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Cushing's Syndrome: Epidemiology and Developments in Disease Management

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Cushing's Syndrome: Epidemiology and Developments in Disease Management Disease/Medical Condition 1 CUSHING SYNDROME Date of Publication: June 20, 2019 (also known as “Cushing’s syndrome” [CS], “hyperadrenocorticism”, and “hypercortisolism”; includes “Cushing disease” [also known as “Cushing’s disease” or “CD”] and “iatrogenic Cushing syndrome”) Is the initiation of non-invasive dental hygiene procedures* contra-indicated? No. ■ Is medical consult advised? — Yes, if previously undiagnosed Cushing syndrome is suspected2. — Yes, if previously diagnosed Cushing syndrome (or its underlying contributory cause) is suspected to be suboptimally managed. Is the initiation of invasive dental hygiene procedures contra-indicated?** Yes, pending clearance by physician (typically endocrinologist or family physician). ■ Is medical consult advised? .......................................... See above. ■ Is medical clearance required? — Yes, hypercortisolism predisposes the patient/client to immunosuppression. — Yes, prolonged use and/or high doses of systemic steroids (implicated in causation of iatrogenic CS) may predispose the patient/client to secondary adrenal insufficiency, particularly in the context of abrupt exogenous steroid withdrawal or peri-procedure stress. — Yes, for patients/clients on long-term glucocorticoid therapy, in order to assess, advise, and prescribe (as appropriate) possible corticosteroid supplementation prior to dental/dental hygiene procedures3. ■ Is antibiotic prophylaxis required? ................................. Possibly. Antibiotic prophylaxis should be considered for patients/clients at risk of immunosuppression and hence infection (e.g., incompletely treated Cushing disease, or prolonged use and/or high doses of systemic steroids for underlying disease management). ■ Is postponing treatment advised? — Yes, if patient/client has previously undiagnosed or inadequately managed Cushing syndrome. — Yes, if patient/client is medically unstable. — Yes, if status of associated medical conditions poses a risk to the patient/client (e.g., uncontrolled, severe hypertension) or the dental hygienist (e.g., mania or psychosis). Oral management implications ■ From a dental hygienist perspective, Cushing syndrome is of less acute concern than adrenal insufficiency (i.e., inadequate production of endogenous glucocorticoids). Nonetheless, Cushing syndrome does have a number of oral management implications. ■ For patients/clients on chronic corticosteroid therapy (which can result in secondary adrenal insufficiency), determination should be made whether corticosteroid supplementation is required before dental/dental hygiene treatment. For most patients/clients, however, steroid supplementation is not indicated for dental hygiene procedures. ■ Dental/dental hygiene management includes prevention of infections and prevention of pathologic fractures during chair transfers and during dental surgery. 1 The definition of Cushing syndrome varies according to the authority, sometimes being limited to endogenous causes only. This fact sheet takes a more encompassing definitional approach and thus also includes exogenous causation. 2 Tests for Cushing’s syndrome include the dexamethasone suppression test, as well as urine and saliva cortisol tests. 3 Most patients/clients on chronic corticosteroid therapy (and therefore at risk of secondary adrenal insufficiency) do not require supplemental doses of steroid for general, routine dental/dental hygiene procedures or even for most oral surgical procedures. cont’d on next page... Disease/Medical Condition CUSHING SYNDROME (also known as “Cushing’s syndrome” [CS], “hyperadrenocorticism”, and “hypercortisolism”; includes “Cushing disease” [also known as “Cushing’s disease” or “CD”] and “iatrogenic Cushing syndrome”) Oral management implications (cont’d) ■ The dental hygienist should be alert for cognitive impairment associated with untreated Cushing syndrome. Furthermore, associated conditions such as hypertension and diabetes should be appropriately assessed (e.g., taking of blood pressure prior to implementing procedures). ■ Because of the increased risk of peptic ulcer disease in patients/clients using long-term steroids, aspirin and other non- steroidal anti-inflammatory medications (NSAIDs) should generally be avoided for pain control. Oral manifestations ■ Alveolar bone loss (i.e., osteoporosis of the jaw) can result from hypercortisolism. This in turn can contribute to tooth loss, as can periodontal disease resulting from decreased white cell migration. ■ Oral candidiasis occurs at elevated rates. ■ Risk of infection may be increased with complex dental procedures. Related signs and symptoms ■ Cushing syndrome is a constellation of clinical features related to either exposure to excessive levels of cortisol4 secreted endogenously from the adrenal glands5 (e.g., due to Cushing disease6, adrenal adenoma7, or bilateral adrenal hyperplasia) or to chronic excessive levels of exogenous glucocorticoid (“cortisol-like”) medication8 (e.g., prednisone). ■ Cushing disease (comprising about 80% of endogenous CS) is uncommon, with population prevalence estimated at 5.5 per 100,000 population (equating to about 800 active cases in Ontario and 2000 cases in Canada), with diagnosis peaking in the fourth decade of life with female predominance. However, Cushing syndrome as a whole (all causes, including Cushing’s disease) is thought to be much more common, given that exogenous glucocorticoids — used to treat many diseases — are the most common cause of CS. ■ Classic signs/symptoms include: weight gain (particularly central obesity); a broad, round face (“moon face”); a collection of fat (“buffalo hump”) on the upper back; purple abdominal striae (i.e., linear “stretch” marks); thinned skin; hirsutism (excessive body hair); acne; proximal muscle weakness; wasting of extremities; and hypertension. Blood cell distribution may also be altered, resulting in lymphopenia and eosinopenia. ■ Associated conditions may include: menstrual irregularity; decreased libido; glucose intolerance (leading to diabetes mellitus); dyslipidemia; premature atherosclerosis; thromboembolic disease; heart failure; osteoporosis (contributing to vertebral and other bone fractures); impaired healing; and psychiatric disorders (e.g., cognitive dysfunction, anxiety disorders, depression, mania, and psychosis). 4 The high levels of glucocorticoid alter protein, fat, and carbohydrate metabolism, as well as the effects of insulin and vasculature homeostasis. 5 The adrenal glands are small glands located on the superior pole of each kidney. The adrenal cortex (90% of the gland) produces and secretes corticosteroid hormones (including glucocorticoids, mineralocorticoids, and androgens). The adrenal medulla secretes catecholamines; namely, epinephrine and norepinephrine. 6 In Cushing disease, the cause of cortisol hypersecretion is a pituitary tumour (usually a benign adenoma) that oversecretes adrenocorticotropic hormone (ACTH), thus overstimulating the adrenal glands’ cortisol production. Transphenoidal surgery may be used to selectively remove the tumour. Second-line therapies include radiotherapy, drug therapy, or bilateral adrenalectomy. 7 An adrenal adenoma (also known as adrenocortical adenoma) is a benign tumour (usually unilateral) of the adrenal cortex. It can present as Cushing syndrome, primary aldosteronism, or hyperandrogenism. Treatment may involve removal of part or all of the adrenal gland, which may be preceded by drug therapy to reduce cortisol production prior to surgery. 8 Glucocorticoid medication-induced Cushing syndrome is known as iatrogenic Cushing syndrome. cont’d on next page... 2 Disease/Medical Condition CUSHING SYNDROME (also known as “Cushing’s syndrome” [CS], “hyperadrenocorticism”, and “hypercortisolism”; includes “Cushing disease” [also known as “Cushing’s disease” or “CD”] and “iatrogenic Cushing syndrome”) Related signs and symptoms (cont’d) ■ Long-term use of steroid medications can increase risks for insomnia, cataract formation, glaucoma, peptic ulceration, growth suppression in children, and delayed wound healing. ■ Patients/clients at risk of developing iatrogenic Cushing syndrome include those on chronic glucocorticoid therapy for a variety of diseases, such as chronic asthma, rheumatoid arthritis, and lupus erythematosus. ■ Unlike the acute, life-threatening situation that may occur with acute cortisol deficiency (i.e., adrenal crisis), cortisol hypersecretion does not usually result in a medical emergency. However, poorly controlled cortisol levels in patients/clients with Cushing disease can lead to repeated hospitalizations, significant morbidity, and premature death. References and sources of more detailed information (cont’d) ■ College of Dental Hygienists of Ontario, CDHO Advisory Disorders of the Adrenal Gland, 2011-02-01. http://www.cdho.org/Advisories/CDHO_Advisory_Disorders_of_the_Adrenal_Gland.pdf ■ Sharma ST, Nieman LK, Feelders RA. Cushing's syndrome: epidemiology and developments in disease management. Clin Epidemiol. 2015;7:281-93. Published 2015 Apr 17. doi:10.2147/CLEP.S44336. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407747/ ■ Carlos Fabue L, Jiménez Soriano Y, Sarrión Perez MG. Dental management of patients with endocrine disorders. J Clin Exp Dent. 2010;2(4):e196-203. http://www.medicinaoral.com/odo/volumenes/v2i4/jcedv2i4p196.pdf ■ Uum SV, Hurry M, Petrella R, et al. Management of Patients with Cushing’s Disease: A Canadian Cost of Illness Analysis. J Popul Ther Clin Pharmacol. 2014;21(3):e503-e517. http://www.jptcp.com/articles/management-of-patients-with-cushings-disease-a-canadian-cost-of-illness-analysis.pdf
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