Uses of Glucocorticoids

Glucocorticoids are used in two primary situations to evaluate and treat endocrine disorders and to help resolve the symptoms of a variety of nonendocrine problems. These two major applications are discussed below. 

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Transactivation. Protein synthesis is initiated or inhibited by the action of the activated GR on DNA. The use of glucocorticoids leads to antiinflammatory effects by first controlling gene expression, which subsequentiy leads to the synthesis and/or suppression of inflammation regulatory proteins. 

Glucocorticoids are widely used to treat a variety of inflammatory and immune diseases. With the recognition that airway inflammation is present even in patients with mild asthma, treatment with glucocorticoids is now the mainstay of asthma therapy. Consequently, by far the most common use of glucocorticoids today is in the treatment of asthma and inhaled glucocorticoids have now become established as first-line treatment in adults and children with persistent asthma, the commonest chronic airway inflammatory disease. 

The use of glucocorticoids for tuberculous meningitis remains controversial. The administration of steroids such as oral prednisone, 60 to 80 mg/ day (1 to 2 mg/kg/day in children), or 0.2 mg/kg/day of IV dexametha-sone, tapered over 4 to 8 weeks, improves neurologic sequelae and survival in adults and decrease mortality, long-term neurologic complications, and permanent sequelae in children. 

Primary osteoporosis is the most common form of the condition. The secondary form of osteoporosis is diagnosed when an illness and/or medications are present with a negative impact on BMD. Examples of common chronic conditions in old people that can cause secondary osteoporosis are seen in Box 5.14. Examples of drugs that can cause secondary osteoporosis are glucocorticoids, too high doses of thyroid hormone, anticonvulsants, and heparin. Especially the use of glucocorticoids has been known to cause severe osteoporosis even within a short period of treatment. Depending on the doses the development of osteoporosis can occur within a few weeks or months. 

Several drugs are known to affect calcium metabolism and to Induce calcium loss (42). Amongst these are the use of glucocorticoids and thyroid extract. The use of both of these drugs can lead to the development of osteoporosis. It Is less well known that several other... 

Short-term use of glucocorticoids, even in massive dosages, is less likely to produce harmful reactions. They can, however, produce a variety of effects that are neither limited to high doses nor to long-term therapy. When a low dose of steroids (prednisone) was given for several months to a 38-year-old man to treat eczema of his hands and feet, he developed bilateral avascular necrosis (AVN) of the femur. He therefore had total bilateral hip replacement, and several experts have attributed his AVN to the steroid administration. The man sued his allergist, who settled the lawsuit shortly before trial for approximately 400,000. Most practitioners, however, are unaware of the risk of short-term or low-dose steroids. Yet many of these cases can be found in the courts, the literature, and the MedWatch databases. 

Long term use of glucocorticoids is associated with several adverse effects. High circulating... 

Table 39-2 Some Therapeutic Indications for the Use of Glucocorticoids in Nonadrenal Disorders. ...

Bacterial keratitis is one of the most frequent ophthalmic infections. In a meta-analysis of publications from 1950 to 2000, the use of a topical glucocorticoid before the diagnosis of bacterial keratitis significantly predisposed to ulcerative keratitis in eyes with preexisting corneal disease (OR = 2.63 95% Cl = 1.41, 4.91). Previous glucocorticoid use significantly increased the risk of antibiotic failure or other infectious complications (OR = 3.75 95% Cl = 2.52, 5.58). The use of glucocorticoids with an antibiotic for the treatment of bacterial keratitis did not increase the risk of complications, but neither did it improve the outcome of treatment. 

In a retrospective study, postoperative infectious complications were evaluated in 159 patients with inflammatory bowel disease undergoing elective surgery (317). Immunosuppression consisted of glucocorticoid monotherapy (n = 56), a glucocorticoid + azathioprine or mercaptopurine (n — 52), and neither a glucocorticoid nor azathioprine or mercaptopurine (n — 51). The adjusted odds ratios for any infection and major infections in patients who took glucocorticoid were 3.69 and 5.54 respectively, and in patients who took azathioprine or mercaptopurine 1.68 and 1.20. Thus, preoperative use of glucocorticoid in patients with inflammatory bowel disease increased the risk of postoperative infectious complications. 

In a retrospective study, the use of glucocorticoids during Pneumocystis jiroveci pneumonia (mean total dose methylprednisolone 420 mg, mean treatment duration 12 days) did not increase the risk of development or relapse of tuberculosis or other AIDS-related diseases (SEDA-20, 377 322). The study included 129 patients (72 who took glucocorticoids and 57 who did not) who were... 

Pneumocystis jiroveci pneumonia has been precipitated or aggravated by glucocorticoids (SEDA-20, 377 SEDA-22, 450 272,350,351). There is some concern about the use of glucocorticoids as adjunctive therapy in patients with AIDS who develop Pneumocystis jiroveci pneumonia. The immunosuppressant properties of glucocorticoids have been reported to enhance the risk of tuberculosis and other AIDS-related diseases (for example Kaposi s sarcoma or cytomegalovirus infection). 

Hyperadrenalism has never otherwise been reported after the sequential use of glucocorticoids for fetal lung maturation. 

Clinicians should not prescribe glucocorticoid-containing eye-drops unless they have performed a slit-lamp examination with tonometry, have assurance of appropriate followup, and understand the differential diagnosis, evaluation, and treatment. Unless clearly indicated, prescribing volumes larger than 5 ml or providing refillable prescriptions should be avoided. It should be stressed that excessive use of glucocorticoids can result in corneal Herpes infection and mycosis. 

Three vision-threatening complications have been described due to the indiscriminate use of glucocorticoid-containing eyedrops (431). 

Brambilla, G., M. Fiori, and E. Pierdominici. 1998. A possible correlation between the blood leukocyte formula and the use of glucocorticoids as growth promoters in beef cattle. Veterin. Res. Commun. 22 457 165. 

MacDonald RG, Panush RS, Pepine CJ, Rationale for use of glucocorticoids in modification of restenosis after percutaneous transluminal coronary angioplasty. Am J Cardiol 1987 60 B56-B60. 

In certain therapeutic situations, rapid presystemic elimination may be desirable. An important example is the use of glucocorticoids in the treatment of asthma. Because a significant portion of inhaled drug is swallowed, glucocorticoids with complete presystemic elimination entail only a minimal systemic load for the organism (p.340). The use of acetylsalicylic acid for inhibition of thrombocyte aggregation (see p.155) provides an example of a desirable presystemic conversion. 

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