Iatrogenic Cushing’s Syndrome Due to Topical Ocular Glucocorticoid Treatment

Abstract

Iatrogenic Cushing’s syndrome (CS) is a severe adverse effect of systemic glucocorticoid (GC) therapy in children, but is extremely rare in the setting of topical ocular GC therapy. In this article, we report the case of a 9-year-old girl suffering from idiopathic uveitis who developed CS due to topical ocular GC treatment. She was referred to the ophthalmology department with a complaint of painful eyes, at which time she was diagnosed with bilateral iridocyclitis and started on a treatment of betamethasone sodium phosphate eye drops. Six months after the initiation of topical ocular GC treatment, she was referred to our pediatric department with stunted growth, truncal obesity, purple skin striate, buffalo hump, and moon face. Because her serum cortisol and plasma adrenocorticotropic hormone levels were undetectable, she was diagnosed with iatrogenic CS. After the doses of topical ocular GC were reduced, the clinical symptoms of CS were improved. The fact that the amount of topical ocular GC with our patient was apparently less than that of similar previous cases tempted us to perform genetic analysis of her NR3C1 gene. We found that our patient had a single heterozygous nucleotide substitution in the 3′ untranslated region of the NR3C1 gene, which may explain why she developed CS. However, additional investigations are required to determine if our findings can be extrapolated to other patients. In conclusion, clinicians should be aware that even extremely low doses of topical ocular steroid therapy can cause iatrogenic CS.

Tear Film Pharmacokinetics and Systemic Absorption Following Topical Administration of 1% Prednisolone Acetate Ophthalmic Suspension in Dogs

“…Plasma prednisolone levels detected in our dogs, albeit relatively small and potentially 50-100-fold lower than other routes of administration (oral, peribulbar or subconjunctival injection) (39-41), are not completely without risk. Topical corticotherapy has been associated with systemic adverse effects in dogs of diverse size and body weight, namely suppression of the hypothalamic-hypophyseal-adrenal axis (up to the development of iatrogenic Cushing's) and hepatic glycogen accumulation (42)(43)(44)(45), with similar concerns being reported in human patients (46,47). Taken together, though topical prednisolone acetate is an excellent drug for inflammatory and immune-mediated diseases of the anterior segment of the eye, caution must be exercised to prevent unwanted and potentially serious adverse effects, regardless of a patient's size.…”

Cataract management in children: a review of the literature and current practice across five large UK centres

“…Up to one fifth of children develop raised intraocular pressure, with onset at weeks or months after starting topical steroids [91,92]. Frequent topical steroids can also lead to growth suppression [93], Cushing syndrome [94] and hypothalamic-pituitary-adrenal axis suppression [95], which in turn can cause adrenal insufficiency. The symptoms and signs of this include: failure to thrive, weakness, hypotension, hypoglycaemia, nausea, vomiting and adrenal crises.…”

Cushing's syndrome caused by use of synthetic ocular steroid

“…14 To the best of our knowledge, fewer than 10 cases of CS developing following ocular steroid application have previously been reported. [2][3][4][5][6][7][8][9][10] The clinical and hormonal profiles of these cases are summarized in Fluorometholone has been administered in a range of indications. One study reported that allergic conjunctivitis was the second most common indication of fluorometholone use in children.…”

“…CS due to topical ocular steroids is very rare. All reported cases of iatrogenic CS were caused by the use of relatively potent steroids, including prednisolone, dexamethasone and betamethasone . Fluorometholone is a modified corticosteroid regarded as having fewer side effects than other steroids.…”

“…All reported cases of iatrogenic CS were caused by the use of relatively potent steroids, including prednisolone, dexamethasone and betamethasone. [2][3][4][5][6][7][8][9][10] Fluorometholone is a modified corticosteroid regarded as having fewer side effects than other steroids. It is therefore used relatively more extensively than other potent steroids in several different indications in paediatric ophthalmology.…”