Betamethasone syndrome

Betamethasone, as with all steroids, is used to suppress inflammatory reactions. It can be used topically or systemically. Indications for its use include eczema, asthma and congenital adrenal hyperplasia. It is contraindicated in ocular herpes simplex and in the red eye syndrome since it may clear the symptoms while not addressing the infective component of the underlying condition. 

Lung maturation in the fetus is regulated by the fetal secretion of cortisol. Treatment of the mother with large doses of glucocorticoid reduces the incidence of respiratory distress syndrome in infants delivered prematurely. When delivery is anticipated before 34 weeks of gestation, intramuscular betamethasone, 12 mg, followed by an additional dose of 12 mg 18-24 hours later, is commonly used. Betamethasone is chosen because maternal protein binding and placental metabolism of this corticosteroid is less than that of cortisol, allowing increased transfer across the placenta to the fetus. 

In 534 individuals aged 30 years, whose mothers had participated in a double-blind, randomized, placebo-controlled trial of antenatal betamethasone (two intramuscular doses 24 hours apart) for the prevention of neonatal respiratory distress syndrome, there were no differences between those exposed to betamethasone and placebo in body size, blood lipids, blood pressure, plasma cortisol, prevalence of diabetes, or history of cardiovascular disease (397). After the oral glucose tolerance test, those who had been exposed to betamethasone had higher plasma insulin concentrations at 30 minutes (61 versus 52 mIU/1) and lower glucose concentrations at 120 minutes (4.8 versus 5.1 mmol/1) than did those exposed to placebo. Antenatal exposure to betamethasone might result in insulin resistance in adult offspring, but has no effect on cardiovascular risk factors at 30 years of age. 

In 192 adult offspring (mean age 31 years) of mothers who had taken part in a randomized controlled trial of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome (87 exposed to betamethasone two doses 24 hours apart, and 105 exposed to placebo) there were no alterations in cognitive functioning, working memory and attention, psychiatric morbidity, handedness, or health-related quality-of-life in adulthood (400). 

There have been reports of Cushing s syndrome after prolonged use of intranasal betamethasone 0.1% for chronic catarrh in two boys (443) and from an interaction of nasal fluticasone with ritonavir (444). 

An 87-year-old woman received intra-articular betamethasone (Diprophos) 7 mg on three occasions for painful knee joints over 6 months. Six weeks after the last injection she developed diffuse pain and contractures in the legs, fatigue, nausea, abdominal pain, and weight loss of 6 kg. Both knee joints were tender but there was no effusion. Her serum sodium concentration was 123 mmol/1, serum osmolality 254 mosmol/kg, urine sodium 136 mmol/1, and urinary osmolality 373 mosmol/kg. The syndrome of inappropriate antidiuretic hormone secretion was diagnosed, but despite treatment she remained drowsy and hyponatremic. About a week later, she developed hypotension and symptoms of an acute abdomen. Further investigations showed that her basal cortisol concentration was low (36 nmol/1) but it increased to 481 nmol/1 after a short tetracosactide test, consistent with acute adrenal crisis. She recovered rapidly after treatment with oral hydrocortisone, but still required glucocorticoid substitution several months later. 

Cushing s syndrome occurred in a 65-year-old woman with ulcerative colitis who received a daily betamethasone enema (471). 

Findlay CA, Macdonald JF, Wallace AM, Geddes N, Donaldson MD. Childhood Cushing s syndrome induced by betamethasone nose drops, and repeat prescriptions. BMJ 1998 317(7160) 739-40. 

Tsuruoka S, Sugimoto K, Fujimura A. Drug-induced Cushing syndrome in a patient with ulcerative colitis after betamethasone enema evaluation of plasma drug concentration. Ther Drug Monit 1998 20(4) 387-9. 

The percutaneous absorption of high-potency topical glucocorticoids has been documented, but hypothalamic-pituitary-adrenal axis suppression, leading to clinically significant adrenal insufficiency or Cushing s syndrome, is infrequent. Two patients developed adrenal suppression after the unregulated use of betamethasone dipropionate 0.05% ointment (about 80 g/week) or clobetasol 0.05% ointment (up to 100 g/week), obtained without prescription to treat psoriasis (362). 

A number of clinical trials have demonstrated the benefit of administering antenatal corticosteroids for the prevention of respiratory distress syndrome, intraventricular hemorrhage, and death in infants delivered prematurely. The current chnical recommendation is to administer betamethasone 12 mg intramuscularly every 24 hours for two doses or dexamethasone 6 mg intramuscularly every 12 hours for four doses to pregnant women between 24 and 34 weeks gestation who are at risk for preterm delivery within the next 7 days. Benefits from antenatal corticosteroids are believed to begin within 24 hours. It has been found that repeat corticosteroid administration does not produce any improvement in outcomes for infants and may trend toward harm. ... 

Glucocorticoids such as betamethasone (12 mg intramuscularly every 24 hours for two doses) or dexamethasone (6 mg intramuscularly every 12 hours for four doses) are used frequently in the setting of premature labor to decrease the incidence of respiratory distress syndrome, intraventricular hemorrhage, and death in babies delivered prematurely. 

Vermeer BJ, Heremans GFP (1974) A case of growth retardation and Cushing s syndrome due to excessive application of betamethasone-17-valerate ointment. Der-matologica 149 299-304... 

Ballard, P. L., Granberg, P. and Ballard, R. A. (1975) Glucocorticoid levels in maternal and cord serum after prenatal betamethasone therapy to prevent respiratory distress syndrome. J. din. Invest., 56, 1548. 

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