Parathyroid Surgery Benefits
Benefits of parathyroid surgery at UCLA in Los Angeles,
California
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 | Parathyroid
Surgery Blog >>
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:
- Bones – Parathyroid bone disease, osteoporosis, fractures
- Stones – Kidney stones
- Moans – Abdominal pain, nausea, constipation, pancreatitis, peptic
ulcer disease
- Groans – Muscle weakness, pain in the muscles and joints
- Neuropsychiatric overtones – Fatigue, delirium, depression, memory
loss
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Figure 1. Strength of evidence behind potential benefits of
parathyroid surgery.
View
larger image >>
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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 (See
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).
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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:
- Blood calcium level more than 1.0 mg/dL above normal
- 24-hour urinary calcium excretion greater than 400 mg/day
- Kidney function reduced by 30% below normal
- Bone mineral density reduced by 2.5 standard deviations below young, healthy controls
- Age less than 50
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.
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| Figure 2. Bone mineral density improves after parathyroid
surgery. Patients having surgery are shown in teal, patients not having surgery are shown
in burgundy. Figures show changes in bone density at 1, 4, 7, and 10 years after surgery.
Parathyroid surgery leads to prompt increases in bone density in both the spine and hip.
These improvements continue for 10 years after surgery. (Adapted from Silverberg, NEJM 1999) View
larger image >> |
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 >>.
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| Figure 3. Parathyroid surgery improves bone mineral
density in all patients with primary hyperparathyroidism. Asymptomatic patients meeting NIH
criteria for parathyroid surgery (biochemically severe disease, shown in teal) gain bone
mass after parathyroid surgery. The same is true for patients not meeting NIH criteria for
parathyroid surgery (biochemically mild disease, shown in burgundy). Bone density measurements
were taken before and one year after parathyroid surgery. (Adapted from Nakaoka, JCEM 2000) View
larger image >> |
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).
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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).
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| Figure 4. Reduction in kidney stone events after
parathyroid surgery. Immediately prior to surgery, the risk of stone events is approximately
400 times normal. That risk rapidly declines during the first year following surgery, though
a return to completely normal risk levels takes several additional years. (Adapted from Mollerup,
BMJ 2002). View larger image >> |
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.
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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 >> .
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| Figure 5. Most common symptoms in primary hyperparathyroidism.
Individuals with primary hyperparathyroidism (shown in burgundy) are more likely to suffer
from the symptoms listed above when compared to individuals without parathyroid disease (shown
in teal). (Adapted from Chan, Ann Surg 1995; and Eigelberger Ann Surg 2004). View
larger image >> |
They include fatigue, exhaustion, pain in the muscles and bones, weakness, frequent
urination, constipation, depression, and others.
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| Figure 6 Symptom frequency is not related to disease
severity. Among individuals with primary hyperparathyroidism, those with biochemically mild
disease (shown in burgundy) are equally likely to experience symptoms when compared to those
with biochemically severe disease (shown in teal). (Adapted from Eigelberger Ann Surg 2004) View
larger image >> |
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).
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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).
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| Figure 7. Symptoms improve after parathyroid surgery.
After surgery, individuals with primary hyperparathyroidism (shown in burgundy) experience
a marked decrease in the symptoms listed above when compared to individuals without parathyroid
disease, who underwent a thyroid operation (shown in teal). Overall, approximately 70% of
patients who undergo parathyroid surgery experience improvement in one or more of their symptoms.
Equivalent rates of improvement are seen for patients with biochemically mild disease (those
not meeting NIH criteria for surgery) and those with biochemically severe disease (those
meeting NIH criteria for surgery). (Adapted from Chan, Ann Surg 1995; and Eigelberger Ann
Surg 2004) View larger image >> |
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.
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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
( Figure 8).
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Figure 8. Worldwide trends in parathyroid surgery.
Members of the International Association of Endocrine Surgeons have reported increasing rates
of parathyroid surgery across all continents. (Adapted from Sackett, Arch Surg 2002)
View
larger image >> |
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.
- Primary hyperparathyroidism affects many organ systems of the body.
- Most patients with primary hyperparathyroidism have significant health problems associated
with the condition.
- Individuals with mild parathyroid disease and severe parathyroid disease are very similar,
and individuals in both categories are likely to benefit from parathyroid surgery.
- Improvements in bone health after parathyroid surgery are consistent and well-established.
- Reductions in kidney stone events after parathyroid surgery are consistent and well-established.
- About 70% of people experience improvements in health-related quality of life after parathyroid
surgery.
- Other conditions associated with primary hyperparathyroidism continue to be investigated.
- Elderly individuals may benefit significantly from parathyroid surgery and should not
be denied this option.
- Improvements in surgical technique have made parathyroid surgery a better option for
many people worldwide.
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nationwide follow-up study of 1201 patients. World J Surg, 27: 343-349, 2003.
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