Case Study Management
How is the dexamethasone test used to assess pituitary function?
The Dexamethasone suppression test determines whether the secretion of the adrenocorticotrophic (ACTH) hormone by the pituitary can be suppressed. During the dexamethasone test, a person receives dexamethasone, a strong synthetic glucocorticoid medicine (Ueland et al., 2017). After that, some blood is drawn to measure the cortisol levels in the blood. Dexamethasone is a synthetic steroid that binds to the same receptors as cortisol. Dexamethasone reduces the release of adrenocorticotrophic (ACTH) hormone in normal people, thus lowering cortisol levels in the blood.
The dexamethasone test is conducted when the doctor suspects that a patient is producing too much cortisol. The test is done to diagnose Cushing syndrome and identify its cause. The dexamethasone test can either be low or high dose, and the most common ones are done overnight. The low dose test requires one to get a milligram of dexamethasone at 11 pm, and the healthcare provider draws blood the next morning at 8 am. The high dose test starts with a healthcare provider taking a cortisol test in the morning of the test. The patient receives 8 milligrams of dexamethasone at 11 pm, and then blood is drawn the next morning at 8 am.
The low dose test determines whether the body is producing too much of the ACTH hormone. The high dose test helps determine whether the problem is in the pituitary gland, in which the case a person is diagnosed with Cushing disease. The typical results for the test are, on a low dose, the patient should have a plasma cortisol level of fewer than 1.8 micrograms per deciliter during the 8 am test. On a high dose, there should be over 50% reduction in plasma cortisol. Abnormal results on a low dose test show that the patient is releasing cortisol abnormally. On a low dose, it could indicate Cushing syndrome due to an adrenal tumour whereby cortisol is being produced, pituitary tumour where ACTH is produced, or a tumour in the body where ACTH is produced. The high dose is the most effective because it distinguishes a pituitary cause, which is the Cushing disease, from other conditions.
How Steroid Hormones like Cortisol are metabolized in the body
Steroid hormones are essential in the body because they help in the coordination of physiological and behavioural responses used in specific biological processes such as reproduction (Morgan et al., 2018). Steroid hormones are synthesized in the endocrine glands such as the gonads, and the adrenal glands before they are released into the bloodstream.
Although steroid hormones have a simple chemical structure, they occur in many active biological forms. This is due to two reasons, the first being the full range of compounds secreted by their synthesizing tissues and secondly because they are extensively metabolized.
The metabolism of steroid hormones occurs in the liver, kidneys to some extent, and target issues. The liver and the kidney are the main sites for inactivation of hormones and catabolism, also known as hormone inactivation. After metabolism, the hormones may need to be converted into their active forms to conduct their biological responses. Since steroids are lipophilic, they quickly diffuse through the cell membranes. Therefore they have a large distribution volume. When in their target tissues, the steroids become concentrated through a mechanism of uptake that relies on the binding to intracellular proteins. A high concentration of the steroids is also found in the adipose tissue, even if they are not a target of hormone action
Advantages of using the 24-hour urine test to measure Cortisol Hormone
The 24-hour urine test is used to measure the amount of cortisol present in a person’s blood. The urine test is vital in the diagnosis of various medical conditions. The medical conditions determined by the cortisol test are Cushing’s syndrome, Addison disease, and all situations that may affect the pituitary and the adrenal glands. The 24-hour urine test for the cortisol hormone is accurate because it involves the collection of all urine in 24 hours. The urine is collected multiple times because the amount of cortisol in the body changes throughout the day.
The cortisol test is also essential in managing Addison disease or Cushing’s syndrome among people who have been diagnosed with the disease. The 24-hour urine test monitors their treatment to determine whether their cortisol levels are too low or too high throughout the day, upon which they are given the appropriate treatment.
Difference between the action of ACTH and Cortisol on target cells
The adrenocorticotrophic (ACTH) hormone is made in the pituitary gland to respond to the hypothalamus release of the corticotrophin-releasing hormone. After the two hormones are released, the adrenal glands produce a hormone called cortisol, which helps with stress management in the body. The levels of cortisol in the blood have to be always controlled because the hormone is needed for life. When the ACTH levels in the blood rise, the cortisol levels fall. ACTH levels in the blood are usually high in the morning between 6, and 8 am, and the lowest between 6 pm and 11 pm. Cortisol levels are measured at the same time as the ACTH levels, and they should always be low in the blood. If the cortisol levels are high, one has to be tested for Cushing’s disease and other pituitary related factors. The ACTH hormone is released in bursts, and so its levels in the blood vary each minute.
The adrenocorticotrophic (ACTH) hormone stimulates the release of steroids by binding to plasma membrane receptors of adrenocortical cells that have a high affinity (Lightman, Birnie & Conway-Campbell, 2020). The interaction of ACTH with the receptors activates the adenyl cyclase and stimulates the production of intracellular cyclic AMP. The cyclic AMP that is formed activates some intracellular phosphoprotein kinases that act as a mediation between acute and chronic effects on steroidogenesis.
ACTH then stimulates the release and synthesis of cortisol within two to three minutes. This happens when ACTH increases cholesterol formation. Increased cholesterol in the body is stimulated by increased cholesterol esterase activity and decreased cholesterol ester synthetase activity. Cortisol then stimulates gluconeogenesis, which refers to the breaking down of fats to provide metabolic substances that are converted to glucose in the liver.
Cortisol exists in both bound and unbound forms. The bound way is the cortisol-binding globulin known as transcortin. The free unbound cortisol is replenished by the transcortin and that which is secreted from the adrenal cortex. The cortisol hormone binds to a receptor in the cytoplasm, which enters the cell’s nucleus to prevent the transcription of genes and thus alters the production of messenger ribonucleic acid. Cortisol manages stress levels by avoiding the uptake of glucose in other tissues except for the central nervous system. Cortisol also contains anti-inflammatory and anti-allergic properties. This is because it inhibits the production of inflammatory cytokines.
References
Lightman, S. L., Birnie, M. T., & Conway-Campbell, B. L. (2020). Dynamics of ACTH and cortisol secretion and implications for disease. Endocrine Reviews, 41(3), bnaa002.
Morgan, R. A., Keen, J. A., Homer, N., Nixon, M., McKinnon-Garvin, A. M., Moses-Williams, J. A., … & Walker, B. R. (2018). Dysregulation of cortisol metabolism in equine pituitary pars intermedia dysfunction. Endocrinology, 159(11), 3791-3800.
Ueland, G. Å., Methlie, P., Kellmann, R., Bjørgaas, M., Åsvold, B. O., Thorstensen, K., … & Husebye, E. S. (2017). Simultaneous assay of cortisol and dexamethasone improved diagnostic accuracy of the dexamethasone suppression test. European journal of endocrinology, 176(6), 705-713.