Long term effects of aromatase inhibitor treatment in patients with aromatase excess syndrome
IntroductionAromatase excess syndrome (AEXS) is a rare, autosomal dominant disorder, characterized by enhanced aromatization of androgens and estrogen excess. In males it is characterized by pre-/peripubertal gynecomastia, hypogonadotropic hypogonadism, advanced bone age and short adult height. Only...
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Frontiers Media S.A.
2024-11-01
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| author | Eleni Z. Giannopoulou Eleni Z. Giannopoulou Stephanie Brandt Stephanie Brandt Stephanie Brandt Stefanie Zorn Stefanie Zorn Stefanie Zorn Christian Denzer Christian Denzer Julia von Schnurbein Julia von Schnurbein Maki Fukami Alexander Kaiser Martin Schmidt Martin Wabitsch Martin Wabitsch Martin Wabitsch |
| author_facet | Eleni Z. Giannopoulou Eleni Z. Giannopoulou Stephanie Brandt Stephanie Brandt Stephanie Brandt Stefanie Zorn Stefanie Zorn Stefanie Zorn Christian Denzer Christian Denzer Julia von Schnurbein Julia von Schnurbein Maki Fukami Alexander Kaiser Martin Schmidt Martin Wabitsch Martin Wabitsch Martin Wabitsch |
| author_sort | Eleni Z. Giannopoulou |
| collection | DOAJ |
| description | IntroductionAromatase excess syndrome (AEXS) is a rare, autosomal dominant disorder, characterized by enhanced aromatization of androgens and estrogen excess. In males it is characterized by pre-/peripubertal gynecomastia, hypogonadotropic hypogonadism, advanced bone age and short adult height. Only a few female patients have been described so far.MethodsWe report on a family with four members with AEXS and present the long-term effects of aromatase inhibitor use in three of them. Genetic analysis showed a monoallelic 0.3-Mb deletion in 15q21, involving parts of CYP19A1, GLDN and DMXL2 in all four patients with AEXS.ResultsThe index patient (male, 8 years old) presented with gynecomastia and accelerated growth and bone age. With start of puberty, estradiol levels increased, while testosterone levels remained low. Gynecomastia progressed and a mastectomy was performed twice. Presuming AEXS, a therapy with letrozole was initiated at the age of 19 years. Low-dose letrozole treatment was associated with an increase in testicular volume, increase in virilization and improvement in physical strength and libido. His brother (age 3 years) presented with accelerated growth and bone age. Treatment with letrozole, which was started at the age of 7 years, resulted in achieving an adult height of 179 cm and prevented the appearance of gynecomastia. His sister (age 6 years), who presented with premature thelarche and accelerated growth and bone age, was treated with an estrogen receptor modulator and a GnRH analog followed by letrozole treatment. Menarche occurred at age 13.5 years and adult height was 158 cm. Their father had an early, accelerated growth with an adult height of 171 cm, a delayed puberty and no gynecomastia. In vitro studies provided evidence for involvement of aromatase induction in atypical cells and an increased range of potential mechanisms regulating aromatase activity due to the presence of the mutated allele.DiscussionIn conclusion, we observed a phenotypic variability within family members with AEXS carrying the same CYP19A1 microdeletion. When started early, treatment with letrozole was found to prevent the development of gynecomastia and increase adult height in one patient. In adult life, low-dose letrozole treatment resulted in improved physical strength and libido in the index patient. |
| format | Article |
| id | doaj-art-c6c6bf26e3ef4b56a3c5ca972976d5e2 |
| institution | Kabale University |
| issn | 1664-2392 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Endocrinology |
| spelling | doaj-art-c6c6bf26e3ef4b56a3c5ca972976d5e22024-11-20T04:36:47ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922024-11-011510.3389/fendo.2024.14878841487884Long term effects of aromatase inhibitor treatment in patients with aromatase excess syndromeEleni Z. Giannopoulou0Eleni Z. Giannopoulou1Stephanie Brandt2Stephanie Brandt3Stephanie Brandt4Stefanie Zorn5Stefanie Zorn6Stefanie Zorn7Christian Denzer8Christian Denzer9Julia von Schnurbein10Julia von Schnurbein11Maki Fukami12Alexander Kaiser13Martin Schmidt14Martin Wabitsch15Martin Wabitsch16Martin Wabitsch17Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, GermanyCenter for Rare Endocrine Disease at the University of Ulm, Ulm, GermanyDivision of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, GermanyCenter for Rare Endocrine Disease at the University of Ulm, Ulm, GermanyGerman Center for Child and Adolescent Health, partner site Ulm, Ulm, GermanyDivision of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, GermanyCenter for Rare Endocrine Disease at the University of Ulm, Ulm, GermanyGerman Center for Child and Adolescent Health, partner site Ulm, Ulm, GermanyDivision of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, GermanyCenter for Rare Endocrine Disease at the University of Ulm, Ulm, GermanyDivision of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, GermanyCenter for Rare Endocrine Disease at the University of Ulm, Ulm, GermanyDepartment of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, JapanInstitute for Biochemistry II, Jena University Hospital, Friedrich Schiller University, Jena, GermanyInstitute for Biochemistry II, Jena University Hospital, Friedrich Schiller University, Jena, GermanyDivision of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, GermanyCenter for Rare Endocrine Disease at the University of Ulm, Ulm, GermanyGerman Center for Child and Adolescent Health, partner site Ulm, Ulm, GermanyIntroductionAromatase excess syndrome (AEXS) is a rare, autosomal dominant disorder, characterized by enhanced aromatization of androgens and estrogen excess. In males it is characterized by pre-/peripubertal gynecomastia, hypogonadotropic hypogonadism, advanced bone age and short adult height. Only a few female patients have been described so far.MethodsWe report on a family with four members with AEXS and present the long-term effects of aromatase inhibitor use in three of them. Genetic analysis showed a monoallelic 0.3-Mb deletion in 15q21, involving parts of CYP19A1, GLDN and DMXL2 in all four patients with AEXS.ResultsThe index patient (male, 8 years old) presented with gynecomastia and accelerated growth and bone age. With start of puberty, estradiol levels increased, while testosterone levels remained low. Gynecomastia progressed and a mastectomy was performed twice. Presuming AEXS, a therapy with letrozole was initiated at the age of 19 years. Low-dose letrozole treatment was associated with an increase in testicular volume, increase in virilization and improvement in physical strength and libido. His brother (age 3 years) presented with accelerated growth and bone age. Treatment with letrozole, which was started at the age of 7 years, resulted in achieving an adult height of 179 cm and prevented the appearance of gynecomastia. His sister (age 6 years), who presented with premature thelarche and accelerated growth and bone age, was treated with an estrogen receptor modulator and a GnRH analog followed by letrozole treatment. Menarche occurred at age 13.5 years and adult height was 158 cm. Their father had an early, accelerated growth with an adult height of 171 cm, a delayed puberty and no gynecomastia. In vitro studies provided evidence for involvement of aromatase induction in atypical cells and an increased range of potential mechanisms regulating aromatase activity due to the presence of the mutated allele.DiscussionIn conclusion, we observed a phenotypic variability within family members with AEXS carrying the same CYP19A1 microdeletion. When started early, treatment with letrozole was found to prevent the development of gynecomastia and increase adult height in one patient. In adult life, low-dose letrozole treatment resulted in improved physical strength and libido in the index patient.https://www.frontiersin.org/articles/10.3389/fendo.2024.1487884/fullgynecomastiaestradiolaromataseletrozoletestosterone |
| spellingShingle | Eleni Z. Giannopoulou Eleni Z. Giannopoulou Stephanie Brandt Stephanie Brandt Stephanie Brandt Stefanie Zorn Stefanie Zorn Stefanie Zorn Christian Denzer Christian Denzer Julia von Schnurbein Julia von Schnurbein Maki Fukami Alexander Kaiser Martin Schmidt Martin Wabitsch Martin Wabitsch Martin Wabitsch Long term effects of aromatase inhibitor treatment in patients with aromatase excess syndrome Frontiers in Endocrinology gynecomastia estradiol aromatase letrozole testosterone |
| title | Long term effects of aromatase inhibitor treatment in patients with aromatase excess syndrome |
| title_full | Long term effects of aromatase inhibitor treatment in patients with aromatase excess syndrome |
| title_fullStr | Long term effects of aromatase inhibitor treatment in patients with aromatase excess syndrome |
| title_full_unstemmed | Long term effects of aromatase inhibitor treatment in patients with aromatase excess syndrome |
| title_short | Long term effects of aromatase inhibitor treatment in patients with aromatase excess syndrome |
| title_sort | long term effects of aromatase inhibitor treatment in patients with aromatase excess syndrome |
| topic | gynecomastia estradiol aromatase letrozole testosterone |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2024.1487884/full |
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