Objective : Adrenocortical carcinoma is an uncommon malignancy with a very aggressive course. The incidence is approximately 0.72 per million cases per year. After surgery, adjuvant mitotane therapy remained the mainstay of treatment for ACC. The adjuvant treatment with mitotane is associated with beneficial effects on outcome of ACC but it also has some unwanted effects on various hormonal axis. Here we will discuss the effect of mitotane on thyroid function after more than two years of therapy in our patient.
Patient is a 40 year old male who was found to have an incidental mass of 5cm in the right adrenal that was nonfunctioning. He underwent robotic right adrenalectomy. Mitotane was started after the surgery due to high risk features seen on pathology. His thyroid function test was normal at the start of treatment. After starting the mitotane his main complaints were fatigue and intermittent diarrhea. It took almost 6-8 months to reach therapeutic levels of mitotane (10-14 mcg/ml). After one year of tumor bed radiation and two years of mitotane therapy he developed a recurrence in mesentery close to right colon. The mass was removed with partial colectomy.
During his course of mitotane therapy his thyroid profile was monitored periodically. His TSH was found to be low to low normal and FT4 remained below normal after being on mitotane for two years. His low FT4 was confirmed with equilibrium dialysis method. The picture points towards secondary/central hypothyroidism which was reported previously in association with mitotane treatment.
Mitotane is a toxic drug with a narrow therapeutic index. Marked reduction in FT4 levels and secondary hypothyroidism are observed in some patient. Mitotane treatment is thought to increase thyroxine-binding globulin and also compete with thyroxine for thyroxine-binding globulin sites. However, these mechanisms don’t completely explain the pattern of low FT4, with low normal FT3 and TSH levels. These findings generally points towards central hypothyroidism. To decide on treatment for hypothyroidism it is important to recognize the signs and symptoms as the presentation of hypothyroidism also mimics the general side effects of mitotane chemotherapy and malignancy itself.
Due to risk of developing hypothyroidism on mitotane therapy and the complexity of presentation it is important to understand the changes in hormonal levels and proper monitoring by an expert physician, as treatment of hypothyroidism can improve the quality of life.
Huntington, West Virginia
First year fellow at Marshall university Huntington west Virginia