It felt like a knife slicing through his right side. The young man lay in bed and tried not to move. He'd had this pain off and on for years — usually when he was nervous, and he was very nervous that Sunday morning. He was supposed to start a new job the next day.
1. THE PATIENT'S STORY
The pain had never been that bad before. A hot shower helped, but not for long; afterward, he couldn't bend at the waist without gasping. Slowly the pain began to ease, and the next day, he was well enough to start his new position — as a doctor, training for a specialty in cancer.
Although he felt comfortable with his self-diagnosis of a jittery stomach, his wife — also a doctor — did not. At her insistence, he made an appointment with the primary-care doctor he'd been assigned at the Mayo Clinic.
2. THE DOCTOR'S STORY
When Dr. Eric Tangalos met his new patient, his impression was that he was a pretty healthy guy. Tall and slender, he had a ready smile and an earnest, easygoing manner. "Tell me what brought you in," he asked the patient.
3. THE PATIENT'S LIST
a) Abdominal pain: Normally it was intermittent and manageable, but it became quite severe that one time. He didn't have diarrhea or blood in his stool, and other than that one day, the pain hadn't interfered with his activities. He hadn't lost any weight.
b) Hypercalcemia: A routine blood test the year before showed too much calcium in his system.
c) Rash: He had some red spots on his nose that were bothersome and, he thought, unattractive. And he was getting more of them every year.
4. THE VISIT
Other than these complaints, the patient told Dr. Tangalos, he had no medical problems. He'd never been in the hospital, was rarely sick and had not even broken a bone. He was married and had a daughter who was 2. The patient didn't smoke and rarely drank. He was physically active.
On examination, the patient certainly seemed healthy. The bumps on his nose were small, firm and slightly red. Tangalos wasn't sure what they were and decided to send the young doctor to a dermatologist. Then he turned his attention to the elevated calcium level. Should he refer him to an endocrinologist, too? In either case, he definitely needed to order some tests to help find where that came from.
5. POSSIBLE DIAGNOSES
Cancer: Metastatic spread of the cancer to the bone can cause calcium in the blood to rise.
Vitamin D intoxication: Calcium increases when there is too much vitamin D, often the result of taking too many supplements.
Sarcoidosis: A disease in which immune-system cells cluster to form lumps called granulomas in various organs. These granulomas create too much activated vitamin D, which leads to the absorption of excessive amounts of calcium.
Familial hypocalciuric hypercalcemia: An inherited inability to get rid of calcium in the urine. It's rare but will cause high calcium levels (also known as hypercalcemia). It rarely causes any other symptoms.
Hyperthyroidism: Too much thyroid hormone often leaches calcium from the bones, causing hypercalcemia and osteoporosis.
Hyperparathyroidism: This is the most common cause of elevated calcium levels. The parathyroid gland helps regulate the amount of calcium in the blood. Small tumors can form on these tiny glands, which makes them produce too much of the hormone and thus too much calcium.
6. THE PATIENT'S SELF-DIAGNOSIS
There was one more thing the young man wanted to bring up, but it was a little embarrassing. Sometimes medical students or doctors will convince themselves that they have the diseases they are studying. This patient spent the past couple of years reading about cancer in preparation for his fellowship, and now he wondered if he had one.
Both his father and his father's brother died young from cancer. His uncle died at 52 from a tumor of the pituitary gland. His father — a nonsmoker — died at 49 of lung cancer. And his father also had high calcium levels.
There are only a couple of inherited diseases that can cause increased calcium levels. One in particular, the patient explained, seemed to fit: MEN — multiple endocrine neoplasia, a rare, inherited predisposition to develop tumors (or neoplasms) — seemed a likely diagnosis for his father and uncle and, uncomfortably, for himself as well.
Could he have MEN, he asked his new internist. The doctor was interested but not convinced. "This is unlikely but not outlandish," he told the patient. Although an unusual presentation of a common disease is far more likely than even a classic presentation of a rarity, Tangalos had to admit, the young man's story was compelling. But first he would have to look for the usual suspects.
7. TEST RESULTS
The internist ordered a chest X-ray and a series of blood tests. The chest X-ray was normal — it wasn't sarcoidosis or Hodgkin's disease. The blood tests showed that it wasn't too much vitamin D or hyperthyroidism. Indeed all the blood tests were normal except for high calcium levels. And the parathyroid hormone level (PTH) was normal, but it shouldn't have been. PTH should be low when calcium is high. That suggested there was something wrong with the parathyroid gland.
When he saw these results, Tangalos was glad he had arranged for the young man to see an endocrinologist. Hyperparathyroidism and a family history of cancer certainly suggested MEN. The endocrinologist tested the patient for the gene. It was positive. He and his father, and probably his uncle, all had the disease.
8. THE DIAGNOSIS
There are three types of multiple endocrine neoplasia. MEN Type 1 — the kind this patient had — is the most common.
Current thinking is that patients with MEN 1 are missing one of the genes that suppress the formation of tumors. Almost everyone with MEN 1 will have high calcium levels because of 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. Other types of tumors are also seen. The patient's father had a characteristic type of lung cancer. The bumps on the young doctor's nose are also common in those with this rare disease.
The goal in treatment is to catch and, when necessary, remove tumors as they arise. Patients with MEN 1 should get regular CT scans and other studies to monitor body sites that may be affected.
The patient had multiple tumors on his parathyroid glands; he recently had surgery to remove them. Small tumors were also found in his pancreas. So far, these 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? Once Dr. Tangalos had the results of the blood test, it seemed obvious enough. There's a mnemonic that doctors use to help remember the classic symptoms of high calcium: stones, bones, abdominal groans and psychic moans. High calcium can cause kidney stones, bone pain, abdominal pain and a variety of neurologic and muscular problems. Current thinking is that the abdominal pain is caused by gas and constipation — two common problems in those with high levels of calcium.
9. THE ROAD AHEAD
For this patient, the greatest challenge is that his children have a 50-50 chance of inheriting his tendency to grow tumors. His daughter was tested when he received his diagnosis. She tested negative. He and his wife wanted another child but weren't allowed to adopt because of his genetic disease. After long deliberation, they decided to have a second child. They haven't decided when to test their son, now 9 months old.
