Steroids – Good, Bad, and Ugly

Field: Medicine (Health Sciences)

Glucocorticoids play a very pertinent role in treating many endocrine and nonendocrine disorders. Generally, it is either life-saving or modulates the course of the disease and gives the patient a better life. However, at the same time, we do notice steroids being used injudiciously. Steroids can act like a double-edged sword with compelling evidence of benefits with lesser chances of adverse effects if used in proper dosage and for a limited time. Still, the wrong dose and/or duration and oblivious withdrawal after longer days of administration can have disastrous effects. Then, it may be prescribed by unqualified persons, street hawkers, and pharmacy workers for various health issues as an elixir. Recognition of these irrational usages, followed by side effects, many of which are related to poor metabolic health, is important. Awareness of such ill effects as steroid-induced diabetes, hypertension, dyslipidemia, coronary artery disease, osteoporosis, psychiatric issues, insomnia, and weight gain is very important. Occult glucocorticoid exposure is quite common these days and one of the major causes of exogenous Cushing syndrome. There is an increasing trend of dietary supplements with hidden drugs or ingredients. Supplements are not classified as medicines but rather as food products, thus making it possible to bypass the regulatory standards of the Food and Drug Administration.[1] Many over-the-counter "adrenal support" supplements have been found to contain steroids, are promoted as natural products, and are freely available these days either online or with retailers. Occult use of steroids can many time cause diagnostic challenges. Clinicians should counsel their patients on the potential dangers of using unregulated over-the-counter supplements. THE "GOOD" The "Good" of exogenous corticoids is their similarity to the endogenous hormone cortisol. They have properties such as anti-inflammatory and immunosuppression and are used for physiological replacement in a few endocrine disorders. Knowing the right indication, dose, formulation, and duration is very important. Certain good practice guidelines can be kept handy while prescribing steroids. Initiate only if there is published evidence of objective therapeutic benefit. Use only after specific therapies fail Identify a specific therapeutic objective Use objective criteria of response Administer sufficient glucocorticoids for the time necessary to achieve the desired response One can terminate if the objective therapeutic benefit is not observed when expected, complications arise, or maximum benefit has been achieved Shorter-acting preparations like hydrocortisone that mimic endogenous circadian rhythm may be preferred over longer-acting preparations such as dexamethasone and betamethasone.[2] THE "BAD" The "Bad" of exogenous corticoids includes their wide array of adverse effects ranging from mild-to-severe toxicity. Much individual variation in side effects has been seen. The effects are contemplated by differences in bioavailability related to gene expression repression or activation and are still poorly understood.[3] The dose and duration of therapy are the most important independent risk factors for influencing adverse effects. Some side effects follow a linear dose–response pattern where the chances increase with an increase in the dose (ecchymosis, cushingoid features, parchment-like skin, sleep disturbances, and leg edema). Others follow threshold dose–response patterns with increased chances beyond a certain threshold value (weight gain and epistaxis at a prednisolone dose >5 mg daily, depression, hypertension, and glaucoma at a dose >7.5 mg daily). Various steps should be considered to limit the bad effects of glucocorticoids, like the use of the lowest dose of glucocorticoids for the shortest period needed to achieve the treatment goals, to avoid bedtime administration of glucocorticoids (GCs), and preexisting comorbid conditions should be managed more vigilantly when concurrent glucocorticoids are required. Constant monitoring of patients, under treatment, for adverse effects is required who may benefit from additional intervention. THE "UGLY" The "Ugly" side of exogenous corticoids is the scariest one and involves great challenges while steroids are being stopped. Failure to withdraw steroids because of long-standing exposure to exogenous steroids leading to hypothalamic–pituitary–adrenal axis suppression and adrenal atrophy makes it a great challenge. There are symptoms of glucocorticoid withdrawal and unavoidable adrenal insufficiency. Steroids should be withdrawn if the maximum desired therapeutic benefit has been obtained, there is an inadequate therapeutic benefit after an adequate trial, or side effects become serious or uncontrollable with medication. The major endocrinology societies (Endocrine Society [United States], Society for Endocrinology [United Kingdom (UK)], and European Society of Endocrinology) do not currently issue clinical guidance on addressing glucocorticoid-induced adrenal insufficiency. UK clinicians can refer to the British National Formulary, which advice slower glucocorticoid withdrawal if patients have taken more than 40 mg prednisolone (or equivalent) daily for more than 1 week; any dose for more than 3 weeks, repeat a short course of oral steroids within 1 year of stopping long-term glucocorticoid therapy; or have other risk factors for adrenal suppression. About tapering, they advise rapidly cutting down to a physiological dose (7.5 mg prednisolone daily or equivalent) and slow reduction after that.[4] However, a systematic review suggests that the evidence supporting these recommendations is not robust.[5] It highlights that adrenal insufficiency can happen at any dose, route, or duration of steroids, so clinicians have to be vigilant for glucocorticoid-induced adrenal insufficiency with all degrees of exposure and counsel patients accordingly. Despite the widespread use of glucocorticoids, the evidence guiding its management originates from very heterogeneous studies in design, patient population, sample size, types and regimens of glucocorticoids used, and assessment of adrenal function. The evidence level is low, resulting in variation in management across different centers and clinicians. Mitigating these side effects of steroids and minimizing the burden on the patient are very important. A lot has to be done at individual, societal, national, and international levels, and this can be achieved through collaboration to raise patient and clinician awareness. Steroid stewardship is a crucial step to prescribe and monitor glucocorticoids rationally while balancing benefits and potential risks, especially for patients requiring this therapy.[6] It is the joint responsibility of the prescribing clinicians and other specialists who monitor the patient, the clinical pharmacologist, the pharmacist, the clinical nurse, and the hospital administrator to ensure effective steroid stewardship. This approach includes measures such as preprescription screening, rational prescription, and medical care during corticosteroid use, along with appropriate monitoring after discontinued corticosteroid use. The time is right for endocrinologists to unite and generate data to quantify the extent of glucocorticoid misuse. In addition, they should focus on regulated steroid use in the community and bring this matter to the attention of drug regulators and the government. Community-based audits, manufacturing and sales audits, pharmacy audits, audits of steroid contamination in alternate medications, and prescription and laboratory audits are some of the effective measures that can be undertaken to curb the misuse of corticoids.[7] In summary, a balanced approach to steroid use is essential, considering both benefits and potential risks while implementing strategies to optimize patient outcomes and minimize adverse effects. Steroid stewardship and increased awareness among health-care professionals, patients, and regulatory bodies are crucial to achieving responsible and safe steroid use.