The "Mona Lisa" is so iconic that few people actually take the time to really look at the half-length portrait. But examine the Leonardo da Vinci creation for a few minutes and there’s one inevitable conclusion: something’s not right with the sitter. That’s exactly what happened to Mandeep R. Mehra, medical director of the Heart & Vascular Center at Brigham and Women's Hospital in Boston. While standing in line last summer at the Louvre, he took a long look at the portrait and decided that Italian noblewoman Lisa Gherardini, who the work is thought to be of, likely suffered from hypothyroidism.

“I had the chance to just stand there for an hour and a half staring at nothing but this painting,” Mehra tells Yasmin Tayag at Inverse. “I’m not an artist. I don’t know how to appreciate art. But I do sure know how to make a clinical diagnosis.”

What caught his eye wasn’t Da Vinci’s masterful sfumato technique or strange use of perspective. Instead, it was the subject's yellowing skin, thin, lank hair, receding hairline and lack of eyebrows. Mehra noticed other peculiarities: There is a perceptible bump between her nose and inner eye, likely a cholesterol deposit; fleshy bulges on the right side her neck could be the beginning of a goiter; and a lump between her index and forefinger could be a lipoma. In a Letter to the Editor published in the journal Mayo Clinic Proceedings, Mehra and his co-author Hilary Campbell of the University of California, Santa Barbara, argue that all of these symptoms add up to clinical hypothyroidism, a condition in which the thyroid gland produces an insufficient amount of certain critical hormones.

The diagnosis would explain the painting’s eerie smile. “The more characteristic reason for why that smile is not a full-blown smile or is partially asymmetric is probably hypothyroidism,” Mehra tells Tayag, “because when you have hypothyroidism you’re a little depressed, and your facial muscles are puffy and weak. You can’t even bring yourself to a full smile.”

Gherardini’s personal history adds some credence to Mehra’s theory. Rachael Rettner at LiveScience reports that it’s believed merchant Francesco del Giocondo, who was married to Gherardini, commissioned the portrait to commemorate the birth of their second son around 1503. Pregnancy, it turns out, can set off hypothyroidism. As for the possible goiter forming on her neck, the researchers report in the paper that iodine deficiency due to the poor diet in the Florentine region during this period often led to thyroid problems and the formation of goiters, which appear in many artworks from this time and period.

Of course, this is not the first time that Mona Lisa has been diagnosed. In 2010, a Sicilian professor of pathological anatomy suggested that Gherardini suffered from high cholesterol, leading to the lump near her eye and the lipoma on her hand. Another diagnosis—as the co-authors point out in the letter—came in 2004, when a group of doctors suggested that the hand swelling and skin lesions could represent hyperlipidemia and premature atherosclerosis and that the famous smile was a symptom of Bell’s palsy.

But Mehra and Campbell dismiss these claims. Recent scholarship shows Gherardini lived to the age of 63, quite long for her time, meaning that it’s unlikely she died of early-onset heart disease or a lipid disorder. Instead, they argue hypothyroidism explains all of the painting's many symptoms.

However, they admit their diagnosis is not the last word. It’s possible that Gherardini plucked out her eyebrows on purpose, which was not uncommon for women during the Italian Renaissance. The yellow skin and eyes may simply be an artifact of the varnish on the painting discoloring over time. And the smile may just be a result of Da Vinci’s skill blending objects into one another so finely that it often obscured discrete lines, like smiling lips.

Odds are there will never be a definitive answer of what was up with the “Mona Lisa,” and that is partially what makes it great. “Certainly, we should also admit that our unifying theory may be as plausible as the multiple explanations provided, each open to individual and collective bias,” the authors conclude. “In many ways, it is the allure of the imperfections of disease that give this masterpiece its mysterious reality and charm.”