On Thursday, we challenged Well readers to figure out the mystery of a 29-year-old doctor who had abdominal pain, elevated calcium levels and bumps on his nose, and whose father and uncle had died young from unusual cancers.
More than 300 of you shared your thoughts about this case, and a remarkable number of you got it right.
The correct diagnosis is …
Multiple endocrine neoplasia Type 1.
The first right answer came less than an hour after the case had been posted. It came from Michelle Longmire, a first-year dermatology resident at Stanford Medical Center in Palo Alto, Calif. She told me that she had just finished studying for the night and saw the case and got caught up. She said she used to be called the “zebra hunter” in medical school because she was always looking for unusual diagnoses. Here she found one.
Many readers correctly identified an overactive parathyroid gland as the cause of this patient’s high calcium levels. The clue was that the amount of parathyroid hormone in his blood was normal, even when the amount of calcium in the blood was high. Parathyroid hormone is one of the key enzymes in regulating calcium. When calcium is high – as was the case with this young man – the parathyroid hormone level should have been very low. It wasn’t. So, it was the overactive parathyroid gland that was driving the high calcium.
But there was more going on than just a simple case of an overactive parathyroid gland. The patient’s father had elevated calcium levels as well, and the father and his brother had died young — at 49 and 52, respectively. Another clue.
The Diagnosis:
Multiple endocrine neoplasia, or MEN, is marked by a rare inherited predisposition to develop tumors, or neoplasia, in various endocrine glands. There are three types of this disease, all rare. MEN Type 1 — which is what this patient had — is the most common.
In MEN 1, patients are at risk of developing tumors in the parathyroid gland, the pituitary gland (located in the brain) and the pancreas. Doctors believe that those who are affected with MEN 1 are born missing one of the genes that suppresses tumor formation, leaving them vulnerable to development of these growths. Virtually everyone with MEN 1 will have high calcium levels resulting from tumors in the parathyroid gland. Around a third will also develop tumors in the pancreas or, as in this young man’s uncle, in the pituitary gland.
Treatment goals are to catch and, when necessary, remove tumors as they arise. Patients with MEN 1 should therefore get regular CT scans and other studies to monitor body sites that may be affected.
How the Diagnosis Was Made:
The patient was just 7 when his father was found to have lung cancer. Like 10 to 15 percent of those with this type of cancer, his father had never smoked. Why did he develop lung cancer? The question haunted the boy. In part, that’s why he went into medicine — and why he ended up specializing in cancer.
When the young doctor learned that his calcium was high, his mother told him that his father had struggled with the same problem. That got him thinking: What could cause high calcium in both father and son? When asked that way, the answers are pretty limited. It could be coincidence — high calcium is a relatively common problem. But it could also be something he’d inherited.
Although there is a genetic condition called familial hypocalciuric hypercalcemia, in which patients can’t get rid of calcium through the urine, it is a fairly benign disease and wouldn’t account for his father’s or his uncle’s early deaths from cancer. Of greater interest to this young doctor were the inherited forms of hyperparathyroidism, which often occur in patients who have some form of MEN. The patient quickly focused on MEN as a likely diagnosis for his father and uncle and, uncomfortably, possibly for himself as well.
His uncle’s pituitary tumor was consistent with MEN 1. Additional reading suggested the little bumps on the patient’s nose – the fibroadenomas – were also a symptom of this disease. But what, then, to make of his father’s lung cancer? As the young doctor continued to read, he learned that MEN 1 is also associated with some unusual forms of lung cancers. It all seemed to fit.
He suggested the diagnosis to his internist, Dr. Tangalos, at their first meeting. The doctor was interested but not convinced. “This is unlikely, but not outlandish,” he told the patient. “Nonetheless, I will take your concerns seriously.”
Although an unusual presentation of a common disease is far more likely than even a classic presentation of a rarity, the young man’s story was compelling. And when the test results suggested that the high levels of calcium were a result of overproduction of parathyroid hormone, Dr. Tangalos was glad he had already arranged for the young man to see an endocrinologist.
What the Specialists Found:
The endocrinologist, Dr. Ann Kearns, ordered a test to look for the genetic abnormality seen in most cases of MEN 1. The test came back positive, proof that the young doctor has the disease.
But even before the result of the genetic test came back, Dr. Kearns began looking for any of the tumors associated with MEN 1. She ordered an M.R.I. of his brain to look for pituitary tumors. The M.R.I. result was normal, but a scan of his parathyroid revealed multiple tumors, as did an ultrasound of his pancreas.
The patient is getting his parathyroid gland removed in a couple of weeks. So far, the tumors in his pancreas are too small to do any damage — and there’s a good chance they will stay that way.
And what about the abdominal pain that brought him to the doctor’s office in the first place? How does that all fit? Once Dr. Tangalos had the results of the blood test, it seemed obvious enough. It was a symptom of his high calcium. There’s a mnemonic that doctors use to help remember the classic symptoms of high calcium levels: stones, bones, abdominal groans and psychic moans. High calcium can cause kidney stones, bone pain, abdominal pain and a variety of neurological and muscular problems, including impaired concentration, confusion, fatigue and muscle weakness. Current thinking is that the abdominal pain is a result of gas and constipation, two common problems in patients with high levels of calcium in their system.
The Road Ahead:
For this patient, the greatest challenge is the heritable nature of this disease. His children have a 50-50 chance of inheriting this tendency to grow tumors. His 4-year-old daughter underwent genetic testing. She tested negative — she doesn’t have the disease. He and his wife still haven’t figured out the best time to test their son. He’s only 2.
