Simonetta Vespucci might be one of the vital painted girls of the Italian Renaissance. Sandro Botticelli is extensively believed to have used her as his mannequin for Venus, and she or he seems, reworked and idealised, throughout a number of of his most well-known works.
She died in 1476, aged simply 23. For hundreds of years, historians have assumed tuberculosis was guilty – it was frequent, it was typically deadly, and it fitted the sample of a younger girl fading shortly.
In 2019, my colleagues and I proposed a unique rationalization. We examined the portraits attributed to Botticelli alongside written descriptions from the interval, searching for whether or not the identical girl’s face modified in ways in which may replicate an underlying sickness.
What we discovered was a gradual shift in her options throughout a number of work – refined modifications to the jaw, the forehead, the tender tissue of the face. These are the form of modifications seen in sufferers with a pituitary adenoma, a tumour of the small gland on the base of the mind that controls hormone manufacturing.
Particularly, we suspected a tumour secreting each progress hormone and prolactin. Extra of those hormones can alter facial contours over time and, in some instances, trigger surprising lactation – and one allegorical determine in Botticelli’s work seems to depict precisely that symptom.

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Our 2019 paper was cautious. We weren’t claiming proof – we had been providing a believable medical studying of the visible proof, constructed by combining artwork historical past with scientific endocrinology.
Now, in a new paper printed in Endocrinology, Diabetes and Metabolism, my group and I’ve gone additional. We consider Simonetta’s dying itself – sudden, speedy, and dramatic based on modern accounts – is in keeping with a selected medical emergency: pituitary tumour apoplexy.
Apoplexy happens when a pituitary tumour bleeds or quickly swells. It usually causes a sudden and extreme headache, lack of imaginative and prescient, confusion, and a swift decline because the physique’s hormonal regulation collapses.
We argue that this might clarify one thing that tuberculosis alone struggles to account for: how a beforehand wholesome younger girl went from obvious wellness to dying inside a brief interval. Continual infections similar to tuberculosis normally trigger a slower, extra seen decline.
Three strands of proof
Our case rests on three strands of proof. First, the bodily modifications seen throughout the portraits – Botticelli painted her a number of occasions, from the 1470s via to the posthumous Beginning of Venus (1482–1485) – suggesting a tumour rising over months or years.
Second, the signs described in chronicles of her last sickness (letters exchanged between Piero Vespucci and Lorenzo de’ Medici, describing her collapse at a ball and the complications, hallucinations, vomiting and fever that adopted), which align intently with the scientific presentation of apoplexy.
Third, two documented occasions within the months earlier than her dying – her collapse throughout vigorous dancing at a ball, and an alleged violent encounter with Alfonso II of Aragon, Duke of Calabria – that might plausibly have triggered a bleed or sudden tumour enlargement.
None of this quantities to certainty. There isn’t any tissue pattern from 1476, no scan, no solution to study Simonetta immediately – solely work, letters, and scientific reasoning utilized 5 centuries after the very fact.
What we will say is {that a} tumour able to slowly reshaping an individual’s face can be succesful, if it ruptures, of killing them shortly. Put collectively, the portraits and the historic document inform a extra full story than both can alone.
We hope this encourages each historians and medical professionals to look once more at instances like Simonetta’s. Medical data can generally reply questions that pure historic document can’t. And, in flip, historic puzzles can push medication to suppose otherwise about how illness unfolds within the physique over time.









