Doctors continue to look for clues to former U.S. President John F. Kennedy's secret medical history, 50 years after his assassination.

At 43, Kennedy was the youngest man elected U.S. president following a campaign that portrayed him as the epitome of youth and vigour. But a review of Kennedy’s White House medical records and correspondence from his physicians revealed a complex medical history.

JFK Caroline Kennedy

In this Nov. 9, 1960 photo, Caroline Kennedy gets a piggy-back ride from her father, Sen. John F. Kennedy, in Hyannis Port, Mass. (The Associated Press)

This week — a half century after his death in Dallas — the Annals of Internal Medicine released a 2009 review titled "Endocrine and autoimmune aspects of the health history of John F. Kennedy," to the media.

During the 1960 presidential campaign, JFK's diagnosis of Addison's disease was covered up and wasn't disclosed until the 1976 publication of the book, The Search for JFK, by Joan and Clay Blair.

Obit-Kenneth Battelle

A Jan. 20, 1961 photo shows President John F. Kennedy and first lady Jacqueline Kennedy as they attend one of five inaugural balls in Washington. Lifelong friend Lem Billings said pictures of Kennedy show he appeared heavier in January 1961 than in July 1960, with a total weight gain of about 15 pounds. (The Associated Press)

"The crux of the cover-up rested on the cleverly worded statement claiming that Kennedy 'does not now nor has he ever had an ailment described classically as Addison’s disease, which is a tuberculose [sic] destruction of the adrenal gland,'" Dr. Lee Mandel of the U.S. Navy Medical Corps in Chesapeake, Va. wrote in the journal.

In fact, Mandel noted, Addison's disease has an autoimmune cause in nearly 80 per cent of cases and tuberculosis accounts for only 10 per cent — a narrow definition that successfully deflected further questions.

The Addison's disease was diagnosed when Kennedy was 30 years old and he was found to have hypothyroidism when he was a senator.

The combination of autoimmune adrenal disease and hypothyroidism is consistent with a rare autoimmune endocrine disorder called autoimmune polyendocrine syndrome type 2, or APS2, the journal's editors said.

While it is "probable that Kennedy had APS2," confirmatory antibodies are essential to the diagnosis. But it's still unknown whether Kennedy was tested for these because the office records of his endocrinologist, Dr. Eugene Cohen, are not available to researchers.

The article also outlines JFK's medical profile from sources including:

  • Letters from his doctors to his father documenting the boy's exceedingly low blood pressure in 1940.
  • Comments from a pathology resident present at the autopsy who confirmed Kennedy had almost no adrenal tissue, consistent with "adrenal atrophy," despite a lack of comments on the adrenal glands in the official autopsy.
  • Statements by historian Robert Dallek and his medical consultant, Dr. Jeffrey Kelman, that Kennedy took testosterone to keep his weight up, and statements from friends, doctors and relatives about his weight gain.
  • Family history: Kennedy's younger sister, Eunice, had Addison's disease and his son, John F. Kennedy Jr., had Graves disease.
  • Gastrointestinal symptoms JFK was known to have, such as cramping, diarrhea, and the inability to gain weight for most of his life.
  • Testosterone prescription, which may have been started during the 1960 presidential campaign. Mandel said testosterone was probably needed because of long-term steroid replacement therapy or possibly the autoimmune disease. When he started testosterone therapy remains a matter of conjecture.