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Think Like a Doctor: Packing on the Pounds Solved!



On Thursday we challenged Well readers to take on the case of a 59-year-old woman who had not been able to stop gaining weight. I presented the case as it was presented to the doctor who made the diagnosis and asked for the final piece of data provided by the patient as well as the correct cause of her symptoms.

I thought the tough part of this case was something that few of my readers would have to contend with – that her complaints and past medical history were quite ordinary. Like many of us, she was overweight and she came to the doctor because she had difficulty losing weight. In the background she also had high blood pressure, obstructive sleep apnea and low back pain, knee pain and leg swelling. These are some of the most common reasons patients seek medical attention. Although her problems were run of the mill, the cause was not. And many of you had no difficulty spotting this zebra.

The correct diagnosis was…


The last piece of data, provided by the patient, was a photograph taken several years before. It was only by seeing the changes in the patient’s face that had occurred over the past few years that the doctor recognized that this patient’s problem was unusual.

The first person to make this diagnosis was Dr. Clare O’Connor, a physician in the second year of her training in internal medicine. She plans to subspecialize in endocrinology. She says it was the swollen legs that didn’t compress that gave her the first clue. Well done.

The Diagnosis

Acromegaly is a rare disease caused by an excess of growth hormone, usually due to a tumor in the pituitary gland of the brain. The disease’s name, from the Greek, serves as a fitting description of the most obvious symptoms: great (mega) extremity (akron). The tumor secretes a protein called growth hormone that signals the liver to produce a substance called insulin-like growth factor 1, or IGF 1, which in turn tells cells throughout the body to start proliferating.

With the flood of IGF 1, soft tissues throughout the body begin to grow. This becomes visible as hands, feet, cheeks, lips and tongue enlarge. Although these are the changes that can be observed, other structures are similarly affected, causing cardiac problems (usually enlargement of the heart muscle or valves), respiratory problems (usually obstructive sleep apnea), metabolic problems such as diabetes, and excessive sweating and musculoskeletal problems such as carpal tunnel syndrome. The patient had all of these problems except diabetes.

Eventually, usually after years of untreated disease, bone will start to expand as well. This patient’s feet weren’t just swollen, the bones themselves were larger. The difference between the patient’s face in the doctor’s office and that in the picture wasn’t due to the years that had passed but to changes in their very structure. The lips, tongue and nose were broader. The bone of the chin was thicker, the cheeks wider.

Worth a Thousand Words

Once Dr. Donald Smith, the doctor who saw the patient at Mount Sinai Hospital, heard the summary of the case from the doctor in training who saw her first, he turned to the patient. Did she have anything to add?

She thought for a moment and then said, “Let me show you a picture.” She reached over to her purse and pulled out her driver’s license. That’s me just a few years ago, she told him. The picture showed an attractive middle-aged woman who bore little resemblance to the one before him. That’s when Dr. Smith knew that there was something more than simple weight gain at work.

It wasn’t low thyroid hormone causing this, he decided. A patient gaining this much weight due to thyroid disease should have other symptoms typical of thyroid disease as well.

Two other possibilities came to mind. Both were diseases of hormonal excess; both were characterized by rapid weight gain. First was Cushing’s disease, which is caused by an overproduction of one of the fight-or-flight hormones called cortisol; the second was acromegaly, which is caused by too much growth hormone.

How the Diagnosis Was Made

Dr. Smith looked at the patient, seeking clues that suggested either condition. He saw that just below her neck on her upper back was a subtle area of enlargement. This discrete accumulation of fat, known as a buffalo hump, can occur with normal weight gain, but it is also frequently seen in patients with Cushing’s disease.

Do you bruise more easily these days, he asked? Cushing’s makes the skin fragile, and it bruises more easily. No, she hadn’t seen that. Did she have dark purple stretch marks on her stomach from the weight gain? The rapid expansion of the abdomen can cause the fragile skin of these patients to develop stretch lines. No, again. So maybe not Cushing’s.

Have you changed shoe sizes in the past couple of years? the doctor asked. Enlargement of the hands and feet is rare but is the hallmark of acromegaly. Yes, she exclaimed. Just a few years ago she wore a size 8. Now she can barely squeeze into a size 13.

Can I look at your teeth, the doctor asked. He saw that there were gaps between most of her teeth. Was that new? Yes. She had been told that was from gum disease. “You don’t have gum disease. You have acromegaly,” the doctor declared confidently. The new spaces were evidence that her jaw had, like her feet, simply grown larger.

Dr. Smith referred the patient to Dr. Eliza B. Geer, an endocrinologist who specialized in diseases of the pituitary at Mount Sinai Hospital. She measured the level of growth hormone and IGF 1. Both were dramatically elevated. The final test was a glucose tolerance test. A sugary drink would normally suppress IGF 1. The patient’s level was unaffected. That confirmed the diagnosis; she had acromegaly. An M.R.I. scan revealed a tiny tumor on the pituitary, and a few weeks later the patient had surgery to remove the growth.

The Real Mystery

From the first moment I heard of this case I wondered, how could this have been missed? How could a woman go through such dramatic changes and not have her doctor think: acromegaly.

And yet this is a diagnosis that is frequently missed. The average time to diagnosis is five years. And, like this patient, most people with acromegaly are seen by many doctors before the correct diagnosis is made. Indeed, it is said that patients are more likely to be diagnosed by a doctor who has never seen them before than by their longstanding regular doctor – because these changes take place slowly, over years.

But in wondering about this missed diagnosis, I suddenly recalled a missed case of my own just over a decade ago. I was a few years into my practice and had a patient who had the same string of common problems: She was overweight, and she had high blood pressure, obstructive sleep apnea, spinal stenosis and carpal tunnel syndrome. She worked hard to keep all of her medical problems well controlled. She was really a model patient. One week she was seen by one of the trainees in my practice. That doctor took one look at her and saw what I had not. She ordered the test for acromegaly. Like this patient, my hardworking patient had clearly had acromegaly for years.

Missing the Diagnosis

How do we miss this disease? Acromegaly manifests itself in two ways. First, by causing a series of ordinary diseases that are among the most common problems that bring patients to the doctor. Most patients with these medical problems don’t have acromegaly.

It’s the second manifestation that may be the real issue for me and other doctors. The disease clearly causes changes in the face. The picture in my head of what acromegaly looks like is based on two actors affected with the disease: Richard Kiel, who played the murderous character Jaws in the James Bond movies, and Ted Cassidy, who played Lurch in the television series “The Addams Family.”

But those images are misleading. These actors had acromegaly during childhood, before their bones had stopped growing, and so the effect of the disease was profound and permanent. Their bodies were literally shaped by the disease. Mr. Kiel was 7-foot-2. Mr. Cassidy was 6-foot-9. Both had an exaggerated version of the facial changes of bony overgrowth, with prominent brows and massive jaws. Because of these dramatic changes, those who get the excess growth hormone before puberty are said to have gigantism, rather than acromegaly.

In contrast, when the disease strikes during adulthood, the bones have very limited ability to grow. The changes are thus more subtle and so, often enough, the diagnosis is missed.

This patient decided to show her doctor the photograph after a remark made by her sister. What’s happened to your face? she asked. That’s when the patient began to believe that the distressing changes she saw in the mirror weren’t just from getting older.

How the Patient Fared

The patient had surgery to remove the tumor nine months ago and now feels great. She had attributed so many of her symptoms – the fatigue, the sweatiness, the pain in virtually every joint — to getting older and heavier. But it’s clear now that they were caused by the hormonal excess.

The bony changes will be with her forever (goodbye, size 8 feet). But she’s happy that she can see her ankles once more and will finally be able to lose some weight.

Think Like a Doctor: Packing on the Pounds

The Challenge: Can you figure out why a 59-year-old woman keeps gaining weight?

Every month, the Diagnosis column of The New York Times Magazine asks Well readers to try their hand at solving a medical mystery. Below you will find the story of a woman who has been gaining weight despite years of work to lose it. Was this, as the patient worried, a result of menopause, or was there something else going on? She was frustrated and aggravated, but should she be worried?

Below I provide much of the information available to the doctor who made the diagnosis. Regular readers may assume that this, like so many of my cases, is the zebra. But is it? The first reader to offer the correct diagnosis, along with the missing piece of data that helped the doctor get there, will receive a signed copy of my book, “Every Patient Tells a Story,” and the satisfaction of solving a real life case.

The Patient’s Story

“I just can’t seem to lose weight,” the 59-year-old woman said quietly. She’d done everything, she told the young doctor. Weight Watchers. Exercise. She drank more water. She ate more vegetables. She tried eating less fat, then only “good” fat. She kept food diaries, downloaded calorie counters. She’d done it all.

And not only was she not losing weight, these past few years she just kept on gaining. Despite all of her hard work, she’d put on maybe 50 pounds in the past year.

More Than Skin Deep?

She decided to go to Dr. Donald Smith, an endocrinologist at Mount Sinai Hospital in New York. She’d seen the doctor years earlier in a documentary on weight loss surgery on TV. The fact that he was an endocrinologist made him a doubly good choice for her because she worried that the real cause of her weight gain was hormonal.

She first met with the doctor in training who was working with Dr. Smith as part of her endocrinology fellowship. She’d never been skinny, she told the young doctor. But she’d never been heavy like this before, either. She was 5-foot-4, and throughout her 20s and 30s she’d weighed 170 to 180 pounds. It was a comfortable weight for her, easy to maintain. Then, in her mid-40s, weight maintenance was no longer easy and the pounds started to accumulate, slowly at first, then rapidly.

She was considering bariatric surgery, but first she wanted to know, was this just a consequence of menopause? She had thyroid disease and had been on the same dose of medication for years. Could something have happened to her body so that the drug was no longer working for her?

The Patient’s History

Did she have any of the symptoms associated with a low thyroid hormone level, the young doctor queried? Fatigue? Oh yes, these days she always seemed to be tired. Had she seen any changes in her hair or skin? No. Any constipation? No. Do you get cold more easily these days? Never. Indeed, these days she usually felt hot and sweaty.

Any other medical problems, the doctor asked?

Oh sure, she replied promptly. She had high blood pressure and high cholesterol — both well controlled with medications. She also had obstructive sleep apnea, a disorder in which the trachea, the breathing tube connecting the lungs with the nose and mouth, collapses during sleep, causing the sufferer to stop breathing and awaken many times throughout the night. But she had a machine that helped keep her trachea open and used it every night.

In addition, she had low back pain from a place where her spine had become narrow. She had knee pain and carpal tunnel syndrome. She didn’t smoke or drink and had worked as a nurse until the pain in her back, legs and hands forced her to retire early.

Big, Bigger, Biggest

After a quick examination, the young doctor stepped out of the exam room. She returned a few minutes later with Dr. Smith. He looked to be in his mid-60s and had a kind face and friendly smile, just as the patient recalled from the TV show she’d seen him on. The young doctor briefly summarized what she and the patient had talked about. When she finished, Dr. Smith turned to the patient and asked if there was anything she’d like to add.

She thought for a moment. All she could say, really, was that she didn’t understand why she was getting so much bigger. She was gaining weight, but it wasn’t just that. Her legs and feet were huge. She used to have nice ankles, but now you could hardly see them. Her regular doctor, a cardiologist, gave her a diuretic, but it really hadn’t done a thing, she told him.

Not Just the Legs

Dr. Smith leaned over to look at her lower legs a little more closely. They were quite swollen. And yet when he pressed his thumb against the skin there was none of the give he would have expected in such bloated-looking limbs. Usually with swelling from edema, which occurs when extra fluid leaks from the blood vessels into the soft tissues, any firm pressure will leave a deep impression.

The presence of apparent engorgement that doesn’t compress suggested that the patient may have a condition called lymphedema, an accumulation of fluid rich in white blood cells that is normally collected from the tissues and then drained through the tiny vessels of the lymph system. If these vessels somehow become blocked, the fluid backs up and the skin around them becomes thick, inflamed and eventually scarred.

It’s not just my legs, the woman added. It was everything. Maybe this sounded crazy, she told him, but she didn’t feel like she was living in her own body. She’d explained this to many doctors. They’d just encouraged her to lose weight.

Over the years, the patient had been to many doctors. You can review some of the lab results her various doctors had ordered in the two years before she’d come to see Dr. Smith.

Review the patient’s lab results from 2013 here.

2013 Labs

The patient’s labs.

Review the patient’s lab results from 2015 here.

2015 Labs

The patient’s labs.

You can also review the note from her last visit to her regular doctor, a cardiologist, here.

Cardiology Note

The patient’s visit with a cardiologist.

Solving the Mystery

There was one more piece of data that led Dr. Smith — eventually — to the answer. Can you figure out what that missing piece of information might be? And the diagnosis it led to?

Post your answers in the comments section. The first reader to figure out both parts of the puzzle will get a signed copy of my book and that special satisfaction of solving a mystery that my readers know so well.

I’ll post the answer tomorrow.

Rules and Regulations: Post your questions and diagnosis in the comments section below. The correct answer will appear Friday on Well. The winner will be contacted. Reader comments may also appear in a coming issue of The New York Times Magazine.

Sleep Problems Tied to Type 2 Diabetes


Women with sleeping difficulties are at increased risk for Type 2 diabetes, researchers report.

Scientists used data from 133,353 women who were generally healthy at the start of the study. During 10 years of follow-up, they found 6,407 cases of Type 2 diabetes.

The researchers looked at four sleep problems: self-reported difficulty falling or staying asleep, frequent snoring, sleep duration of less than six hours, and either sleep apnea or rotating shift work. The study is in Diabetologia.

Self-reported difficulty sleeping was associated with higher B.M.I., less physical activity, and more hypertension and depression. But even after adjusting for these and other health and behavioral characteristics, sleeping difficulty was still associated with a 22 percent increased risk for Type 2 diabetes.

Compared to women with no sleep problems, those with two of the sleep conditions studied had double the risk, and those with all four had almost four times the risk of developing the illness.

The senior author, Dr. Frank B. Hu, a professor of nutrition and epidemiology at Harvard, said that sleep problems are associated with excess secretion of two hormones: ghrelin, which increases appetite, and cortisol, which increases stress and insulin resistance. Both are linked to metabolic problems that increase the risk for diabetes.

“And,” he added, “it’s not just quantity of sleep, but quality as well” that is associated with these health risks.