title: Growth Hormone With Aromatase Inhibitor May Improve Height in CYP11B1 Congenital Adrenal Hyperplasia.
abstract: With an estimated prevalence of 1 in 100 000 births, 11β-hydroxylase deficiency is the second most common form of congenital adrenal hyperplasia (CAH) and is caused by mutations in CYP11B1 Clinical features include virilization, early gonadotropin-independent precocious puberty, hypertension, and reduced stature. The current mainstay of management is with glucocorticoids to replace deficient steroids and to minimize adrenal sex hormone overproduction, thus preventing virilization and optimizing growth. We report a patient with CAH who had been suboptimally treated and presented to us at 6 years of age with precocious puberty, hypertension, tall stature, advanced bone age, and a predicted final height of 150 cm. Hormonal profiles and genetic analysis confirmed a diagnosis of 11β-hydroxylase deficiency. In addition to glucocorticoid replacement, the patient was commenced on growth hormone and a third-generation aromatase inhibitor, anastrozole, in an attempt to optimize his growth. After the initiation of this treatment, the patient's growth rate improved significantly and bone age advancement slowed. The patient reached a final height of 177.5 cm (0.81 SD score), 11.5 cm above his mid-parental height. This patient is only the second reported case of the use of an aromatase inhibitor in combination with growth hormone to optimize height in 11β-hydroxylase-deficient CAH. This novel treatment proved to be highly efficacious, with no adverse effects. It may therefore provide a promising option to promote growth in exceptional circumstances in individuals with 11β-hydroxylase deficiency presenting late with advanced skeletal maturation and consequent short stature.
authors.affiliation: Bristol Royal Hospital for Children, Bristol, United Kingdom; katherine.hawton@nhs.net.
authors.forename: Katherine
authors.initials: K
authors.lastname: Hawton
authors.affiliation: Genetics and Epigenetics in Health and Disease Section, Genetics and Genomic Medicine Programme, UCL Institute of Child Health and Great Ormond Street Hospital, London, United Kingdom.
authors.forename: Sandra
authors.initials: S
authors.lastname: Walton-Betancourth
authors.affiliation: University College London Hospital, London, United Kingdom; and.
authors.forename: Gill
authors.initials: G
authors.lastname: Rumsby
authors.affiliation: Whittington Hospital, London, United Kingdom.
authors.forename: Joseph
authors.initials: J
authors.lastname: Raine
authors.affiliation: Genetics and Epigenetics in Health and Disease Section, Genetics and Genomic Medicine Programme, UCL Institute of Child Health and Great Ormond Street Hospital, London, United Kingdom.
authors.forename: Mehul
authors.initials: M
authors.lastname: Dattani
mesh_terms: D000293:Adolescent; D000312:Adrenal Hyperplasia, Congenital / Q000150:complications / Q000188:drug therapy*; D000077384:Anastrozole; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D006130:Growth Disorders / Q000188:drug therapy* / Q000209:etiology; D013006:Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D006854:Hydrocortisone / Q000627:therapeutic use; D008297:Male; D009570:Nitriles / Q000627:therapeutic use*; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D000077384:Anastrozole; D013006:Growth Hormone; D006854:Hydrocortisone