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Cited by 36Thyroid Disorders and TreatmentsAdrenal Hormones and DisordersAdrenal and Paraganglionic Tumors

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·2016·Clinical Endocrinology
DOI 10.1111/cen.12868
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Abstract

INTRODUCTION: Mitotane, a steroidogenesis inhibitor with adrenolytic properties used to treat adrenocortical cancer (ACC), can affect thyroid function. A reduction of FT4 levels with normal FT3 and TSH has been described in these patients. Using an in vitro murine model, the secretory capacity of thyrotrophic cells has been shown to be inhibited by mitotane. OBJECTIVE: To investigate the pathogenesis of thyroid abnormalities in mitotane-treated patients with ACC. PATIENTS AND METHODS: In five female patients with ACC (median age 47; range 31-65) treated with mitotane (dosage 1·5 g/day; 1·0-3·0), we analysed the pattern of TSH and thyroid function index (FT4, FT3 and FT3/FT4 ratio) compared to an age- and gender-matched control group. The in vivo secretory activity of the thyrotrophic cells was evaluated using a standard TRH test (200 μg), and the response was compared to both a group of age-matched female controls (n = 10) and central hypothyroid patients (n = 10). RESULTS: Basal TSH (median 1·54 mU/l; range 1·20-2·17) was normal and scattered around our median reference value, FT3 levels (median 3·80 pmol/l; 3·30-4·29) were normal but below the median reference value of 4·37 pmol/l and FT4 levels were below the normal range in all patients (median 8·40 pmol/l; 7·6-9·9). FT3/FT4 ratio was in the upper range in 4 patients and higher than normal in one patient. A blunted TSH response to TRH was observed in mitotane-treated patients. ΔTSH (absolute TSH response, peak TSH minus basal TSH) was 3·65 (range 3·53-5·26), 12·37 (range 7·55-19·97) and 1·32 mU/l (range 0·52-4·66) in mitotane-treated patients, controls and central hypothyroid patients, respectively. PRL secretion was normal. CONCLUSIONS: Mitotane-treated patients with ACC showed low FT4, normal FT3 and TSH and impaired TSH response to TRH, characteristic of central hypothyroidism. Furthermore, the elevated FT3/FT4 ratio of these subjects reflects an enhanced T4 to T3 conversion rate, a compensatory mechanism characteristic of thyroid function changes observed in hypothyroid conditions. This finding thus confirms in vitro studies and may have a therapeutic implication for treatment with thyroid hormones, as suggested by current guidelines for this specific condition.

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Crossref · 10.1111/cen.12868

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  • Five women with mitotane-treated adrenocortical carcinoma showed features of central hypothyroidism, namely low FT4, normal FT3 and TSH, with impaired TSH response to TRH; mitotane increased serum FT3/FT4 ratio, suggesting enhanced T4 to T3 conversion, a compensatory mechanism of hypothyroidism.

    “Five women with mitotane-treated ACC showed features of CH, namely low FT4, normal FT3 and TSH, with impaired TSH response to TRH (91). Mitotane increased serum FT3/FT4 ratio, suggesting enhanced T4 to T3 conversion, a compensatory mechanism of hypothyroidism (91).”

    From L-T4 therapy in the presence of pharmacological interferents (2020) · cites this paper as [91]

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Authors
Russo, M., Scollo, C., Pellegriti, G., Cotta, O. R., Squatrito, S., Frasca, F., Cannavò, S., & Gullo, D.
Affiliations
  • University of Catania (IT)
  • University of Messina (IT)
Corresponding author
Gullo, Damiano
ORCID
Venue
Clinical Endocrinology
Publisher
Wiley
Published
2015-08-18
Volume
84
Issue
4
Pages
614-619
ISSN
  • 0300-0664 (ISSN-L)
  • 1365-2265
DOI
10.1111/cen.12868
OpenAlex
W1958763602
Cited by
36
References
26
Citations by year
2026: 1 · 2025: 2 · 2024: 5 · 2023: 2 · 2022: 3 · 2021: 2 · 2020: 5 · 2019: 5 · 2018: 6 · 2017: 3 · 2016: 2
FWCI
3.18
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Clinical Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
Keywords
mitotane, adrenocortical carcinoma, central hypothyroidism, thyroid function, free thyroxine, TSH response, TRH stimulation test, thyrotrophs, steroidogenesis inhibition, drug-induced thyroid dysfunction, prolactin, FT3/FT4 ratio, thyrotropin-releasing hormone, thyroid-stimulating hormone, pituitary gland
MeSH terms
Adrenal Cortex Neoplasms, Adult, Aged, Female, Humans, Hypothyroidism, Middle Aged, Mitotane, Retrospective Studies, Thyroid Function Tests, Thyrotropin, Thyroxine, Triiodothyronine, Antineoplastic Agents, Hormonal

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