Hyperparathyroidism Is Underdiagnosed and Undertreated, Particularly in the Elderly

A new study shows that only a quarter of eligible patients are referred for testing for PHPT

With Calyani Ganesan MD, Richard Prinz MD, Carolyn Seib MD, and Brian Finnerty MD

Endoscopic surgerySurgery for hyperparathyroidism used to be invasive, but has become an endoscopic procedure with minimal risk.

The prevalence of primary hyperparathyroidism (PHPT) is increasing, leading more patients to deal with potentially serious outcomes such as osteoporosis and fractures, recurrent kidney stones, and chronic kidney disease.

New study findings on primary hyperparathyroidism

The study used data from more than 7,500 Veteran’s Administration patients who presented with kidney stones with hypercalcemia between 2008 and 2013. Of that group, 24.8% of those with a kidney stone and high calcium, and 34.8% of those with hypercalcemia were tested. Among patients with CCI’s under 3, only 33.6% received parathyroid hormone tests. Overall, of the 5% of kidney stone patients who presented with hypercalcemia, just under a quarter ended up being tested.

Study author Calyani Ganesan MD, MS, a clinical instructor at Stanford University, says many physicians often figure that kidney stones are a unique, acute, discrete event. “But they can be part of systemic issues,” she says. “They are showing up with not just one, but two characteristics of primary hyperparathyroidism, and still not getting screened.”

Kidney stones should be seen as an indicator of possible PHPT 

The first sign of the disease is often kidney stones, Dr. Ganesan notes. “They're the canary in the coal mine, a signal that there might be a problem.”

The high rate of lack of follow-through surprised Ganesan. She says she would have thought at least half of the patients would have been tested.  

“Screen your kidney stone patients,” Ganesan says. “Not everyone is getting screened. If you have a patient with kidney stones, and it is a calcium-based stone, or there is high calcium in the urine, check the calcium levels for hypercalcemia.” And if that test is high, make sure the patient has their parathyroid hormone levels checked.

Patients rarely notice the impact of primary hyperparathyroidism until it is too late – they have been diagnosed with osteoporosis, they have recurrent kidney stones, or they're experiencing symptoms from high calcium levels like fatigue, muscular, or skeletal pain.

 A surprising decline in parathyroidectomies

On the surgical front, another recent study looked at more than 56,000 patient records from private insurance companies between 2004 and 2016. The search found 26,522 had a diagnosis of hyperparathyroidism, yet only 38.1% had surgery within a year of the diagnosis. Younger patients were more likely to have the surgery, as were white patients, and those in the South or Midwest. Over the 12 years, the rate of parathyroidectomy decreased, from 60% of those with an indication in 2004, to 33.1% in 2016. (Patients were considered to have an operative indication for a parathyroidectomy if they were under 50, or had a diagnosis of osteoporosis, kidney stones, or stage 3 kidney disease.) With no indication, the rate of surgery dropped from 48.7% to 31.3%. Of those with at least one indication of primary hyperparathyroidism, just under 39% had a parathyroidectomy.

The authors suggest, “Parathyroidectomy is avoided owing to concern that the operative risks for older adults outweigh the potential benefits related to bone fracture, kidney stone formation, and CKD risk reduction.”

“Risk of this surgery is low – about 1% for complications,” says Dr. Ganesan. “It's well-tolerated.” Older patients who are being excluded are often the ones who would benefit most from surgery, reducing their risk of a life-threatening or altering fracture, cardiac event, or recurrent kidney stones.

Richard Prinz MD, an endocrine surgeon at Northshore Health in Illinois, has studied older patients not getting surgical intervention for primary hyperparathyroidism. A recent study he published in February determined that parathyroidectomy is safe for that older group of patients. The study looked at patients aged 61-79, as well as those over 80, and found there was no difference in complications or mortality between patients under 60 and those over 80. 

“The early forms of these operations were viewed as difficult,” Dr. Prinz says. “They left a large scar, and it was in the neck – a sensitive area where there is opportunity for some serious damage. Patients needed to stay in the hospital to ensure calcium levels stabilized, and it was a very invasive operation."

But all of that has changed, he notes. Now it is a single-day surgery and an endoscopic procedure. “The incision is small, there is minimal pain, and in a few days patients can resume regular activity,” he says. However, there is still a lack of knowledge among both patients and providers of the ease of the procedure. In addition, high calcium results may be viewed as transient, or an anomaly. And the physical symptoms that a patient may experience – brain fog, trouble sleeping, fatigue – are things that are often attributed to old age.

“I think that doctors who are very diligent about referring for testing and then suggesting surgery even to older patients are in the minority,” Dr. Prinz says. “There are plenty of studies that have shown that this is a problem for older patients. We sometimes get into ruts and forget that things change – like how we do this surgery, and the fact that many older patients are not frail. If you have a patient who has had kidney stones, and also is complaining about mood changes, or muscle and joint pain, consider this as a cause. If a patient has had repeat kidney stones, evaluate them.”

Reasons why more patients are not referred on to surgery still remain something of a mystery. Carolyn Seib MD, an endocrine surgeon at Stanford who worked on both the VA study and on the study on referral rates for parathyroidectomy is looking specifically at this topic in a new study currently under review.

Frailty is more important than age in determining the risk of complications

“We know that this is under-diagnosed and undertreated, and that the rate of parathyroidectomy goes down with age. While some of this may be appropriate due to frailty, some of it isn’t," says Dr. Seib.

Dr. Seib says the goal should be to individualize decisions, especially for older people, and try to find treatments that meet their goals. “You need to be able to figure out: What is the risk of repeat kidney stones? What is the risk of fracture? How does that compare to the risk of surgery?" she says.

Many patients older than 75 may have 20 good years left, Seib notes. For them, that surgery may be an easy yes. For another patient who has heart failure, or poorly controlled diabetes, the calculation may be different. “If they have a life expectancy of longer than 5 years, I would consider surgery.”

Patients who are referred for diagnostic testing and show abnormal parathyroid levels should talk to a surgeon, says Seib. “I’ve had patients come to me after 10 years, who have had multiple kidney stones, or a fracture, and they tell me that all those years ago, a doctor told them they just had a lab abnormality.”

The notion that some patients are just too old for surgery is something that impacts thyroid patients, too, says Brendan Finnerty MD, an assistant professor of endocrine and minimally invasive surgery at Weill Cornell Medicine in New York City. He published a paper in June that looked at age as it related to thyroid surgery, and found frailty was better than age at determining the risk of complications.

“If a patient has any endocrine disease that could be potentially cured surgically, they should be evaluated by a surgeon to discuss the risks and benefits of a specific operation,” Dr. Finnerty says. “As more data is published regarding frailty being a better indicator of systemic and procedure-related complications of surgery, the surgeon can tailor a patient-specific treatment plan accordingly. That could include opting for local anesthesia with sedation instead of general anesthesia when appropriate.”

Dr. Finnerty says he keeps patients under active surveillance for an otherwise surgically-treatable disease, “We constantly re-evaluate if the benefits of surgery outweigh the risks. Endocrinologists do a great job counseling patients similarly. However, I think surgeons should still discuss surgical risk stratification with patients, with a focus on frailty.”

“With such low rates of operative management in older adults, it's likely that we aren't utilizing parathyroidectomy appropriately to reduce morbidity from primary hyperparathyroidism in this group,” Seib concludes. “We need to educate providers on the potential benefits of parathyroidectomy in patients of all ages and develop tools that will help providers individualize treatment decisions.”

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