17-β-Hydroxysteroid dehydrogenase III deficiency is clinically characterized by either ambiguous external genitalia or complete female external genitalia at birth; as a consequence of impaired male sexual differentiation in 46,XY individuals, as well as:

- Hypothyroidism

- Cryptorchidism

- Infertility

- Abnormality of metabolism

The symptoms of isolated 17,20-lyase deficiency, in males, include pseudohermaphroditism (i.e., feminized, ambiguous, or mildly underdeveloped (e.g., micropenis, perineal hypospadias, and/or cryptorchidism (undescended testes)) external genitalia), female gender identity, and, in non-complete cases of deficiency where partial virilization occurs, gynecomastia up to Tanner stage V (due to low androgen levels, which results in a lack of suppression of estrogen); in females, amenorrhoea or, in cases of only partial deficiency, merely irregular menses, and enlarged cystic ovaries (due to excessive stimulation by high levels of gonadotropins); and in both sexes, hypergonadotropic hypogonadism (hypogonadism despite high levels of gonadotropins), delayed, impaired, or fully absent adrenarche and puberty with an associated reduction in or complete lack of development of secondary sexual characteristics (sexual infantilism), impaired fertility or complete sterility, tall stature (due to delayed epiphyseal closure), eunuchoid skeletal proportions, delayed or absent bone maturation, and osteoporosis.

The excessive amounts of adrenal testosterone produce little effect on the genitalia of male infants with severe CAH. If a male infant with CAH is not detected by newborn screening, he will appear healthy and normal and be quickly discharged home to his family.

However, the lack of aldosterone results in a high rate of sodium loss in the urine. Urinary sodium concentrations may exceed 50 mEq/L. With this rate of salt loss, the infant cannot maintain blood volume, and hyponatremic dehydration begins to develop by the end of the first week of life. Potassium and acid excretion are also impaired when mineralocorticoid activity is deficient, and hyperkalemia and metabolic acidosis gradually develop. Ability to maintain circulation is further limited by the effect of cortisol deficiency. The early symptoms are spitting and poor weight gain, but most infants with severe CAH develop vomiting, severe dehydration, and circulatory collapse (shock) by the second or third week of life.

When brought to a hospital, the 1-3 week old infant will be both underweight and dehydrated by appearance. Blood pressure may be low. Basic chemistries will reveal hyponatremia, with a serum Na typically between 105 and 125 mEq/L. Hyperkalemia in these infants can be extreme—levels of K above 10 mEq/L are not unusual—as can the degree of metabolic acidosis. Hypoglycemia may be present. This is termed a salt-wasting crisis and rapidly causes death if not treated.

As ill as these infants can be, they respond rapidly to treatment with hydrocortisone and intravenous saline and dextrose quickly restores blood volume, blood pressure, and body sodium content, and reverses the hyperkalemia. With appropriate treatment, most infants are out of danger within 24 hours.

The symptoms of CAH vary depending upon the form of CAH and the sex of the patient. Symptoms can include:

Due to inadequate mineralocorticoids:

- vomiting due to salt-wasting leading to dehydration and death

Due to excess androgens:

- functional and average sized penis in cases involving extreme virilization (but no sperm)

- ambiguous genitalia, in some females, such that it can be initially difficult to identify external genitalia as "male" or "female".

- early pubic hair and rapid growth in childhood

- precocious puberty or failure of puberty to occur (sexual infantilism: absent or delayed puberty)

- excessive facial hair, virilization, and/or menstrual irregularity in adolescence

- infertility due to anovulation

- clitoromegaly, enlarged clitoris and shallow vagina

Due to insufficient androgens and estrogens:

- Undervirilization in XY males, which can result in apparently female external genitalia

- In females, hypogonadism can cause sexual infantilism or abnormal pubertal development, infertility, and other reproductive system abnormalities

Virilization of genetically female (XX) infants usually produces obvious genital ambiguity. Inside the pelvis, the ovaries are normal and since they have not been exposed to testicular antimullerian hormone (MIF), the uterus, fallopian tubes, upper vagina, and other mullerian structures are normally formed as well. However, the high levels of testosterone in the blood can enlarge the phallus, partially or completely close the vaginal opening, enclose the urethral groove so that it opens at the base of the phallus, on the shaft or even at the tip like a boy. Testosterone can cause the labial skin to become as thin and rugated as a scrotum, but cannot produce palpable gonads (i.e., testes) in the folds.

Thus, depending on the severity of hyperandrogenism, a female infant can be mildly affected, obviously ambiguous, or so severely virilized as to appear to be a male. Andrea Prader devised the following Prader scale as a way of describing the degree of virilization.

- An infant at stage 1 has a mildly large clitoris and slightly reduced vaginal opening size. This degree may go unnoticed or may be simply assumed to be within normal variation.

- Stages 2 and 3 represent progressively more severe degrees of virilization. The genitalia are obviously abnormal to the eye, with a phallus intermediate in size and a small vaginal opening.

- Stage 4 looks more male than female, with an empty scrotum and a phallus the size of a normal penis, but not quite free enough of the perineum to be pulled onto the abdomen toward the umbilicus (i.e., what is termed a chordee in a male). The single small urethral/vaginal opening at the base or on the shaft of the phallus would be considered a hypospadias in a male. X-rays taken after dye injection into this opening reveal the internal connection with the upper vagina and uterus. This common opening can predispose to urinary obstruction and infection.

- Stage 5 denotes complete male virilization, with a normally formed penis with the urethral opening at or near the tip. The scrotum is normally formed but empty. The internal pelvic organs include normal ovaries and uterus, and the vagina connects internally with the urethra as in Stage 4. These infants are not visibly ambiguous, and are usually assumed to be ordinary boys with undescended testes. In most cases, the diagnosis of CAH is not suspected until signs of salt-wasting develop a week later.

When the genitalia are determined to be ambiguous at birth, CAH is one of the leading diagnostic possibilities. Evaluation reveals the presence of a uterus, extreme elevation of 17OHP, levels of testosterone approaching or exceeding the male range but low AMH levels. The karyotype is that of an ordinary female: 46,XX. With this information, the diagnosis of CAH is readily made and female sex confirmed.

Evaluation of ambiguous genitalia is described in detail elsewhere. In most cases it is possible to confirm and assign female sex within 12–36 hours of birth. The exception are the rare, completely virilized genetic females (Prader stage 5), who present the most challenging assignment and surgery dilemmas, discussed below.

When the degree of ambiguity is obvious, corrective surgery is usually offered and performed. As reconstructive surgery on infant genitalia has become a focus of controversy, the issues are described in more detail below.

Congenital adrenal hyperplasia (CAH) are any of several autosomal recessive diseases resulting from mutations of genes for enzymes mediating the biochemical steps of production of mineralocorticoids, glucocorticoids or sex steroids from cholesterol by the adrenal glands (steroidogenesis).

Most of these conditions involve excessive or deficient production of sex steroids and can alter development of primary or secondary sex characteristics in some affected infants, children, or adults.

One of the main characteristics of this disorder is adrenal insufficiency, which is a reduction in adrenal gland function resulting from incomplete development of the gland's outer layer (the adrenal cortex). Adrenal insufficiency typically begins in infancy or in childhood and can cause vomiting, difficulty with feeding, dehydration, extremely low blood sugar (hypoglycemia), low sodium levels, and shock. However, adult-onset cases have also been described. See also Addison's Disease.

Affected males may also lack male sex hormones, which leads to underdeveloped reproductive tissues, undescended testicles (cryptorchidism), delayed puberty, and an inability to father children (infertility). These characteristics are known as hypogonadotropic hypogonadism. Females are rarely affected by this disorder, but a few cases have been reported of adrenal insufficiency or a lack of female sex hormones, resulting in underdeveloped reproductive tissues, delayed puberty, and an absence of menstruation.

17β-Hydroxysteroid dehydrogenase III deficiency is a rare disorder of sexual development, or intersex condition, affecting testosterone biosynthesis by 17β-hydroxysteroid dehydrogenase III (17β-HSD III), which can produce impaired virilization (historically termed male pseudohermaphroditism) of genetically male infants and children and excessive virilization of female adults. It is an autosomal recessive condition and is one of the few disorders of sexual development that can affect the primary and/or secondary sex characteristics of both males and females.

This syndrome is inherited as an autosomal disease. It affects both males and females but the phenotype differs. In both sexes sensorineural deafness occurs but in females ovarian dysgenesis also occurs.

XX gonadal dysgenesis is a type of female hypogonadism in which no functional ovaries are present to induce puberty in an otherwise normal girl whose karyotype is found to be 46,XX. With nonfunctional "streak" ovaries she is low in estrogen levels (hypoestrogenic) and has high levels of FSH and LH. Estrogen and progesterone therapy is usually then commenced.

The mineralocorticoid aspect of severe 3β-HSD CAH is similar to those of 21-hydroxylase deficiency. Like other enzymes involved in early stages of both aldosterone and cortisol synthesis, the severe form of 3β-HSD deficiency can result in life-threatening salt-wasting in early infancy. Salt-wasting is managed acutely with saline and high-dose hydrocortisone, and long-term fludrocortisone.

X-linked adrenal hypoplasia congenita is a genetic disorder that mainly affects males. It involves many endocrine tissues in the body, especially the adrenal glands.

Isolated 17,20-lyase deficiency (ILD), also called isolated 17,20-desmolase deficiency, is a rare endocrine and autosomal recessive genetic disorder which is characterized by a complete or partial loss of 17,20-lyase activity and, in turn, impaired production of the androgen and estrogen sex steroids. The condition manifests itself as pseudohermaphroditism (partially or fully underdeveloped genitalia) in males, in whom it is considered to be a form of intersex, and, in both sexes, as a reduced or absent puberty/lack of development of secondary sexual characteristics, resulting in a somewhat childlike appearance in adulthood (if left untreated).

Unlike the case of combined 17α-hydroxylase/17,20-lyase deficiency, isolated 17,20-lyase deficiency does not affect glucocorticoid production (or mineralocorticoid levels), and for that reason, does not result in adrenal hyperplasia or hypertension.

The symptoms of Leydig cell hypoplasia include pseudohermaphroditism (i.e., feminized, ambiguous, or relatively mildly underdeveloped (e.g., micropenis, severe hypospadias, and/or cryptorchidism (undescended testes)) external genitalia), a female gender identity or gender variance, hypergonadotropic hypogonadism (hypogonadism despite high levels of gonadotropins), delayed, impaired, or fully absent puberty with an associated reduction in or complete lack of development of secondary sexual characteristics (sexual infantilism), impaired fertility or complete sterility, tall stature (due to delayed epiphyseal closure), eunuchoid skeletal proportions, delayed or absent bone maturation, and osteoporosis.

Congenital adrenal hyperplasia due to 3β-hydroxysteroid dehydrogenase deficiency is an uncommon form of congenital adrenal hyperplasia (CAH) resulting from a mutation in the gene for one of the key enzymes in cortisol synthesis by the adrenal gland, 3β-hydroxysteroid dehydrogenase (3β-HSD) type II (HSD3B2). As a result, higher levels of 17OH-pregnenolone appear in the blood with adrenocorticotropic hormone (ACTH) challenge, which stimulates adrenal corticosteroid synthesis.

There is a wide spectrum of clinical presentations of 3β-HSD CAH, from mild to severe forms. The uncommon severe form results from a complete loss of enzymatic activity and manifests itself in infancy as salt wasting due to the loss of mineralocorticoids. Milder forms resulting from incomplete loss of 3β-HSD type II function do not present with adrenal crisis, but can still produce virilization of genetically female infants and undervirilization of genetically male infants. As a result, this form of primary hypoadrenalism is the only form of CAH that can cause ambiguous genitalia in both genetic sexes.

Approximately one-third of all women with Turner syndrome have a thyroid disorder. Usually it is hypothyroidism, specifically Hashimoto's thyroiditis. If detected, it can be easily treated with thyroid hormone supplements.

Leydig cell hypoplasia (or aplasia) (LCH), also known as Leydig cell agenesis, is a rare autosomal recessive genetic and endocrine syndrome affecting an estimated 1 in 1,000,000 genetic males. It is characterized by an inability of the body to respond to luteinizing hormone (LH), a gonadotropin which is normally responsible for signaling Leydig cells of the testicles to produce testosterone and other androgen sex hormones. The condition manifests itself as pseudohermaphroditism (partially or fully underdeveloped genitalia), hypergonadotropic hypogonadism (decreased or lack of production of sex steroids by the gonads despite high circulating levels of gonadotropins), reduced or absent puberty (lack of development of secondary sexual characteristics, resulting in sexual infantilism if left untreated), and infertility.

Leydig cell hypoplasia does not occur in biological females as they do not have either Leydig cells or testicles. However, the cause of the condition in males, luteinizing hormone insensitivity, does affect females, and because LH plays a role in the female reproductive system, it can result in primary amenorrhea or oligomenorrhea (absent or reduced menstruation), infertility due to anovulation, and ovarian cysts.

A related condition is follicle-stimulating hormone (FSH) insensitivity, which presents with similar symptoms to those of Leydig cell hypoplasia but with the symptoms in the respective sexes reversed (i.e., hypogonadism and sexual infantilism in females and merely problems with fertility in males). Despite their similar causes, FSH insensitivity is considerably less common in comparison to LH insensitivity.

Most infants born with lipoid 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).

The term “pure gonadal dysgenesis” (PGD) has been used to distinguish a group of patients from gonadal dysgenesis related to Turner syndrome. In the latter a distinct chromosomal aberration is present, while in PGD the chromosomal constellation is either 46,XX or 46,XY. Thus XX gonadal dysgenesis is also referred to as "PGD, 46 XX", and XY gonadal dysgenesis as "PGD, 46,XY" or Swyer syndrome. Patients with PGD have a normal chromosomal constellation but may have localized genetic alterations.

Turner syndrome does not typically cause intellectual disability or impair cognition. However, learning difficulties are common among women with Turner syndrome, particularly a specific difficulty in perceiving spatial relationships, such as nonverbal learning disorder. This may also manifest itself as a difficulty with motor control or with mathematics. While it is not correctable, in most cases it does not cause difficulty in daily living. Most Turner syndrome patients are employed as adults and lead productive lives.

Also, a rare variety of Turner syndrome, known as "Ring-X Turner syndrome", has about a 60% association with intellectual disability. This variety accounts for around 2–4% of all Turner syndrome cases.

As babies and children, XXY males may have weaker muscles and reduced strength. As they grow older, they tend to become taller than average. They may have less muscle control and coordination than other boys of their age.

During puberty, the physical traits of the syndrome become more evident; because these boys do not produce as much testosterone as other boys, they have a less muscular body, less facial and body hair, and broader hips. As teens, XXY males may develop breast tissue and also have weaker bones, and a lower energy level than other males.

By adulthood, XXY males look similar to males without the condition, although they are often taller. In adults, possible characteristics vary widely and include little to no sign of affectedness, a , youthful build and facial appearance, or a rounded body type with some degree of gynecomastia (increased breast tissue). Gynecomastia is present to some extent in about a third of affected individuals, a slightly higher percentage than in the XY population. About 10% of XXY males have gynecomastia noticeable enough that they may choose to have cosmetic surgery.

Affected males are often infertile, or may have reduced fertility. Advanced reproductive assistance is sometimes possible.

The term "hypogonadism" in XXY symptoms is often misinterpreted to mean "small testicles" when it means decreased testicular hormone/endocrine function. Because of this (primary) hypogonadism, individuals will often have a low serum testosterone level but high serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels. Despite this misunderstanding of the term, however, it is true that XXY men may also have microorchidism (i.e., small testicles).

The testicle size of affected males are usually less than 2 cm in length (and always shorter than 3.5 cm), 1 cm in width and 4 ml in volume.

XXY males are also more likely than other men to have certain health problems that typically affect females, such as autoimmune disorders, breast cancer, venous thromboembolic disease, and osteoporosis. In contrast to these potentially increased risks, it is currently thought that rare X-linked recessive conditions occur less frequently in XXY males than in normal XY males, since these conditions are transmitted by genes on the X chromosome, and people with two X chromosomes are typically only carriers rather than affected by these X-linked recessive conditions.

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.

Serkal syndrome is an autosomal recessive disorder in XX humans. It is caused by loss of function in WNT4, a protein involved in sex development. The main outcome is female to male sex reversal.

Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy's disease, is a severe neurodegenerative syndrome that is associated with a particular mutation of the androgen receptor's polyglutamine tract called a trinucleotide repeat expansion. SBMA results when the length of the polyglutamine tract exceeds 40 repetitions.

Although technically a variant of MAIS, SBMA's presentation is not typical of androgen insensitivity; symptoms do not occur until adulthood and include neuromuscular defects as well as signs of androgen inaction. Neuromuscular symptoms include progressive proximal muscle weakness, atrophy, and fasciculations. Symptoms of androgen insensitivity experienced by men with SBMA are also progressive and include testicular atrophy, severe oligospermia or azoospermia, gynecomastia, and feminized skin changes despite elevated androgen levels. Disease onset, which usually affects the proximal musculature first, occurs in the third to fifth decades of life, and is often preceded by muscular cramps on exertion, tremor of the hands, and elevated muscle creatine kinase. SBMA is often misdiagnosed as amyotrophic lateral sclerosis (ALS) (also known as Lou Gehrig's disease).

The symptoms of SBMA are thought to be brought about by two simultaneous pathways involving the toxic misfolding of proteins and loss of AR functionality. The polyglutamine tract in affected pedigrees tends to increase in length over generations, a phenomenon known as "anticipation", leading to an increase in the severity of the disease as well as a decrease in the age of onset for each subsequent generation of a family affected by SBMA.

Lipoid congenital adrenal hyperplasia is an endocrine disorder that is an uncommon and potentially lethal form of congenital adrenal hyperplasia (CAH). It arises from defects in the earliest stages of steroid hormone synthesis: the transport of cholesterol into the mitochondria and the conversion of cholesterol to pregnenolone—the first step in the synthesis of all steroid hormones. Lipoid CAH causes mineralocorticoid deficiency in affected infants and children. Male infants are severely undervirilized causing their external genitalia to look feminine. The adrenals are large and filled with lipid globules derived from cholesterol.

Although similar in some ways to true hermaphroditism, the conditions can be distinguished histologically and by karyotyping. The observable characteristics (phenotype) of this condition are highly variable, ranging from gonadal dysgenesis in males, to Turner-like females and phenotypically normal males. The phenotypical expression may be ambiguous, intersex, or male or female depending on the extent of the mosaicism. The most common presentation of 45,X/46,XY karyotype is phenotypically normal male, next being genital ambiguity.

There is a range of chromosomal anomalies within 45,X/46,XY where the variations are very complex, and the actual result in living individuals is often not a simple picture. Most patients with this karyotype are known to have abnormal gonadal histology and heights considerably below their genetic potential. High gonadotropin levels have been described in both male and female patients, as well as low levels of testosterone in male patients. Dosage loss of SHOX gene is commonly associated with short stature. Psychomotor development is normal.

As the gonads may not be symmetrical, the development of the Müllerian duct and Wolffian duct may be asymmetrical, too. Because of the presence of dysgenetic gonadal tissue and Y chromosome material, there is a high risk of the development of a gonadoblastoma.