Abstract
Androgen insensitivity syndromes have different phenotypes, depending on severity of the receptor defect, which in turn depends on the type of androgen receptor gene mutation. A molecular genetic based subclassificalion may help to define those, who are responsive to high dose androgen therapy. We report two brothers who were successfully treated with high doses of iestosterone.
Patients: Two brothers, 11 5/12(A) and 15 3/12 (B) years, had micropenis, penoscrotat hypospadias and chordee. Penis size was 3 and 3.5 cm, resp.
Results: Basal serum hormone levels (LH, FSH, testosterone, DHT) were prepuberlal in (A), LH was increased in (B) (13,3 U/L). The androgon sensitivity test revealed a partial defect of androgen action, as evidenced by a decreased SHBG response to the anabolic steroid stanozolol (nadir 71% and 66 %, resp.). DNA analysis revealed a single base substitution (T to G) in the hormone-binding region (exon 7) of the androgen receptor gene which causes a Val → Leu substitution in codon 866. Treatment was initiated with 500 mg testosterone enanthale, im, every 2 weeks. Penis size increased to 8.5 (A) and 9 (B) cm, pubic hair reached Tanner stage 5, voice broke, a moustache, axillary hair and gynecomastia appeared. Erections and ejaculations were reported. Under treatment serum levels of testosterone (71,1 (A). 1-17,3 (B) nmol/L) and estradiol (191 (A), 396 (B) pmol/L) were increased (2 weeks after the last injection).
Conclusion: High dose androgen treatment produced pubertal virilization and phallic growth in both patients. The partial impairment of androgen receptor function may be overcome by supraphysiological serum concentrations of testosterone. Thus, such treatment seems to be indicated in certain patients with partial androgen insensitivity, in particular in patients with the Val → Leu substitution in codon 866 of the hormone-binding domain of the androgen receptor.
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Sinnecker, G., Hiort, O., Brack, C. et al. PARTIAL ANDROGEN INSENSITIVITY DUE TO VAL → LEU SUBSTITUTION IN CODON 866 OF THE ANDROGEN RECEPTOR CAN BE TREATED WITH HIGH DOSES OF TESTOSTERONE. Pediatr Res 33 (Suppl 5), S17 (1993). https://doi.org/10.1203/00006450-199305001-00083
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DOI: https://doi.org/10.1203/00006450-199305001-00083
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