Glucocorticoids

Abstract

Various toxicities: 13 case reports In a retrospective study involving 14 patients, 13 patients [8 female patients and 5 male patients] aged 0.41–12 years were described, who developed iatrogenic Cushing’s syndrome, adrenal insufficiency, adrenal atrophy, hepatosteatosis or hypertriglyceridaemia during treatment with methylprednisolone, prednisolone, diflucortolone/isoconazole, clobetasol, dexamethasone or betamethasone valerate [not all dosages, indications and outcomes stated; time to reactions onsets not stated]. A 12-year-old girl (patient 1) developed iatrogenic Cushing’s syndrome, hypertriglyceridaemia and adrenal insufficiency during treatment with methylprednisolone for idiopathic thrombocytopenic purpura. The girl had been receiving oral methylprednisolone pulse therapy 2–3 times for 24 months for idiopathic thrombocytopenic purpura. The total dose of methylprednisolone pulse therapy was 91250mg. She was brought to hospital due to the features suggestive of Cushing’s syndrome. On admission, physical examination revealed buffalo hump, moon face, central obesity and purple striae. Ophthalmologic examination revealed bilateral posterior segment cataract. Her BP was 120/75mm Hg. Further investigations revealed the following: fasting glucose 348 mg/dL, insulin 17.07 μIU/mL, calcium 9.1 mg/dL, phosphorus 4.8 mg/dL, 25-hydroxyvitamin D 18.93 ng/mL, AST 11 U/L, ALT 13 U/L, ALP 99 U/L, total cholesterol 186 mg/dL, triglycerides 186 mg/dL, low-density lipoprotein 87 mg/dL, high-density lipoprotein 62 mg/dL, basal cortisol 3.73 μg/dL and basal ACTH <5 pg/mL. Based on her symptoms and laboratory findings, she was diagnosed with iatrogenic Cushing’s syndrome, adrenal insufficiency, hypertriglyceridaemia and hyperglycaemia. An abdominal ultrasonography showed splenomegaly. She received treatment with metformin for hyperglycaemia. She underwent splenectomy for idiopathic thrombocytopenic purpura. She was treated with methylprednisolone (15 mg/m2/d), since she had received a total of 5000mg of methylprednisolone via oral route over 5 days before the admission. It was found that the hypothalamo-pituitary-adrenal (HPA) axis normalised in 40 days. A 0.21-year-old boy (patient 2) developed iatrogenic Cushing’s syndrome, adrenal atrophy, adrenal insufficiency and hypertriglyceridaemia during treatment with prednisolone. The boy, who had congenital cataract, had been receiving oral prednisolone for 1.6 months. A pediatrician had prescribed him prednisolone before the congenital cataract surgery. He was brought to hospital due to puffiness on the face and abdomen. Physical examination revealed moon face, central obesity, facial acne, oral and diaper candidiasis. Investigations revealed the following: fasting glucose 91 mg/dL, calcium 10.2 mg/dL, phosphorus 5.9 mg/dL, 25-hydroxyvitamin D 37.10 ng/mL, 1,25-dihydroxyvitamin D 2.30 ng/mL, AST 44 U/L, ALT 67 U/L, total cholesterol 361 mg/dL, triglycerides 143 mg/dL, low-density lipoprotein 263 mg/dL, high-density lipoprotein 69 mg/dL, basal cortisol 2.1 μg/dL, stimulated cortisol 5.4 μg/dL and basal ACTH 7.48 pg/mL. Based on his symptoms and laboratory findings, he was diagnosed with iatrogenic Cushing’s syndrome, adrenal insufficiency, hypertriglyceridaemia and hypercalcaemia. An abdominal ultrasonography showed bilateral nephrocalcinosis. Persistent adrenal insufficiency was detected due to adrenal atrophy. He received treatment with hydrocortisone and fludrocortisone for adrenal atrophy. He also received treatment with furosemide and pamidronic-acid [pamidronate] for hypercalcaemia. A 9-year-old girl (patient 3) developed iatrogenic Cushing’s syndrome, hypertriglyceridaemia, hepatosteatosis and adrenal insufficiency during treatment with methylprednisolone for skin rashes. The girl had been receiving oral methylprednisolone for the treatment of skin rashes for 1 month. Methylprednisolone was prescribed by a pediatrician. She was brought to hospital with maculopapular rash. On admission, physical examination revealed moon face, central obesity and widespread maculopapular rash in the whole body. Her BP was 110/60mm Hg. Investigations revealed the following: fasting glucose 168 mg/dL, calcium 8.7 mg/dL, phosphorus 3.5 mg/dL, AST 254 U/L, ALT 331 U/L, ALP 180 U/L, total cholesterol 142 mg/dL, triglycerides 270 mg/dL, low-density lipoprotein 66 mg/dL, high-density lipoprotein 22 mg/dL, basal cortisol 0.6 μg/dL, basal ACTH 15.3 pg/mL and stimulated cortisol 6.21 μg/dL. Based on her symptoms and laboratory findings, she was diagnosed with iatrogenic Cushing’s syndrome, hypertriglyceridaemia and adrenal insufficiency. An abdominal ultrasonography showed grade 2 hepatosteatosis. She received treatment with hydrocortisone. It was found that the HPA axis normalised in 150 days. A 0.56-year-old girl (patient 4) developed iatrogenic Cushing’s syndrome, hypertriglyceridaemia and adrenal insufficiency during treatment with diflucortolone/isoconazole for diaper dermatitis. The girl had been receiving topical diflucortolone/isoconazole cream [diflucortolone valerate 0.3% and isoconazole nitrate containing cream] for diaper dermatitis since her birth. The diflucortolone/isoconazole cream was applied by her mother. She was brought to hospital due to pubic hair. On admission, physical examination revealed diffuse fine hair in the genital and sacral region. Investigations revealed the following: fasting glucose 99 mg/dL, insulin 3.5 μIU/mL, calcium 10.3 mg/dL, phosphorus 5.5 mg/dL, AST 52 U/L, ALT 28 U/L, total cholesterol 149 mg/dL, triglycerides 75 mg/dL, low-density lipoprotein 98 mg/dL, high-density lipoprotein 36 mg/dL, basal cortisol 4.52 μg/dL, basal ACTH 19 pg/mL and stimulated cortisol 16.3 μg/dL. Based on her symptoms and laboratory findings, she was diagnosed with iatrogenic Cushing’s syndrome, hypertriglyceridaemia and adrenal insufficiency. It was found that the HPA axis normalised in 51 days. A 0.41-year-old girl (patient 5) developed iatrogenic Cushing’s syndrome and adrenal insufficiency during treatment with diflucortolone/isoconazole for diaper dermatitis. The girl had been receiving topical diflucortolone/isoconazole cream [Diflucortolone valerate 0.3% and isoconazole nitrate containing cream] for diaper dermatitis since birth. The diflucortolone/ isoconazole cream was applied by her mother. She was brought to hospital due to a rapid weight gain. On admission, physical examination revealed moon face, central obesity and prominent skin folds. Investigations revealed the following: basal cortisol <1 μg/dL and basal ACTH <1 pg/mL. Based on her symptoms and laboratory findings, she was diagnosed with iatrogenic Cushing’s syndrome and adrenal insufficiency. Her parents refused further investigations and therapy. A 2.45-year-old boy (patient 6) developed iatrogenic Cushing’s syndrome and adrenal insufficiency during treatment with clobetasol for diaper dermatitis. The boy had been receiving topical clobetasol cream [clobetasol propionate 0.05% containing cream] for diaper dermatitis for 7 months. Clobetasol cream was applied by his mother. He was brought to hospital due to hair on the face. On admission, physical examination revealed moon face, central obesity and widespread hypertrichosis. Investigations revealed the following: calcium 9.9 mg/dL, phosphorus 5.4 mg/dL, AST 17 U/L, ALT 41 U/L, ALP 325 U/L, basal cortisol <1 μg/dL, basal ACTH 19.5 pg/mL and stimulated cortisol 3 μg/dL. Based on his symptoms and laboratory findings, he was diagnosed with iatrogenic Cushing’s syndrome and adrenal insufficiency. He was treated with hydrocortisone. It was found that the HPA axis normalised in 60 days. A 1.08-year-old boy (patient 7) developed iatrogenic Cushing’s syndrome and adrenal insufficiency during treatment with clobetasol for diaper dermatitis. The boy had been receiving topical clobetasol cream [clobetasol propionate 0.05% containing cream] for diaper dermatitis for 2 months. Clobetasol cream was applied by his mother. He was brought to hospital due to a widespread hypertrichosis. On admission, physical examination showed moon face. Investigations revealed the following: calcium 10.1 mg/dL, phosphorus 5.5 mg/dL, ALT 11 U/L, AST 28 U/L, ALP 308 U/L, triglycerides 69 mg/dL, basal cortisol 7.85 μg/dL, basal ACTH 37 pg/mL and stimulated cortisol 9.44 μg/dL. Based on his symptoms and laboratory findings, he was diagnosed with 1