Endocrinology

Qualitative hCG testing detects the presence of hCG and is routinely used to confirm pregnancy.

Quantitative hCG testing, often called beta hCG, measures the amount of hCG present in the blood. It may be ordered to help diagnose an ectopic pregnancy, to help diagnose and monitor a pregnancy that may be failing, and/or to monitor a woman after a miscarriage.

A quantitative hCG test may also be ordered to help diagnose gestational trophoblastic disease or germ cell tumors of the testes or ovary. It may be ordered at regular intervals to monitor the effectiveness of treatment for these conditions and to detect tumor recurrence.

Since progesterone levels vary throughout the menstrual cycle, multiple (serial) measurements can be used to help recognize and manage some causes of infertility. Progesterone can be measured to determine whether or not a woman has ovulated, to determine when ovulation occurred, and to monitor the success of induced ovulation.

In early pregnancy, progesterone measurements may be used, along with human chorionic gonadotropin (hCG) testing, to help diagnose an ectopic or failing pregnancy. Progesterone levels may also be ordered to monitor a high-risk pregnancy to help evaluate placenta and fetal health. Decreased levels are seen in ectopic pregnancies and in miscarriages.

If a woman is receiving progesterone injections to help support her early pregnancy, her progesterone levels may be monitored on a regular basis to help determine the effectiveness of that treatment.

Progesterone levels may be ordered, along with other tests such as an FSH, LH, hCG, thyroid tests, clotting tests, and aCBC (Complete Blood Count), to help determine the cause of abnormal uterine bleeding in non-pregnant women.

Testosterone testing is used to diagnose several conditions in men, women, girls, and boys. Examples of some of these conditions include:

• Delayed or precocious (early) puberty in boys
• Decreased sex drive in men and women
• Erectile dysfunction in men
• Infertility in men and women
• Testicular tumors in men
• Hypothalamus or pituitary disorders
• Hirsutism and virilization in girls and women

Typically, a test for total testosterone is used for diagnosis. The total testosterone test measures testosterone that is bound to proteins in the blood (e.g., albumin and sex-hormone binding globulin [SHBG]) as well as testosterone that is not bound. However, a test for free or bioavailable testosterone may be used if, for example, the level of SHBG in the blood is abnormal.

Testosterone testing is used to diagnose several conditions in men, women, girls, and boys. Examples of some of these conditions include:

• Delayed or precocious (early) puberty in boys
• Decreased sex drive in men and women
• Erectile dysfunction in men
• Infertility in men and women
• Testicular tumors in men
• Hypothalamus or pituitary disorders
• Hirsutism and virilization in girls and women

Typically, a test for total testosterone is used for diagnosis. The total testosterone test measures testosterone that is bound to proteins in the blood (e.g., albumin and sex-hormone binding globulin [SHBG]) as well as testosterone that is not bound. However, a test for free or bioavailable testosterone may be used if, for example, the level of SHBG in the blood is abnormal.

Prolactin levels are used, along with other hormone tests, to help:

• Determine the cause of galactorrhea
• Determine the cause of headaches and visual disturbances
• Diagnose infertility and erectile dysfunction in males
• Diagnose infertility in females
• Diagnose prolactinomas
• Evaluate anterior pituitary function (along with other hormones)
• Monitor treatment of prolactinomas and detect recurrences

FSH is often used in conjunction with other tests (LH, testosterone, estradiol, and progesterone) in the workup of infertilityin both men and women. FSH levels are used to help determine the reason a man has a low sperm count. FSH levels are also useful in the investigation of menstrual irregularities and to aid in the diagnosis of pituitary disorders or diseases involving the ovaries or testes. In children, FSH and LH are used to diagnose delayed or precocious (early) puberty.

LH is often used in conjunction with other tests (FSH, testosterone, estradiol and progesterone) in the workup of infertilityin both men and women. LH levels are also useful in the investigation of menstrual irregularities and to aid in the diagnosis of pituitary disorders or diseases involving the ovaries or testes.

Once a baseline urine test has been completed, further urine testing may be used to detect the surge in LH that indicates that ovulation will occur in the next 1-2 days.

In children, FSH and LH are used to diagnose delayed and precocious (early) puberty.

LH is sometimes measured in relation to gonadotropin releasing hormone (GnRH) to distinguish between primary or secondary disorders involving the hypothalamus, pituitary gland, or the gonads. GnRH is the hormone produced by the hypothalamus that stimulates the pituitary to release LH and FSH. For this test, a baseline blood sample is drawn and then the patient is given an injection of GnRH. Subsequent blood samples are drawn at specified times and the level of LH is measured. This test can help differentiate between disease of the ovaries or testes (primary) and a disorder of the pituitary or hypothalamus (secondary). It is also often helpful in the evaluation of precocious or delayed puberty.

Estrogen tests may be used for a variety of reasons:

• Estrone levels may be elevated in patients with polycystic ovarian syndrome and endometriosis. Tests may be used to aid in the diagnosis of an ovarian tumor, Turner syndrome, and hypopituitarism. In males, it may help in the diagnosis of the cause of gynecomastia or in the detection of estrogen-producing tumors.
• Estradiol levels are used in evaluating ovarian function. Estradiol levels are increased in cases of early (precocious) puberty in girls and gynecomastia in men. Its main use has been in the differential diagnosis of amenorrhea – for example, to determine whether the cause is menopause, pregnancy, or a medical problem. In assisted reproductive technology (ART), serial measurements are used to monitor follicle development in the ovary in the days prior to in vitro fertilization. Estradiol is also sometimes used to monitor menopausal hormone replacement therapy. A doctor may sometimes order a total estrogens test. This test measures estrone and estradiol together but does not measure estriol.
• Estriol may sometimes be ordered serially to help monitor a high risk pregnancy. When it is used this way, each sample should be drawn at the same time each day. An unconjugated estriol test, one that measures estriol that is not bound to a protein, is one of the components of the triple or quad screen. Decreased levels have been associated with various genetic disorders including Down syndrome, neural tube defects, and adrenal abnormalities. It is ordered during pregnancy, along with maternal alpha-fetoprotein (AFP maternal), human chorionic gonadotropin (hCG), and inhibin-A tests, to assess the risk of carrying a fetus with certain abnormalities.

DHEAS, testosterone, and several other androgens are used to evaluate adrenal function and to distinguish androgen-secreting conditions that are caused by the adrenal glands from those that originate in the ovaries or testes. DHEAS can be measured to help diagnose tumors in the cortex of the adrenal gland (adrenocortical tumors), adrenal cancers, andcongenital adrenal hyperplasia or adult-onset adrenal hyperplasia and to separate these conditions from ovarian tumorsand cancers.

Concentrations of DHEAS are often measured, along with other hormones such as FSH, LH, prolactin, estrogen, and testosterone, to help diagnose polycystic ovarian syndrome (PCOS) and to help rule out other causes of infertility,amenorrhea, and hirsutism.

DHEAS levels may be ordered, along with other hormones, to investigate and diagnose the cause of virilization in young girls and early (precocious) puberty in young boys.

The total IgE test may be used to screen for and detect allergic diseases. It may be ordered by itself, before, or along withallergen-specific IgE tests – depending upon whether or not a person or doctor has identified potential substances to which the person may be allergic.

IgE can be increased with parasitic infections, so a total IgE test is sometimes used as a screening test if a parasitic infection is suspected.

A cortisol test may be ordered to screen for and help diagnose Cushing syndrome, a group of signs and symptomsassociated with excess cortisol. Blood cortisol testing evaluates both protein-bound and free cortisol while urine testing evaluates only free cortisol, which should correlate with the levels of free cortisol in the blood. Sometimes salivary cortisol is also ordered to help detect Cushing syndrome.

Blood cortisol is also used to help diagnose adrenal insufficiency and Addison disease, conditions in which the adrenal glands do not function properly.

Multiple blood and/or saliva cortisol levels collected at different times, such as at 8 am and 4 pm, can be used to evaluate both cortisol concentrations and diurnal variation. Normally, the level of cortisol in the blood rises and falls in a "diurnal variation" pattern, peaking early in the morning then declining throughout the day and reaching its lowest level about midnight. A 24-hour urine cortisol sample will not show diurnal variation; it will measure the total amount of unbound cortisol excreted in 24 hours.

If an abnormal level of cortisol is detected, a doctor will do additional testing to help confirm the findings and to help determine its cause:

If a person has a high cortisol level, a doctor may perform a dexamethasone suppression test to help determine whether the cause is related to excess ACTH production by the pituitary. This test involves analyzing a baseline sample for cortisol, then giving the person oral dexamethasone (a synthetic glucocorticoid) and measuring cortisol levels in subsequent timed samples. Dexamethasone suppresses ACTH production and should decrease cortisol production if the source of the excess is pituitary-related. There are a few variations of this test. An overnight test may be used to help screen for Cushing syndrome. Longer tests help confirm initial findings. For these, the medication is usually given (either low or high dose) every 6 hours for either 2 or 4 days prior to blood or urine collection. Separate 24-hour urine samples are collected prior to and throughout the testing period and then the blood and urine samples are measured for cortisol and evaluated.

If the findings of the initial blood and/or urine tests indicate insufficient cortisol production, a doctor may order an ACTH stimulation test. This test involves measuring the concentration of cortisol in a person's blood before and after an injection of synthetic ACTH. If the adrenal glands are functioning normally, then cortisol levels will rise with the ACTH stimulation. If they are damaged or not functioning properly, then the response will be limited. A longer version of this test (1-3 days) may be performed to help distinguish between adrenal and pituitary insufficiency.

The test for sex hormone binding globulin (SHBG) is primarily ordered in conjunction with other tests to evaluate the status of a person's androgen levels - the male hormones. With men, the issue of concern is testosterone deficiency, while with women the concern is excess testosterone production. A total testosterone may be ordered prior to or along with a SHBG test.

SHBG and testosterone levels may be ordered on an adult male to help determine the cause of infertility, a decreased sex drive, and erectile dysfunction, especially when total testosterone results are inconsistent with clinical signs.

In women, small amounts of testosterone are produced by the ovaries and adrenal glands. Even slight increases in testosterone production can disrupt the balance of hormones and cause symptoms such as lack of menstruation (amenorrhea), infertility, acne, and male pattern hair growth (hirsutism). These symptoms and others are often seen withpolycystic ovarian syndrome, a condition characterized by an excess production of androgens. SHBG and testosterone testing may be useful in helping to detect and evaluate excess testosterone production and/or decreased SHBG concentrations.

Testing for free testosterone, albumin level, and one or more other sex hormones, such as prolactin, estradiol, and LH (lutenizing hormone), may also be performed to evaluate a person's existing balance of hormones.

Sometimes, a total testosterone and SHBG are ordered to evaluate free androgens by calculating the Free Androgen Index (FAI). This equation gives doctors an idea of the quantity of testosterone that is not bound (bioavailable testosterone) to SHBG and is calculated as follows: FAI = Total Testosterone / SHBG. In males, a fall in testosterone causes a rise in SHBG, so an FAI or another measure (bioavailable testosterone) is often ordered to detect low levels of free testosterone, which may cause decreased sex drive, loss of muscle mass, decreased bone mass, or occasionally problems with having erections (erectile dysfunction). An elevated FAI may be useful in the evaluation of androgenic alopecia (balding), hirsutism, and severe acne where testosterone levels may be normal.

ACTH levels in the blood are measured to help detect, diagnose, and monitor conditions associated with excessive or deficient cortisol in the body. These conditions include:

• Cushing's disease: excess cortisol that is due to an ACTH-producing tumor in the pituitary gland (usually a benigntumor)
• Cushing's syndrome: refers to the symptoms and signs associated with excess exposure to cortisol. In addition to Cushing's disease, Cushing's syndrome may be due to an adrenal tumor, adrenal hyperplasia, the use of steroid medications, or due to an ACTH-producing tumor that is ectopic, located outside the pituitary (such as in the lungs).
• Addison's disease, primary adrenal insufficiency: decreased cortisol production due to adrenal gland damage
• Secondary adrenal insufficiency: decreased cortisol production because of pituitary dysfunction
• Hypopituitarism: pituitary dysfunction or damage that leads to decreased (or no) hormone production by the pituitary, including ACTH production

Measuring both ACTH and cortisol can help to differentiate among some of these conditions because the level of ACTH normally changes in the opposite direction to the level of cortisol.

An intact PTH is the most frequently ordered parathyroid hormone test. It is ordered to help diagnose the reason for a low or high calcium level and to help distinguish between parathyroid-related and non-parathyroid-related causes. It may also be ordered to monitor the effectiveness of treatment when a patient has a parathyroid-related condition. A calcium test is almost always ordered along with a PTH test. It is not just the levels in the blood that are important, but the balance between them and the response of the parathyroid glands to changing levels of calcium. Usually doctors are concerned about either severe imbalances in calcium regulation that may require medical intervention or in persistent imbalances that indicate an underlying problem.

PTH levels can be used to monitor people who have conditions or diseases that cause chronic calcium imbalances or to monitor those who have had surgery or other treatment for parathyroid tumors.

Anti-Mullerian hormone (AMH) is not a routinely ordered test but may be useful in specific circumstances. Women of childbearing age may have an AMH test ordered along with other hormone tests, such as estradiol and FSH, to estimate the remaining time left to conceive (ovarian reserve). These tests are also useful in evaluating ovarian function and possibly in predicting the onset of menopause.

AMH may sometimes be ordered on a woman who will be undergoing assisted reproduction procedures such as in vitrofertilization (IVF); the concentration of AMH present is related to her likely responsiveness to treatment. A low level of AMH reflects poor ovarian response, indicating that a decreased number of eggs would be retrieved after ovarian stimulation. For this purpose, it is typically ordered along with other hormone tests and a transvaginal ultrasound (to count the number of follicles as a reflection of the woman's egg supply).

AMH can be elevated with polycystic ovarian syndrome (PCOS) due to the increased number of follicles and may be ordered to evaluate this condition.

Some ovarian cancers produce increased levels of AMH and/or inhibin B, which may be used as tumor markers to help evaluate response to treatment and monitor for recurrence.

In an infant with genitals that are not clearly male or female (ambiguous genitalia), an AMH test may be ordered along with chromosome testing, hormone testing, and sometimes imaging scans to help determine the sex of the baby. In an infant boy born with no visible testicles, low levels of AMH may account for the ambiguity of genitalia. If the testicles have not descended but are present in the abdomen, this test may be used to help determine whether they are functioning normally by measuring the AMH level.