It was the end of August when Thad returned from his Caribbean honeymoon, sporting a rich tan and a look of contentment. But as he sat in my exam room he complained to me that he felt tired. “Tired after a honeymoon?” I said. “Sounds about right.”

“No, it’s not that,” he said with a smile. “This is not like any kind of tired I’ve felt before.” Healthy and fit his entire life, Thad was a young physician about to begin his orthopedic specialty training. I trusted him to be an accurate observer, and so I inquired about other possible symptoms he might have had. Then I examined him for evidence of conditions that can cause fatigue, like anemia. All was in order, I reassured him, but just to be certain, I drew some blood for screening tests.

Two days later the lab reported that all the results were normal save one: Thad’s level of thyroid hormone was low. Now his symptoms made sense. The thyroid gland, sitting low along the front of the throat, manufactures the hormone and releases it into the bloodstream, which carries it throughout the body to play a critical regulatory—mostly stimulatory—role in almost all body functions. When there isn’t enough of the hormone, things generally slow down, including the metabolism. Weight may go up, mental activity may get sluggish, and fatigue may develop. Though not common in twentysomethings, hypothyroidism can occur at almost any age.

In the United States the most common reason for a drop in thyroid hormone production is autoimmune thyroiditis, an attack on the thyroid gland by the body’s own defense mechanisms. Normally our finely tuned immune system fends off only foreign material, like microbes, and leaves the body’s own tissues alone. But for reasons that are not well understood, the immune cells will sometimes attack a normal organ, gradually destroying it and turning it into useless scar tissue. The treatment for chronic thyroiditis is to replace the missing hormone with pills taken daily.

Thad was relieved that we had found an explanation for his persistent fatigue. He began taking the replacement thyroid hormone, confident that he would soon see his energy restored. He knew that thousands of people take thyroid hormone every day and live perfectly normal lives. But when I next heard from Thad he told me that he was still tired. It had been four months since we last spoke.

He said he had been too busy since then to return for a check of his hormone levels. Could it be that the dose I had prescribed for him was too low? I arranged for Thad to have a repeat blood test, which soon confirmed that his thyroid hormone blood levels were perfectly normal. The replacement dose was just right—but Thad wasn’t. Something other than hypothyroidism was causing him to feel unwell.

Fatigue is a singularly nonspecific symptom; the list of possible causes is one of the longest in all of medicine, ranging from malignancies, infected heart valves, and anemia to just plain lack of sleep. Consequently, when a patient’s sole complaint is tiredness, the underlying cause can be elusive. In dealing with such a case I often repeat to myself what I have told my medical students countless times: When the history points nowhere, you have to look everywhere. Thad’s history and physical exam would need to be revisited with a fresh eye. I called and asked him to return to the office for another evaluation.

At the follow-up visit it was immediately apparent that Thad had lost weight. Not even his tan could hide the fact that something was amiss. A glance at the vital signs in the chart confirmed that this previously healthy young man had dropped nearly 10 pounds in four months. My level of concern rose. I began working my way through a long list of questions. Though it is tedious and time-consuming, the systematic review of symptoms is a staple of the diagnostician’s armamentarium that more often than not yields important clues. Yet this time nothing new emerged, apart from the fact that Thad had lost not only his energy and some weight but also his appetite. I sat back and looked at my patient, mentally searching myriad diagnoses for ones that fit this clinical picture. It was then that I finally saw it—saw what I had been staring at all along. Sitting across from me was a man who, four months after returning from the Caribbean, was as bronzed as the day he’d come home. And no, I quickly ascertained, he had not been visiting a tanning salon. Appetite, weight, energy—all were diminished. The one thing my patient had not lost was his tan. Why?

Apart from his pigmentation, Thad’s only other noteworthy physical finding was a low-normal blood pressure. When I asked him to rise from a lying to a standing position, his blood pressure fell to a seriously low level, low enough to cause light-headedness and even fainting in most people. But Thad said he felt none of this. “He’s young and fit,” I told myself, “and the problem has come on gradually. His system’s been able to adapt.” But what was the problem?