success of cervical exploration for patients with asymptomatic primary hyperparathyroidism

6
Success of Cervical Exploration for Patients with Asymptomatic Primary Hyperparathyroidism Sean D. Coston, MD, Jeffrey J. Pelton, MD, San Antonio, Texas BACKGROUND: This study examined the success and safety of cervical exploration in patients with asymptomatic primary hyperparathyroidism com- pared with those with symptomatic disease. METHODS: Records of patients undergoing cervi- cal exploration for primary hyperparathyroidism from June 1990 to October 1996 were reviewed. Patients were divided into three groups: (1) asymptomatic, (2) symptomatic, and (3) afflicted (those with associated complications). Informa- tion collected consisted of preoperative and postoperative symptoms, serum calcium and parathyroid hormone levels (PTH), and descrip- tions of pathologic and operative findings. RESULTS: Sixty-one patients were identified. Nineteen (31%) had no symptoms, 21 (34%) had subjective symptoms, and 21 had associated conditions, as described. Average preoperative and postoperative calcium levels were 11.5 mg% and 8.5 mg%, respectively. Average PTH levels also fell from 142 pg/mL to 49 pg/mL after sur- gery. Preoperative and postoperative calcium and PTH levels for the three groups showed no significant differences. The success of surgery in identifying pathology ranged from 90.5% to 95%, and again showed no difference among the three groups. Long-term morbidity (>6 months) in all groups was 0%. CONCLUSIONS: Cervical exploration and parathy- roidectomy for asymptomatic primary hyper- parathryoidism is safe and has similar success rates in identifying pathology and correcting bio- chemical abnormalities compared with patients with symptomatic disease. Am J Surg. 1999; 177:69 –74. © 1999 by Excerpta Medica, Inc. T he approach to the patient with primary hyperpara- thyroidism (HPT) has undergone considerable evo- lution since the first parathyroidectomy approxi- mately 72 years ago. 1 Diagnosis initially had centered on clinical manifestations of osteitis fibrosa cystica and hyper- calcemia, the result of increased mobilization of calcium reserves by the effects of parathyroid hormone. However, the more recent use of automated serum chemistries and radioimmunoassays now make the diagnosis of primary HPT easier. More patients with asymptomatic primary HPT are therefore now diagnosed incidentally on serum chemistry panels obtained for other reasons. The surgical management of this latter group has become a controver- sial topic for the last 2 decades. Purnell et al 2,3 at the Mayo Clinic described the first prospective attempt to observe a large cohort of patients with asymptomatic primary HPT. In those studies, a group of 147 patients with asymptomatic primary HPT were followed up 10 years. After 5 years, 29 patients (20%) had required surgical intervention. 3 Of particular concern, pa- tients not requiring surgery progressively dropped out of the study. Eventually, 24 asymptomatic patients of the nonsur- gical group (16% of the total cohort) left the study. 4 The authors also concluded that no criteria were found to predict whether asymptomatic patients would eventually require surgery. The remainder of the patients in that series, however, never developed symptoms, and 12 pa- tients with initial mild hypercalcemia had a normal serum calcium at the conclusion of the study. 4 Other retrospec- tive series have shown that long-term survival, without progression of the disease, does occur in some patients. 5,6 Corlew et al 7 followed up a series of 47 patients with asymptomatic primary HPT for five years, and found four deaths (8.5%) directly attributable to complications re- lated to untreated primary HPT. In total, 16 of 47 patients (34%) either died or suffered a complication known to be associated with primary HPT by conclusion of the study. 7 Numerous others have noted benefits in decreased bone turnover, improved neuromuscular symptoms, and im- proved psychiatric symptomatology following parathyroid- ectomy. 8 –12 The National Institutes of Health (NIH) therefore con- vened a Consensus Development Conference Panel in October 1990 to address the issue of surgery in asymptom- atic patients with primary HPT. The panel concluded that surgical exploration remains the current and acceptable treatment for primary HPT, but noted that asymptomatic disease did not mandate a referral for surgery. 13 Indications for surgical treatment in asymptomatic patients were spec- ified (Table I). The panel did not, however, attempt to examine the natural history of primary HPT, and did not From the Department of General Surgery, Section of Surgical Oncology, Wilford Hall USAF Medical Center, San Antonio, Texas. The opinions expressed in this article are those of the authors alone, and are not the opinions of the United States Air Force or the Department of Defense. Requests for reprints should be addressed to Jeffrey J. Pelton, MD, Section of Surgical Oncology/MKSG, Wilford Hall USAF Medical Center, 2200 Bergquist Drive, Suite 1, Lackland AFB, Texas 78236. Manuscript submitted April 21, 1998 and accepted in revised form September 8, 1998. © 1999 by Excerpta Medica, Inc. 0002-9610/99/$–see front matter 69 All rights reserved. PII S0002-9610(98)00307-9

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Page 1: Success of cervical exploration for patients with asymptomatic primary hyperparathyroidism

Success of Cervical Exploration for Patientswith Asymptomatic Primary

HyperparathyroidismSean D. Coston, MD, Jeffrey J. Pelton, MD, San Antonio, Texas

BACKGROUND: This study examined the successand safety of cervical exploration in patients withasymptomatic primary hyperparathyroidism com-pared with those with symptomatic disease.

METHODS: Records of patients undergoing cervi-cal exploration for primary hyperparathyroidismfrom June 1990 to October 1996 were reviewed.Patients were divided into three groups: (1)asymptomatic, (2) symptomatic, and (3) afflicted(those with associated complications). Informa-tion collected consisted of preoperative andpostoperative symptoms, serum calcium andparathyroid hormone levels (PTH), and descrip-tions of pathologic and operative findings.

RESULTS: Sixty-one patients were identified.Nineteen (31%) had no symptoms, 21 (34%) hadsubjective symptoms, and 21 had associatedconditions, as described. Average preoperativeand postoperative calcium levels were 11.5 mg%and 8.5 mg%, respectively. Average PTH levelsalso fell from 142 pg/mL to 49 pg/mL after sur-gery. Preoperative and postoperative calciumand PTH levels for the three groups showed nosignificant differences. The success of surgery inidentifying pathology ranged from 90.5% to 95%,and again showed no difference among the threegroups. Long-term morbidity (>6 months) in allgroups was 0%.

CONCLUSIONS: Cervical exploration and parathy-roidectomy for asymptomatic primary hyper-parathryoidism is safe and has similar successrates in identifying pathology and correcting bio-chemical abnormalities compared with patientswith symptomatic disease. Am J Surg. 1999;177:69–74. © 1999 by Excerpta Medica, Inc.

The approach to the patient with primary hyperpara-thyroidism (HPT) has undergone considerable evo-lution since the first parathyroidectomy approxi-

mately 72 years ago.1 Diagnosis initially had centered onclinical manifestations of osteitis fibrosa cystica and hyper-calcemia, the result of increased mobilization of calciumreserves by the effects of parathyroid hormone. However,the more recent use of automated serum chemistries andradioimmunoassays now make the diagnosis of primaryHPT easier. More patients with asymptomatic primaryHPT are therefore now diagnosed incidentally on serumchemistry panels obtained for other reasons. The surgicalmanagement of this latter group has become a controver-sial topic for the last 2 decades.

Purnell et al2,3 at the Mayo Clinic described the firstprospective attempt to observe a large cohort of patientswith asymptomatic primary HPT. In those studies, a groupof 147 patients with asymptomatic primary HPT werefollowed up 10 years. After 5 years, 29 patients (20%) hadrequired surgical intervention.3 Of particular concern, pa-tients not requiring surgery progressively dropped out of thestudy. Eventually, 24 asymptomatic patients of the nonsur-gical group (16% of the total cohort) left the study.4 Theauthors also concluded that no criteria were found topredict whether asymptomatic patients would eventuallyrequire surgery. The remainder of the patients in thatseries, however, never developed symptoms, and 12 pa-tients with initial mild hypercalcemia had a normal serumcalcium at the conclusion of the study.4 Other retrospec-tive series have shown that long-term survival, withoutprogression of the disease, does occur in some patients.5,6

Corlew et al7followed up a series of 47 patients withasymptomatic primary HPT for five years, and found fourdeaths (8.5%) directly attributable to complications re-lated to untreated primary HPT. In total, 16 of 47 patients(34%) either died or suffered a complication known to beassociated with primary HPT by conclusion of the study.7

Numerous others have noted benefits in decreased boneturnover, improved neuromuscular symptoms, and im-proved psychiatric symptomatology following parathyroid-ectomy.8–12

The National Institutes of Health (NIH) therefore con-vened a Consensus Development Conference Panel inOctober 1990 to address the issue of surgery in asymptom-atic patients with primary HPT. The panel concluded thatsurgical exploration remains the current and acceptabletreatment for primary HPT, but noted that asymptomaticdisease did not mandate a referral for surgery.13 Indicationsfor surgical treatment in asymptomatic patients were spec-ified (Table I). The panel did not, however, attempt toexamine the natural history of primary HPT, and did not

From the Department of General Surgery, Section of SurgicalOncology, Wilford Hall USAF Medical Center, San Antonio,Texas. The opinions expressed in this article are those of theauthors alone, and are not the opinions of the United States AirForce or the Department of Defense.

Requests for reprints should be addressed to Jeffrey J. Pelton,MD, Section of Surgical Oncology/MKSG, Wilford Hall USAFMedical Center, 2200 Bergquist Drive, Suite 1, Lackland AFB,Texas 78236.

Manuscript submitted April 21, 1998 and accepted in revisedform September 8, 1998.

© 1999 by Excerpta Medica, Inc. 0002-9610/99/$–see front matter 69All rights reserved. PII S0002-9610(98)00307-9

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address whether surgery in the asymptomatic patient was assuccessful as in the symptomatic patient.

This study examined the success rates of cervical explo-ration in asymptomatic and symptomatic patients withprimary HPT. Success in this study was defined as correctidentification of parathyroid pathology and correction ofabnormal preoperative serum calcium and parathyroid hor-mone (PTH) levels. It was postulated that the parathyroidpathology in early, asymptomatic disease might be moredifficult to detect. Parathyroid adenomas, for example,might be smaller and more difficult to locate. Likewise, onemight expect the parathyroid glands in early hyperplasia tobe smaller and more difficult to distinguish from normalparathyroid glands. Therefore, an attempt to stratify theseverity of disease was made, by classifying patients withprimary HPT into three groups, ranging from asymptom-atic patients to those with objective complications of thedisease. The success of identifying parathyroid pathologyand correcting biochemical abnormalities was then corre-lated for each of the three groups.

METHODSThe records of all patients admitted for cervical explora-

tion with the diagnosis of hyperparathyroidism betweenJune 1990 and October 1996 were reviewed. Patients withthe diagnosis of secondary or tertiary disease were ex-cluded. The information collected from the charts con-sisted of preoperative and postoperative symptoms andbiochemical data, and descriptions of pathologic and in-traoperative findings. In each case, a comprehensive list ofsymptoms and afflictions known to be associated withprimary HPT was used to screen each record (Table II).The biochemical data obtained included preoperative andpostoperative PTH levels, and preoperative and postoper-ative serum calcium levels. Results of any localization stud-ies were also noted. Pathologic and operative findings werenoted from the final pathology report and operative report.

Patients were divided into three groups based on theircomposite of symptoms and associated illnesses. Group 1was the asymptomatic group: patients who were diagnosedby biochemical studies and had none of the complaints or

conditions listed in Table II. Group 2 consisted of symp-tomatic patients, who had any of the symptoms listed inTable II, but without associated physical complications ofthe disease. Group 3 was termed the afflicted group, andconsisted of patients who had physical manifestations ofthe disease, such as nephrolithiasis, bone fracture, pepticulcer disease , pancreatitis, and radiographically-provenosteopenia (Table II).

The extent of preoperative localization work-up was alsonoted for each group. Localizing studies employed in theentire patient series included ultrasound, magnetic reso-nance imaging (MRI), technetium Tc 99m-sestamibiscans, and selective venous sampling.

A data sheet was created allowing tabulation of all pre-operative and postoperative biochemical data, as describedabove. The data sheet also included a list of the symptomsand associated afflictions outlined in Table II. Each patientrecord was screened noting the presence or absence ofthese symptoms and afflictions. Biochemical data, symp-toms, afflictions, results of localizing studies, pathologicfindings, and operative findings were noted on the datasheet for each patient record.

Bilateral parathyroid exploration was performed in a sys-tematic manner in all patients undergoing initial cervicalexploration. Fifty-four of the 61 explorations (88%) wereperformed by two surgeons. Goals of exploration includedidentification of all four glands and classification of diseaseas adenomatous or hyperplastic. Excision of abnormal, en-larged glands was performed, once all four glands had beenexposed and examined. In cases of hyperplasia, subtotalparathyroidectomy (excision of three and one-half glands)was performed. Total parathyroidectomy with autotrans-plantation was not performed. In cases of solitary or bilat-eral adenomas, the diseased parathyroid tissue was removedand a single normal gland was biopsied. All other grosslynormal parathyroid tissue was left undisturbed.

Follow-up results at 1 month, 6 months, and 1 year aftersurgery was obtained in all patients. Each patient wasevaluated for short-term (,6 months) and long-term (.6months) morbidity. This evaluation consisted of notingvoice changes relating to recurrent laryngeal nerve injuryand/or hypoparathyroidism requiring oral calcium and Vi-tamin D supplementation. No follow-up data were col-lected beyond 1 year.

TABLE ISummary of Clinical and Biochemical Indications* for

Parathyroidectomy in the Asymptomatic Patient

Elevation of serum calcium level of 1 to 1.6 mg/dL (0.25 to 0.4mMol/L) above the accepted normal range

Creatinine clearance reduction of 30% compared with age-matched normal persons

A confirmed 24-hour total urine calcium excretion of more than400 mg

Bone mass more than 2 standard deviations less than age,gender, and race matched control persons

When medical surveillance is not possible or suitableWhen patients request surgeryWhen coexistent illness complicates medical management

optionsPatients less than 50 years of age

* As determined by the National Institutes of Health Consensus DevelopmentConference of October 1990.13

TABLE IISymptoms, Clinical Findings, and Disease Processes

Associated with or Caused by Primary Hyperparathyroidism

Symptoms Associated Afflictions

Polydipsia NephrolithiasisPolyuria Hematuria from passage of stoneFatigue Bone fractureBone pain/joint pain HypertensionConstipation PancreatitisDepression Weight lossMemory loss OsteopeniaChanges in personality Peptic ulcer diseaseNausea/heartburn GoutPruritusLoss of appetiteAbdominal pain

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Serum calcium and PTH levels were compared preoper-ative and postoperatively for each of the three studygroups. The average values for these tests were comparedusing a three-group analysis of variance (ANOVA). A“success of surgery” rate was computed for each of the threegroups. Success of surgery was defined as definitive identi-fication of parathyroid pathology (ie, identification of ad-enomatous or hyperplastic glands) allowing for surgicalcorrection, with a subsequent normalization of the serumcalcium and PTH levels. Definitive identification was con-firmed by examination of final pathology reports. The suc-cess rate of surgery in the asymptomatic group (group 1)was then compared with the successful identification ratesfor the symptomatic groups (groups 2 and 3) using a Fish-er’s exact test.

The weights of parathyroid adenomas were recorded,when available, from the pathology report in each case.The mean weight and standard deviation were calculatedfor each group, and statistical comparisons of parathyroidweight between asymptomatic (group 1) and symptomaticpatients (groups 2 and 3) were made using a two-tailed ttest.

RESULTSSixty-one patients with the diagnosis of primary hyper-

parathyroidism were identified. The average age was 56years, with a range of 19 to 85 years. Thirty-five patientswere female, 26 were male. Nineteen (31%) of the patientshad no symptoms (group 1). Twenty-one (34%) had sub-jective symptoms (group 2). The afflicted group (group 3)consisted of 21 patients (34%) with the associated condi-tions previously described. Two patients in the study hadundergone previous parathyroidectomy. Thirty-four sup-plemental studies for localization were performed on 26patients.

The symptoms noted by group 2 patients and the afflic-tions reported by group 3 patients are presented in TableIII. Forty-five occurrences of symptoms were noted by the

group 2 patients, and 25 episodes of physical affliction werenoted by the group 3 patients. Twenty-two patients re-ported more than one symptom and/or physical affliction.Bone and joint pain was the most frequently reportedsymptom (16 of 45, 36%) and nephrolithiasis was the mostcommon physical affliction (15 of 25, 60%).

Of the 61 patients with the diagnosis of primary hyper-parathyroidism, 60 patients had documented preoperativeserum calcium levels. Preoperative PTH levels were avail-able in 56 cases. The average preoperative PTH level forthe entire series of patients was 142 pg/mL (normal 10 to65 pg/mL), with a range of 26 to 1,149 pg/mL. The averagepreoperative serum calcium level was 11.5 mg% (normal 9to 10.5 mg%). The serum calcium level was elevated above10.6 mg% in 55 of 60 patients (92%).

Localizing studies were not frequently obtained in theinitial evaluation of primary hyperparathyroidism at ourinsitution. Four ultrasound studies were documented, and 3of these were not helpful. Only 1 of 6 MRI studies defin-itively identified a parathyroid adenoma. Three venoussamplings were performed, all on reoperative candidates.Only 1 of these studies successfuly localized a parathyroidadenoma. A total of 21 sestamibi scans were performed. Ofthese, 7 (33%) were not helpful, 13 (62%) lateralized tothe side of the pathology, and 1 (5%) lateralized to the sidecontralateral to the pathology. Of the sestamibi scans thatlateralized correctly, 7 (33% of the total) also identified thesuperior/inferior adenoma position correctly.

Fifty-one (85.2%) solitary adenomas were identified inthe series. One patient (1.6%) had two adenomas. Fourpatients (6.6%) had hyperplasia. Three patients (4.5%)had no identifiable pathology, and 1 (1.6%) had parathy-roid tissue in the resected thymus that was not appreciatedgrossly at the time of surgery.

In group 1, the asymptomatic group, 15 of 19 patients(79%) had solitary adenomas, 1 (5%) had two adenomas,and 2 (10.5%) were diagnosed with hyperplasia. All ofthese were treated with appropriate resection of diseasedparathyroid tissue, as described in the preceding section.One patient (5.3%) in the asymptomatic group had noabnormal pathology identified. Surgical exploration, there-fore, resulted in a 94.7% success rate of identifying para-thyroid pathology in the asymptomatic group.

Of the subjectively symptomatic group (group 2), 18 of 21patients (85%) had adenomas, 2 (9.5%) had hyperplasia,and 1 (4.7%) had no pathology identified. Eighteen of the21 patients (86%) with associated complications (group 3)had adenomas. This latter group had no hyperplasia cases,and two explorations (9.5%) were unsuccessful in identi-fying any pathology. Both unsuccessful cases in the thirdgroup were reoperations.

Of the 61 patients, 59 had both preoperative and post-operative serum calcium data available and 19 had bothpreoperative and postoperative PTH data. After surgery,the average serum calcium level for all patients was 8.5mg%. The postoperative serum calcium levels were notsignificantly different between the three groups studied(Table IV). The data points for PTH were evenly distrib-uted between the three groups. Postoperative PTH levelsdeclined to normal, with an an average of 48.8 pg/mL for

TABLE IIISymptoms and Physical Afflictions Reported* by Patients in

Groups 2 and 3

Number of Patients

Group 2 (n 5 21) symptomsBone/joint pain 16Fatigue 13Constipation 5Abdominal pain 4Irritability/mood swings 3Depression 2Polyuria 1Loss of appetite 1Group 3 (n 5 21) afflictionsNephrolithiasis 15Osteopenia 3Hematuria 3Peptic ulcer disease 2Bone fracture 1Renal insufficiency 1

* Some patients reported several symptoms and/or afflictions.

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THE AMERICAN JOURNAL OF SURGERY® VOLUME 177 JANUARY 1999 71

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the entire series. No differences were noted among any ofthe three individual groups (Table IV).

The overall success rate in identifying parathyroid pathol-ogy in the entire series was 93.4%. The success rate in theasymptomatic group was 94.7%. Patients with complica-tions of hyperparathyroidism (group 3) had the lowestoverall success rate of surgery (90.5%). However, the twofailures of surgical treatment in this group were both reop-erations after failed cervical explorations at other institu-tions. There were no significant differences in the successrates of surgery between the two symptomatic groups ascompared with the asymptomatic group (Table IV).

Adenoma weights were available from the pathology re-port in 45 cases. The mean weight of parathyroid adenomasin asymptomatic patients (group 1, n 5 10) was 666.4 mg,with a standard deviation of 416.9 mg. Symptomatic pa-tients (groups 2 and 3 combined, n 5 35) had a meanparathyroid adenoma weight of 840.5 mg, with a standarddeviation of 605.7 mg. The difference in adenoma weightbetween symptomatic and asymptomatic patients was notstatistically significant (P 5 0.59, t test).

The overall incidence of complications was 6.5%. Theseincluded 2 patients from the asymptomatic group withtransient (,1 month) hypocalcemia postoperatively, and 2patients from the group with associated complications(group 3) who had persistent (.1 month) hypocalcemia.These patients received supplemental oral calcium andVitamin D. All hypocalcemia cases resolved within 6months postoperatively. There were therefore no cases ofpermanent hypoparathyroidism. There were no cases ofrecurrent laryngeal nerve injuries.

COMMENTSTreatment of the patient with asymptomatic primary

HPT remains a controversial topic despite 2 decades ofdiscussion on the subject. Ironically, as Chan et al14 haveiterated, there even remains no precise definition of asymp-tomatic primary HPT, despite the fact than an NIH con-sensus panel has convened on how the entity should betreated. In fact, Chan et al14 and Clark et al15 have foundthat more careful questioning of these patients, which they

achieved by means of a detailed questionnaire, will disclosesome degree of symptoms in almost all cases. In their series,only 2 of 104 patients (1.9%) so questioned were trulyasymptomatic.14,15 Parathyroidectomy proved to be highlybeneficial, with improvement of symptoms or associatedconditions in 94.7% of cases.14 The benefits of parathy-roidectomy are well-described in other series as well,8,16,17

but controversy persists on how successful the procedure isin treating the patient with asymptomatic primary HPT.The lack of a clear definition of the disease and an unclearnatural history therefore fuel the controversy.

Only two studies in the recent literature describe thesuccess of surgical exploration in patients with asymptom-atic primary HPT. Attie and Khafif18 retrospectively re-viewed a series of 75 asymptomatic patients over a 7-yearperiod. In their series, 68 of 75 patients (90%) had solitaryadenomas, 6 had multiple adenomas, and only 1 had diffusehyperplasia. Interestingly, the average size of the parathy-roid adenomas in patients explored for asymptomatic pri-mary HPT was relatively small, compared with the size oftumors removed from symptomatic patients, although theauthors do not quantify size measurements. All 75 patientsin that series were rendered normocalcemic after parathy-roidectomy without postoperative complications. Russelland Edis19 at the Mayo Clinic reported a series of 500asymptomatic patients undergoing cervical explorationover a 6-year period. Patients with “biochemical” HPT(serum calcium ,11 mg%) had a statistically significantincrease in the incidence of negative cervical explorationscompared with patients who had either symptoms, compli-cations, or a serum calcium greater than 11 mg%.19 How-ever, the success in identifying parathyroid pathology washigh in both groups: 91.7% in the biochemical group and93.6% in the symptomatic group. Given the latter, and thelow incidence of complications in the series, the authorsrecommended cervical exploration in asymptomatic pa-tients.

Our study likewise showed that cervical exploration forasymptomatic primary HPT was as successful in identifyingparathyroid pathology and correcting biochemical abnor-malities as exploration in symptomatic patients. The suc-

TABLE IVMean Preoperative and Postoperative Biochemical Data for the Three Groups of Patients

Group

Preoperative Postoperative Success ofSurgeryPTH Ca PTH Ca

1 98.1 11.2 38.8 8.4 94.7%(19) (15) (19) (6) (19)

P 5 0.58–0.6 P 5 0.23–0.64 P 5 0.55–0.6 P 5 0.25–0.952 179.2 11.5 52.3 8.4 95.3%(21) (17) (20) (7) (21) P 5 1.0

P 5 0.58–0.99 P 5 0.64–0.72 P 5 0.55–0.99 P 5 0.39–0.953 140.4 11.7 54.7 8.7 90.5%(21) (14) (21) (6) (19) P 5 1.0

P 5 0.61–0.99 P 5 0.23–0.72 P 5 0.6–0.99 P 5 0.25–0.39All 142.4 11.5 48.8 8.5 93.4%(61) (47) (60) (19) (59)

The number of patients/data points are reported in parentheses. Also shown is the success rate of surgery in identifying parathyroid pathology. Group 1 5asymptomatic; group 2 5 symptoms only; group 3 5 symptoms 1 complications (see Methods). The P values for the laboratory values are reported as ranges ina three-group ANOVA (see Methods). The P values for success of surgery represent comparison of the symptomatic groups (groups 2 and 3) to the asymptomaticgroup (group 1) in a Fisher’s exact test.

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cess rates were also no different in patients with subjectivesymptoms only (group 2, 95.3%), compared with thosewith more severe, objective manifestations of the disease(group 3, 90.5%). It is curious to note that group 3, thegroup with the more severe manifestations, had the loweroverall success rate. However, it should be recalled that thetwo failures in this group were both reoperations followingprior negative initial explorations at other institutions.The difference in surgical success between these two groupswas also not statistically significant (P 5 1.0, Fisher’s exacttest). Thus, although the manifestation of symptoms inprimary hyperparathyroidism may be progressive, the abil-ity to surgically identify diseased parathyroid tissue is thesame, regardless of the clinical severity of the disease atpresentation.

Measurements of the size of parathyroid adenomas in thisseries showed no significant difference in asymptomaticpatients, as compared with those with symptoms or affli-cations. Thus, it appears that the glands are similarly dis-eased, whether manifestations are present or not, and thepresumed earlier clinical disease state in asymptomaticpatients does not correlate either with extent of parathy-roid pathology or the ability to identify that pathology atcervical exploration. The spectrum of pathology in theasymptomatic patients in this series is also similar to thatquoted for symptomatic disease: approximately 90% ade-noma, 10% hyperplasia.20,21 This is similar to the spectrumof pathology reported in the previous studies of asymptom-atic patients described above.18,19

The potential complications of cervical exploration hasled some to propose less morbid operative approaches, suchas unilateral neck exploration or intraoperative localizingstrategies such as hand-held lymphoscintigraphy. Our in-stitutional bias has been toward the more thorough oper-ative approach of bilateral cervical exploration. A mini-malist approach in the patient population in this serieswould have potentially missed 6 of 61 cases (9.8%) ofbilateral adenomas, ectopic parathyroid tissue, or hyperpla-sia. The permanent (.6-month duration) complicationrate in this series was 0% and the short-term (, 6-monthduration) complication rate was 6.5%. Most importantly,the overall incidence of complications in this series was nodifferent between asymptomatic and symptomatic patientsundergoing exploration.

The classification of patients into symptomatic, afflicted,and asymptomatic groups was performed as carefully aspossible in a retrospective review. It is possible that some ofthe asymptomatic patients, under direct questioning, mighthave noted more subtle manifestations of disease, particu-larly regarding subjective symptoms such as fatigue, depres-sion, and bone pain. Indeed, as has been mentioned, someseries report that less than 2% of patients with HPT aretruly asymptomatic when asked to respond to detailedquestionnaires.14,15 Therefore, the difficulty of exactly doc-umenting the presence or absence of all symptoms of HPTin this series is recognized. However, patient response todirect questioning is sometimes also difficult to interpret,particularly in assessing subjective symptoms (ie, does oc-casional arthritic joint pain represent “bone pain”?). Fur-thermore, the patient population in this study was cared forby the same group of eight staff endocrinologists, and the

majority (88%) were operated on by the same two staffsurgeons. This represents a fairly uniform application ofsurgical and nonsurgical practice guidelines, includingscreening for disease symptoms during the history-takingportion of the examination. It is, therefore, felt that thisgroup of patients was well screened for preoperative symp-toms, within the limitations outlined above.

It should be noted that this retrospective study attemptedto define only the immediate success rate of surgery inidentifying parathyroid pathology and biochemically cor-recting asymptomatic primary HPT. The study does notanswer the question of whether early surgical interventionin asymptomatic patients alters long-term outcome in thesepatients. Several prior studies have indicated that patientswith primary HPT, particularly elderly patients, who wereobserved rather than surgically treated had an increasedmortality risk, primarily from cardiovascular disease.15,22–24

Graham et al25 reported that accelerated bone turnoverrate (as measured by strontium space, alkaline phosphataseactivity, and urinary hydroxyproline), in 72 patients withasymptomatic primary HPT returned to normal after par-athyroidectomy. Roka et al26 reported a series of 176 pa-tients followed up to 22 years after parathyroidectomy.Interestingly, 14 of 176 patients (7.9%) eventually died ofcauses related to primary HPT (7 deaths due to renalfailure, 5 fatal hypertensive strokes, and 2 deaths due topancreatitis) even after parathyroidectomy. All of thedeaths, however, occurred in patients who presented ini-tially with symptoms; none of the asymptomatic patients inthe series died of HPT-related afflictions.

The long-term benefits of surgical intervention in pa-tients with asymptomatic primary HPT are well-docu-mented. These benefits, as well as the high success rate andlow complication rate of surgery reported in our series andothers, indicate that cervical exploration in patients withasymptomatic primary HPT is successful, beneficial, andlow risk. The operation should continue to be offered tothese patients.

Large, multicenter, long-term randomized clinical studies,as suggested by the NIH consensus panel and others,13,27

would definitively detail the natural history of untreatedasymptomatic primary HPT. It would be helpful and inter-esting to see such a study, but given the cumbersomenature of coordinating such a task, and the reputed bene-fits, success, and minimal morbidity of surgery for asymp-tomatic primary HPT, it is unlikely that such studies willbe accomplished.

CONCLUSIONSurgical exploration and resection of diseased parathyroid

tissue is as effective in the asymptomatic patient as insymptomatic patients in identifying diseased parathyroidtissue, and in reducing serum calcium levels and correctingthe PTH level. Additionally, the operation can be per-formed with an equivalent low incidence of risks andcomplications.

REFERENCES1. Mandl F. Therapeutischer versuch bei ostitis fibrosa generalisatamittels exstirpation lines epithelkorperchentumors. Wein KlinWochenschr. 1925;50:1343.2. Purnell DC, Smith LH, Scholz DA, et al. Primary

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CERVICAL EXPLORATION FOR ASYMPTOMATIC PRIMARY HYPERPARATHYROIDISM/COSTON AND PELTON

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