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Although evidence is fragmentary, general belief is that work on the painting began in 1503. Subsequently, the painting was taken to France in 1516, completed there, and adorned the court of King Francis I until its permanent display in the Louvre in 1797 (Figure) .
The Mona Lisa, also referred to as La Gioconda (or La Joconde), attracted medical attention in 2004 when a team of rheumatologists and endocrinologists pointed to the presence of potential cutaneous abnormalities captured in the stunningly detailed portrait that suggested the presence of a lipid disorder. Dequeker et al
suggested that the skin lesions noted on the inner end of the left upper eyelid were highly suggestive of xanthalesma and the swelling depicted on the dorsum of the right hand, resting upon the left, was consistent with a subcutaneous lipoma. These findings led them to postulate the connection between hyperlipidemia and consequent ischemic heart disease, which may have led to Gherardini’s demise. Thus, they defined this observed constellation to consist of a possible familial form of hyperlipidemia leading to premature atherosclerosis. In their excellent work, these authors also point to the possibility that the mysterious smile may have been a residual of a Bell’s palsy. Arguments that reduce compatibility with a familial or genetic cause of the disorder include the absence of corneal arcus or an extensive family history of premature death. Importantly, Lisa Gherardini (1479-1542) lived to be 63 years of age (not 37 years of age as has been erroneously reported
We believe that a more unifying diagnosis, that of clinical hypothyroidism, is evident and more likely in this uncannily detailed portrayal.
The painting suggests a yellowish discoloration of the skin, which is known to occur in hypothyroidism because of impaired hepatic conversion of carotene to vitamin A, resulting in excess deposition of serum carotene in the stratum corneum.
The black veil that hangs below what appears to be a large forehead indicates a receding hair line, with hair that appears to be thinned. A complete lack of eyebrows or other hair throughout the pale skin further supports this diagnosis, and cascading hair down the side appears coarse in character.
Curiously, a close look at the neck does insinuate the possible presence of a diffuse enlargement such as a goiter. The xanthelasma could certainly represent a secondary hyperlipidemia, and swelling in the dorsum of the right hand may be a xanthoma or a lipoma, further supporting the presence of a systematic metabolic dyslipidemia as often noted in advanced stages of hypothyroidism. In this circumstance, if Lisa Gherardini was indeed suffering from severe hypothyroidism or its consequences, the mysterious smile may at one level be representative of some psychomotor retardation and muscle weakness leading to a less than fully blossomed smile. An even more intriguing diagnosis could suggest the presence of hypothyroidism in concordance with primary biliary cirrhosis.
However, we believe that the answer may be simpler and epidemiologically supported as a postpartum hypothyroidism.
There are at least 2 distinct natural history-supporting data that support this diagnosis of hypothyroidism. First, during the Renaissance period, eating habits in Italy were primarily vegetarian, based on cereals, root vegetables, and legumes, and with little meat, as opposed to dietary patterns in Northern Europe where livestock was more developed. Seafood was uncommon inland and famine was common, because harvest was often scarce, with only 16 full harvest seasons from 1375 to 1791 in the Tuscany region.
postulated that the Mona Lisa had a “puffy neck,” suggesting a goiter. Evidence of this is noted in several works of art during that period wherein figures are often depicted with goiters. Sterpetti et al
studied thyroid swellings in the art of the Italian Renaissance and concluded that such depictions were very common and were the most prevalent pathological condition shown in Byzantine artworks, noting 70 paintings and 10 sculptures with a thyroid swelling (we adapt a few examples from this work in the Table). As a contemporary example, in 1999, the Pappano population-based study in Italy concluded that in this southern Italian population, the prevalence of a goiter was 59.8% in adults, suggesting that it is still a problem of agricultural rural populations even in modern times.
The second important evidence supporting the theory that Lisa Gherardini had hypothyroidism is the fact that she had given birth to her male child, Andrea, recently within months before sitting for the painting.
This, coupled with the living conditions and iodine-deficient diet of this period in the Florentine region, would have characteristically led to the secondary manifestations of underlying hypothyroidism.
TableThyroid Swellings Depicted in Italian Renaissance Art
Although we have attempted to provide a unifying hypothesis for the Mona Lisa, we admit that the truth may lie elsewhere. A possibility for the loss of facial and bodily hair may be in intentional depilation, which was practiced in those times, with techniques catalogued in Gli Experimenti by Caterina Sforza during the Italian Renaissance.
The yellowish discoloration may represent age-related changes (perhaps from the use of varnish, which may yellow over time) rather than an original depiction as such. The smile may be due to da Vinci’s experiments with a technique called sfumato, which allows tones and colors to fade into each other without discrete lines like smoke or blurred dimensions.
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. In summary, we believe that the enigma of the Mona Lisa can be resolved by a simple medical diagnosis of a hypothyroidism-related illness that could have been the result of a peripartum thyroiditis accentuated by the living conditions of the Renaissance. In many ways, it is the allure of the imperfections of disease that give this masterpiece its mysterious reality and charm.
Despite weighing just 10 to 20 g in the average adult (or approximately 1-2/10,000th of an average human), the thyroid gland exerts an outsized influence over a broad array of normal physiologic functions, which greatly belies its petite size; this effect reflects the widespread expression of thyroid hormone receptors throughout the human body.1 When thyroid dysfunction (either hypothyroidism or hyperthyroidism) occurs, significant alterations in normal physiology can result, with the degree of pathology generally related to the degree of dysfunction and the rate at which the dysfunction develops, with more rapid onset associated with greater physiologic perturbation.
The interest by Ponzetto and colleagues in our work defining the medical diagnosis of the iconic Mona Lisa painting is appreciated.1 The authors agree with the diagnosis presented, but offer another pathophysiological hypothesis, that of autoimmune implications of Helicobacter pylori infection, and argue that this could account for provoking autoimmune thyroiditis during pregnancy. They also go on to contest that nutritional deficiency of iodine was less central in elucidating the uncanny findings recorded in the painting by Leonardo da Vinci.
Mehra and Campbell1 presented the interesting clinical case of Mona Lisa, the portrait by Leonardo da Vinci of the wife of a rich merchant in Florence, in whom they diagnose postpartum hypothyroidism. The hypothesis is likely as autoimmunity may develop after delivery, and autoimmune thyroid diseases were and still are extremely prevalent in Italy, as these researchers rightly point out.1 Mehra and Campbell hypothesized that iodine deficiency could be a plausible explanation for putative hypothyroidism; however, it is difficult to believe that the diet of a rich merchant’s wife would lack fishes, mollusks, and oysters and hence iodine.
In the September 2018 issue of Mayo Clinic Proceedings, Mehra and Campbell1 gave a lovely and elegant review of the Mona Lisa painting and posited a medical explanation for the mystery of the lady as painted by the great master Leonardo da Vinci. Their insights tied hypothyroidism with attendant hyperlipidemia, lipoma, and xanthelasma as the cause of the enigmatic smile and her gaze. There is merit to this diagnosis, and this should be heavily weighted in the differential diagnosis analysis. Other analysts have attributed this to neurosyphilis,2 postpartum Bell's palsy,3 dentition problems,3 hyperlipidemia,4 and strabismus.