During Illness and Emergency
Phyllis W. Speiser, MD
Often adrenal insufficiency has a slow, insidious course, but in some cases develops rather suddenly. The underlying problems include low blood sugar, low blood sodium, dehydration, low blood pressure, all predisposing the individual to heart failure and shock (collapse).
The classic form of congenital adrenal hyperplasia (CAH) should be considered in the differential diagnosis of adrenal insufficiency or crisis, especially in the infant. These days, with many states performing newborn screening for CAH, it is much less likely for CAH patients to go into shock. With newborn screening, most cases of severe or classic “salt-wasting” CAH are detected before crisis occurs. These individuals lack an enzyme, steroid 21-hydroxylase, and cannot adequately produce either cortisol or aldosterone, and must take hormone replacement therapy. Failure to begin treatment in a timely manner, medical non-compliance, inadequate dosing, or failure to adequately absorb oral medications may all contribute to adrenal crisis. Thus, it is essential for the CAH patient to receive regular check-ups with measurement of appropriate blood hormone levels to assess whether he/she is receiving the right medication dose. Recent studies also have shown that CAH patients are also somewhat deficient in epinephrine and norepinephrine, although doctors do not replace these hormones.
Among all patients with classic CAH (21-hydroxylase deficiency form), about 25% actually have sufficient aldosterone to maintain salt balance. These people are termed “simple virilizers.” Because testing to distinguish salt-wasters from simple virilizers is somewhat complicated, and because physicians often do not wish to risk an adrenal crisis when they are uncertain of the child’s aldosterone status, many “simple virilizers” will be treated with cortisol replacement and added oral Florinef (an aldosterone substitute known generically as fludrocortisone) to enhance salt balance. Over time, as the child grows accustomed to eating foods with higher salt content, the Florinef dose is tapered, and eventually discontinued, although cortisol replacement is continued lifelong. Simple virilizers rarely experience adrenal crises. There are many known cases of such individuals having grown to adulthood and old age without ever having had the benefit of diagnosis or treatment, and without ever having a crisis, even during or after major surgery.
Among the problems untreated classic CAH patients have are adrenal, testicular or ovarian tumors; untreated women with CAH have excess body hair and fertility difficulties. Thus, it is not advisable for individuals diagnosed with classic CAH to ever abandon cortisol replacement treatment. Salt-wasters most often also require additional Florinef and/or salt tablets indefinitely.
With increasing awareness among physicians, and with more sensitive newborn screening methods, there are now many individuals diagnosed at an early age with mild, or nonclassic, CAH. In contrast to classic CAH, this is not a life-threatening disease. Many individuals have no obvious symptoms of the mild 21-hydroxylase enzyme deficiency, and can live quite normally without any medical treatment. There is no danger of adrenal insufficiency or crisis. Symptomatic individuals may come to medical attention in childhood with early onset of puberty, in the teen years with acne, young women with excess facial and/or body hair, irregular menstrual periods, or in young adult life with fertility problems. These complaints can be remedied with hormone therapy, usually a low dose of cortisol replacement medication. Such medications include hydrocortisone (favored in treatment of children for the low incidence of side effects), prednisone or dexamethasone. Once a person has been taking corticol replacement drugs for an extended length of time, the body becomes somewhat dependent on the medications. This means that one’s own adrenal gland is “lazy” and cannot respond to stress as well as it might have done before taking the medications. If a patient were to abruptly stop taking cortisol replacement medications after many months or years, adrenal crisis could ensue. Nonclassic CAH patients, because they have only a mild impediment to producing cortisol, can often discontinue their medications, but this should be done gradually under medical supervision, so as not to precipitate adrenal crisis.
Parents and physicians should be aware of clinical clues to the diagnosis of adrenal insufficiency. Infants may be jittery, listless, or have convulsions due to low blood sugar or blood sodium. These chemical changes can be detected by blood testing. Chronic adrenal insufficiency will result in failure to gain weight. Older children may exhibit fatigue, malaise, muscle aches, headache, abdominal pain, nausea, vomiting, salt-craving, and weight loss with cortisol and/or aldosterone deficiencies.
In suspected chronic adrenal insufficiency, careful review of growth and weight gain is critical to understanding the nature of the problem. A severe drop in blood pressure after the person rises from lying down is a sensitive indication of dehydration and potential signal of adrenal crisis. In untreated primary adrenal insufficiency, physical examination often shows dark skin pigmentation, especially of non-sun-exposed areas such as palms, soles, and gums.
Prompt recognition of adrenal insufficiency is the key to a good outcome. People with CAH or any other condition associated with adrenal insufficiency (such as Addison’s disease) should always carry medical identification cards or wear medical identification tags to alert emergency medical personnel to their needs. Timely initiation of stress doses of cortisol replacement and salt and sugar intravenous fluid therapy are the most important factors, and are life-saving. At-home emergency therapy can be administered, if there will be a delay in reaching the hospital. This can be accomplished with an intramuscular injection of hydrocortisone (25 mg for infants, 50 mg for children, 100 mg for adults), or more readily with hydrocortisone-containing rectal suppositories. The latter are simple to administer and rapidly absorbed, and do not require special equipment or training to give. If the individual is conscious, clear electrolyte fluids should also be provided (sports drinks such as Gatorade or Powerade are ideal). The patient should then be seen by his/her physician, or in an emergency treatment facility. CAH patients and others with adrenal insufficiency should consider carrying a letter from their physician describing their condition and treatment needs whenever travelling.
Primary care practitioners and school health personnel should be informed of necessary measures in case of shock. Classic CAH and Addison’s disease are unremitting conditions, requiring lifelong treatment. Nevertheless, most patients lead unrestricted and productive lives. Patients receiving low dose maintenance cortisol and aldosterone replacement therapy are not at risk for serious side effects from these medications. There are no significant interactions of these medications with other commonly used drugs.