ESPE Abstracts (2022) 95 P1-534

ESPE2022 Poster Category 1 Multisystem Endocrine Disorders (24 abstracts)

Successful treatment of neonatal Cushing in a paediatric patient with McCune Albright Syndrome (MAS) by using metyrapone suppositories

Diana-Alexandra Ertl 1,2 , Gerda Ratzinger-Stoeger 3 , Maria Anzengruber 4 , Katharina Skoll 4 , Adalbert Raimann 1,2 , Franz Gabor 4 & Gabriele Haeusler 1,2

1Department of Pediatrics and Adolescent Medicine, Division of Pulmonology, Allergology and Endocrinology, Medical University of Vienna, Vienna, Austria; 2Vienna Bone and Growth Center, Vienna, Austria; 3Pharmacy Department, Vienna General Hospital, Medical University Campus, Vienna, Austria; 4Division of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Faculty of Life Sciences, Vienna, Austria

We present the case of a now 20 months old female patient, in whom we diagnosed MAS on the basis of pseudoprecocious puberty and hypercorticism at the age of 10 months. Medical history and photodocumentation suggested that symptoms of hypercorticism were present soon after birth. At age 4 months thelarche had occurred, followed by vaginal bleeding at age 5 months. At first presentation at our outpatient clinic, the girl was severely short (-5 SDS), with only minimally advanced bone age, Tanner stages were B3, P3-4. The endocrine evaluation confirmed peripheral ovarian and adrenal over-secretion. Additional findings included hepatopathy, hypertriglyceridemia, hypercholesterinaemia, proteinuria, and secondary arterial hypertension. In light of the hepatopathy, we decided to start the off-label treatment with metyrapone. Being aware of the challenges of this treatment with the only available product (gelatine capsule containing liquid metyrapone) and reports on local irritation and significant side effects after the oral and intrarectal administration of liquid metyrapone, diluted or undiluted, we decided to go for the rectal application as suppositories. Just one previous case report mentions the unsuccessful attempt of using metyrapone suppositories, without further information on the preparation or dosage. Our hospital pharmacy developed the preparation technique. The suppositories were characterized in terms of detectable metyrapone content, storage stability, as well as release of metyrapone from the matrix. The storage stability of metyrapone in the dosage form was studied over a period of six weeks at 4°C. Within the first three weeks the drug content varied by ± 3% and, during the whole timeframe, less than 10% was degraded. The release of metyrapone from the suppository was characterized using the flow-through cell, optimized for lipophilic formulations according to the European Pharmacopoeia (type C). A rapid disintegration of the dosage form after 6 minutes was followed by a gradual release and dissolution of metyrapone. We started with the dose of 300mg/m2/day (one administration every 6h), with the intention to “block and replace”, using repeated measurements of serum morning and 23:00 cortisol, salivary cortisol and 24h urine steroid profile. After two weeks, we discharged our patient with normal cortisol levels, without additional hydrocortisone substitution and with a total dose of 900 mg/m2/day. Triglycerides and cholesterol normalised after 8 months, arterial hypertension after 1 month, growth velocity improved progressively.

Conclusion: we present the first successful, long-term use of metyrapone as suppository, with no adverse side effects and striking clinical and biochemical improvement.

Volume 95

60th Annual ESPE (ESPE 2022)

Rome, Italy
15 Sep 2022 - 17 Sep 2022

European Society for Paediatric Endocrinology 

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