Adult height in patients with familial male-limited precocious puberty and the role of an aromatase inhibitor in patient management
-
Laura C. Lane
,
Josephine Flowers
Abstract
Background:
There is little adult height data in patients with familial male-limited precocious puberty (FMPP) and no management consensus. We assessed the treatment and adult height in local patients with FMPP and those reported in the literature.
Methods:
Growth data were obtained on four local patients with FMPP and a search performed to obtain management details and adult height data on cases in the literature. UK (90) population standards were used to calculate standard deviation scores (SDS).
Results:
Adult height data were available on 25 men with FMPP of whom 21 were treated. Median adult height SDS of patients was −1.5 SD with a mid-parental target of −0.6 SD (p=0.1). Eight patients (32%) had an adult height above the mid-parental target and seven patients (28%) had a height >2 SD below the mean. The median height SD was −0.03 in untreated patients and +0.5 SD in those receiving an aromatase inhibitor. There was no relationship between height and age at presentation.
Conclusions:
Aromatase inhibitor therapy is associated with a positive height outcome in FMPP but the outcome with and without intervention is unpredictable. Clinicians need to be cautious when counselling families about the potential height outcome in FMPP.
Author contributions: LC Lane performed the literature search and co-wrote the manuscript with TC. JF and HJ contributed to patient management and reviewed earlier versions of the manuscript. All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Schedewie HK, Reiter EO, Beitins IZ, Seyed S, Wooten VD, et al. Testicular Leydig cell hyperplasia as a cause of familial sexual precocity. J Clin Endocrinol Metab 1981;52:271–8.10.1210/jcem-52-2-271Search in Google Scholar
2. Nagasaki K, Katsumata N, Ogawa Y, Kikuchi T, Uchiyama M. Testicular novel C617Y mutation in the 7th transmembrane segment of luteinizing hormone/choriogonadotropin receptor in a Japanese boy with peripheral precocious puberty. Endocr J 2010;57:1055–60.10.1507/endocrj.K10E-227Search in Google Scholar
3. Laue L, Wu SM, Kudo M, Hsueh AJ, Cutler GB Jr., et al. Heterogeneity of activating mutations of the human luteinizing hormone receptor in male-limited precocious puberty. Biochem Mol Med 1996;58:192–8.10.1006/bmme.1996.0048Search in Google Scholar
4. Rosenthal SM, Grumbach MM, Kaplan SL. Gonadotropin-independent familial sexual precocity with premature Leydig and germinal cell maturation (familial testotoxicosis): effects of a potent luteinizing hormone-releasing factor agonist and medroxyprogesterone acetate therapy in four cases. J Clin Endocrinol Metab 1983;57:571–9.10.1210/jcem-57-3-571Search in Google Scholar
5. Shenker A, Laue L, Kosugi S, Merendino JJ Jr., Minegishi T, et al. A constitutively activating mutation of the luteinizing hormone receptor in familial male precocious puberty. Nature 1993;365:652–4.10.1038/365652a0Search in Google Scholar
6. Laue L, Chan WY, Hsueh AJ, Kudo M, Hsu SY, et al. Genetic heterogeneity of constitutively activating mutations of the human luteinizing hormone receptor in familial male-limited precocious puberty. Proc Natl Acad Sci USA 1995;92:1906–10.10.1073/pnas.92.6.1906Search in Google Scholar
7. Gromoll J, Partsch CJ, Simoni M, Nordhoff V, Sippell WG, et al. A mutation in the first transmembrane domain of the lutropin receptor causes male precocious puberty. J Clin Endocrinol Metab 1998;83:476–80.10.1210/jcem.83.2.4579Search in Google Scholar
8. Latronico AC, Shinozaki H, Guerra G Jr., Pereira MA, Lemos Marini SH, et al. Gonadotropin-independent precocious puberty due to luteinizing hormone receptor mutations in Brazilian boys: a novel constitutively activating mutation in the first transmembrane helix. J Clin Endocrinol Metab 2000;85:4799–805.Search in Google Scholar
9. Siviero-Miachon AA, Kizys MM, Ribeiro MM, Garcia FE, Spinola-Castro AM, et al. Cosegregation of a novel mutation in the sixth transmembrane segment of the luteinizing/choriogonadotropin hormone receptor with two Brazilian siblings with severe testotoxicosis. Endocr Res 2017;42:117–24.10.1080/07435800.2016.1217005Search in Google Scholar
10. Özcabı B, Bucak FT, Ceylaner S, Özcan R, Büyükünal C, et al. Testotoxicosis: report of two cases, one with a novel mutation in LHCGR gene. J Clin Res Pediatr Endocrinol 2015;7:242–8.10.4274/jcrpe.2067Search in Google Scholar
11. Gondos B, Egli CA, Rosenthal SM, Grumbach MM. Testicular changes in gonadotropin-independent familial male sexual precocity. Familial testotoxicosis. Arch Pathol Lab Med 1985;109:990–5.10.1016/S0022-5347(17)45800-9Search in Google Scholar
12. Egli CA, Rosenthal SM, Grumbach MM, Montalvo JM, Gondos B. Pituitary gonadotropin-independent male-limited autosomal dominant sexual precocity in nine generations: familial testotoxicosis. J Pediatr 1985;106:33.10.1016/S0022-3476(85)80460-1Search in Google Scholar
13. Latronico AC, Lins TS, Brito VN, Arnhold IJ, Mendonca BB. The effect of distinct activating mutations of the luteinizing hormone receptor gene on the pituitary–gonadal axis in both sexes. Clin Endocrinol 2000;53:609–13.10.1046/j.1365-2265.2000.01135.xSearch in Google Scholar PubMed
14. Schoelwer M, Eugster EA. Treatment of peripheral precocious puberty. Endocr Dev 2016;29:230–9.10.1159/000438895Search in Google Scholar PubMed PubMed Central
15. Holland FJ, Kirsch SE, Selby R. Gonadotropin-independent precocious puberty (“testotoxicosis”): influence of maturational status on response to ketoconazole. J Clin Endocrinol Metab 1987;64:328–33.10.1210/jcem-64-2-328Search in Google Scholar PubMed
16. Almeida MQ, Brito VN, Lins TS, Guerra-Junior G, de Castro M, et al. Long-term treatment of familial male-limited precocious puberty (testotoxicosis) with cyproterone acetate or ketoconazole. Clin Endocrinol 2008;69:93–8.10.1111/j.1365-2265.2007.03160.xSearch in Google Scholar PubMed
17. Bertelloni S, Baroncelli GI, Lala R, Cappa M, Matarazzo P, et al. Long-term outcome of male-limited gonadotropin-independent precocious puberty. Horm Res 1997;48:235–910.1159/000185521Search in Google Scholar PubMed
18. Evans BA, Bowen DJ, Smith PJ, Clayton PE, Gregory JW. A new point mutation in the luteinising hormone receptor gene in familial and sporadic male limited precocious puberty: genotype does not always correlate with phenotype. J Med Genet 1996;33:143–7.10.1136/jmg.33.2.143Search in Google Scholar PubMed PubMed Central
19. Tanner JM, Goldstein H, Whitehouse RH. Standards for children’s height at ages 2-9 years allowing for heights of parents. Arch Dis Child 1970;45:755–62.10.1136/adc.45.244.755Search in Google Scholar PubMed PubMed Central
20. Soriano-Guillén L, Lahlou N, Chauvet G, Roger M, Chaussain JL, et al. Adult height after ketoconazole treatment in patients with familial male-limited precocious puberty. J Clin Endocrinol Metab 2005;90:147–51.10.1210/jc.2004-1438Search in Google Scholar PubMed
21. Jeha GS, Lowenthal ED, Chan WY, Wu SM, Karaviti LP. Variable presentation of precocious puberty associated with the D564G mutation of the LHCGR gene in children with testotoxicosis. J Pediatr 2006;149:271–4.10.1016/j.jpeds.2006.03.017Search in Google Scholar PubMed
22. Yoshizawa-Ogasawara A, Katsumata N, Horikawa R, Satoh M, Urakami T, et al. Third-generation aromatase inhibitor improved adult height in a Japanese boy with testotoxicosis. Clin Pediatr Endocrinol 2014;23:53–8.10.1297/cpe.23.53Search in Google Scholar PubMed PubMed Central
23. Partsch CJ, Krone N, Riepe FG, Gromoll J, Sippell WG. Long-term follow-up of spontaneous development in a boy with familial male precocious puberty. Horm Res 2004;62:177–81.10.1159/000080887Search in Google Scholar PubMed
24. Ito Y, Yano K, Mitamura R, Oka R, Okuno A, et al. Sporadic testotoxicosis in Japanese children: report of 4 cases. Horm Res 1992;1:95–100.10.1297/cpe.1.95Search in Google Scholar
25. Cole TJ, Green PJ. Smoothing reference centile curves: the LMS method and penalized likelihood. Stat Med 1992;11:1305–19.10.1002/sim.4780111005Search in Google Scholar PubMed
26. Müller J, Gondos B, Kosugi S, Mori T, Shenker A. Severe testotoxicosis phenotype associated with Asp578-->Tyr mutation of the lutrophin/choriogonadotrophin receptor gene. J Med Genet 1998;35:340–1.10.1136/jmg.35.4.340Search in Google Scholar PubMed PubMed Central
27. Rajfer J, Sikka SC, Rivera F, Handelsman DJ. Mechanism of inhibition of human testicular steroidogenesis by oral ketoconazole. J Clin Endocrinol Metab 1986;63:1193–8.10.1210/jcem-63-5-1193Search in Google Scholar PubMed
28. Wit JM, Hero M, Nunez SB. Aromatase inhibitors in pediatrics. Nat Rev Endocrinol 2011;8:135–47.10.1038/nrendo.2011.161Search in Google Scholar PubMed
29. Babovic-Vuksanovic D, Donaldson MD, Gibson NA, Wallace AM. Hazards of ketoconazole therapy in testotoxicosis. Acta Paediatr 1994;83:994–7.10.1111/j.1651-2227.1994.tb13192.xSearch in Google Scholar PubMed
30. Lenz AM, Shulman D, Eugster EA, Rahhal S, Fuqua JS, et al. Bicalutamide and third-generation aromatase inhibitors in testotoxicosis. Pediatrics 2010;126:728–33.10.1542/peds.2010-0596Search in Google Scholar PubMed PubMed Central
31. Tessaris D, Matarazzo P, Mussa A, Tuli G, Verna F, et al. Combined treatment with bicalutamide and anastrozole in a young boy with peripheral precocious puberty due to McCune-Albright Syndrome. Endocr J 2012;59:111–7.10.1507/endocrj.EJ11-0214Search in Google Scholar PubMed
32. Reiter EO, Mauras N, McCormick K, Kulshreshtha B, Amrhein J, et al. Bicalutamide plus anastrozole for the treatment of gonadotropin-independent precocious puberty in boys with testotoxicosis: a phase II, open-label pilot study (BATT). J Pediatr Endocrinol Metab 2010;23:999–1009.10.1515/jpem.2010.161Search in Google Scholar PubMed
33. Kreher NC, Pescovitz OH, Delameter P, Tiulpakov A, Hochberg Z. Treatment of familial male-limited precocious puberty with bicalutamide and anastrozole. J Pediatr 2006;149:416–20.10.1016/j.jpeds.2006.04.027Search in Google Scholar PubMed
34. Eyssette-Guerreau S, Pinto G, Sultan A, Le Merrer M, Sultan C, et al. Effectiveness of anastrozole and cyproterone acetate in two brothers with familial male precocious puberty. J Pediatr Endocrinol Metab 2008;21:995–1002.10.1515/JPEM.2008.21.10.995Search in Google Scholar PubMed
35. Hero M, Toiviainen-Salo S, Wickman S, Mäkitie O, Dunkel L. Vertebral morphology in aromatase inhibitor-treated males with idiopathic short stature or constitutional delay of puberty. J Bone Miner Res 2010;25:1536–43.10.1002/jbmr.56Search in Google Scholar PubMed
36. Hero M, Norjavaara E, Dunkel L. Inhibition of estrogen biosynthesis with a potent aromatase inhibitor increases predicted adult height in boys with idiopathic short stature: a randomized controlled trial. J Clin Endocrinol Metab 2005;90:6396–402.10.1210/jc.2005-1392Search in Google Scholar PubMed
37. Mauras N, Ross JL, Gagliardi P, Yu YM, Hossain J, et al. Randomized trial of aromatase inhibitors, growth hormone, or combination in pubertal boys with idiopathic, short stature. J Clin Endocrinol Metab 2016;101:4984–93.10.1210/jc.2016-2891Search in Google Scholar PubMed PubMed Central
38. Corvol P, Michaud A, Menard J, Freifeld M, Mahoudeau J. Antiandrogenic effect of spirolactones: mechanism of action. Endocrinology 1975;97:52–8.10.1210/endo-97-1-52Search in Google Scholar PubMed
39. Geisler J, Lønning PE. Aromatase inhibition: translation into a successful therapeutic approach. Clin Cancer Res 2005;11:2809–21.10.1158/1078-0432.CCR-04-2187Search in Google Scholar PubMed
40. Neely EK, Kumar RB, Payne SL, Ranadive SA, Suchet DI. Letrozole vs anastrozole for height augmentation in short pubertal males: first year data. J Clin Endocrinol Metab 2014;99:4086–93.10.1210/jc.2014-2432Search in Google Scholar PubMed
41. Leschek EW, Jones J, Barnes KM, Hill SC, Cutler GB Jr. Six-year results of spironolactone and testolactone treatment of familial male-limited precocious puberty with addition of deslorelin after central puberty onset. J Clin Endocrinol Metab 1999;84:175–8.10.1210/jcem.84.1.5413Search in Google Scholar PubMed
42. Mitre N, Lteif A. Treatment of familial male-limited precocious puberty (testotoxicosis) with anastrozole and bicalutamide in a boy with a novel mutation in the luteinizing hormone receptor. J Pediatr Endocrinol Metab 2009;22:1163–7.10.1515/JPEM.2009.22.12.1163Search in Google Scholar
©2018 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Review
- Review and evaluation of patient-centered psychosocial assessments for children with central precocious puberty or early puberty
- Mini Review
- Childhood obesity: how long should we wait to predict weight?
- Original Articles
- Glycated hemoglobin A1c as a screening test for detecting type 2 diabetes mellitus in obese children and adolescents
- Effect of a multidisciplinary treatment program on eating behavior in overweight and obese preschool children
- Cord blood klotho levels are inversely associated with leptin in healthy Latino neonates at risk for obesity
- Still too little, too late? Ten years of growth hormone therapy baseline data from the NordiNet® International Outcome Study
- Body composition and metabolic health of young male adults with childhood-onset multiple pituitary hormone deficiency after cessation of growth hormone treatment
- Hematuria as an adverse outcome following provocative growth hormone stimulation testing in children
- Bone mineral density comparison of adolescents with constitutional thinness and anorexia nervosa
- Adult height in patients with familial male-limited precocious puberty and the role of an aromatase inhibitor in patient management
- Association between UCP polymorphisms and adipokines with obesity in Mexican adolescents
- Impact of childhood type 1 diabetes on maternal work-family relations
- Case Reports
- Hyperthyroidism in an infant of a mother with autoimmune hypothyroidism with positive TSH receptor antibodies
- Sanjad-Sakati syndrome with macrocytic anemia and failure to thrive: a case from South Jordan
- In iodine-induced thyrotoxicosis, steroid therapy today could keep the surgical knife at bay
- Graves’ disease following allogenic hematopoietic stem cell transplantation for severe aplastic anemia: case report and literature review
Articles in the same Issue
- Frontmatter
- Review
- Review and evaluation of patient-centered psychosocial assessments for children with central precocious puberty or early puberty
- Mini Review
- Childhood obesity: how long should we wait to predict weight?
- Original Articles
- Glycated hemoglobin A1c as a screening test for detecting type 2 diabetes mellitus in obese children and adolescents
- Effect of a multidisciplinary treatment program on eating behavior in overweight and obese preschool children
- Cord blood klotho levels are inversely associated with leptin in healthy Latino neonates at risk for obesity
- Still too little, too late? Ten years of growth hormone therapy baseline data from the NordiNet® International Outcome Study
- Body composition and metabolic health of young male adults with childhood-onset multiple pituitary hormone deficiency after cessation of growth hormone treatment
- Hematuria as an adverse outcome following provocative growth hormone stimulation testing in children
- Bone mineral density comparison of adolescents with constitutional thinness and anorexia nervosa
- Adult height in patients with familial male-limited precocious puberty and the role of an aromatase inhibitor in patient management
- Association between UCP polymorphisms and adipokines with obesity in Mexican adolescents
- Impact of childhood type 1 diabetes on maternal work-family relations
- Case Reports
- Hyperthyroidism in an infant of a mother with autoimmune hypothyroidism with positive TSH receptor antibodies
- Sanjad-Sakati syndrome with macrocytic anemia and failure to thrive: a case from South Jordan
- In iodine-induced thyrotoxicosis, steroid therapy today could keep the surgical knife at bay
- Graves’ disease following allogenic hematopoietic stem cell transplantation for severe aplastic anemia: case report and literature review
