What are the objective benefits of parathyroid surgery?

The decision for surgery in primary hyperparathyroidism is based on: 

1. Establishing a clear biochemical diagnosis using blood and urine testing. Patients who stand to gain the most from parathyroid surgery have elevated blood calcium levels (total calcium usually 10.4 mg/dL or greater) and either an elevated (>65 pg/mL) or inappropriately normal (40-65 pg/mL) parathyroid hormone (PTH level). The exact ranges may vary slightly depending on the laboratory. Urine testing, consisting of a 24-hour urine calcium measurement, is not always necessary but can be helpful in clarifying the diagnosis in borderline or ambiguous cases.
2. Assessing for any end-organ damage, most often in the form of osteopenia (mild bone loss) or osteoporosis (severe bone loss). Bone mineral density (BMD) assessment, performed using dual-energy X-ray absorptiometry (DEXA or DXA scan), is useful in most patients with primary hyperparathyroidism. The typical patient with primary hyperparathyroidism is a woman over 50, who is likely to be post-menopausal. The loss of estrogen during menopause puts women at risk for osteoporosis, and having primary hyperparathyroidism on top of that can cause serious bone loss. Patients with both osteopenia and osteoporosis benefit from parathyroid surgery. 
3. Accounting for the overall health of the patient and their ability to undergo the stress of an operation under anesthesia. Most patients are healthy enough to undergo parathyroid surgery. A rule of thumb is, if a patient is able to climb one standard flight of stairs without experiencing chest pain or shortness of breath, then they are able to tolerate the stress of parathyroid surgery. Patients who can climb two flights of stairs are certainly fine to proceed with parathyroid surgery.
4. Estimating the life expectancy of the patient. The benefits of parathyroid surgery are greater in younger patients. Parathyroid surgery is like an investment that pays dividends over time, principally by reducing the long-term risk of major fractures (most importantly hip fractures, which lead often to disability and sometimes to death). It is common for us to perform parathyroid surgery in patients in their 60s, 70s, and 80s. In general, if a patient has a life expectancy of 3 years or more, parathyroid surgery is a good investment.
5. Predicting the probability of an improvement in health following parathyroid surgery. Primary hyperparathyroidism affects multiple organ systems. The probability of health improvement in each domain varies and is described below.

Skeleton (Osteoporosis and fractures)

The skeleton is the most important end-organ that is affected by primary hyperparathyroidism. Improvements in bone mineral density after parathyroid surgery have been consistently shown in every study conducted on the topic over the past 25 years. Without surgery, patients with primary hyperparathyroidism experience steady declines in bone mineral density at all sites (forearm, hip, and spine) over time, leading to osteopenia and eventually osteoporosis. Patients who have parathyroid surgery experience either stabilized or increased bone mineral density – this is measurable 2, 5, and 10 years after surgery. In fact, the gap in bone mineral density between surgically treated patients and non-surgically treated patients grows wider with time.

Parathyroid surgery for primary hyperparathyroidism reduces the risk of major fractures. This has been proven in two large-scale studies. Let us imagine a hypothetical population of 2,000 people with primary hyperparathyroidism: half of them have parathyroid surgery and half of them do not. They are followed forward in time for 10 years. What are the rates of fracture?

In the table above, the 10-year risk of hip fracture without parathyroid surgery is 1 in 18 patients, compared to 1 in 50 with parathyroid surgery, meaning that parathyroid surgery reduces hip fracture risk by 64%. This is a very large effect. The data above also show that approximately 10 parathyroid operations performed results in one major fracture prevented.

With the exception of patients who have other health conditions causing bone loss, such as those who take steroid medications for inflammatory diseases, almost all patients who have parathyroid surgery for primary hyperparathyroidism can expect increased bone mineral density and reduced fracture risk. This is the single most important benefit of parathyroid surgery. Preventing fractures helps people to maintain independence in older adulthood. Approximately 20% of people who suffer a hip fracture will go on to die within two years. Of those who survive, most require one year of rehabilitation, and many will permanently lose the ability to walk unassisted. Treating hip fractures costs the United States approximately $15 billion dollars per year. Avoiding major fractures is essential to your health.

There is broad agreement in the medical community that patients with primary hyperparathyroidism and osteoporosis should have parathyroid surgery. We believe that patients with osteopenia (mild bone loss) should also have parathyroid surgery. The reason is as follows: if we operate only on patients with osteoporosis (severe bone loss), a significant number of them will have fractures after parathyroid surgery (i.e. despite having parathyroid surgery, sadly). Their bones have fallen into such poor condition that, even after parathyroid surgery, it takes several years for the bones to recover – during that time, they remain at risk for fracture while in that “valley” of very low bone density. A better strategy is to avoid osteoporosis altogether by moving the operation forward in time. Indeed, patients with primary hyperparathyroidism and osteopenia who have parathyroid surgery have long-term fracture rates that are identical those with normal bone mineral density. They have been restored to full health. More information on this in Table 2 below.

The first thing you might notice in Table 2 is that more fractures occur in patients with osteoporosis than in those with osteopenia – which makes sense, because osteoporosis represents a more serious degree of bone loss. But the most important finding here is that parathyroid surgery prevents fractures in both patients with osteoporosis and those with osteopenia. In fact, when you look at “Any Fracture,” you see that the beneficial effect of parathyroid surgery is actually greater in patients with osteopenia (49% risk reduction vs 15% in osteoporosis). 

This is an opportune moment to clarify that treating primary hyperparathyroidism with medicines does not work. Multiple studies have examined using cinacalcet (Sensipar, a medicine that lowers the blood calcium level) or bone-building drugs (denosumab/Prolia or bisphosphonates such as alendronate/Fosamax, risedronate/Actonel, ibandronate/Boniva, and zoledronate/Zometa) to treat primary hyperparathyroidism and they have collectively shown that the only way to reduce fracture risk is through parathyroid surgery. We are also frequently asked whether bone-building drugs should be taken after parathyroid surgery. Only one study (from our group) has looked at this question, and it showed that taking bisphosphonates soon after parathyroid surgery can actually cancel out the beneficial effect of surgery on fracture risk. For this reason, we currently recommend that patients who undergo parathyroid surgery avoid bisphosphonates for at least 2 years after surgery. After surgery, we recommend only the following 3 things: adequate dietary calcium intake (500-1200 mg daily and not more), adequate vitamin D intake (1000-2000 international units daily and not more), and weight-bearing exercise (ideally weight training or other resistance exercise). 

Kidney (Kidney function and kidney stone risk)

It was previously believed that surgery for primary hyperparathyroidism would protect the kidneys from damage related to high blood calcium levels. In 2023, two major research studies addressed this question. One of them found that kidney protection was only observed in patients under age 60. The other one found that kidney protection was only observed in patients with a blood calcium level greater than 11.5 mg/dL, who make up 16% of all patients with primary hyperparathyroidism (84% of patients have blood calcium levels between 10.5 and 11.5). The overall conclusion is that the protective effect of parathyroid surgery on kidney function was probably overstated in the past, and should generally be a minor consideration when making the decision for surgery. Turning to kidney stones (also known as nephrolithiasis), it was also previously believed that surgery for primary hyperparathyroidism could potentially stop kidney stones completely. Two major studies in 2022 challenged this belief. One found that parathyroid surgery had no effect on kidney stone risk. The other found that parathyroid surgery prolonged the time to kidney stone recurrence. In other words, for patients with primary hyperparathyroidism and kidney stones, having surgery caused episodes of kidney stones to become less frequent, but did not eliminate the risk of future stones. Taken together, these studies show that parathyroid surgery is modestly helpful in reducing kidney stone risk. This is because many people (about 8% of adults) have kidney stones; though 80% of kidney stones contain calcium, most episodes of kidney stones have nothing to do with primary hyperparathyroidism. Therefore, people with both primary hyperparathyroidism and kidney stones may sometimes be experiencing a simple coincidence, where the hyperparathyroidism is not actually causing the stones. Having said that, kidney stones are so painful that most patients are willing to try just about anything to avoid having another one. So many of these patients, and their doctors, are in favor of proceeding with parathyroid surgery. 

Cardiovascular system (heart attack, heart failure, stroke, blood pressure)

Some studies have shown increased rates of cardiovascular disease in patients with primary hyperparathyroidism that were mitigated by parathyroid surgery. These findings have generally not been supported by subsequent, higher-quality evidence. Parathyroid surgery appears to have negligible effects on blood pressure. 

Quality of life issues

This is something that patients care a lot about. Unfortunately, the internet is full of misinformation on this topic, and it is easy for the sophisticated reader to tell that overstating quality of life improvements after parathyroid surgery is nothing more than marketing. Quality of life before and after surgery for primary hyperparathyroidism has been studied quite extensively in both retrospective studies (those that look backward in time, which study larger populations but are considered low- to moderate-quality evidence because of design flaws) and prospective studies (those that recruit patients, randomly assign treatments, and then look forward in time at their outcomes, which are often smaller but considered the highest quality).

Looking at these studies together, surgery for primary hyperparathyroidism leads to modest improvements in bodily pain, general health, vitality (energy level/fatigue), and mental health. The effect sizes ranged from 10-30%. Mental health improvements were seen in the domains of anxiety and depression. 

Quality of life: What we see clinically

In our practice, we advise people to have realistic expectations regarding what parathyroid surgery can do to improve quality of life. The majority of patients who undergo surgery seem to experience some improvement, most often in energy level, cognition (mental function and memory), bodily aches and pains (usually from the hips down), and frequency of urination (less getting up to urinate at night). These changes are usually minor but sometimes can be more pronounced. Not everyone feels better after surgery – about one-third of patients don’t feel any difference. Among patients who do experience improved quality of life, some feel a difference soon after surgery (within 1-2 weeks), and others feel a difference after a few months. The reason behind this is that most patients with primary hyperparathyroidism complain of decreased quality of life (most often fatigue). However, fatigue has many causes, and may not be related to hyperparathyroidism. This is just common sense. People with serious mental health conditions, such as clinical depression and generalized anxiety disorder, cannot expect these conditions to be cured by parathyroid surgery. It is also not realistic to believe that parathyroid surgery will treat other miscellaneous common health complaints such as weight gain, hair loss, sleeplessness, and headaches, which generally have nothing to do with the parathyroid glands or calcium levels.

Having said this, many patients with fatigue, bodily pain, or mild features of depression and anxiety and primary hyperparathyroidism choose to have parathyroid surgery. We find that normalizing the blood calcium level “crosses off” hyperparathyroidism from the list of potential causes for their decreased quality of life, allowing them to then refocus their attention, and that of their health care team, on other potential causes.

Summary

Who benefits from parathyroid surgery? In a word, people with classic primary hyperparathyroidism (calcium 10.4 mg/dL or greater and PTH >65 pg/mL) and those with normohormonal primary hyperparathyroidism (calcium 10.4 mg/dL or greater and PTH 40-65 pg/mL) who can climb at least 1 flight of stairs and have life expectancy greater than 3 years. 

This means that most people with primary hyperparathyroidism are good candidates for surgery. The typical person with primary hyperparathyroidism is a generally healthy 50- to 70-year-old woman with a blood calcium level of 10.4-11.0 mg/dL. If your blood calcium is high (10.4 mg/dL or greater) on more than one occasion, there is a 90%-99% chance that you have primary hyperparathyroidism. In that event, a PTH level should be checked to confirm the diagnosis. Thereafter, it is often useful, especially for women, to check the bone mineral density. If you have either osteopenia or osteoporosis, you should strongly consider having parathyroid surgery, as it will reduce your fracture risk over the next 10 years. If you have normal bone density, it is ok to wait (observation instead of surgery). Under observation, the blood calcium should be checked twice per year (to ensure that the level does not rise to more dangerous levels >11.5 mg/dL) and the bone density should be checked every other year. Keep in mind that most people with normal bone density who live more than 5 years will eventually show signs of bone loss.

[Side note: If you have normocalcemic primary hyperparathyroidism, defined by a calcium level of <10.4 mg/dL and a PTH level >65 pg/mL in the presence of normal kidney function and normal vitamin D levels (at least 20 ng/mL and preferably 30-50 ng/mL), the benefit of parathyroid surgery is uncertain. Please see the page and the video below for more information on normocalcemic primar hyperparathyroidism.]

The main reason to have surgery for primary hyperparathyroidism is to preserve your bone health and avoid fractures. And that is reason enough, because major fractures in older adulthood lead to disability and sometimes death. The other benefits are small and inconsistent in comparison, and have been overstated in the past. Quality of life improvements are often seen, but may be minor and cannot be guaranteed. It is important for people to have realistic expectations about this.

Today, about 25-35% of people with primary hyperparathyroidism have parathyroid surgery in the United States. This figure is far below what it should be, according to even the most conservative guidelines. A dozen studies, performed in a variety of populations (individual states in the US, certain insurance groups, the Veterans Administration, academic health systems) have all shown that primary hyperparathyroidism is underdiagnosed and undertreated. This is such a serious and widespread problem that we implemented an electronic decision-support tool (simple AI program) within our health system to improve the rate of appropriate diagnosis. If the number of people appropriately referred for parathyroid surgery were increased in this country, many fractures would be prevented.

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