Endocrine Abstracts

Background: Aromatase inhibitors block the aromatization of androgens to oestrogen. They are used off-label to delay bone maturation where bone age (BA) is advanced secondary to androgen excess. Side effects include hair loss, headache, decreased appetite, bone pain, drowsiness, and osteoporosis. There is limited data on Anastrozole’s safety in paediatrics. We report our experience (Anastrozole 1 mg OD) in 4 pre-pubertal boys with advanced BA.

Case 1: Presented at eight years with paternal concerns about early puberty. On examination A1/P1/G1. Urine steroid profile (USP) and genetic testing confirmed compound heterozygous 21-hydroxylase (21OH) deficiency CAH. Short synacthen (SST) results were 172, 292 and 319 nmol/l at 0, 30 and 60 min, respectively. BA advanced (11.2 at 8.12 years; +3.37 SDS). He was commenced on Anastrozole aged 9.5 years, which was tolerated well.

Case 2: 2.9-year-old presented with peripheral precious puberty A1/G2/P2, followed by genetic confirmation of simple virilizing non-salt wasting CAH. Despite cortisol replacement therapy (15.4 mg/m² per day) and good adherence, BA continued to advance (Table 1). He was started on Anastrozole & subsequent BA showed marked improvement without side effects.Table 1 Chronological age (CA) and BA pre- and post-Anastrozole

Case 3: 2-week-old boy presented with salt wasting and was diagnosed with 21OHD CAH. Despite glucocorticoid replacement (14 mg/m² per day), BA continued to advance (10.4 at CA 7.1 years). Anastrozole was commenced. After two weeks, he developed severe headaches, which resolved following Anastrozole cessation.

Case 4: 6-year-old presented with paternal early puberty concerns (pre-pubertal on examination). Background of MAMLD1 mutation associated with familial non-syndromic hypospadias and early puberty followed by testicular failure. BA was 12.1 at 7.7 CA at Anastrozole commencement. He experienced nausea, tiredness, and hair loss; his medication was stopped for two weeks. He restarted it and tolerated it well.

Conclusion: Two out of four patients experienced significant side effects of Anastrozole which improved on cessation. Careful counselling of side effects is important before treatment initiation.