Mitotane treatment in patients with adrenocortical cancer causes central hypothyroidism

Russo, Marco; Scollo, Claudia; Pellegriti, Gabriella; Cotta, Oana Ruxandra; Squatrito, Sebastiano; Frasca, Francesco; Cannavò, Salvatore; Gullo, Damiano

doi:10.1111/cen.12868

Cited by 31 publications

(40 citation statements)

References 27 publications

(60 reference statements)

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“…[69] Recent studies showed that mitotane directly interacts with lipid membranes by intercalation of mitotane into phospholipidic bilayers impacting on membrane. [70] The most common side effects are gastrointestinal disorders (inflammation of the lining, vomiting, diarrhea, nausea, and epigastric discomfort), neurological side effects (ataxia, paraesthesia, dizziness, drowsiness, mental impairment, polyneuropathy, motor disorder, headache, and confusion), hematological and lymphatic disorders (leukopenia, prolonged bleeding time), musculoskeletal disorders (myasthenia gravis), metabolic and nutritional disorders (anorexia, hypercholesterolemia, and central hypothyroidism), [71] general disorders (asthenia), and as conditions of the skin and subcutaneous tissue (skin rash). Lesions linked to lichen planus have been described in cutaneous [72] level but not on the oral and genital mucosa.…”

Section: Discussionmentioning

confidence: 99%

Oral and vulvo-vaginal lichenoid reactions due to mitotane (Lysodren)

Schmouchkovitch¹,

Herry²,

Thuillier

et al. 2017

Medicine

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Background:The purpose of pharmacovigilance (drug safety) is collection, detection, assessment, monitoring, and prevention of adverse effects with pharmaceutical products. It is meant to identify, characterize, prevent, or minimize actual or potential risks relating to medicinal products. To prevent these adverse effects and improve our practice, health professionals have a duty to report side effects to assess this risk and evaluate the benefit/risk requirements. Mitotane (Lysodren) is used for treating adrenocortical carcinoma. Currently, no side effects concerning oral and genital mucosa have been reported.Case Summary:This case report is about a 50 years old woman. Six months after the initiation on mitotane treatment, she developed erosive lesions located on the oral and vaginal mucosa. These drug reactions were diagnosed as erosive lichen planus by the biopsy. This lichenoid lesions were resistant to the usual treatments, mitotane being at the time not replaceable.Conclusion:This case describes an unreported adverse effect of mitotane, it is – to our knowledge – the 1st description of erosive lichenoid drug reaction due to Mitotane.

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Section: Discussionmentioning

confidence: 99%

Oral and vulvo-vaginal lichenoid reactions due to mitotane (Lysodren)

Schmouchkovitch¹,

Herry²,

Thuillier

et al. 2017

Medicine

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“…The possibility of evolution of CeH should be ruled out in patients with pituitary lesions after the start of replacement therapies with recombinant human growth hormone (rhGH) or estrogen (see [1]) (Recommendation 8) as well as in those receiving particular drugs (Recommendation 9), in particular rexinoids (like bex- arotene, an agonist of retinoid X receptor that is approved for clinical use, primarily for treatment of cutaneous Tcell lymphoma) [38] or mitotane (reported to exert toxic effects on thyrotropes) [39]. Several other drugs (e.g., glucocorticoids, anti-epileptics, somatostatin) have transient or controversial TSH-suppressive effects [1,38] (see Table 3).…”

Section: Acquired Ceh Formsmentioning

confidence: 99%

2018 European Thyroid Association (ETA) Guidelines on the Diagnosis and Management of Central Hypothyroidism

Persani¹,

Brabant

Dattani³

et al. 2018

Eur Thyroid J

153

145

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Objectives: Central hypothyroidism (CeH) is a rare form of hypothyroidism characterized by insufficient thyroid stimulation due to disturbed pituitary and/or hypothalamic functioning. Due to its origin and the whole clinical context, CeH represents a challenging condition in clinical practice as it is characterized by suboptimal accuracy of clinical and biochemical parameters for diagnosis and management. Since no expert consensus or guidance for this condition is currently available, a task force of experts received the commitment from the European Thyroid Association (ETA) to prepare this document based on the principles of clinical evidence. Study Design: The task force started to work in February 2017 and after a careful selection of appropriate references (cohort studies, case reports, expert opinions), a preliminary presentation and live discussion during the 2017 ETA meeting, and several revision rounds, has prepared a list of recommendations to support the diagnosis and management of patients with CeH. Results: Due to the particular challenges of this rare condition in the different ages, the target users of this guidance are pediatric and adult endocrinologists. Experts agreed on the need to recognize and treat overt CeH at all ages, whereas treatment of milder forms may be dispensable in the elderly (> 75 years). Conclusions: Despite the lack of randomized controlled clinical trials, the experts provide 34 recommendations supported by variable levels of strength that should improve the quality of life of the affected patients and reduce the metabolic and hormonal consequences of inadequate management.

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“…Central hypothyroidism may develop in patients treated with high-dose bexarotene because of direct suppression of pituitary TSH secretion [118]. Mitotane, used for the treatment of adrenocortical carcinoma, can cause hypothyroidism due to abnormal TSH secretion [119]. Finally, central hypothyroidism can also occur in the setting of immune checkpoint inhibitor-induced hypophysitis [117, 120].…”

Section: Thyroid Dysfunction Due To Non-radioactive Systemic Therapiesmentioning

confidence: 99%

Thyroid Sequelae of Pediatric Cancer Therapy

Waguespack

2018

Horm Res Paediatr

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The hypothalamic-pituitary-thyroid axis is a common site of unintended, acquired disease either during or after the treatment of cancer. Children treated with external radiation therapy are at the highest risk for developing a thyroid-related late effect, but thyroid dysfunction and second primary thyroid neoplasms can also occur after treatment with radiopharmaceutical agents such as ¹³¹I-metaiodobenzylguanidine. Increasingly recognized is the development of early thyroid dysfunction as an off-target consequence of the more novel cancer therapeutics such as the tyrosine kinase inhibitors and immune checkpoint inhibitors. Thyroid sequelae resulting from irradiation may manifest only after years to decades of follow-up, and their resultant clinical symptoms may be indolent and non-specific. Therefore, lifelong monitoring of the childhood cancer survivor at risk for thyroid disease is paramount. In this comprehensive review, the myriad thyroid adverse effects resulting from pediatric cancer treatment are discussed and an overview of screening and treatment of these thyroid sequelae provided.

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Mitotane treatment in patients with adrenocortical cancer causes central hypothyroidism

Cited by 31 publications

References 27 publications

Oral and vulvo-vaginal lichenoid reactions due to mitotane (Lysodren)

Oral and vulvo-vaginal lichenoid reactions due to mitotane (Lysodren)

2018 European Thyroid Association (ETA) Guidelines on the Diagnosis and Management of Central Hypothyroidism

Thyroid Sequelae of Pediatric Cancer Therapy

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