Introduction In a recent contribution (Pozzilli & Nicolai, 2021) it has been postulated that Cosimo I de' Medici (1519-1574), the second Duke of Florence, was affected by an endocrinological condition (Pozzilli & Nicolai, 2021); the authors maintain to have identified a case of severe Graves' disease (untreated hyperthyroidism, atrial fibrillation and thyroid eye disease) in the bronze statue of Cosimo I de' Medici forged by Benv-enuto Cellini in between 1545 and 1547. Materials and Methods A careful examination of the artistic sources, the medical primary sources and the paleopathological findings was performed with the aim of assessing the likelihood of Cosimo I de' Medici's diagnosis of severe Graves' disease, following recent guidelines on the integration of non-osteological sources in retrospective paleopathological analyses (Ruhli et al., 2016; Mitchell, 2017; Nerlich et al., 2021; Varotto et al., 2022). Discussion From a medical point of view, it shall be underlined that Cosimo I's adult life was plagued by obesity (Arba et al., 2014); this condition is incompatible with a diagnosis of Graves' disease since severe hyperthyroidism accelerates the body's metabolism and causes an unintentional weight loss independently from the food intake. Piero the Gouty Lorenzo and his brother Giuliano all had thick-necks and an Adam's Apple; these can be appreciated both in Lorenzo the Magnificent's life-like terracotta by Verrocchio and Benintendi (ca. 1478, National Museum of Art, Washington, USA) (Figure li), in his portrait in The Confirmation of the Franciscan Rule, one of Domenico Ghirlandaio's frescoes in the Sassetti Chapel in S. Trinita (Florence)) (Figure lj) and by his posthumous portrait by