Addison’s disease or adrenal insufficiency is a very rare hormonal disorder. It is so rare that this condition is often not discussed in end of life care. It can be useful to understand Addison’s disease and the management of this condition as many of these patients are on steroid therapy that may overlap with the hospice plan of care. This highlights importance of obtaining a complete and accurate medical history on admission to ensure that we have a full understanding of why the patient is on a current medication therapy.
Addison’s disease is a result of a hormanal change in the adrenal glands. The adrenal glands are walnut sized organs that sit on top of the kidneys. Their function is to produce cortisol, aldosterone, and DHEA (dehydroepiandrosterone) which are necessary for many functions in the body. There are two types of adrenal insufficiency: primary adrenal insufficiency and secondary adrenal insufficiency. Primary adrenal insufficiency occurs when the adrenals cannot produce enough cortisol and/or aldosterone due to some type of damage to the adrenals caused by an infection, virus, or autoimmunity. Approximately 80% of Addison’s disease is caused by an autoimmune disorder. This is when the body’s immune system attacks its own organs. Secondary adrenal insufficiency occurs when the pituitary in the brain fails to produce ACTH (adrenocortisotropin). Secondary adrenal insufficiency may be caused by the abrupt discontinuation of high doses of steroids, surgical removal of pituitary tumor, or a change in the pituitary gland function. ACTH is needed to stimulate the production of cortisol. If the ACTH is low, the cortisol will also be low.
The HPA axis (hypothalamic-pituitary-adrenal axis) is a negative feedback mechanism which functions to control cortisol levels. In the brain, the hypothalamus releases corticotrophin releasing hormone(CRH) which then signals the pituitary to release ACTH. ACTH signals the adrenals to make cortisol. When cortisol levels peak, there is a negative feedback that tells the hypothalamus to stop releasing CRH and thus the pituitary to stop making ACTH.
Cortisol, a glucocorticoid, aldosterone, a mineralcorticoid, and DHEA, sex hormones, have many functions in the human body. Cortisol helps to maintain blood pressure, regulate metabolism, and slows the inflammatory response. Aldosterone works to maintain blood pressure and balance sodium and potassium. If aldosterone is low, sodium is decreased and potassium is increased. DHEA makes the sex hormones androgen and estrogen.
The symptoms of adrenal insufficiency include: weight loss, fatigue, abdominal pain, muscle weakness, nausea and vomiting, hypotension, dizziness, hypoglycemia, and salt craving. Additionally, hyperpigmentation can occur in primary adrenal insufficiency. This is due to the high ACTH stimulation the melanocytes in the skin especially in the skin folds, elbows, knees, and palms of the hands.
The primary treatment for adrenal insufficiency is the replacement of oral hydrocortisone (a glucocorticoid) plus or minus fludrocortisone (a mineralcorticoid). If the patient becomes ill or has an accident and is unable to swallow, the injectable form of hydrocortisone must be administered. Events such as surgery or pregnancy would also cause those with adrenal insufficiency to be managed with the injectable formulation instead of oral. When a patient becomes ill, they must follow a stress dosing plan by doubling or tripling the steroid doses dependent on the numerical value of the fever as the body requires more cortisol to deal with the acute illness.
Patients must be very compliant or they could end up in an Addisonian crisis which could lead to shock and death. Symptoms of an adrenal crisis include: low blood pressure, low blood sodium, low blood glucose, and high blood potassium.
Adrenal insufficiency is diagnosed through blood and urine tests. This will help to determine the cortisol level. If the cortisol level is low, an ACTH stimulation test will be done. The patient will be given an IV injection of synthetic ACTH and samples of blood, urine or both are taken before and after the injection. If the cortisol rises in response to the ACTH, Addison’s can be ruled out. A little or no increase indicates adrenal insufficiency. If the ACTH test is abnormal, a CRH stimulation test can be done to determine the cause of the adrenal insufficiency. A patient is injected with synthetic CRH and blood is taken before, 30, 60, 90, 120 minutes after the injection. Addison’s patients will produce a high ACTH with no cortisol response. Those with secondary adrenal insufficiency will fail to produce ACTH or it is delayed. If it is delayed, the hypothalamus is the cause. If no ACTH is produced, the pituitary is the cause. Other tests may include an ultrasound of the abdomen to see if there are structural abnormalities in the adrenals, a tuberculin test, and antibody blood tests.
Those with adrenal insufficiency should always wear a medic alert bracelet to indicate that they are cortisol dependant. They also need to always carry the injectable form of the corticosteroid in the event of an emergency.
There is still a lot to learn with adrenal insufficiency. The recent article, The Diagnosis and Treatment of Primary Adrenal Insufficiency in the Journal of Clinical Endocrinology acknowledges that diagnostic procedures and treatment strategies are far from optimal. They also state that the validity of the adrenal function tests are questionable. Salivary cortisol testing which has been done by functional medicine for many years is only recently being acknowledged in the medical world as a biomarker. Liquid chromatography testing is also being studied as a diagnostic test. Additionally, replacing cortisol has no effect on the HPA axis and ACTH levels remain high. Drugs such as rituximab and tetracosactide has resulted in regeneration of cortisol production. Immunomodulatory treatment to stop the autoimmune response may eventually be the treatment for those with autoimmune adrenal insufficiency. They have also documented a successful adrenal transplantation. As you can see, much work needs done so that adrenal insufficiency can have a cure and not just a treatment.
1. Bornstein, SR, Bruno A, Wiebke A, Andreas B, Don-Wauchope A, Hammer GD, et al. "Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline." The Journal of Clinical Endocrinology & Metabolism 101.2 (2016): 364-89. Web.
2. Loechner, K. "Adrenal Insufficiency and Addison's Disease." N.p., May 2014. Web. 12 Feb. 2016.