Currently, in the United States and over 40 other countries, every child born is screened for 21-hydroxylaase CAH at birth. This test will detect elevated levels of 17-hydroxy-progesterone (17-OHP). Detecting high levels of 17-OHP enables early detection of CAH. Newborns detected early enough can be placed on medication and live a relatively normal life.

The screening process, however, is characterized by a high false positive rate. In one study, CAH screening had the lowest positive predictive value (111 true-positive cases among 20,647 abnormal screening results in a 2-year period, or 0.53%, compared with 6.36% for biotinidase deficiency, 1.84% for congenital hypo-thyroidism, 0.56% for classic galactosemia, and 2.9% for phenylketonuria). According to this estimate, 200 unaffected newborns required clinical and laboratory follow-up for every true case of CAH.

Genetic analysis can be helpful to confirm a diagnosis of CAH but it is not necessary if classic clinical and laboratory findings are present.

In classic 21-hydroxylase deficiency, laboratory studies will show:

Classic 21-hydroxylase deficiency typically causes 17α-hydroxyprogesterone blood levels >242 nmol/L. (For comparison, a full-term infant at three days of age should have <3 nmol/L. Many neonatal screening programs have specific reference ranges by weight and gestational age because high levels may be seen in premature infants without CAH.) Salt-wasting patients tend to have higher 17α-hydroxyprogesterone levels than non-salt-wasting patients. In mild cases, 17α-hydroxyprogesterone may not be elevated in a particular random blood sample, but it will rise during a corticotropin stimulation test.

Conditions justifying newborn screening for any disorder include (1) a simple test with an acceptable sensitivity and specificity, (2) a dire consequence if not diagnosed early, (3) an effective treatment if diagnosed, and (4) a frequency in the population high enough to justify the expense. In the last decade more states and countries are adopting newborn screening for salt-wasting CAH due to 21-hydroxylase deficiency, which leads to death in the first month of life if not recognized.

The salt-wasting form of CAH has an incidence of 1 in 15,000 births and is potentially fatal within a month if untreated. Steroid replacement is a simple, effective treatment. However, the screening test itself is less than perfect. While the 17α-hydroxyprogesterone level is easy to measure and sensitive (rarely missing real cases), the test has a poorer specificity. Screening programs in the United States have reported that 99% of positive screens turn out to be false positives upon investigation of the infant. This is a higher rate of false positives than the screening tests for many other congenital metabolic diseases.

When a positive result is detected, the infant must be referred to a pediatric endocrinologist to confirm or disprove the diagnosis. Since most infants with salt-wasting CAH become critically ill by 2 weeks of age, the evaluation must be done rapidly despite the high false positive rate.

Levels of 17α-hydroxyprogesterone, androstenedione, and cortisol may play a role in screening.

Like the other forms of CAH, suspicion of severe 3β-HSD CAH is usually raised by the appearance of the genitalia at birth or by development of a salt-wasting crisis in the first month of life. The diagnosis is usually confirmed by the distinctive pattern of adrenal steroids: elevated pregnenolone, 17α-hydroxypregnenolone, DHEA, and renin. In clinical circumstances this form of CAH has sometimes been difficult to distinguish from the more common 21-hydroxylase deficient CAH because of the 17OHP elevation, or from simple premature adrenarche because of the DHEA elevation.

Since CAH is an autosomal recessive disease, most children with CAH are born to parents unaware of the risk and with no family history. Each child will have a 25% chance of being born with the disease. Families typically wish to minimize the degree of virilization of a girl. There is no known prenatal harm to a male fetus from CAH, so treatment can begin at birth.

Adrenal glands of female fetuses with CAH begin producing excess testosterone by the 9th week of gestation. The most important aspects of virilization (urogenital closure and phallic urethra) occur between 8 and 12 weeks. Theoretically, if enough glucocorticoid could be supplied to the fetus to reduce adrenal testosterone production by the 9th week, virilization could be prevented and the difficult decision about timing of surgery avoided.

The challenge of preventing severe virilization of girls is twofold: detection of CAH at the beginning of the pregnancy, and delivery of an effective amount of glucocorticoid to the fetus without causing harm to the mother.

The first problem has not yet been entirely solved, but it has been shown that if dexamethasone is taken by a pregnant woman, enough can cross the placenta to suppress fetal adrenal function.

At present no program screens for risk in families who have not yet had a child with CAH. For families desiring to avoid virilization of a second child, the current strategy is to start dexamethasone as soon as a pregnancy has been confirmed even though at that point the chance that the pregnancy is a girl with CAH is only 12.5%. Dexamethasone is taken by the mother each day until it can be safely determined whether she is carrying an affected girl.

Whether the fetus is an affected girl can be determined by chorionic villus sampling at 9–11 weeks of gestation, or by amniocentesis at 15–18 weeks gestation. In each case the fetal sex can be determined quickly, and if the fetus is a male the dexamethasone can be discontinued. If female, fetal DNA is analyzed to see if she carries one of the known abnormal alleles of the "CYP21" gene. If so, dexamethasone is continued for the remainder of the pregnancy at a dose of about 1 mg daily.

Most mothers who have followed this treatment plan have experienced at least mild cushingoid effects from the glucocorticoid but have borne daughters whose genitalia are much less virilized.

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.

Management of salt-wasting crises and mineralocorticoid treatment are as for other forms of salt-wasting congenital adrenal hyperplasias: saline and fludrocortisone.

Glucocorticoids can be provided at minimal replacement doses because there is no need for suppression of excessive adrenal androgens or mineralocorticoids. As with other forms of adrenal insufficiency, extra glucocorticoid is needed for stress coverage.

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.

The best diagnostic tool to confirm adrenal insufficiency is the ACTH stimulation test; however, if a patient is suspected to be suffering from an acute adrenal crisis, immediate treatment with IV corticosteroids is imperative and should not be delayed for any testing, as the patient's health can deteriorate rapidly and result in death without replacing the corticosteroids.

Dexamethasone should be used as the corticosteroid if the plan is to do the ACTH stimulation test at a later time as it is the only corticosteroid that will not affect the test results.

If not performed during crisis, then labs to be run should include: random cortisol, serum ACTH, aldosterone, renin, potassium and sodium. A CT of the adrenal glands can be used to check for structural abnormalities of the adrenal glands. An MRI of the pituitary can be used to check for structural abnormalities of the pituitary. However, in order to check the functionality of the Hypothalamic Pituitary Adrenal (HPA) Axis the entire axis must be tested by way of ACTH stimulation test, CRH stimulation test and perhaps an Insulin Tolerance Test (ITT). In order to check for Addison’s Disease, the auto-immune type of primary adrenal insufficiency, labs should be drawn to check 21-hydroxylase autoantibodies.

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.

"Congenital adrenal hyperplasia" (CAH) refers to any of several autosomal recessive diseases resulting from defects in steps of the synthesis of cortisol from cholesterol by the adrenal glands. All of the forms of CAH involve excessive or defective production of sex steroids and can prevent or impair development of primary or secondary sex characteristics in affected infants, children, and adults. Many also involve excessive or defective production of mineralocorticoids, which can cause hypertension or salt wasting, respectively.

The most common type of CAH is due to deficiency of 21-hydroxylase. 11β-Hydroxylase deficient congenital adrenal hyperplasia is one of the less common types of CAH due to deficiencies of other proteins and enzymes involved in cortisol synthesis. Other uncommon types are described in individual articles (links below).

11β-OH CAH resembles 21-hydroxylase deficient CAH in its androgenic manifestations: partial virilization and ambiguous genitalia of genetically female infants, childhood virilization of both sexes, and rarer cases of virilization or infertility of adolescent and adult women. The mineralocorticoid effect differs: hypertension is usually the clinical clue that a patient has 11- rather than 21-hydroxylase CAH. Diagnosis of 11β-OH CAH is usually confirmed by demonstration of marked elevations of 11-deoxycortisol and 11-deoxycorticosterone (DOC), the substrates of 11β-hydroxylase. Management is similar to that of 21-hydroxylase deficient CAH except that mineralocorticoids need not be replaced.

XX females with lipoid CAH may need estrogen replacement at or after puberty. Active intervention has been used to preserve the possibility of fertility and conception in lipoid CAH females. In a case report in 2009, a woman with late onset lipoid CAH due to StAR deficiency underwent hormone replacement therapy in combination with an assisted fertility technique, intracytoplasmic sperm injection. This led to ovulation and with implantation of the in vitro fertilized egg, a successful birth.

Female patients may show symptoms of hyperandrogenism in their early life, but physicians become more concerned when the patient is in her late teens or older.

Hyperandrogenism is most often diagnosed by checking for signs of hirsutism according to a standardized method that scores the range of excess hair growth.

Checking medical history and a physical examination of symptoms are used for an initial diagnosis. Patient history assessed includes age at thelarche, adrenarche, and menarche; patterns of menstruation; obesity; reproductive history; and the start and advancement of hyperandrogenism symptoms. Patterns of menstruation are examined since irregular patterns may appear with hirsutism. Family history is also assessed for occurrences of hyperandrogenism symptoms or obesity in other family members.

A laboratory test can also be done on the patient to evaluate levels of FSH, LH, DHEAS, prolactin, 17OHP, and total and free testosterone in the patient's blood. Abnormally high levels of any of these hormones help in diagnosing hyperandrogenism.

In suspected cases of Addison's disease, demonstration of low adrenal hormone levels even after appropriate stimulation (called the ACTH stimulation test or synacthen test) with synthetic pituitary ACTH hormone tetracosactide is needed for the diagnosis. Two tests are performed, the short and the long test. It should be noted that dexamethasone does not cross-react with the assay and can be administered concomitantly during testing.

The short test compares blood cortisol levels before and after 250 micrograms of tetracosactide (intramuscular or intravenous) is given. If, one hour later, plasma cortisol exceeds 170 nmol/l and has risen by at least 330 nmol/l to at least 690 nmol/l, adrenal failure is excluded. If the short test is abnormal, the long test is used to differentiate between primary adrenal insufficiency and secondary adrenocortical insufficiency.

The long test uses 1 mg tetracosactide (intramuscular). Blood is taken 1, 4, 8, and 24 hr later. Normal plasma cortisol level should reach 1000 nmol/l by 4 hr. In primary Addison's disease, the cortisol level is reduced at all stages, whereas in secondary corticoadrenal insufficiency, a delayed but normal response is seen.

Other tests may be performed to distinguish between various causes of hypoadrenalism, including renin and adrenocorticotropic hormone levels, as well as medical imaging - usually in the form of ultrasound, computed tomography or magnetic resonance imaging.

Adrenoleukodystrophy, and the milder form, adrenomyeloneuropathy, cause adrenal insufficiency combined with neurological symptoms. These diseases are estimated to be the cause of adrenal insufficiency in about 35% of male patients with idiopathic Addison’s disease, and should be considered in the differential diagnosis of any male with adrenal insufficiency. Diagnosis is made by a blood test to detect very long chain fatty acids.

Primary hyperaldosteronism can be mimicked by Liddle syndrome, and by ingestion of licorice and other foods containing glycyrrhizin. In one case report, hypertension and quadriparesis resulted from intoxication with a non-alcoholic pastis (an anise-flavored aperitif containing glycyrrhizinic acid).

Some people only use Conn's syndrome for when it occurs due to an adrenal adenoma (a type of benign tumor). In practice, however, the terms are often used interchangeably, regardless of the underlying physiology.

Since risk factors are not known and vary among individuals with hyperandrogegism, there is no sure method to prevent this medical condition. Therefore, more longterm studies are needed first to find a cause for the condition before being able to find a sufficient method of prevention.

However, there are a few things that can help avoid long-term medical issues related to hyperandrogenism like PCOS. Getting checked by a medical professional for hyperandrogenism; especially if one has a family history of the condition, irregular periods, or diabetes; can be beneficial. Watching your weight and diet is also important in decreasing your chances, especially in obese females, since continued exercise and maintaining a healthy diet leads to an improved menstrual cycle as well as to decreased insulin levels and androgen concentrations.

Hypoadrenocorticism is often tentatively diagnosed on the basis of history, physical findings, clinical pathology, and, for primary adrenal insufficiency, characteristic electrolyte abnormalities.

- Clinical pathology - Abnormalities may be identified on hematology, biochemistry and urinalysis. Elevated concentrations of potassium (hyperkalemia), and low sodium and chloride values (hyponatremia and hypochloremia) are the classic electrolyte alterations. The sodium/potassium ratio often is <27 (normal is between 27:1 and 40:1) and maybe <20 in animals with primary adrenal insufficiency. However, not all dogs have an abnormal electrolyte ratio during an Addisonian episode.

- ECG - The severity of the ECG abnormalities correlates with the severity of the hyperkalemia. Therefore the ECG can be used to identify and estimate the severity of hyperkalemia and to monitor changes in serum potassium during therapy.

- Diagnostic imaging - Abdominal ultrasound may reveal small adrenal glands, suggesting adrenocortical atrophy. However, finding normal-sized adrenal glands does not rule out hypoadrenocorticism. Rarely, megaesophagus is evident on radiographs.

- ACTH stimulation test - Confirmation requires evaluation of an ACTH stimulation test. Basline plasma cortisol and urine cortisol/Cr ratios are unreliable for confirming the diagnosis. One major diagnostic criterion is abnormally decreased post-ACTH plasma cortisol. Normal plasma cortisol after ACTH stimulation rules out adrenal insufficiency. The only accurate test for hypoadrenocorticism is an ACTH stimulation test.

The ACTH stimulation test does not distinguish between primary and secondary hypoadrenocorticism, or adrenocortical destruction caused by mitotane overdose. Differentiation between primary and secondary hypoadrenocorticism can be made by periodically measuring serum electrolytes, baseline endogenous ACTH, or possibly serum or plasma aldosterone during the ACTH stimulation test. While most corticosteroid drugs will invalidate the results of an ACTH test, dexamethasone may be used in the event of an Addison's emergency without fear of compromising the results of the test.

In general, hypoadrenocorticism is underdiagnosed in dogs, and one must have a clinical suspicion of it as an underlying disorder for many presenting complaints. Females are overrepresented, and the disease often appears in middle age (four to seven years), although any age or gender may be affected. Dogs with hypoadrenocorticism may also have one of several autoimmune disorders. Because it is an endocrine disorder, they may also suffer from neuropathy and some endocrine-related eye diseases.

A complete physical evaluation should be done prior to initiating more extensive studies, the examiner should differentiate between widespread body hair increase and male pattern virilization. One method of evaluating hirsutism is the Ferriman-Gallwey Score which gives a score based on the amount and location of hair growth on a woman. After the physical examination, laboratory studies and imaging studies can be done to rule out further causes.

Diagnosis of patients with even mild hirsutism should include assessment of ovulation and ovarian ultrasound, due to the high prevalence of polycystic ovary syndrome (PCOS), as well as 17α-hydroxyprogesterone (because of the possibility of finding nonclassic 21-hydroxylase deficiency). Many women present with an elevated serum dehydroepiandrosterone sulfate (DHEA-S) level. Levels greater than 700 μg/dL are indicative of adrenal gland dysfunction, particularly congenital adrenal hyperplasia due to 21-hydroxylase deficiency. However, PCOS and idiopathic hirsutism make up 90% of cases.

Other blood value that may be evaluated in the workup of hirsutism include:

- androgens; androstenedione, testosterone

- thyroid function panel; thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4)

- prolactin

If no underlying cause can be identified, the condition is considered idiopathic.

Due to the strong link between PPID and insulin resistance, testing is recommended for all horses suspected or confirmed to be suffering from PPID. There are two tests commonly used for insulin resistance: the oral sugar test and fasting insulin blood concentration.

The fasting insulin concentration involves giving a horse a single flake of hay at 10 pm the night before testing, with blood being drawn the following morning. Both insulin and glucose blood levels are measured. Hyperinsulinemia suggests insulin resistance, but normal or low fasting insulin does not rule out PPID. This test is easy to perform, but is less sensitive than the oral sugar test. It is best used in cases where risks of laminitis make the oral sugar test potentially unsafe.

The oral sugar test also requires giving the horse only a single flake of hay at 10pm the night before the test. The following morning, karo corn syrup is given orally, and glucose and insulin levels are measured at 60 and 90 minutes after administration. Normal or excessively high insulin levels are diagnostic. However, equivocal test results require retesting at a later date, or performing a different test. A similar test is available outside the US, in areas where corn-syrup products are less readily available, where horses are given a morning meal of chaff with dextrose powder, and blood insulin levels are measured 2 hours later.

Although corticoid-to-creatinine ratios are generally higher in horses with PPID, numerous false positives and false negatives occur with this test, so it is not recommended.

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.

Breeds that began in the Pacific Rim, among them Akitas and Shiba Inus, tend to have higher potassium values in laboratory test, and elevated levels are not abnormal. Dogs who do not have hypoadrenocorticism have normal values on ACTH tests.

Males and females may be treated with hormone replacement therapy (i.e., with androgens and estrogens, respectively), which will result in normal sexual development and resolve most symptoms. In the case of 46,XY (genetically male) individuals who are phenotypically female and/or identify as the female gender, they should be treated with estrogens instead. Removal of the undescended testes should be performed in 46,XY females to prevent their malignant degeneration, whereas in 46,XY males surgical correction of the genitals is generally required, and, if necessary, an orchidopexy (relocation of the undescended testes to the scrotum) may be performed as well. Namely in genetic females presenting with ovarian cysts, GnRH analogues may be used to control high FSH and LH levels if they are unresponsive to estrogens.

Routine laboratory investigations may show:

- Hypercalcemia

- Hypoglycemia, low blood sugar (worse in children due to loss of glucocorticoid's glucogenic effects)

- Hyponatremia (low blood sodium levels), due to loss of production of the hormone aldosterone, to the kidney's inability to excrete free water in the absence of sufficient cortisol, and also the effect of corticotropin-releasing hormone to stimulate secretion of ADH.

- Hyperkalemia (raised blood potassium levels), due to loss of production of the hormone aldosterone.

- Eosinophilia and lymphocytosis (increased number of eosinophils or lymphocytes, two types of white blood cells)

- Metabolic acidosis (increased blood acidity), also is due to loss of the hormone aldosterone because sodium reabsorption in the distal tubule is linked with acid/hydrogen ion (H) secretion. Absent or insufficient levels of aldosterone stimulation of the renal distal tubule leads to sodium wasting in the urine and H retention in the serum.