Leda is a 38-year-old woman who began to experience weight gain, mood swings, and weakness. When her periods became irregular, she went to her physician

Question

Leda's physician heard the symptoms Leda was concerned about and then ordered a 24-hour free cortisol urine test and an overnight dexamethasone suppression test and measured her serum ACTH levels. The results indicated that Leda had Cushing disease, a condition caused by the hypersecretion of ACTH by the anterior pituitary and resulting in elevated cortisol levels. To confirm the diagnosis, Leda's physician ordered a cranial MRI to identify the presence of a pituitary tumor.

The dexamethasone test involves the administration of a synthetic glucocorticoid (i.e., cortisol). Knowing what you do about negative feedback mechanisms, how might this test be used to assess pituitary function?

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

Protein-based and steroid-based hormones trigger cellular responses in different ways. What are the differences between the mechanism of action of ACTH and cortisol on target cells?

Answer 1

Suppression tests are particularly valuable when determining the hyperfunction of an endocrine gland. In an intact negative feedback mechanism, the administration of a hormone would suppress the action of the endocrine gland regulating its release. Therefore, in a healthy individual, the administration of a glucocorticoid would suppress the activity of the hypothalamic-pituitary complex. If suppression does not occur, the pituitary may be in a state of hyperfunction and unresponsive to serum cortisol levels.

Cortisol and other steroid hormones are inactivated when bound to protein carriers. The hormones are conjugated in the liver and then excreted in the bile and urine. By measuring hormone levels in the urine, hormone status is more accurately determined from a 24-hour sample instead of an isolated sample from one moment in the day. Urine is also easy to collect and less invasive than blood sampling.

Protein-based hormones exert their effects by binding to surface receptors on cell membranes. The binding of the hormone may act to stimulate the activity of second messengers (i.e., cAMP). Alternatively, the binding may initiate a direct response by the cell by causing ion (i.e., calcium) channels to open. Steroid hormones are fat soluble and therefore pass directly through the cell membrane. Once inside the cell, they bind to intracellular receptors. These hormone-messenger complexes move to the nucleus and act to stimulate or suppress the gene activity of the cell. Whether by surface or intracellular receptors, hormones act to alter the protein synthesis and therefore function of the cell.