The Missing Diagnosis

By Laura Freeman 

When you studied endocrine disorders in medical school, did you get the impression that primary hyperthyroidism was a rare disease you were unlikely to see often—maybe only one or two cases per hundred patients?

Endocrine surgeons have a different message for healthcare providers. There may be more people than we realize who suffer for months or even years without knowing what is really behind their symptoms. Why? No one thought to run two simple labs to detect one of the few devastating diseases that can be completely cured with an outpatient procedure.

“After seeing so many cases, I’m convinced we have a lot more people walking around with hyperparathyroidism than we once suspected. It has so many symptoms that mimic other diseases that unless the right two labs are run and the relationship between their values noticed, the symptoms are likely to look like something else,” UAB endocrine surgeon Jessica Fazendin, MD said.

It’s frustrating for both physicians and patients when prescriptions fails to help. It can undermine the doctor/patient relationship and sow the seeds of doubt.

Not recognizing hyperparathyroidism can also send a whole series of dominos falling, undermining a previously stable condition because problems are attributed to the wrong disease. For example, when a patient’s labs suggest possible kidney damage, a physician might discontinue stomach medication which could result in a resurgence of extreme GERD with all the associated complications.

“An endocrinologist can look at the results of these two tests and they usually know with fairly high confidence what is going on,” Fazendin said. “But keep in mind that the disorder can show up in three different combinations. In the classic version, both the calcium and PTH are high. But it is possible for either the calcium or the PTH to look relatively normal. It’s important to consider how those values relate to each other. If calcium levels are low, it should be stimulating PTH to go higher, to release more calcium from the bones. If calcium levels are high, PTH should be falling to slow the release of calcium.”

What are the clues that suggest these two tests should be added to a patient’s labs? Some patients seem to be at greater risk for developing the disease. Incidence tends to increase with age, though it can occur in younger people. It’s more common in females than males. If your patient has had thyroid problems the parathyroid glands may also be more likely to develop issues.

“If you look over a patient’s history and notice that calcium levels are gradually creeping higher, or you get back a bone density test showing osteopenia or osteoporosis in patients who get plenty of calcium and vitamin D in their diet, the next question is what is their PTH doing?” Fazendin said.

“Hyperparathyroidism can present with a laundry list of symptoms because calcium and PTH circulate through the bloodstream to the entire body. However, not every patient gets every symptom, and which symptoms are worse tend to be different in different patients.

“Crushing fatigue that’s chronic is the most commonly reported complaint. Kidney stones from too much calcium should be investigated, and so should an increase in fractures or bones that break from a minor force.”

Labs that suggest the kidneys are not doing well need a closer look, and patients may experience gastric issues, especially constipation that is worse than previously experienced.  There may be neurological changes, including brain fog, depression, anxiety, and difficulty sleeping. Patients may notice more difficulty retrieving words and facts they could previously recall. This symptom shouldn’t be automatically attributed to dementia or side effects of medication in patients who haven’t been screened for hyperparathyroidism. Some cardiologists suggest watching for heart rhythm changes and calcification in blood vessels.

“Patients might say they’ve aged five years in the past six months,” Fazendin said. They also tend to have a lot of muscle, bone and joint pain with more mobility issues. It may seem like they’re having an arthritis or fibromyalgia flare that goes on and on, or they could wonder if they are experiencing the onset of a major movement disorder. It’s remarkable to see how much better they feel once the disease is gone.”

In some cases, for instance when patients are on blood thinners and can’t come off for a while, or when their condition is too frail for anesthesia, surgery may have to wait. To prevent more damage to organs and bones, it may be necessary to prescribe calcitonin to block the excess calcium and prevent further organ damage  However, the monthly cost of that medication can be expensive and is likely to require prior approval. Since the drug is commonly used in dialysis patients, a letter from the physician may be needed to explain why a patient not on dialysis needs it and why the hyperparathyroidism isn’t being treated with surgery.

When confirming the need for surgery and scheduling it, finding an endocrine surgeon with extensive experience in dealing with parathyroid problems is worthwhile.

“A normal parathyroid gland is about the size of a grain of rice,” Fazendin said. “There are four of them, with two usually situated on either side of the thyroid gland, but they can hide. You have to find which one on more is causing the problem. The glands can be deeper in some people than in others. If one is growing into an adenoma, the weight of it may pull it out of position so it isn’t where you expect it to be.

“You are working with a tiny incision on a person’s neck and trying to position it so the scar will be hidden in the normal lines and folds. You are also working near nerves that control speech and you have to be careful not to damage the thyroid and stay clear of nerves and major veins and arteries supplying the brain.”

It may be worth getting insurance approval for a test that could give the surgeon a better sense of where the glands are located by injecting a tracer. “This can be particularly helpful when you have more fragile patients,” Fazendin said. “Depending on the location, you may be able to use a lighter combination of anesthesia and get through the surgery faster if the imaging gives you a sense of which parathyroid gland is the most likely culprit and exactly where it is.

“The fastest case I ever had took only eighteen minutes, but more difficult cases can take a while. If the problem gland is located near a major nerve not far from the spine, you are going to need heavier anesthesia.

“Although removing one enlarged parathyroid may solve the problem, others may also be overactive. Fortunately, PTH levels change quickly. Ten minutes after removing the adenoma, we can check again. If the PTH is looking good, we’re done. If not, we move on to the next most likely gland. If all four of the parathyroid glands are overactive, at least part of the healthiest looking gland will need to remain to provide the hormone, and the patient’s levels will be followed.

“Fortunately, the adenomas are usually benign. Only one case in a hundred comes back from pathology showing a malignancy and needs to be referred to oncology.

“We show patients how to take care of their incisions to minimize scarring, and have them check back a couple of times to verify their labs and see how they are doing. They usually feel better fairly quickly. Six months later, it’s like meeting a whole new person.

“That’s why I enjoy working with hyperparathyroid patients. It’s one disease I can cure with an outpatient procedure and it makes such a difference in their quality of life.”