Topical Glucocorticoids Can Trigger Cushing’s Syndrome in Children

Researchers caution care must be used when prescribing these medications

Teresa Carvalho, MS avatar

by Teresa Carvalho, MS |

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A baby sleeps with his head on a pillow while a plush toy rests on his belly.

Young children may be at high risk of developing Cushing’s syndrome after having a highly potent topical glucocorticoid applied to the skin, two case reports show.

The researchers emphasized that physicians who prescribe these medications must be aware for this potential side effect and closely monitor patients. They also highlighted that patients and/or their parents should be informed about possible complications and trained in applying the treatment in its dosage, duration, and frequency.

The study, “Topical glucocorticoid application causing iatrogenic Cushing’s syndrome followed by secondary adrenal insufficiency in infants: two case reports,” was published in the Journal of Medical Case Reports.

Cushing’s syndrome occurs when there’s too much stress hormone cortisol, which can be caused by prolonged use of man-made glucocorticoids, steroid medications to reduce inflammation.

This syndrome is very rare in children, with most cases being related to administering glucocorticoids by mouth or tube feeding. Cases of Cushing’s syndrome in children due to the topical use of glucocorticoids are rarely reported.

The effects of topical glucocorticoids depend on several factors, including the type of medication, its ability to be absorbed and used by the body, the integrity of the skin, the use of air- and water-tight trauma medical dressings, the frequency and duration of treatment, the presence of inflammation, and where it’s being applied.

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Two cases of Cushing’s with topical glucocorticoids

Researchers in Germany reported the cases of a 2-year-old Iranian girl and a 6-month-old Syrian boy who developed Cushing’s syndrome after being treated with topical glucocorticoids. The girl received dexamethasone and the boy clobetasol.

The girl had many complications after she was born, including congenital glaucoma, an eye condition that can damage the optic nerve. She underwent several eye surgeries, after which she was treated with dexamethasone eye drops at a dose of 0.3 mg/day.

She had short stature and low body mass index. A hormonal assessment excluded several conditions, such as hypothyroidism (or low thyroid hormone levels), lack of growth hormone, bone mineralization deficiency, abnormal absorption of food nutrients (malabsorption), poor kidney or liver function, anemia (reduced red blood cells), and chronic inflammation.

Brain imaging scans showed a normal pituitary gland and blood tests found no cortisol and low levels of adrenocorticotropic hormone (ACTH) – a signaling molecule released by the pituitary gland that triggers the adrenal glands to release cortisol.

ACTH and corticotropin-releasing hormone (CRH) stimulation tests confirmed the girl’s adrenal glands were unable to produce enough cortisol, called adrenal insufficiency.

Further blood tests showed dexamethasone at levels of 1.02 nanomoles/L (nmol/L), indicating the medication was being significantly absorbed by the body.

According to the researchers, the eyes have a high capacity to reabsorb topical medications. To reduce this risk, “it is advisable to apply finger pressure to the lacrimal sac for 1–2 minutes after instillation [given by drops] of dexamethasone eye drops to decrease the risk of resorption and systemic effects.”

A few weeks later, after the dexamethasone was gradually decreased to 0.15 mg/day, the girl recovered her growth, her appetite improved, and cortisol production was normal.

The second case is of a newborn who developed scabies when he was in a refugee camp. The itching persisted after he was treated with permethrin and he then received a cream containing clobetasol propionate 0.05% at a daily dosage of 2 grams/day for at least four weeks. Clobetasol is estimated to be 600 times stronger than hydrocortisone, another cortisol-like steroid medication.

When admitted to the hospital, the boy had a Cushing’s-like moon face and scratch marks on his belly. Low blood levels of ACTH and morning cortisol were found — ACTH at 1.3 picomoles/L (pmol/L, normal range, 2.2–11 pmol/L) and morning cortisol at 14 nmol/L (normal range, 155–552 nmol).

Urine tests revealed very low levels of cortisone (a naturally-occurring corticosteroid) and undetectable cortisol levels.

“It is known that the use of 2 g/day of 0.05% clobetasol propionate can decrease morning cortisol levels after only a few days and use over 100 g/week can lead to the development of features of CS [Cushing’s syndrome] and symptoms of adrenal insufficiency,” the researchers wrote.

The boy was diagnosed with adrenal insufficiency secondary to Cushing’s syndrome and started an oral treatment with hydrocortisone, at 9 mg per square meter of body surface per day (mg/m2/day) divided in three doses. His mother was trained on dose adaptation in case of emergency and the clobetasol propionate was stopped.

In these cases, “abrupt discontinuation of long-standing glucocorticoid treatment should be avoided,” the researchers wrote. “A reduction scheme should be provided and explained in detail to the parents.”

A few weeks later, the boy still had adrenal insufficiency with low blood levels of morning cortisol and ACTH, but his moon face features improved. He continued the treatment with hydrocortisone. A follow-up was unable to be done after his family was transferred to a refugee camp in Germany.

The researchers concluded that “young infants are at high risk of developing Cushing’s syndrome from topically applied highly potent glucocorticoids.”

“Precise recommendations of treatment dosage, duration, and frequency must be given to the parents, and if necessary, with the help of an interpreter,” they said.