-hydroxylase deficiency, 17,20-lyase deficiency, 17β-hydroxysteroid dehydrogenase III deficiency, and lipoid congenital adrenal hyperplasia.

- Gonadotropin resistance (e.g., due to inactivating mutations in the gonadotropin receptors) - Leydig cell hypoplasia (or insensitivity to LH) in males, FSH insensitivity in females, and LH and FSH resistance due to mutations in the "GNAS" gene (termed pseudohypoparathyroidism type 1A).

Acquired causes (due to damage to or dysfunction of the gonads) include ovarian torsion, vanishing/anorchia, orchitis, premature ovarian failure, ovarian resistance syndrome, trauma, surgery, autoimmunity, chemotherapy, radiation, infections (e.g., sexually-transmitted diseases), toxins (e.g., endocrine disruptors), and drugs (e.g., antiandrogens, opioids, alcohol).

The most common cause of Cushing's syndrome is the taking of glucocorticoids prescribed by a health care practitioner to treat other diseases (called iatrogenic Cushing's syndrome). This can be an effect of corticosteroid treatment of a variety of disorders such as asthma and rheumatoid arthritis, or in immunosuppression after an organ transplant. Administration of synthetic ACTH is also possible, but ACTH is less often prescribed due to cost and lesser utility. Although rare, Cushing's syndrome can also be due to the use of medroxyprogesterone acetate. In this form of Cushing's, the adrenal glands atrophy due to lack of stimulation by ACTH, since glucocorticoids downregulate production of ACTH. Cushing's syndrome in childhood usually results from use of glucocorticoid medication.

Endogenous Cushing's syndrome results from some derangement of the body's own system of secreting cortisol. Normally, ACTH is released from the pituitary gland when necessary to stimulate the release of cortisol from the adrenal glands.

- In pituitary Cushing's, a benign pituitary adenoma secretes ACTH. This is also known as Cushing's disease and is responsible for 70% of endogenous Cushing's syndrome.

- In adrenal Cushing's, excess cortisol is produced by adrenal gland tumors, hyperplastic adrenal glands, or adrenal glands with nodular adrenal hyperplasia.

- Tumors outside the normal pituitary-adrenal system can produce ACTH (occasionally with CRH) that affects the adrenal glands. This etiology is called ectopic or paraneoplastic Cushing's disease and is seen in diseases such as small cell lung cancer.

- Finally, rare cases of CRH-secreting tumors (without ACTH secretion) have been reported, which stimulates pituitary ACTH production.

The condition is due to:

- Bilateral idiopathic (micronodular) adrenal hyperplasia (66%)

- Adrenal adenoma (Conn's syndrome) (33%)

- Primary (unilateral) adrenal hyperplasia—2% of cases

- Aldosterone-producing adrenocortical carcinoma—<1% of cases

- Familial Hyperaldosteronism (FH)

- Glucocorticoid-remediable aldosteronism (FH type I)—<1% of cases

- FH type II (APA or IHA)—<2% of cases

- Ectopic aldosterone-producing adenoma or carcinoma—< 0.1% of cases

Hirsutism can be caused by either an increased level of androgens, the male hormones, or an oversensitivity of hair follicles to androgens. Male hormones such as testosterone stimulate hair growth, increase size and intensify the growth and pigmentation of hair. Other symptoms associated with a high level of male hormones include acne, deepening of the voice, and increased muscle mass. The condition is called hyperandrogenism.

Growing evidence implicates high circulating levels of insulin in women for the development of hirsutism. This theory is speculated to be consistent with the observation that obese (and thus presumably insulin resistant hyperinsulinemic) women are at high risk of becoming hirsute. Further, treatments that lower insulin levels will lead to a reduction in hirsutism.

It is speculated that insulin, at high enough concentration, stimulates the ovarian theca cells to produce androgens. There may also be an effect of high levels of insulin to activate insulin-like growth factor 1 (IGF-1) receptor in those same cells. Again, the result is increased androgen production.

Signs that are suggestive of an androgen-secreting tumor in a patient with hirsutism is rapid onset, virilization and palpable abdominal mass.

The following are conditions and situations that have been associated with hyperandrogenism and hence hirsutism in women:

- Hyperinsulinemia (insulin excess) or hypoinsulinemia (insulin deficiency or resistance as in diabetes).

- Ovarian cysts such as in polycystic ovary syndrome (PCOS), the most common cause in women.

- Ovarian tumors such as granulosa tumors, thecomas, Sertoli–Leydig cell tumors (androblastomas), and gynandroblastomas, as well as ovarian cancer.

- Hyperthecosis.

- Pregnancy.

- Adrenal gland tumors, adrenocortical adenomas, and adrenocortical carcinoma, as well as adrenal hyperplasia due to pituitary adenomas (as in Cushing's syndrome).

- hCG-secreting tumors

- Inborn errors of steroid metabolism such as in congenital adrenal hyperplasia, most commonly caused by 21-hydroxylase deficiency.

- Acromegaly and gigantism (growth hormone and IGF-1 excess), usually due to pituitary tumors.

- Use of certain medications such as androgens/anabolic steroids, phenytoin, and minoxidil.

Causes of hirsutism not related to hyperandrogenism include:

- Porphyria cutanea tarda.

- Minoxidil