Pain, General | June 28, 2016 | Author: The Super Pharmacist
Corticosteroids are naturally occurring hormones in the human body that play a central role in a wide range of physiological processes including immune system response, the regulation of inflammation, metabolising carbohydrates and maintaining blood electrolyte levels.
Corticosteroids are classified by potency, ranging from Class 1 (super potent) to Class 7 (least potent). Potency is a simple indicator of the strength of each treatment.
Although corticosteroids have many evidenced benefits in relation to the treatment of a range of common complaints, their therapeutic use has to be balanced against the risk of serious adverse effects resulting from their use, particularly for extended treatments. High potency corticosteroids have been evidenced to inhibit adrenal gland function, particularly in children.
The adrenal glands are two small glands that sit on top of the kidneys and they produce two essential hormones: cortisol and aldosterone.
A 2014 retrospective cohort study of 60 children taking a prolonged course of glucocorticoids evidencing that 1 in 5 with steroid-dependent diseases would experience adrenal suppression, resulting in adrenal insufficiency (1).
Adrenal insufficiency is a condition in which the adrenal cortex is damaged or destroyed, reducing the output of adrenal hormones such as glucocorticoids (cortisol) and/or mineralocorticoids (aldosterone).
Primary insufficiency, also known as Addison’s Disease, is an autoimmune disorder that results in the inability of the adrenal gland to produce enough steroid hormones.
Secondary insufficiency, where there is inadequate stimulation of adrenal glands, is most commonly caused by the excessive use of corticosteroids. It can also be caused by certain antipsychotic medications such as chloropromazine and steroid production from tumours (2).
Diagnosis is often delayed due to the non-specific nature of symptoms which include fatigue, lethargy, muscle weakness, the need to urinate frequently, a craving for salty foods and low mood (3).
In more serious cases, untreated adrenal insufficiency can result in dangerously low levels of hormones being produced, sending the body into adrenal crisis. This is classified as a medical emergency that can be fatal, and is characterised by severe dehydration, severe vomiting and diarrhoea, headache, rapid shallow breathing, and cold, clammy skin.
Prednisone, a commonly used corticosteroid, is a particularly effective immunosuppressant drug and is commonly used in the treatment of inflammatory illnesses and some forms of cancer.
Dosage is usually somewhere between 5-60mg daily depending on the illness that is being treated, which includes COPD, allergic disorders, ulcerative colitis, adrenocortisol insufficiency, tuberculosis and pericarditis. It is also regularly used in the recipients of an organ donation to help prevent the body from rejecting the transplant.
As with all other corticosteroids, it does carry the risk of significant adverse effects if treatment and dosage are not carefully managed and observed.
The long term use of prednisone at a high dosage can be problematic and regularly leads to adrenal suppression if taken at a dose > 40mg for 7 days or more (4). At this dose, individuals may temporarily lose the ability to manufacture natural cortisol, which in turn creates a physical dependency on prednisone.
The dependency is created as a result of glucocorticoid analogue drugs such as prednisone down-regulating the natural synthesis of glucocorticoids. For this reason, any exposure to the ongoing use of prednisone for more than 7 days requires patients to steadily withdrawal from its use via a weaning process: abruptly stopping the use of prednisone can cause adrenal shock or adrenal crisis (also often referred to as an Addison’s crisis, but it is not exclusive to individuals who have primary adrenal insufficiency).
The length of the weaning process will be dependent on the length of the time that the drug has been taken, as well as the dosage – this could range from anywhere from a few days to weeks and even months if the patient has been on long-term treatment that has not been well managed.
Where patients must be on long term corticosteroid treatment, the effects of prednisone are often mitigated through:
As the impact of all corticosteroids are dose dependent, the weaning process will most often involve a simple reduction of the dose of a measured period of time.
The underlying medical reason for treatment, as well as the likelihood of compliance or relapse in the patient, will also be considered in determining the length of time over which weaning should take place.
As prednisone inhibits the feedback of the hypothalamus, decreasing corticotropin-releasing hormone (CRH) and the amount of adrenocorticotropic hormone (ACTH), the body requires a period of time to begin synthesis of CRH and ACTH and for the adrenal glands to begin functioning normally again (6).
Many patients also report mood swings and symptoms of depression, as well as significant weight gain (7). Unfortunately for patients there is no way to mitigate the side effects of weaning: sticking strictly to the terms of using prednisolone over a short period of time is the best defence against the avoidable side effects associated with its withdrawal.
1 Sidoroff M, Kolho KL (2014) Screening for adrenal suppression in children with inflammatory bowel disease discontinuing glucocorticoid therapy (2014) BMC Gastroenterol 24(14)51-56
2 Zhang H, Liu C, Ji, Liu Z et al (2008) Prednisone adding to usual care treatment for refractory decompensated congestive heart failure International Heart Journal 49(5):587–95
3 Marik PE, Pastores SM, Annane D, et al (2008) Recommendations for the diagnosis and management of corticosteroid insufficiency Crit Care Med 36(6):1937-49
4 Neary N, Nieman L (2010) Adrenal insufficiency: etiology, diagnosis and treatment Curr Opin Endocrinol Diabetes Obes 17(3):217-23
5 Marek P (2009) Critical Illness-Related Corticosteroid Insufficiency Chest 135(1): 181-193
6 Shulman DI, Palmert MR, Kemp SF (2007) Adrenal insufficiency: still a cause of morbidity and death in childhood J Pediatrics 119(2):e484
7 Grossman AB (2010) Clinical Review: The diagnosis and management of central hypoadrenalism J Clin Endocrinol Metab 95(11):4855-63