Background: Masculinisation tempo on sex-steroid replacement in boys with multiple pituitary hormone deficiencies (MPHD) and pubertal growth spurts on adequate GH-treatment regimens were unknown in 1989 and are still not optimal.
Objective and Hypotheses: A hypothesis driven prototype trial1,2 was initiated in the late 80ies aiming to mimic normal puberty3 regarding both degree and tempo of masculinisation and pubertal height gain and adult height (AH). For the first time, low testosterone doses were used together with rhGH-doses of ≥=33ug/kg/day.
Study Design: Approved by Swedish Ethical Committees, testosterone-treatment was given to MPHD boys, a subgroup in a randomised national trial on rhGH-doses during puberty (TRN 88-177).
10 boys with ≥one prepubertal year on rhGH treatment 33µg/kg/day were randomized to rhGH 33/67µg/kg/day during puberty (Genotropin®,Kabi/Pharmacia/Pfizer). Sex-steroid replacement was oral testosterone undecanoat (Undestor®,Organon), in increasing doses (10, 20, 40mg/d) followed by parenteral Testoviron depot®,(Schering).
Methods: Genital development was assessed according to Tanner3 (stage 1-5).
Height outcome: AHSDS vs total height reference. Pubertal height gain was estimated as change (Δ) from heightSDS at start of testosterone replacement (vs prepubertal height reference) to AH. Results are given as median (range).
Results: The MPHD boys had a history of oncology treatment (n =3) or congenital anomaly (n=7). Age at start of testosterone replacement was median 13.8yrs (range 11.8 to15.8).
Genitalia Development: Time from start of testosterone (G1) until G2 was 1.1yrs (0.3-3.0); G2-G3 1.2yrs (0.6-2.1); G3-G4 1.2yrs (0.3-2.3); puberty time G2-G4 2.5yrs (1.7-3.2); G1-Gmax 4.8yrs (2.2-5.8). Age at treatment start was late, but the masculinization tempo G1-G3 became within published3 normal ranges. 8/10 needed parenteral testosterone for progress from G3 to G4/5.
Height Outcome: Total pubertal gain in heightSDS was +0.58 (-0.51 to 2.33); expressed in cm 32.0 (19.7-37.2). AHSDS was 0.36 (-0.34 to 1.38); expressed in cm 182.8 (178.2-189.5).
According to GH doses: GH33 ΔHSDS 0.24 (-0.51 to 0.58), GH67 ΔHSDS 1.8 (-0.29 to 2.33).
Conclusion: This hypothesis driven prototype trial initiated in 1989, show for the first time that it is possible to normalize puberty in boys with MPHD, both regarding tempo of genitalia development, pubertal growth spurt and AH using a low dose therapy with testosterone and adequate rhGH doses. Induction with oral testosterone dose was favourable for genital development and growth, but was insufficient for complete maturation. These positive results will allow puberty induction in MPHD boys at normal age.
1,2Albertsson-Wikland etal, Acta.Paed.1999;88(suppl):80-84;&Horm.Res.Ped.2014; 82:158-170.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology