Have scientists just solved a 550-year-old medical case?

The following essay is reproduced with permission from The conversationan online publication covering the latest research.

Simonetta Vespucci is probably one of the most painted women of the Italian Renaissance. Sandro Botticelli is widely believed to have used her as a model for Venus, and she appears, transformed and idealized, in many of his most famous works.

She died in 1476, aged just 23. For centuries, historians have assumed tuberculosis was to blame – it was common, it was often fatal, and it fit the pattern of a young woman who quickly disappears.

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In 2019, my colleagues and I offered a different explanation. We examined portraits attributed to Botticelli as well as written descriptions from the period, investigating whether the same woman’s face had changed in a way that might reflect an underlying illness.

What we discovered was a gradual change in his features across several paintings: subtle changes to the jawline, the eyebrow, the soft tissues of the face. These are the kinds of changes seen in patients with pituitary adenoma, a tumor of the small gland at the base of the brain that controls hormone production.

Specifically, we suspected a tumor secreting both growth hormone and prolactin. An excess of these hormones can change facial contours over time and, in some cases, cause unexpected lactation – and an allegorical figure in Botticelli’s work seems to describe exactly this symptom.

Our 2019 article was cautious. We were not claiming proof – we were offering a plausible medical reading of the visual evidence, constructed by combining art history and clinical endocrinology.

Now in a new paper published in Endocrinology, Diabetes and Metabolism, my team and I went further. We believe that the death of Simonetta herself – sudden, rapid and dramatic according to contemporary accounts – is consistent with a specific medical emergency: apoplexy from a pituitary tumor.

Apoplexy occurs when a pituitary tumor bleeds or swells rapidly. This usually causes a sudden, severe headache, vision loss, confusion, and rapid decline as the body’s hormonal regulation breaks down.

We think this would explain something that tuberculosis alone struggles to explain: how a previously healthy young woman went from apparent well-being to death in a short period of time. Chronic infections such as tuberculosis generally cause a slower, more visible decline.

Our argument rests on three elements of evidence. First, the physical changes visible in the portraits – Botticelli painted her several times, from the 1470s until the posthumous Birth of Venus (1482-1485) – suggesting a tumor developing over months or years.

Second, the symptoms described in the chronicles of his last illness (letters exchanged between Piero Vespucci and Lorenzo de’ Medici, describing his collapse at a ball and the headaches, hallucinations, vomiting and fever that followed), which closely correspond to the clinical presentation of apoplexy.

Third, two documented events in the months before his death – his collapse during vigorous dancing at a ball and an alleged violent encounter with Alfonso II of Aragon, Duke of Calabria – which could plausibly have triggered hemorrhage or sudden expansion of the tumor.

None of this is a certainty. There are no fabric samples from 1476, no scans, no way to directly examine Simonetta – only paintings, letters and clinical reasoning applied five centuries after the fact.

What can be said is that a tumor capable of slowly reshaping a person’s face is also capable, if it ruptures, of killing them quickly. Taken together, the portraits and historical documents tell a more complete story than any of them could alone.

We hope this will encourage historians and medical professionals to re-examine cases like Simonetta’s. Medical knowledge can sometimes answer questions that pure historical records cannot. And, in turn, historical puzzles can push medicine to think differently about how disease develops in the body over time.

This article was originally published on The conversation. Read the original article.