In:
Clinical Endocrinology, Wiley, Vol. 84, No. 4 ( 2016-04), p. 614-619
Abstract:
Mitotane, a steroidogenesis inhibitor with adrenolytic properties used to treat adrenocortical cancer ( ACC ), can affect thyroid function. A reduction of FT 4 levels with normal FT 3 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 ( FT 4, FT 3 and FT 3/ FT 4 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, FT 3 levels (median 3·80 pmol/l; 3·30–4·29) were normal but below the median reference value of 4·37 pmol/l and FT 4 levels were below the normal range in all patients (median 8·40 pmol/l; 7·6–9·9). FT 3/ FT 4 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. Δ TSH (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 FT 4, normal FT 3 and TSH and impaired TSH response to TRH , characteristic of central hypothyroidism. Furthermore, the elevated FT 3/ FT 4 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.
Type of Medium:
Online Resource
ISSN:
0300-0664
,
1365-2265
DOI:
10.1111/cen.2016.84.issue-4
Language:
English
Publisher:
Wiley
Publication Date:
2016
detail.hit.zdb_id:
2004597-9
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