Pregnancy in a Patient With Adrenal Carcinoma Treated With Mitotane: A Case Report and Review of Literature

Abstract

Context: Adrenocortical carcinoma (ACC) affects patients in a broad age group, including young women. Mitotane, an adrenolytic agent, is the mainstay of treatment after surgical removal of the tumor. There is extreme paucity of information regarding the effect of mitotane on childbearing potential and pregnancy outcome.Objective: The aim of the study was to describe and discuss the case of an ACC patient who conceived while on mitotane treatment. Current literature is reviewed. Patient and Methods:A 33-year-old woman received mitotane treatment for 4 years due to metastatic ACC. Despite nearly therapeutic blood levels of the drug, the patient had regular menstruation and was able to conceive. Mitotane was stopped at gestation week 6. Although the drug continued to be detected in considerable amounts, the fetus developed normally, including morphologically intact adrenal glands. At gestation week 21, pregnancy was terminated due to ACC recurrence. Mitotane levels were undetectable in fetal cord blood and amniotic fluid. Conclusion:Our report suggests that mitotane, despite its action as an endocrine disruptor, does not affect normal gonadal function or an ability to conceive. The concern of placental transfer by this hydrophobic compound is not supported by our findings. However, we do not recommend drawing conclusions regarding the safety of mitotane in pregnancy, based on 1 or several case reports. Until more data are available, pregnancy should be avoided in women being treated with mitotane for ACC. years, with rapid development of facial and ankle edema, hirsutism, supraclavicular fat pads, and easy bruising. Cushing's syndrome was diagnosed by 9 times the upper limit of normal urinary free cortisol and abnormal overnight dexamethasone suppression test. ACTH was undetectable. Abdominal computer tomography revealed a right adrenal mass measuring 7.5 cm in its longest diameter, with baseline Hounsfield unit density of 30, undergoing contrast enhancement to 66 and no contrast washout on late 10-minute scan. According to the above parameters, adrenal carcinoma was suspected. No metastases were seen on abdominal and lung computer tomography scan and on fluorodeoxyglucose (FDG)-positron emission tomography (PET). Electrolytes were normal at presentation, but over a period of 10 days, hypokalemia evolved, indicating overt hypercortisolism. It responded to treatment with aldospirone. At this point, ketoconazole was administered.Urinary free cortisol had fallen from 1018 to 313 mg/d after 2 days of therapy and to 130 mg/d after 4 days.

Foetal exposure to mitotane/Op'DDD: Post‐natal study of four children

“…To our knowledge, this is the first reported series describing post‐natal outcome of children born after in utero exposure to mitotane. Only six previous mitotane‐exposed pregnancies have been reported, essentially as isolated case reports and, in most cases, leading to interruption of the pregnancy (Summarized in Table ).…”

“…Women becoming pregnant while being treated with mitotane may be advised by some experts to terminate the pregnancy.However, little is firmly established about the teratogenic or mutagenic effects of this drug. Firstly, no animal studies have been conducted to evaluate teratogenic effects and very few exposed pregnancies have been reported during the last 30 years, and the majority of these were interrupted before term . Additionally, data are almost completely lacking concerning infants born after in utero exposure to mitotane.…”

Adrenocortical Carcinoma - A 25 Years Tertiary Centre Experience and Short Review of the Literature

“…Several collaborative efforts have been made and much has been published [1,2] but the best strategy is still unclear and advancements are needed in order to improve diagnosis, therapy and clinical outcome [5]. Surgery is the only potential curative treatment [6] and mitotane remains the mainstay treatment after surgical removal of the tumour [7]. The role of radiotherapy and salvage therapies are not completely established [1] and the diagnosis is still too late and the prognosis poor.…”

Cabergoline treatment for recurrent Cushing’s disease during pregnancy

“…5 Data are scarce regarding the effect of Mitotane treatment on the human fetus and its safety during pregnancy has yet to be demonstrated. 12,13 Functional D2 receptors were found to be expressed in about 80% of corticotroph pituitary adenomas.…”