Mitotane in the treatment of childhood adrenocortical carcinoma: a potent endocrine disruptor
Adrenocortical carcinoma (ACC) during childhood is a rare malignant tumor that frequently results in glucocorticoid and/or androgen excess. When there are signs of microscopic or macroscopic residual disease, adjuvant therapy is recommended with mitotane, an adrenolytic and cytotoxic drug. In additi...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Bioscientifica
2018-08-01
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| Series: | Endocrinology, Diabetes & Metabolism Case Reports |
| Online Access: | https://edm.bioscientifica.com/view/journals/edm/2018/1/EDM18-0059.xml |
| _version_ | 1811256770627108864 |
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| author | Philip D Oddie Benjamin B Albert Paul L Hofman Craig Jefferies Stephen Laughton Philippa J Carter |
| author_facet | Philip D Oddie Benjamin B Albert Paul L Hofman Craig Jefferies Stephen Laughton Philippa J Carter |
| author_sort | Philip D Oddie |
| collection | DOAJ |
| description | Adrenocortical carcinoma (ACC) during childhood is a rare malignant tumor that frequently results in glucocorticoid and/or androgen excess. When there are signs of microscopic or macroscopic residual disease, adjuvant therapy is recommended with mitotane, an adrenolytic and cytotoxic drug. In addition to the anticipated side effect of adrenal insufficiency, mitotane is known to cause gynecomastia and hypothyroidism in adults. It has never been reported to cause precocious puberty. A 4-year-old girl presented with a 6-week history of virilization and elevated androgen levels and 1-year advancement in bone age. Imaging revealed a right adrenal mass, which was subsequently surgically excised. Histology revealed ACC with multiple unfavorable features, including high mitotic index, capsular invasion and atypical mitoses. Adjuvant chemotherapy was started with mitotane, cisplatin, etoposide and doxorubicin. She experienced severe gastrointestinal side effects and symptomatic adrenal insufficiency, which occurred despite physiological-dose corticosteroid replacement. She also developed hypothyroidism that responded to treatment with levothyroxine and peripheral precocious puberty (PPP) with progressive breast development and rapidly advancing bone age. Five months after discontinuing mitotane, her adrenal insufficiency persisted and she developed secondary central precocious puberty (CPP). This case demonstrates the diverse endocrine complications associated with mitotane therapy, which contrast with the presentation of ACC itself. It also provides the first evidence that the known estrogenic effect of mitotane can manifest as PPP. |
| first_indexed | 2024-04-12T17:46:21Z |
| format | Article |
| id | doaj.art-8bed830c17844c5a9a257936067aa92f |
| institution | Directory Open Access Journal |
| issn | 2052-0573 2052-0573 |
| language | English |
| last_indexed | 2024-04-12T17:46:21Z |
| publishDate | 2018-08-01 |
| publisher | Bioscientifica |
| record_format | Article |
| series | Endocrinology, Diabetes & Metabolism Case Reports |
| spelling | doaj.art-8bed830c17844c5a9a257936067aa92f2022-12-22T03:22:39ZengBioscientificaEndocrinology, Diabetes & Metabolism Case Reports2052-05732052-05732018-08-01111510.1530/EDM-18-0059Mitotane in the treatment of childhood adrenocortical carcinoma: a potent endocrine disruptorPhilip D Oddie0Benjamin B Albert1Paul L Hofman2Craig Jefferies3Stephen Laughton4Philippa J Carter5Medical School, University of Oxford, Oxford, UKLiggins Institute, University of Auckland, Auckland, New ZealandLiggins Institute, University of Auckland, Auckland, New Zealand; Starship Children’s Health, Auckland District Health Board, Auckland, New ZealandLiggins Institute, University of Auckland, Auckland, New Zealand; Starship Children’s Health, Auckland District Health Board, Auckland, New ZealandStarship Children’s Health, Auckland District Health Board, Auckland, New ZealandStarship Children’s Health, Auckland District Health Board, Auckland, New ZealandAdrenocortical carcinoma (ACC) during childhood is a rare malignant tumor that frequently results in glucocorticoid and/or androgen excess. When there are signs of microscopic or macroscopic residual disease, adjuvant therapy is recommended with mitotane, an adrenolytic and cytotoxic drug. In addition to the anticipated side effect of adrenal insufficiency, mitotane is known to cause gynecomastia and hypothyroidism in adults. It has never been reported to cause precocious puberty. A 4-year-old girl presented with a 6-week history of virilization and elevated androgen levels and 1-year advancement in bone age. Imaging revealed a right adrenal mass, which was subsequently surgically excised. Histology revealed ACC with multiple unfavorable features, including high mitotic index, capsular invasion and atypical mitoses. Adjuvant chemotherapy was started with mitotane, cisplatin, etoposide and doxorubicin. She experienced severe gastrointestinal side effects and symptomatic adrenal insufficiency, which occurred despite physiological-dose corticosteroid replacement. She also developed hypothyroidism that responded to treatment with levothyroxine and peripheral precocious puberty (PPP) with progressive breast development and rapidly advancing bone age. Five months after discontinuing mitotane, her adrenal insufficiency persisted and she developed secondary central precocious puberty (CPP). This case demonstrates the diverse endocrine complications associated with mitotane therapy, which contrast with the presentation of ACC itself. It also provides the first evidence that the known estrogenic effect of mitotane can manifest as PPP.https://edm.bioscientifica.com/view/journals/edm/2018/1/EDM18-0059.xml |
| spellingShingle | Philip D Oddie Benjamin B Albert Paul L Hofman Craig Jefferies Stephen Laughton Philippa J Carter Mitotane in the treatment of childhood adrenocortical carcinoma: a potent endocrine disruptor Endocrinology, Diabetes & Metabolism Case Reports |
| title | Mitotane in the treatment of childhood adrenocortical carcinoma: a potent endocrine disruptor |
| title_full | Mitotane in the treatment of childhood adrenocortical carcinoma: a potent endocrine disruptor |
| title_fullStr | Mitotane in the treatment of childhood adrenocortical carcinoma: a potent endocrine disruptor |
| title_full_unstemmed | Mitotane in the treatment of childhood adrenocortical carcinoma: a potent endocrine disruptor |
| title_short | Mitotane in the treatment of childhood adrenocortical carcinoma: a potent endocrine disruptor |
| title_sort | mitotane in the treatment of childhood adrenocortical carcinoma a potent endocrine disruptor |
| url | https://edm.bioscientifica.com/view/journals/edm/2018/1/EDM18-0059.xml |
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