Prolonged treatment with high-dose corticosteroids causes toxic effects that can be life threatening. Besides oral and parenteral administration, transdermal and inhaled corticosteroids have some systemic absorption and can cause similar adverse effects. Patients should be thoroughly informed of the major possible side effects of treatment: insomnia, cognitive and personality changes, weight gain with central obesity, skin thinning and bruising, striae, muscle weakness, polyuria, renal calculi, diabetes mellitus, glaucoma, cataracts, sex hormone suppression, candidiasis, and opportunistic infections (Table 26–15). Prolonged high-dose corticosteroids also increase the risk of hypertension, dyslipidemia, myocardial infarction, stroke, atrial fibrillation or flutter, and heart failure. Gastric ulceration is more common with high-dose corticosteroids, particularly when patients take NSAIDs concurrently. High-dose inhaled corticosteroids predispose to oral thrush and pulmonary nontuberculous mycobacterial infection. To reduce risks, the dosage and duration of corticosteroid administration must be minimized. Immediately following inhaled corticosteroids, proper mouth-washing and gargling can reduce systemic absorption.
Table 26–15.Management of patients receiving systemic corticosteroids. ||Download (.pdf) Table 26–15. Management of patients receiving systemic corticosteroids.
Recommendations for prescribing
Do not administer systemic corticosteroids unless absolutely indicated or more conservative measures have failed.
Keep dosage and duration of administration to the minimum required for adequate treatment.
Screen for tuberculosis with a purified protein derivative (PPD) test or interferon gamma release assay before commencing long-term corticosteroid therapy.
Screen for pregnancy in reproductive age women; recommend contraceptive measures.
Screen for diabetes mellitus before treatment and then every 3–4 months.
Screen for hypertension before treatment and every 3–4 months.
Screen for glaucoma and cataracts before treatment, 3 months after treatment inception, and then at least yearly.
Monitor plasma potassium for hypokalemia and treat as indicated.
Obtain bone densitometry before treatment and then periodically. Treat osteoporosis.
Weigh daily. Use dietary measures to avoid obesity and optimize nutrition.
Measure height frequently and obtain bone densitometry by DXA every 1–2 years to document the degree of axial spine demineralization and compression.
Watch for fungal or yeast infections of skin, nails, mouth, vagina, and rectum, and treat appropriately.
With dosage reduction, watch for signs of adrenal insufficiency or corticosteroid withdrawal syndrome.
Prepare the patient and family for possible adverse effects on mood, memory, and cognitive function.
Teach the patient about the symptoms of hyperglycemia.
Inform the patient about other possible side effects, particularly weight gain, osteoporosis, and aseptic necrosis of bone.
Counsel to avoid smoking and excessive ethanol consumption.
Institute a vigorous physical exercise and isometric regimen tailored to each patient’s abilities or disabilities.
Administer calcium (1 g elemental calcium) and vitamin D3, 400–800 units orally daily.
–Check spot morning urine for calcium; alter dosage to keep urine calcium concentration < 30 mg/dL (< 7.5 mmol/L).
–If the patient is receiving thiazide diuretics, check for hypercalcemia, and administer only 500 mg elemental calcium daily.
If the patient has preexistent osteoporosis or has been receiving corticosteroids for ≥ 3 months, consider prophylaxis:
–Bisphosphonate such as alendronate (70 mg every week orally), zoledronic acid (5 mg every year intravenously) for up to 3–5 years; Or
–Teriparatide, 20 mcg subcutaneously daily for up to 2 years
Avoid prolonged bed rest that will accelerate muscle weakness and bone mineral loss. Ambulate early after fractures.
Avoid elective surgery, if possible. Vitamin A in a daily dose of 20,000 units orally for 1 week may improve wound healing, but it is not prescribed in pregnancy.
Fall prevention strategies: walking assistance (cane, walker, wheelchair, handrails) when required due to weakness or balance problems; avoid activities that could cause falls or other trauma.
For ulcer prophylaxis, if administering corticosteroids with nonsteroidal anti-inflammatory drugs, prescribe a proton pump inhibitor (not required for corticosteroids alone). Avoid large doses of antacids containing aluminum hydroxide (many popular brands) because aluminum hydroxide binds phosphate and may cause a hypophosphatemic osteomalacia that can compound corticosteroid osteoporosis.
Treat infections aggressively. Consider unusual pathogens.
Treat edema as indicated.
Prolonged oral, inhaled, intravenous, or high-dose topical corticosteroid therapy commonly suppresses pituitary ACTH secretion, causing secondary adrenal insufficiency. Adrenal crisis occurs in 5–10% of such patients yearly with an estimated 6% associated mortality.
Most corticosteroids (dexamethasone, prednisone, hydrocortisone, deflazacort, budesonide) are metabolized by the enzyme CYP34A. When drugs that inhibit CYP34A are administered along with even modest doses of corticosteroids (oral, inhaled, intravenous), the blood levels of the corticosteroids rise and can cause iatrogenic Cushing syndrome and secondary adrenal insufficiency. Medications that strongly inhibit CYP34A include itraconazole, ketoconazole, nefazodone, protease inhibitors and cobicistat.
In pregnancy, corticosteroids taken by the mother are transmitted across the placenta to the fetus, causing adverse effects on fetal growth and development as well as childhood cognition and behavior. Therefore, women who are to receive high-dose corticosteroids should be screened for pregnancy and counseled to use contraception.
Osteoporotic fractures (especially vertebral) ultimately occur in about 40% of patients receiving long-term corticosteroid therapy. Osteoporotic fractures can occur even in patients receiving long-term corticosteroid therapy at relatively low doses (eg, 5–7.5 mg prednisone daily). The risk of vertebral fractures increases 14-fold and the risk of hip fractures increases 3-fold. Patients at increased risk for corticosteroid osteoporotic fractures include those who are over age 60 or who have a low BMI, pretreatment osteoporosis, a family history of osteoporosis, or concurrent disease that limits mobility. Avascular necrosis of bone (especially hips) develops in about 15% of patients who receive corticosteroids at high doses (eg, prednisone 15 mg daily or more) for more than 1 month with cumulative prednisone doses of 10 g or more.
Bisphosphonates (eg, alendronate) prevent the development of osteoporosis among patients receiving prolonged courses of corticosteroids (Table 26–15). For patients who are unable to tolerate oral bisphosphonates (due to esophagitis, hiatal hernia, or gastritis), parenteral bisphosphonates can be used. Denosumab inhibits bone resorption but may increase the risk of infection compared to bisphosphonates; therefore, the use of denosumab is not recommended for patients receiving high-dose corticosteroid therapy who are already at an increased risk for infection.
The PTH/PTHrP analogs teriparatide and abaloparatide are anabolic agents that are also effective against corticosteroid-induced osteoporosis. They can be given for a 2-year course and increase bone density more effectively than bisphosphonates. For patients who are currently receiving corticosteroid therapy, however, these analogs increase the risk of hypercalcemia and must be used with great caution; they are most useful for patients with osteoporosis who have stopped high-dose corticosteroid therapy. Following a 2-year course of therapy with these analogs, bone loss and fractures occur quickly after discontinuation, so such therapy is usually followed by bisphosphonate therapy in patients with a history of fracture or osteoporosis by bone densitometry. (See Osteoporosis.) It is wise to follow an organized treatment plan such as the one outlined in Table 26–15.
et al. A review of systemic corticosteroid use in pregnancy and the risk of select pregnancy and birth outcomes. Rheum Dis Clin North Am. 2017 Aug;43(3):489–502.
et al. 2017 American College of Rheumatology guideline for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Rheumatol. 2017 Aug;69(8):1521–37.
et al. Glucocorticoid-induced osteoporosis. N Engl J Med. 2018 Dec 27;379(26):2547–56.
J. Glucocorticoid-induced osteoporosis: an update. Endocrine. 2018 Jul;61(1):7–16.
et al. Predicting recovery of the hypothalamic-pituitary-adrenal axis after prolonged glucocorticoid use. Endocr Pract. 2018 Jan;24(1):14–20.
et al. Dose dependency of iatrogenic glucocorticoid excess and adrenal insufficiency and mortality: a cohort study in England. J Clin Endocrinol Metab. 2019 Sep;104(9):3757–67.
et al. Denosumab
in glucocorticoid-induced osteoporosis: a multicentre, randomised, double-blind, active-controlled, double-dummy, non-inferiority study. Lancet Diabetes Endocrinol. 2018 Jun;6(6):445–54.