Abstract
IntroductionSeveral studies have reported a high frequency of papillary thyroid cancer (PTC) in patients with acromegaly. The aim of this study was to determine the prevalence and predictors of thyroid cancer in patients with acromegaly and to investigate the frequency of the BRAF V600E mutation in PTC patients with and without acromegaly.Materials and MethodsWe conducted a retrospective study of 60 patients with acromegaly. Thyroid ultrasonography (US) and US-guided fine needle aspiration were performed on nodules with sonographic features of malignancy. We selected 16 patients with non-acromegalic PTC as a control group. The BRAF V600E mutation was analyzed in paraffin-embedded surgical specimens of PTC by real-time polymerase chain reaction, and tumor specimens from patients with PTC were stained immunohistochemically with an antibody against insulin-like growth factor-1 receptor β (IGF-1Rβ).ResultsThyroid cancer was found in 15 (25.0%) patients. No differences in age, sex, initial growth hormone (GH) and IGF-1 percentage of the upper limit of normal values or treatment modalities were observed between patients with and without PTC. Acromegaly was active in 12 of 15 patients at the time of PTC diagnosis; uncontrolled acromegaly had a significantly higher frequency in the PTC group (60%) than in the non-PTC group (28.9%) (p = 0.030). The BRAF V600E mutation was present in only 9.1% (1/11) of PTC patients with acromegaly, although 62.5% (10/16) of control patients with PTC had the mutation (p = 0.007). IGF-1Rβ immunostaining showed moderate-to-strong staining in all malignant PTC cells in patients with and without acromegaly. Significantly less staining for IGF-1Rβ was observed in normal adjacent thyroid tissues of PTC patients with acromegaly compared with those without (p = 0.014).ConclusionThe prevalence of PTC in acromegalic patients was high (25%). An uncontrolled hyperactive GH-IGF-1 axis may play a dominant role in the development of PTC rather than the BRAF V600E mutation in patients with acromegaly.
Highlights
Several studies have reported a high frequency of papillary thyroid cancer (PTC) in patients with acromegaly
Sex, initial growth hormone (GH) and insulin-like growth factor-1 (IGF-1) percentage of the upper limit of normal values or treatment modalities were observed between patients with and without PTC
The BRAFV600E mutation was present in only 9.1% (1/11) of PTC patients with acromegaly, 62.5% (10/16) of control patients with PTC had the mutation (p = 0.007)
Summary
Several studies have reported a high frequency of papillary thyroid cancer (PTC) in patients with acromegaly. The aim of this study was to determine the prevalence and predictors of thyroid cancer in patients with acromegaly and to investigate the frequency of the BRAFV600E mutation in PTC patients with and without acromegaly. Several studies have reported a high frequency of thyroid cancer mostly papillary thyroid cancer (PTC) in patients with acromegaly. The BRAFV600E mutation has been shown to cause continuous and uncontrolled activation of the kinase pathway, and it is associated with a poor prognosis for PTC [12]. It is not known whether the BRAF mutation is associated with PTC in patients with acromegaly
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