Clinical signs & symptoms | Background | Improved bone health | Reduced risk of kidney stones | Improved quality of life | Primary hyperparathyroidism & hypertension | Primary hyperparathyroidism, diabetes & obesity | Primary hyperparathyroidism, cardiovascular disease, & premature death | Special case: Parathyroid surgery in the elderly | Conclusion | Summary | References
Primary hyperparathyroidism is a disease of calcium imbalance. Because calcium is an important regulator of many cellular functions in all of the body’s organ systems, the clinical manifestations of primary hyperparathyroidism range widely (1). Classically, medical students are taught the following rhyme to recall the effects of excess blood calcium levels:
When queried about symptoms of hyperparathyroidism, about 95% of individuals with the disease do have one or more of the above complaints (2). That said, it is important to note that many of the symptoms listed above are nonspecific. In other words, the symptoms can be caused by a number of other conditions unrelated to the parathyroid glands. These diagnoses include chronic fatigue syndrome, fibromyalgia, and depression, just to name a few.
Though the benefits of parathyroid surgery are increasingly well-defined, it is not a panacea. However tempting the concept may be, it is not realistic for patients to believe that parathyroid surgery will cure all of a their ills, nor is it appropriate for physicians to create that expectation. Patients who are promised a miracle cure for any condition should exercise great caution (Information about healthy web surfing > from the U.S. National Library of Medicine and the National Institutes of Health).
As is true for most medical treatments, the benefits of parathyroid surgery vary in how well the scientific literature supports them. Certain benefits are clearly established, and others less so. Below, we review the evidence behind health improvements following parathyroid surgery, from the strongest data to the weakest
( Figure 1).
In developed nations, the routine of use laboratory testing and imaging studies has resulted in the identification of two distinct patient populations for many disease processes: symptomatic patients (those who are noticeably suffering from the disease and would clearly benefit from treatment), and asymptomatic patients (those who are unaware of any abnormality). Physicians are generally cautious in recommending surgery for asymptomatic patients, with the idea being that it is hard to make a patient better if s/he is already feeling fine. Recommending surgery for asymptomatic patients, therefore, rests on the clear demonstration of future health benefits and/or the avoidance of problems down the line.
With this in mind, the National Institutes of Health developed a list of criteria for surgery in primary hyperparathyroidism (3). In 2002, parathyroid surgery was recommended for asymptomatic patients meeting one or more of the following criteria:
It is important to note that, in the development of these criteria, only patients with kidney stones and obvious parathyroid bone disease were considered symptomatic. Muscular and neuropsychiatric symptoms, though common, are often considered too vague and difficult to measure systematically. For this reason, these symptoms have frequently been disregarded in prior articles, which is unfortunate since many patients may benefit from parathyroid surgery in the realm of improved quality of life (discussed below). For the sake of simplicity, hereafter we will refer to patients meeting NIH criteria for surgery as having severe parathyroid disease, and those not meeting criteria as having mild disease.
Improvements in bone mineral density following parathyroid surgery are very well established, and patients can routinely expect these benefits soon after surgery.
The single most important article on this topic was written by Silverberg and associates from Columbia University; their findings are represented in
Figure 2 > (4).
They reported that parathyroid surgery for patients with severe primary hyperparathyroidism resulted in significant increases in bone mineral density that were measurable 1 year after surgery and continued for the next 10 years.
A related article examined changes in bone mineral density in patients with mild parathyroid disease (5).
The findings appear in
Figure 3 >.
Nakaoka and associates demonstrated that all patients with primary hyperparathyroidism experience improvements in bone health after parathyroid surgery – this was equally true for patients with mild disease and severe disease.
A more recent article studied fracture risk in patients with primary hyperparathyroidism.
Patients undergoing parathyroid surgery experienced a significant reduction in the risk of fractures, particularly those involving the hip(6).
In the Silverberg article mentioned above, parathyroid surgery was found to completely eliminate future episodes of kidney stones. In contrast, most of the patients in their study who did not undergo surgery continued to have stone events.
Figure 4 >
shows results from a large Danish study examining kidney stone events in patients undergoing parathyroid surgery (7).
The risk of future stone episodes decreased dramatically soon after surgery, though the level of risk did not reach normal levels until several years later.
Therefore, patients with kidney stones who undergo parathyroid surgery can expect major improvements in this area, but a certain number may continue to form new stones for a few years afterwards.
As mentioned above, the majority of patients with primary hyperparathyroidism do report symptoms when they are asked the right questions (2, 8). The most common symptoms are shown in
Figure 5 > .
They include fatigue, exhaustion, pain in the muscles and bones, weakness, frequent urination, constipation, depression, and others.
Eigelberger and associates from the University of California, San Francisco compared the frequency of symptoms in patients with mild parathyroid disease and severe disease
( Figure 6).
They found that all patients with primary hyperparathyroidism were equally likely to suffer from symptoms, and that the majority of patients (approximately 70%) reported improvement in their symptoms after parathyroid surgery
( Figure 7).
Therefore, it appears that symptom frequency and severity in primary hyperparathyroidism have no clear relationship with the calcium level or other biochemical markers.
Even patients with minor laboratory abnormalities frequently experience symptoms.
A small number of well-designed studies have examined quality of life measures in patients with parathyroid disease. Rao and associates noted mild but significant improvements in health related quality of life following parathyroid surgery (9). In another recent study, no such benefits were observed (10). Both of these studies have been criticized because quality of life was measured using generic survey tools rather than questionnaires specifically aimed at symptoms of parathyroid disease. Indeed, when disease-specific tools are used, the quality of life benefit of parathyroid surgery appears to be much greater (11). Controversy remains on this topic.
Our experience at UCLA is compatible with the findings from UCSF: about two-thirds of our patients report improvements in quality of life following parathyroid surgery. In most cases, the changes are noted within days or a few weeks of surgery.
Patients with primary hyperparathyroidism appear more likely to have hypertension than those who do not. However, no clear cause-and-effect relationship between the two processes has been established, and parathyroid surgery does not appear to reliably improve blood pressure (12-14).
In some studies, higher rates of type 2 diabetes and obesity have been found in association with primary hyperparathyroidism (15-19). To date, there has been no systematic evidence to suggest that parathyroid surgery reverses these associated conditions.
Several large scale studies performed in Sweden and Denmark have demonstrated a significantly increased risk of death from cardiovascular disease (stroke, heart attack, heart failure, and abnormal heart rhythms) in patients with primary hyperparathyroidism (20-23) . These studies utilized national health databases covering many thousands of individuals. In some cases, parathyroid surgery was shown to bring patients back down to normal levels of risk (24) .
That said, similar studies performed in the United States have failed to replicate these results (25) , calling into question the generalizability of the findings. The question of whether primary hyperparathyroidism adversely affects cardiovascular health, therefore, remains unanswered. The Scandinavian studies have raised some intriguing possibilities that require further study.
Several studies have indicated that elderly patients with primary hyperparathyroidism experience significant delays before being offered surgery (26, 27) . Almost half of elderly patients in one study experienced mental impairment as a result of their disease. At expert centers, parathyroid surgery involving patients older than 80 years is both effective and uncomplicated (28) . Elderly patients enjoy the same benefits from parathyroid surgery that younger patients do in the areas of health related quality of life and bone density. A growing body of literature suggests that elderly individuals experience improvements in cognitive function and mental status after parathyroid surgery (29) .
The 2002 NIH criteria set out to define a group of patients with severe parathyroid disease who require surgery and a separate group of patients with mild disease who do not. However, as reviewed above, these two groups are indistinguishable in many respects. Patients with severe disease and mild disease are equally likely to have symptoms of primary hyperparathyroidism and are equally likely to benefit from parathyroid surgery.
This fact has led some experts and national physician organizations to conclude that all patients with primary hyperparathyroidism should be considered for parathyroid surgery(30, 31).
(See the 2005 position statement on primary hyperparathyroidism jointly written by the American Association of Clinical Endocrinologists and American Association of Endocrine Surgeons (PDF) >)
Most physicians would agree that the decision to proceed with parathyroid surgery is dependent on the balance of risk and benefit for each individual patient. We recommend that people who are diagnosed with primary hyperparathyroidism discuss this option with an endocrinologist or endocrine surgeon, when appropriate.
Major advances in surgical technique, particularly the advent of focused (minimally invasive) parathyroid surgery, have made parathyroid surgery a better option for increasing numbers of people worldwide
Growing awareness of the health benefits of parathyroid surgery has also driven this trend, which reflects a general shift in the risk-benefit ratio in favor of surgery.
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The Benefits of parathyroid surgery are improved bone health, reduced risk of kidney stones and improved quality of life. About 70 percent of people experience improvements in health-related quality of life after parathyroid surgery. Primary hyperparathyroidism is a disease of calcium imbalance.