Question

A 38 year-old woman began to experience weight gain, mood swings, and weakness, followed by irregular periods. Her doctor ordered a 24-hour free cortisol urine test and an overnight dexamethasone suppression test and measured her serum ACTH levels. It was revealed she had Cushing disease, and it was later confirmed there was the presence of a pituitary tumour.

a. Describe Cushing Syndrome and differentiate the different forms of the disease. Is the patient’s disorder a primary, secondary, or tertiary endocrine disorder? Explain.

b. The dexamethasone test involves the administration of a synthetic glucocorticoid (cortisol). Using your knowledge of negative feedback mechanisms, how might this test be used to assess pituitary function?

c. Describe how steroid hormones, like cortisol, are metabolized in the body. What are the advantages of using a 24-hour urine test to measure this hormone?

Answer 1

a.Cushing’s syndrome or hypercortisolism, occurs due to abnormally high levels of the hormone cortisol for a long time.

Cushing disease is a form of Cushing syndrome,Cushing disease is a condition in which the pituitary gland releases too much adrenocorticotropic hormone (ACTH). The pituitary gland is an organ of the endocrine system.. Other forms of Cushing syndrome include exogenous Cushing syndrome-Exogenous Cushing syndrome is a form of Cushing syndrome that occurs in people taking glucocorticoid (also called corticosteroid, or steroid) hormones, Cushing syndrome caused by adrenal tumor-Cushing syndrome due to adrenal tumor is a form of Cushing syndrome. It occurs when a tumor of the adrenal gland releases excess amounts of the hormone cortisol., and ectopic Cushing syndrome-Ectopic Cushing syndrome is a form of Cushing syndromei in which a tumor outside the pituitary gland produces a hormone called adrenocorticotropic hormone (ACTH)

patient has a primary disorder-Pituitary tumors, also called pituitary adenomas, are noncancerous growths on the pituitary gland. The pituitary gland sits at the base of the brain and is about the size of a pea. The pituitary makes adrenocorticotropic hormone (ACTH) and other hormones. ACTH tells the adrenal glands to make cortisol. These pituitary tumors make too much ACTH, causing the adrenals to make too much cortisol.

b.

During this test, you will receive dexamethasone. This is a strong man-made (synthetic) glucocorticoid medicine. Afterward, your blood is drawn so that the cortisol level in your blood can be measured.

There are two different types of dexamethasone suppression tests: low dose and high dose. Each type can either be done in an overnight (common) or standard (3-day) method (rare). There are different processes that may be used for either test.

This test is done when the provider suspects that your body is producing too much cortisol. It is done to help diagnose Cushing syndrome and identify the cause.

The low-dose test can help tell whether your body is producing too much ACTH. The high-dose test can help determine whether the problem is in the pituitary gland (Cushing disease).

Dexamethasone is a man-made (synthetic) steroid that bids to the same receptor as cortisol. Dexamethasone reduces ACTH release in normal people. Therefore, taking dexamethasone should reduce ACTH level and lead to a decreased cortisol level.

If your pituitary gland produces too much ACTH, you will have an abnormal response to the low-dose test. But you can have a normal response to the high-dose test.

Cortisol level should decrease after you receive dexamethasone.

Low dose:

• Overnight -- 8 a.m. plasma cortisol lower than 1.8 micrograms per deciliter (mcg/dL) or 50 nanomoles per liter (nmol/L)
• Standard -- Urinary free cortisol on day 3 lower than 10 micrograms per day (mcg/day) or 280 nmol/L

High dose:

• Overnight -- greater than 50% reduction in plasma cortisol
• Standard -- greater than 90% reduction in urinary free cortisol.

c.

Hepatic — The major site of cortisol metabolism is the liver. There, cortisol is reduced, oxidized, or hydroxylated, and the products of these reactions are made water soluble by conjugation with sulfate or glucuronic acid to facilitate their excretion in urine.Gas chromatography with mass spectrometry (GC/MS) has provided quantitative data on the urinary excretion of each of these cortisol metabolites, allowing identification of a number of inherited and acquired disorders characterized by abnormal glucocorticoid dynamics.

Reduction — Cortisol is inactivated mainly by reductive disruption of its 3-keto, delta-4 double bond structure. Reduction reactions can also result in "regeneration" of cortisol from its inactive metabolite, cortisone.

●Reduction of the keto group, with formation of a 3-hydroxyl group, is carried out by 3-alpha-hydroxysteroid dehydrogenase.

advantages-

The test is used to evaluate for increased or decreased cortisol production.

Cortisol is a steroid hormone released from the adrenal gland in response to ACTH, a hormone from the anterior pituitary gland in the brain. Cortisol levels rise and fall during the day. Highest levels occur at about 6 to 8 a.m. and lowest levels at about midnight.

Cortisol affects many different body systems. It plays a role in lipid, carbohydrate, and protein metabolism. Cortisol also plays a role in the bone, circulatory, nervous, and immune systems. Cortisol is critical for normal stress responses.

Different diseases, such as Cushing's disease and Addison's disease, can lead to either over- or under-production of cortisol. Urinary free cortisol measurements can help to diagnose these conditions.

Urinary free cortisol is a measurement of the cortisol in the urine that is not attached to other substances. Free cortisol represents the active form of the hormone. The urine measurement directly reflects the blood level of cortisol.