28 Outcomes Analysis in Parathyroid Surgery

28.1 Introduction

Primary hyperparathyroidism (HPTH) is the unregu- lated overproduction of parathyroid hormone (PTH) resulting in abnormal calcium homeostasis. Epidemi- ologic data suggest that the prevalence of this disease is 4 cases per 100,000 persons in the USA [1]. As the third most prevalent endocrine disorder after diabetes mellitus and thyroid disease, primary HPTH is an im- portant public health concern. It is a disorder which affects women at least twice as frequently as men, and the elderly much more than the young. Parathyroid- ectomy, the only potential cure for primary HPTH, was estimated to cost $282 million annually in the USA in 1998 [2]. Overall expenditures (including di- rect and indirect costs) attributed to this disease can be presumed to be much greater today, although no reliable estimate has been published to date [3].

With advancements in laboratory medicine and the development of automated serum screening in the 1970s, the clinical profile of primary HPTH shifted

from the classic hypercalcemic symptoms of “bones, moans, stones, and abdominal groans” to asymptom- atic or “minimally symptomatic” disease, whereby the diagnosis is established in asymptomatic patients when hypercalcemia is incidentally discovered based on a routine chemistry panel. Likewise, the surgical management of primary HPTH has evolved with the advent of minimally invasive parathyroidectomy (MIP) and the development of the rapid PTH assay.

Together, these technologies have revolutionized parathyroidectomy from a procedure performed un- der general anesthesia with bilateral neck exploration to a safer, less-invasive procedure performed in the ambulatory setting through a smaller incision with unilateral neck exploration. Given this frameshift in the epidemiology of primary HPTH, the advent of new technologies, and a relative paucity of parathy- roidectomy outcomes research, there continues to be controversy about the optimal threshold for early sur- gical referral.

28.2 Early Parathyroid Surgery

The original description of the parathyroid gland was made from the dissection of an Indian rhinoceros in 1850 by Sir Richard Owen [4]. However, it was not until 37 years later that a histologic analysis was per- formed by the Swedish medical student, Ivar Sand- ström. His description of the “glandularae parathy- reoidae” attracted little, if any, immediate attention [5]. Early insight into the function of the parathyroids was serendipitous. Anton Wolfer described tetany in a patient who underwent thyroidectomy and inciden- tal total parathyroidectomy in 1879 [6]. Ironically, it was a poor outcome following thyroidectomy that led to a better understanding of the parathyroids.

Diseases attributed to the parathyroids were man- aged with surgery as early as the 1920s. Famous pa- tients include the Viennese tram-car conductor Al- bert Gahne, who underwent two operations by Felix Mandl, and the Merchant Marine captain Charles Martell, who underwent seven operations by Oliver

28 Outcomes Analysis in Parathyroid Surgery

Leon D. Boudourakis and Julie Ann Sosa

Contents

28.1 Introduction . . . 339

28.2 Early Parathyroid Surgery . . . 339 28.3 Obstacles to Performing Parathyroidectomy

Outcomes Research . . . 340 28.4 Predictors of Outcomes

for Parathyroidectomy . . . 340 28.4.1 Patient Demographics . . . 340 28.4.2 Hospital Volume

and Surgeon Experience . . . 341 28.4.3 Surgeon Training and Specialty . . . 342 28.4.4 New Technologies . . . 343

28.5 Outcomes from Parathyroidectomy . . . 344 28.5.1 Clinical Outcomes . . . 344

28.5.2 Economic Outcomes . . . 345 28.5.3 Patient Utilities . . . 345

28.6 Policy Implications for Parathyroid Surgery . . . 346

References . . . 347

Cope and others in New York and Boston; ultimately, a mediastinal parathyroid adenoma was removed [7,8]. Unfortunately, Gahne and Martell succumbed to their disease, and it was not until Issac Olch removed a large parathyroid adenoma from Elva Dawkins in St Louis in 1928 that the first successful parathyroidec- tomy was documented in the USA. However, this was not without postoperative complications; Dawkins suffered from severe hypocalcemia requiring para- thyroid extract and calcium supplementation [9,10].

Thus, early outcomes from parathyroidectomy were dismal, in part because of the relative lack of experi- ence of the surgeons performing the operations (see also Chapter 1 “History of Thyroid and Parathyroid Surgery”).

28.3 Obstacles to Performing Parathyroidectomy Outcomes Research

The first efforts to systematically study outcomes in surgery date from 1979, when Luft and colleagues demonstrated lower mortality rates at high-volume centers compared with low-volume centers in high- risk procedures such as coronary artery bypass graft surgery (CABG), vascular surgery, and transurethral prostatectomy. These studies relentlessly demon- strated a statistically significant association between hospital volume and procedure-specific mortality rates. Patient-mix-adjusted mortality rates were lower by 25% to 41% at hospitals performing more than 200 procedures per year [11]. This set the groundwork for outcomes research for a litany of other high-risk, mor- bid procedures and mortal diseases, where in-hospital and 30-day mortality were meaningful endpoints.

Lower-risk surgical procedures, such as parathy- roidectomy, have received less attention among health services researchers, in large part because mortality is not a meaningful outcome. Large administrative databases conventionally used for surgical outcomes research are most reliable for definitive outcomes, such as death, which hospital coders easily capture.

In contrast, outcomes from parathyroidectomy are often difficult to establish and are measurable only in a delayed fashion after discharge. Also, many claims databases capture inpatient data only, and thus the as- sessment of complications potentially occurring after discharge may be inaccurate. For example, cure after parathyroidectomy is defined as a normal serum cal- cium level six months after surgery. Complications from surgery such as laryngeal nerve injury and per- manent hypoparathyroidism also can be hard to cap-

ture. Neurapraxia is transient, while other laryngeal nerve injuries can be permanent. Indirect laryngos- copy is often delayed several months to distinguish between the two and allow temporary changes to re- solve. MIP is performed in the ambulatory setting, so symptoms and signs of hypoparathyroidism usually are not apparent until well-after discharge, at which point patients typically are managed in the outpatient setting with calcium and/or vitamin D supplementa- tion. Thus, they are not captured by many databases.

To date, there has not been a prospective, con- trolled, multi-institutional trial comparing the clinical and economic outcomes for newer surgical techniques, such as MIP or radio-guided parathy- roidectomy, with traditional parathyroidectomy or medical strategies in the management of asymptom- atic and minimally symptomatic primary HPTH.

28.4 Predictors of Outcomes for Parathyroidectomy

28.4.1 Patient Demographics

There is a substantial body of evidence showing that patients with primary HPTH who are younger than 50 years are at particular risk for going on to develop complications from their disease, such as reduced bone mineral density. As a result, the Consensus De- velopment Conference on Asymptomatic Primary HPTH in 1990 and the Workshop on Asymptomatic Primary HPTH in 2002 held at the National Institutes of Health (NIH) both recommended that all of these patients should be referred for surgical management [12,13]. However, the implication should not be that patients older than 50 years must be treated non-op- eratively. Recent data suggested that parathyroidec- tomy is safe in elderly patients and is associated with high cure rates, low morbidity, short lengths of stay (LOS), and high patient satisfaction.

In a prospective study of 211 patients who under- went parathyroidectomy by one surgeon, Chen et al.

compared outcome data of elderly patients (>70 years of age, n = 36) to younger patients (<70 years of age, n = 148) with hyperparathyroidism. Preoperative symptoms of mental impairment, bone disease, and fa- tigue were more common in elderly patients (P<0.05), and nephrolithiasis was more frequent in younger patients (P<0.03). Despite the higher preoperative PTH levels among the elderly cohort compared to the younger cohort (301.9±63.3 versus 169.2±14.3 pg/

ml, respectively; P<0.05), the rates of cure, morbid-

ity, and mortality associated with parathyroidectomy

were comparable (94.4%, 5.5%, and 0% for the elderly versus 98%, 1.4%, and 0% for younger patients). The more advanced disease seen in elderly patients sug- gests that they are referred for surgery with a higher threshold than younger patients. However, the study results suggest that the benefits of parathyroidectomy outweigh the risks and argue for a lower threshold for referral [14].

28.4.2 Hospital Volume

and Surgeon Experience

In 2002, Birkmeyer et al. firmly established the as- sociation between hospital volume and outcomes for high-risk procedures by examining the experience of 2.5 million patients using data from the Nationwide Inpatient Sample (NIS) and the Medicare claims data- base [15]. Over a six-year period, operative mortality was shown to decrease as hospital volume increased for 14 types of procedures; absolute differences in ad- justed mortality rates between very low and very high volume hospitals ranged from over 12% for pancre- atic resection to 0.2% for carotid endarterectomy.

However, there is no evidence that such a relation- ship exists for relatively low risk parathyroidectomy.

There is evidence that outcomes from parathyroidec- tomy vary widely between individual surgeons and are associated with surgeon experience [16]. Whereas outcomes in high-risk surgery are dependent on hospital volume, outcomes from parathyroidectomy appear to be dependent on individual surgeon skill.

Sosa et al. used a survey of North American members of the American Association of Endocrine Surgeons (AAES) to assess the relationship between physician characteristics, practice patterns, and outcomes [16].

There was a 77% survey response rate. Compared to high-volume surgeons (>50 cases/year), low-volume surgeons (1–15 cases/year) reported significantly higher complication rates after primary operation (1.0% versus 1.9%, respectively; P<0.01), higher reop- eration rates (1.55 versus 3.8%; P<0.001), and higher mortality rates (0.04% versus 1.0%; P<0.05) (Ta- ble 28.1). The associations between current surgical volume and outcomes were present even when adjust- ment was made for the number of years surgeons had been in practice. According to the survey, high-vol- ume surgeons also tended to have lower thresholds to operate with respect to abnormalities in preoperative creatinine clearance, bone densitometry changes, and levels of intact PTH and urinary calcium compared with lower-volume surgeons (Fig. 28.1). Even among a group of high-volume endocrine surgeons, practice patterns and thresholds for surgery varied signifi- cantly. The results of this survey almost certainly un- derestimate the practice pattern variation that exists in the broader surgical community, where surgeons generally have less endocrine surgery expertise and less experience performing parathyroidectomies.

It should be noted that a limitation of this study was that survey results were based on self-report, leading to the potential for respondent reporting bias. Ulti- mately, it is impossible from a cross-sectional study such as this to prove causation, as temporal effects

Table 28.1 Self-reported outcomes of parathyroidectomy and their association with surgeon annual caseload. (NS Not significant;

P>0.05)

Outcome Primary operation Reoperation

Percent with outcome (mean ± SEM)

Outcome-caseload P value

Percent with outcome (mean ± SEM)

Outcome-caseload P value

Eucalcemia 6 months postoperative

95.2±1.0 <0.01 82.7±2.5 NS

Hypocalcemia 6 months postoperative

2.7±1.1 NS 6.3±1.4 NS

Hypercalcemia 6 months postoperative

3.4±1.0 <0.05 8.4±1.2 NS

Minor complications 2.9±0.6 NS 3.3±0.8 NS

Major complications 1.0±0.1 <0.01 2.0±0.2 <0.01

In-hospital death 0.1±0.03 NS 0.1±0.03 NS

a

P value of linear regression model with specified outcome as dependent variable and surgeon’s parathyroidectomy caseload as the

independent variable

cannot be captured. This is still the rudimentary state of the science of outcomes analysis from parathyroid- ectomy. Nevertheless, evidence supporting a volume–

outcome relationship was deemed sufficient to lead the 2002 NIH Workshop on Asymptomatic Primary HPTH to emphasize that “parathyroidectomy should be performed only by experienced, expert parathyroid surgeons” [12]. The late Dr John Doppman cleverly described this when he said that the best preoperative localization test for hyperparathyroidism is to localize an experienced parathyroid surgeon [17].

Currently, a thorough understanding of the na- tional patterns of endocrine surgery is lacking.

Knowledge of clinical practice patterns would allow for a more accurate study of outcomes in the context of surgeon volume and would facilitate the planning of future needs for parathyroid surgery specialists.

It is known that the great majority of operations for

endocrine surgery are performed by surgeons whose clinical practice is not focused heavily in endocrine surgery [18]. In addition, the number of surgeons whose practice is focused in endocrine surgery com- prises a very small percentage of the total number of surgeons who are performing common operations for endocrine problems.

Based on a 2003 review by Saunders et al. using the International Classification of Disease, 9th revision (ICD-9) and the NIS administrative database, only 1.1% of parathyroidectomies performed in the USA between 1998 and 2000 were performed by surgeons with practices that are focused in endocrine surgery (>75% of practice performing parathyroidectomy, thyroidectomy, and adrenalectomy). The majority of parathyroidectomies were performed by general surgeons [18]. There were 14,232 patients who were identified as having undergone parathyroidectomy by 6,100 unique surgeons during the study period.

Surgeons whose practice was focused on endocrine procedures performed 769 parathyroidectomies (5%

of total), while general surgeons (<25% of practice dedicated to endocrine surgery) performed 11,071 parathyroidectomies (78% of total). The 242 highest volume parathyroid surgeons (27–182 parathyroidec- tomies per year) represented only 4% of the surgeons captured in the database, while the 2,995 surgeons who performed only 1–3 parathyroidectomies per year accounted for 49% of the surgeons in the data- base (Fig. 28.2).

28.4.3 Surgeon Training and Specialty

The development of new technologies such as MIP, the rapid intraoperative PTH assay, and radio-guided parathyroidectomy has made parathyroid surgery more complex. Despite this, the Accreditation Coun- cil for Graduate Medical Education (ACGME) sets no minimum number of parathyroid procedures required for completion of a general surgery residency. More- over, the number of parathyroidectomies performed by graduating chief residents varies widely across the country. Recent evidence regarding the operative ex- perience of general surgery residents in parathyroid disease showed the average number of procedures to be between 4.1 and 5.1, with a standard deviation of 3.44. The maximum cumulative number of parathy- roid operations ranged from 25 to 60, and the most common annual caseload was only 2 [19]. With the implementation of the 80-hour resident work week in the USA, it is conceivable that these numbers might decrease even further, raising the question of whether

Fig. 28.1 Relationship between surgeon annual case load and

low, medium, and high thresholds for surgery using intact

parathyroid hormone (iPTH; a), bone densitometry T-score

(b), creatinine clearance (c), and 24-hour urinary calcium (d)

the majority of chief residents in general surgery are competent to perform parathyroidectomy after grad- uation [20].

Although outcomes from parathyroid surgery ap- pear to be associated with experience based on self- reported data, there also are data which show that when residents perform parathyroidectomy under the supervision of an experienced parathyroid surgeon, clinical outcomes are excellent [21]. Willeke et al. re- viewed the outcomes of 230 patients who underwent bilateral neck exploration for primary HPTH at the University of Heidelberg over an eight-year study pe- riod and demonstrated that inexperienced surgeons had comparable clinical outcomes to experienced consultants as long as they were under the supervi- sion of an experienced surgeon (defined as having done >40 parathyroidectomies for primary HPTH).

Complications were observed in 13.5% of patients, with no statistical difference between the experienced and the inexperienced supervised surgeons. There were 11 complications in 75 operations for the expe- rienced surgeons, versus 25 complications in 155 op- erations for the supervised trainees (P = 0.85; differ- ence 2.2%; 95% CI 7% to 11.4%). However, there were

some important differences between the two groups.

Parathyroidectomy was significantly shorter when the operating surgeon was more experienced (median operation time, 85 versus 100 minutes; P<0.001), and experienced surgeons more frequently were able to identify all parathyroid glands (at least four) during exploration than surgeons in training (56 of 75 for a 74.7% success rate, as compared to 80 of 155 for a 51.6% success rate; P<0.001).

28.4.4 New Technologies

In the current era of cost containment, efforts to re- duce LOS and associated costs have resulted in the development of a number of new surgical techniques, including MIP and radio-guided parathyroidectomy.

MIP, described in 1994 by George Irvin and col- leagues at the University of Miami, has dramatically changed the way parathyroidectomy is performed [22]. Unilateral neck exploration is conducted with the rapid PTH assay used as an intraoperative adjunct when patients have had successful preoperative local- ization. In the first report of the procedure, 16 of 18 study patients had sestamibi results that allowed for successful unilateral exploration with intraoperative confirmation of cure via the rapid PTH assay. Patients in the series who underwent MIP had an operative time that was shortened by an average of 54 minutes (90 versus 36 minutes).

Minimally invasive parathyroidectomy is becom- ing the standard of care among endocrine surgeons worldwide [23]. Sacket et al. surveyed members of the International Association of Endocrine Surgeons in 2002 and found that 59% of surgeons who are mem- bers of the Association perform MIP, and in these surgeons’ practices, nearly half of patients with pri- mary HPTH are candidates for the procedure (44%).

There are now data showing that patients undergoing a unilateral procedure facilitated by preoperative lo- calization have a lower incidence of biochemical and severe symptomatic hypocalcemia in the early post- operative period compared with patients undergoing traditional bilateral exploration [24]. In a prospective study of 91 patients with primary HPTH who were randomized to unilateral or bilateral neck exploration at Lund University Hospital, Bergenfelz et al. showed that patients in the bilateral neck exploration group consumed more oral calcium (4.20 versus 1.92 g;

P<0.05), had lower serum calcium values on postoper- ative days 1–4 (2.15 versus 2.26 mmol/l; P<0.05), and had a higher incidence of early severe symptomatic hypocalcemia (11% versus 0%; P<0.05) compared to

Fig. 28.2 Summary of the distribution of surgeons performing

parathyroidectomy and parathyroidectomy cases by four sur-

geon volume groups

patients in the unilateral group. In addition, for pa- tients undergoing surgery for a solitary parathyroid adenoma, unilateral neck exploration was associated with a shorter operative time (62 versus 84 minutes;

P<0.01). The cost of the two procedures, however, did not differ significantly.

Using a computer-generated mathematical model and decision tree analysis, Fahy et al. showed that limited parathyroid surgery facilitated by localization technologies (e.g., rapid PTH assay, preoperative ses- tamibi imaging, and intraoperative radio-guidance) has better clinical and economic outcomes than stan- dard parathyroidectomy with bilateral neck explora- tion [25]. Specifically, the use of these new technolo- gies reduced total charges, risk of persistent primary HPTH, and risk of recurrent laryngeal nerve injury in the decision analysis. Input variables were based on probabilities and costs culled from the literature.

The best outcomes (i.e., greatest cost savings and low- est risk of nerve injury) from limited parathyroid- ectomy were achieved when sestamibi scanning was performed preoperatively and the gamma probe was used intraoperatively. The lowest incidence of per- sistent primary HPTH was seen when preoperative sestamibi scanning was combined with intraoperative use of the rapid PTH assay.

28.5 Outcomes

from Parathyroidectomy

28.5.1 Clinical Outcomes

While complications from untreated primary HPTH sometimes led to death in the early 1900s, such out- comes are rare today. Instead, rare complications in- clude recurrent laryngeal nerve injury, hemorrhage, wound complications, and postoperative hypocal- cemia. Hypocalcemia is generally not severe and is managed successfully in the outpatient setting with calcium and vitamin D supplements. At the Cleve- land Clinic, Tarazi et al. examined 70 consecutive pa- tients who underwent parathyroidectomy for primary HPTH [26]. Only 2 developed symptoms of mild tet- any after discharge, which responded to an increased dose of oral calcium.

Experienced parathyroid surgeons today achieve cure rates of up to 98% with both minimally invasive and conventional techniques [27]. In the largest pub- lished clinical series to date of parathyroid explora- tions compiled by a single surgeon for patients with primary HPTH (n=656), Udelsman demonstrated equivalent cure rates for patients who underwent tra-

ditional parathyroidectomy with bilateral neck explo- ration and MIP (97% versus 99%, respectively). Four hundred and one patients (61%) underwent standard bilateral cervical exploration under general anesthe- sia (13 of these had multiple endocrine neoplasia I or IIA), and 255 patients (39%) underwent MIP. There were no perioperative deaths in the series, and com- plication rates were 3.0% in the conventional group and 1.2% in the MIP group. Patients who underwent MIP were compared to historical controls, so com- parisons were imperfect and tests of statistical signifi- cance were not performed.

There is still not perfect consensus among endo- crinologists and endocrine surgeons about whether patients with minimally symptomatic and asymp- tomatic primary HPTH should undergo surveillance, non-operative (medical) therapy, or early surgery. The value of parathyroidectomy in asymptomatic patients with mild to moderate hypercalcemia has been de- bated because the natural history of primary HPTH is still not well understood, and rapid increases in the serum calcium level and/or progression of symptoms or complications is uncommon in patients with bor- derline hypercalcemia.

The neuromuscular symptoms of primary HPTH vary from series to series in their presentation and response to parathyroidectomy. However, (proximal) muscle weakness detected by examination (i.e., iso- kinetic strength of knee extension and flexion) ap- pears to have a higher prevalence and to have a good response to parathyroidectomy, as does respiratory muscle capacity [28]. Significant increases in bone mineral density occur in the lumbar spine and hip following successful parathyroidectomy, and these improvements are maintained. The changes in bone remodeling and bone density are apparent within six months of parathyroidectomy [29]. Improvements in gastric ulcer incidence and fracture risk after para- thyroidectomy were demonstrated by Vestergaard and Mosekidle, who compared patients with primary HPTH managed with parathyroidectomy versus non- operative strategies [30]. In this Danish nationwide cohort study of 3,213 patients with primary HPTH, 1,934 (60%) underwent surgery and 1,279 (40%) were managed medically. Patients treated with para- thyroidectomy subsequently had a reduced risk of fracture (hazards ratio 0.69; 95% CI 0.56–0.84) and gastric ulcers (0.59; 95% CI 0.41–0.84) compared to similar patients without surgery.

No effect of successful surgery has been noted on

either blood pressure or renal impairment [31]. Both

urinary calcium excretion and the incidence of renal

stones are reduced by successful parathyroidectomy

[32]. There are still no data proving that surgical cure increases life expectancy. A Swedish case-control study showed that 23 patients who underwent para- thyroidectomy had a hazard ratio for death of 0.89, as compared to matched controls in the normal popu- lation. While this difference may be of clinical rele- vance, the study was clearly underpowered to reach statistical significance [33].

Psychiatric symptoms such as mental dullness, confusion, and loss of consciousness have been shown to improve within days after parathyroidectomy, al- though to date it has not been possible to predict which patients are most likely to benefit from surgery [34]. There have been reports of neurocognitive im- pairments associated with this disease, but well-per- formed, controlled clinical trials examining the ef- fect of parathyroidectomy have not been published to date. However, our group at Yale University has preliminary data suggesting that parathyroidectomy significantly improves these impairments [35]. In this ongoing multidisciplinary, prospective study, we compare patients with primary HPTH with benign, euthyroid disease controls. Neurocognitive function is examined preoperatively and postoperatively using several well-validated and novel tests of memory and concentration, such as the Beck Depression Inventory, the Spielberger State/Trait Inventory, the Brief Symp- tom Inventory, the Rey Auditory Verbal Learning Test, and the PGRD Maze Learning Test. Compared to preoperative performance, patients with primary HPTH improve in their learning performance after surgery and appear to function at a level equivalent to the patients with thyroid disease after thyroidectomy.

Preoperatively, patients with primary HPTH show greater delays in their spatial learning than thyroid controls, as evidenced by fewer correct moves per second across five learning trials and in a delayed re- sponse trial. These results suggest that primary HPTH may be associated with a spatial learning deficit and processing that improves with parathyroidectomy.

Longer term follow-up is necessary to reach final con- clusions, but neurocognitive symptoms might be con- sidered in the future as criteria for parathyroidectomy in the treatment of primary HPTH.

28.5.2 Economic Outcomes

Variation in practice patterns has important implica- tions for healthcare costs and quality of care. This is- sue was first addressed in 1980, when a break-even analysis suggested that the cost of early operation for primary HPTH would be exceeded by the cost of

5.5 years of medical surveillance [36]. The economic impact of variation in practice patterns is presumably even greater today, given that the costs of American healthcare have increased in the last two decades. A 1998 national survey of endocrine surgeons by Sosa et al. showed that health expenditures on primary HPTH could exceed $70 million in the USA annu- ally, depending on whether management strategies involving low or high use of resources were employed [2]. Survey respondents (n=109) performed an aver- age of 33 parathyroidectomies annually. Seventy-five percent of respondents reported using localization techniques before initial exploration. Their choice of localization studies varied significantly; in order of preference, these studies were sestamibi (43%), ultra- sonography (28%), and sestamibi with single-photon emission computed tomography (SPECT) (26%).

There was significant variation among endocrine sur- geons in their patients’ average total hospital costs.

Even postoperative surveillance of patients with pri- mary HPTH with laboratory tests and clinic visits was characterized by variation in practice patterns. For example, the number of postoperative office visits to the surgeon varied from one to nine, with median of two visits, whereas the number of iPTH tests (each of which cost $62 in 1998) varied from zero to 11. Over- all, cost per patient undergoing a parathyroidectomy, assuming average use of resources, was about $7,500, but this cost could be $1,000 lower or higher based on assumptions of alternative use of resources, and 70%

of the difference would stem from variation in in-hos- pital costs.

Given that the vast majority of parathyroidecto- mies performed in the USA are performed by non- endocrine surgeons and would not be reflected in this survey, variation in practice patterns might well be even higher. The recent introduction of MIP and other new technologies in parathyroid surgery also makes such studies out of date in 2006. According to Udelsman, the economic impact of MIP on average total hospital charges is significant [27]. In his clinical series, the mean LOS for MIP was 0.24 days, which compared favorably with the average LOS of 1.64 days for patients who underwent standard exploration.

The mean savings per MIP was calculated as $2,693, which represented 49% of the total hospital charge.

28.5.3 Patient Utilities

As long as there continues to be lack of consensus

among clinicians about how to optimize outcomes

for patients with primary HPTH, patient preferences

should be allowed at least in part to mold clinical de- cision making, and studies to measure preferences and quality of life in the field of primary HPTH are needed. Quiros et al. in 2003 asked 61 patients who underwent parathyroidectomy for hyperparathyroid- ism over a 16-month study period to complete a 53- question survey based on the Health Outcomes In- stitute Health Status Questionnaire 2.0 at three time points: before surgery, and 1 month and 3–24 months after surgery [37]. The survey included questions on overall health, daily activities, mood, and medical con- ditions. At both postoperative evaluations, patients’

perception of general health, muscle strength, energy level, and mood significantly improved (P<0.05).

28.6 Policy Implications for Parathyroid Surgery

Given that primary HPTH is more prevalent among the elderly, one could speculate that incidence and prevalence of the disease might increase in the future as the number of Americans over age 65 is projected to grow [36,38]. “Baby boomers” (those born between 1946 and 1964) will begin turning 65 in 2011, when they will number 40.4 million (13% of the popula- tion); by 2030, the number of elderly over age 65 is projected to increase to 70.3 million (20% of the population) (http://www.census.gov/Press-Release/

www/2000/cb00-05.html). Clearly, primary HPTH will continue to be a pressing public health concern, and outcomes research examining the surgical man- agement of the disease must keep pace.

Surgical outcomes research has led policy makers and payers to practice “evidence-based hospital refer- ral.” The most visible of these efforts has been directed by the non-profit Leapfrog Group, which began its initiative in November 2000 in response to a 1999 In- stitute of Medicine (IOM) report which showed that preventable medical errors in hospitals account for approximately 98,000 deaths per year (http://www.

leapfroggroup.org). Leapfrog is an employer-led en- deavor whereby a coalition of more than 150 public and private healthcare purchasers representing over 40 million people encourages improvements in the quality of patient outcomes by directing patient re- ferrals to hospitals which meet minimum-volume standards. Leapfrog requires that hospitals maintain certain procedure-specific volume caseloads per year for high-risk surgical procedures such as CABG (500 procedures per year), coronary angioplasty (400 per year), carotid endarterectomy (100 per year), repair of abdominal aortic aneurysm (30 per year), and esoph- agectomy for cancer (6 per year). There is compelling

evidence that higher volumes is correlated with better outcomes for these procedures [15].

Leapfrog has not included parathyroidectomy among its list of procedures, perhaps in part because there is a paucity of outcomes research in the field.

However, with time this may change, as outcomes data for endocrine surgery are assembled to inform debate. Existing databases do not lend themselves to this purpose, since parathyroidectomy is increas- ingly performed in the ambulatory setting. Therefore, multi-institutional prospective primary data collec- tion will be essential.

The creation of clinical practice guidelines intended to standardize the medical and surgical management of primary HPTH could help in reducing variation in practice patterns. In light of the persistent controversy surrounding the optimal management of asymptom- atic primary HPTH, the NIH established a consensus panel in 1990 and a Workshop in 2002 to formulate and reformulate recommendations to standardize pa- tient care. However, national surveys of endocrinolo- gists and endocrine surgeons showed that the man- agement of primary HPTH is highly variable among both groups and compliance is poor with many of the practice guidelines outlined in the NIH consen- sus statements [16,39]. Among surgeons, thresholds were higher than those recommended by the NIH for younger patients and lower than those recommended for older patients. For example, although both NIH consensus statements recommended surgery for all patients with primary HPTH below 50 years of age, endocrine surgeons in the survey reported using additional laboratory and clinical criteria to decide whether to operate on younger patients [16]. High- volume endocrinologists, who are likely to be most experienced in managing primary HPTH, were more aware of the NIH guidelines than low-volume physi- cians in the 1998 national survey of 374 endocrinolo- gists [39].

It is possible that many surgeons are not aware of the NIH guidelines. Alternatively, they could be aware of the guidelines but intentionally do not follow them;

for example, surgeons might believe that there is not

enough evidence (e.g., prospective randomized tri-

als) supporting the consensus statements. This raises

the question of whether the guidelines are obsolete

and require yet another reformulation, as third-party

payers such as the Leapfrog initiative might use pub-

lished recommendations to guide their reimburse-

ment strategies. Clearly, guidelines for the (surgical)

management of primary HPTH must be more widely

disseminated and strongly recommended if practice

patterns are to be influenced and clinical outcomes

improved.

Clinical pathways are one method healthcare pro- viders and hospital administrators use to standardize care [40]. When a clinical pathway for parathyroidec- tomy was implemented from July 1998 through July 1999 at the University of Virginia Health System, av- erage LOS decreased from 2.4 to 1.5 days (P = 0.26).

This, in turn, had economic implications, with per case average cost decreasing from $5,071 to $4,291 (P = 0.50). Although these differences were not sta- tistically significant due to the relatively small sample size, they can be considered as clinically relevant.

In light of evidence linking surgeon experience with clinical and economic outcomes for parathy- roidectomy, there has been a trend toward the cre- ation of centers of excellence in endocrine surgery and parathyroidectomy. There are a growing number of North American fellowship programs in endocrine surgery; however, none are yet certified. Such high- volume parathyroidectomy centers could facilitate the training of young high-volume surgeons in new techniques such as MIP, as well as the creation of evidence-based referral initiatives in parathyroid sur- gery. However, it also has worrisome implications for access to quality care, especially in rural parts of the country where patients with primary HPTH might be unable to easily access high-volume parathyroid sur- geons because of geographic or economic barriers. It will be important for internists, endocrinologists, sur- geons, payers, and policymakers to work together in a collaborative fashion. Only then will it be possible to prospectively assemble the primary, up-to-date outcomes data needed to optimize practice patterns and allow for a reasonable balance between cost-ef- fectiveness, quality of care, and access to high-volume providers of parathyroidectomy.

References

1. Wermers RA, Khosla S, et al (1997) The rise and fall of primary hyperparathyroidism: a population-based study in Rochester, Minnesota, 1965–1992. Ann Intern Med 126:433–440

2. Sosa JA, Powe NR, et al (1998) Cost implications of dif- ferent surgical management strategies for primary hy- perparathyroidism. Surgery 124:1028–1035; discussion 1035–1036

3. Melton LJ 3rd (2002) The epidemiology of primary hy- perparathyroidism in North America. J Bone Miner Res 17(suppl 2):N12–N17

4. Owen R (1862) On the anatomy of the Indian rhinoceros (Rh. Unicornis, L). Trans Zool Soc Lond 4:31–58

5. Carney JA (1996) The glandulae parathyroideae of Ivar Sandström. Contributions from two continents. Am J Surg Pathol 20:1123–1144

6. Organ CH Jr (2000) The history of parathyroid surgery, 1850–1996: the Excelsior Surgical Society 1998 Edward D.

Churchill Lecture. J Am Coll Surg 191:284–299

7. Bauer FA, Aub JC (1930) A case of osteitis fibrosa cystica (osteomalacia?) with evidence of hyperactivity of the para- thyroid bodies: a metabolic study. J Clin Invest 8:229–248 8. Mandl F (1926) Attempt to treat generalized fibrous oste- itis by extirpation of parathyroid tumor. Zentralbl F Chir 53:260–264

9. Barr D, Bulger H, Dixon H (1929) Hyperparathyroidism.

JAMA 92:951–952

10. Guy C (1929) Tumors of the parathyroid glands. Surg Gy- necol Obstet 48:557–565

11. Luft HS, Bunker JP, Enthoven AC (1979) Should opera- tions be regionalized? The empirical relation between sur- gical volume and mortality. N Engl J Med 301:1364–1369 12. Bilezikian JP, Potts JT Jr, et al (2002) Summary statement

from a workshop on asymptomatic primary hyperpara- thyroidism: a perspective for the 21st century. J Clin En- docrinol Metab 87:5353–5361

13. National Institutes of Health (1990) Diagnosis and man- agement of asymptomatic primary hyperparathyroidism.

National Institutes of Health Consensus Development Conference, 29–31 October 1990. Consens Statement 8:1–18

14. Chen H, Parkerson S, Udelsman R (1998) Parathyroid- ectomy in the elderly: do the benefits outweigh the risks?

World J Surg 22:531–535; discussion 535–536

15. Birkmeyer JD, Siewers AE, et al (2002) Hospital volume and surgical mortality in the United States. N Engl J Med 346:1128–1137

16. Sosa JA, Powe NR, et al (1998) Profile of a clinical prac- tice: thresholds for surgery and surgical outcomes for patients with primary hyperparathyroidism. A national survey of endocrine surgeons. J Clin Endocrinol Metab 83:2658–2665

17. Doppman JL, Miller DL (1991) Localization of parathy- roid tumors in patients with asymptomatic hyperpara- thyroidism and no previous surgery. J Bone Miner Res 6(suppl 2):S153–S158; discussion S159

18. Saunders BD, Wainess RM, et al (2003) Who performs en- docrine operations in the United States? Surgery 134:924–

931; discussion 931

19. Harness JK, Organ CH Jr, Thompson NW (1995) Opera- tive experience of U.S. general surgery residents in thyroid and parathyroid disease. Surgery 118:1063–1069; discus- sion 1069–1070

20. Jarman BT, Miller MR, et al (2004) The 80-hour work week: will we have less-experienced graduating surgeons?

Curr Surg 61:612–615

21. Willeke F, Willeke M, et al (1998) Effect of surgeon ex- pertise on the outcome in primary hyperparathyroidism.

Arch Surg 133:1066–1070; discussion 1071

22. Irvin GL 3rd, Prudhomme DL, et al (1994) A new ap- proach to parathyroidectomy. Ann Surg 219:574–579; dis- cussion 579–581

23. Sackett WR, Barraclough B, et al (2002) Worldwide trends in the surgical treatment of primary hyperparathyroidism in the era of minimally invasive parathyroidectomy. Arch Surg 137:1055–1059

24. Bergenfelz A, Lindblom P, et al (2002) Unilateral versus bilateral neck exploration for primary hyperparathyroid- ism: a prospective randomized controlled trial. Ann Surg 236:543–551

25. Fahy BN, Bold RJ, et al (2002) Modern parathyroid sur- gery: a cost-benefit analysis of localizing strategies. Arch Surg 137:917–922; discussion 922–923

26. Tarazi R, Esselstyn CB Jr, Coccia MR (1984) Parathyroid- ectomy for primary hyperparathyroidism: early discharge.

Surgery 96:1158–1162

27. Udelsman R (2002) Six hundred fifty-six consecutive ex- plorations for primary hyperparathyroidism. Ann Surg 235:665–670; discussion 670–672

28. Joborn C, Joborn H, et al (1988) Maximal isokinetic mus- cle strength in patients with primary hyperparathyroidism before and after parathyroid surgery. Br J Surg 75:77–80 29. Christiansen P, Steiniche T, et al (1999) Primary hyper-

parathyroidism: effect of parathyroidectomy on regional bone mineral density in Danish patients: a three-year fol- low-up study. Bone 25:589–595

30. Vestergaard P, Mosekilde L (2003) Cohort study on effects of parathyroid surgery on multiple outcomes in primary hyperparathyroidism. BMJ 327:530–534

31. Salahudeen AK, Thomas TH, et al (1989) Hypertension and renal dysfunction in primary hyperparathyroidism:

effect of parathyroidectomy. Clin Sci (Colch) 76:289–296

32. Silverberg SJ, Shane E, et al (1999) A 10-year prospective study of primary hyperparathyroidism with or without parathyroid surgery. N Engl J Med 341:1249–1255 33. Lundgren E, Lind L, et al (2001) Increased cardiovascu-

lar mortality and normalized serum calcium in patients with mild hypercalcemia followed up for 25 years. Surgery 130:978–985

34. Joborn C, Hetta J, et al (1989) Self-rated psychiatric symp- toms in patients operated on because of primary hyper- parathyroidism and in patients with long-standing mild hypercalcemia. Surgery 105:72–78

35. Roman S, Sosa JA, et al (2005) Parathyroidectomy im- proves neurocognitive deficits in patients with primary hyperparathyroidism. Surgery (in press)

36. Heath H 3rd, Hodgson SF, Kennedy MA (1980) Primary hyperparathyroidism. Incidence, morbidity, and po- tential economic impact in a community. N Engl J Med 302:189–193

37. Quiros RM, Alef MJ, et al (2003) Health-related quality of life in hyperparathyroidism measurably improves af- ter parathyroidectomy. Surgery 134:675–681; discussion 681–683

38. Tibblin S, Palsson N, Rydberg J (1983) Hyperparathyroid- ism in the elderly. Ann Surg 197:135–138

39. Mahadevia PJ, Sosa JA, et al (2003) Clinical management of primary hyperparathyroidism and thresholds for surgi- cal referral: a national study examining concordance be- tween practice patterns and consensus panel recommen- dations. Endocr Pract 9:494–503

40. Markey DW, McGowan J, Hanks JB (2000) The effect of

clinical pathway implementation on total hospital costs

for thyroidectomy and parathyroidectomy patients. Am

Surg 66:533–538; discussion 538–539