DENTISTRY & MEDICINE ABSTRACT Background. Dental patients with pri- mary or secondary adrenal insufficiency, or AI, may be A D A at risk of experiencing J ✷ ✷ adrenal crisis during or C N O after invasive procedures. O N I Since the mid-1950s, sup- T T Supplemental I A N U C I U plemental steroids in A N G E D R 3 corticosteroids for rather large doses have TICLE been recommended for patients with AI to prevent adrenal crisis. dental patients with Methods. To evaluate the need for sup- plemental steroids in these patients, the adrenal insufficiency authors searched the literature from 1966 to 2000 using MEDLINE and textbooks for Reconsideration of the information that addressed AI and adrenal crisis in dentistry. Reference lists of rele- problem vant publications and review articles also were examined for information about the topic. CRAIG S. MILLER, D.M.D., M.S.; JAMES W. LITTLE, Results. The review identified only four D.M.D., M.S.; DONALD A. FALACE, D.M.D. reports of purported adrenal crisis in den- tistry. Factors associated with the risk of adrenal crisis included the magnitude of or more than 50 years, medicine and dentistry surgery, the use of general anesthetics, the have appreciated the importance of the adrenal health status and stability of the patient, glands in maintaining physiological integrity. and the degree of pain control. This appreciation grew from studies1,2 in the Conclusions. The limited number of 1930s that demonstrated that adrenocortical reported cases strongly suggests that Finsufficiency was associated with electrolyte disturb- adrenal crisis is a rare event in dentistry, ances, and a decade later3 that cortisol prevented hypo- especially for patients with secondary AI, volemia and circulatory collapse associ- and most routine dental procedures can be ated with adrenalectomy. During the performed without glucocorticoid Adrenal crisis is 1940s, organic chemists isolated and supplementation. Clinical Implications. The authors a rare event in elucidated the structures of 28 steroids 4 identify risk conditions for adrenal crisis dentistry, from the adrenal cortex. It was against this background that Hench and col- and suggest new guidelines to prevent this and most leagues5,6 reported the beneficial effects problem in dental patients with AI. routine dental of cortisone in the treatment of diseases procedures can other than adrenocortical insufficiency be performed (for example, rheumatoid arthritis). without These findings ushered in the era of glu- became the standard of care for many 8 glucocorticoid cocorticoid therapy for patients with pri- years. mary adrenal insufficiency, or AI, and Although these recommendations have supplementation. inflammatory connective-tissue disease. served as important guidelines, knowl- The concept of secondary AI evolved edge of the adrenal cortical response to in the early 1950s from reports of patients experiencing physical stressors has been refined refractory hypotension at the end of routine surgical during the past 30 years.9-11 Based on procedures and dying hours later as a consequence of these more recent findings, reconsidera- glucocorticoid therapy withdrawal and resultant AI.7,8 tion of the guidelines for perioperative These outcomes resulted in a list of recommendations glucocorticoid supplementation in den- for perioperative glucocorticoid supplementation that tistry appears needed. We consider gluco- 1570 JADA, Vol. 132, November 2001 Copyright ©1998-2001 American Dental Association. All rights reserved. DENTISTRY & MEDICINE corticoid supplementation in dentistry by ad- istered at a target equal to, or less than, the dressing AI, current medical recommendations, normal daily output of cortisol (that is, 20 to 30 adrenal crisis and identification of risk in den- milligrams per day).18 For example, hydrocorti- tistry, and prescribing guidelines for periopera- sone, which has the equivalent anti-inflammatory tive coverage. potency of cortisol, usually is administered at 20 mg/day; prednisone and prednisolone, which ADRENAL INSUFFICIENCY have four times the anti-inflammatory potency of The adrenal cortex produces mineralocorticoids cortisol, usually are administered at 5 mg/day; and glucocorticoids that are important in main- and dexamethasone, which has 25 times the taining fluid volume. Cortisol, the principal glu- anti-inflammatory potency of cortisol, is admin- cocorticoid, maintains extracellular fluid, istered at 0.75 mg/day. whereas aldosterone, the principal mineralocorti- Such regimens, when administered as a coid, regulates salt and water balance.12 Insuffi- morning dose, are less suppressive because of cient production of these hormones can result the diurnal rhythm of cortisol secretion, from primary or secondary adrenal disease. Pri- resulting in highest levels in the morning. mary adrenocortical insufficiency, also known as Higher and divided daily doses are more sup- Addison’s disease, is uncommon, occurring in pressive, and often begin producing clinical man- about eight people per million population per ifestations of glucocorticoid excess (that is, year, with a prevalence of about 40 to 100 per Cushing’s syndrome) after three weeks of use.20 million.13-15 Although the level of cortisol production in It is caused by a progressive destruction of the patients with secondary AI due to hypothalamic adrenal cortex, usually of an idiopathic nature or pituitary disease can be low because of its (most commonly autoimmune), but also results dependence on the level of circulating ACTH, the from hemorrhage, sepsis, infectious diseases administration of corticosteroids alone does not (such as tuberculosis, human immunodeficiency determine which patients secrete sufficient virus, cytomegalovirus and fungal infection), levels of cortisol in response to stress. For malignancy, adrenalectomy, amyloidosis or example, the average cortisol production rate in drugs.16 Clinical evidence of the deficiency gener- patients with Cushing’s syndrome has been ally arises only after 90 percent of the adrenal reported to be 36 mg/day.21 cortices have been destroyed.17 Affected patients The table presents the signs and symptoms have high levels of adrenocorticotropic hormone, associated with AI and corticosteroid treatment. or ACTH, in blood, and a very low to undetect- The manifestations of primary AI (Addison’s dis- able level of aldosterone and cortisol in blood. ease) relate to a deficiency of aldosterone and Cortisol levels during this disease do not cortisol. The most common complaints are weak- increase in response to stress and ACTH. ness, fatigue and nausea. The most common sign Secondary adrenocortical insufficiency results is melanin hyperpigmentation of the skin and from hypothalamic or pituitary disease, or from mucous membranes. Hypotension, anorexia, the administration of exogenous corticosteroids. fever and weight loss are common findings. Although classified together, these two entities In secondary AI, the severity of symptoms is have different physiological effects. In the ab- often less marked, and normal mineralocorticoid sence of hypothalamic or pituitary function, the function is preserved. The preservation of miner- adrenal cortex undergoes irreversible atrophy.18 alocorticoid function makes it less likely for In contrast, long-term administration of cortico- patients with secondary AI to experience adrenal steroids blunts adrenal cortical function, with crisis than it is for patients with primary AI. variable and reversible effects.19 Cases of Cushing’s syndrome, which is due to chronic glu- hypothalamic-pituitary disease are less common cocorticoid excess, produces several features rec- than those induced by use of corticosteroids. Re- ognizable to the dentist, including plethora (red searchers estimate that 5 percent of adults in the face), moon face, hirsutism, acne, capillary United States regularly use corticosteroids20 and fragility and bruising, hypertension, osteoporosis are at risk of developing secondary adrenocor- and muscle weakness. tical insufficiency. Depending on the inflammatory condition, ADRENAL CRISIS corticosteroids in medicine generally are admin- The most significant acute adverse outcome of AI JADA, Vol. 132, November 2001 1571 Copyright ©1998-2001 American Dental Association. All rights reserved. DENTISTRY & MEDICINE TABLE FEATURES OF ADRENAL INSUFFICIENCY. VARIABLE PRIMARY ADRENAL SECONDARY ADRENAL CUSHING’S SYNDROME ADRENAL CRISIS INSUFFICIENCY INSUFFICIENCY Underlying Glucocorticoid and Glucocorticoid Potential glucocor- Severe glucocorticoid Problem mineralocorticoid deficiency due to ticoid insufficiency deficiency with or deficiency due to hypothalamic or due to long-term without mineralo- destruction or pituitary disease administration of corticoid deficiency due atrophy of corticosteroid for to stress (for example, adrenal gland inflammatory surgery, infection) and condition or organ inability of adrenal transplantation cortex to meet demand Clinical Weakness, Similar to Cushingoid Major categories: Features fatigability, weight primary adrenal features: weight dGastrointestinal loss, hypotension insufficiency gain, moon face, (nausea, vomiting, (may be ortho- except less thin skin, buffalo diarrhea, stomach static), hyperpig- dramatic, no hump (that is, fat cramps) mentation of skin, hyperpigmenta- pad on neck), dHypotension, weak mucous mem- tion and patients central obesity, pulse, profuse branes and creases; tend not to be acne, bruisability, sweating, weak- less common are salt-depleted hypertension