ORIGINAL ARTICLE

Usefulness of preoperative Tc-mibi parathyroid scintigraphyin secondary hyperparathyroidism

Alberto de la Rosa & Jaime Jimeno & Estela Membrilla &

Joan J. Sancho & José A. Pereira & Antonio Sitges-Serra

Received: 16 June 2006 /Accepted: 2 January 2007 / Published online: 9 February 2007# Springer-Verlag 2007

AbstractBackground and aims The usefulness of Tc-mibi parathy-roid scintigraphy (Tc-PS) in planning parathyroidectomy forsecondary hyperparathyroidism is not well known. The aimof this study was to review our experience with Tc-PSconcerning: (1) the identification of hyperplastic glands, (2)detection of major ectopias and (3) prevention of recurrences.Patients and methods Thirty-three consecutive patientsundergoing first-time subtotal parathyroidectomy for renalhyperparathyroidism had a dual-phase planar Tc-PS per-formed, and glands were classified as detected, weak, or notdetected. The number and position of visualized glandswere determined. Parathyroid weight, histology, and theirrelationship to Tc-PS were recorded after surgery.Results Of 132 potential glands, 48 (35%) were localized onthe Tc-PS and 128 (96.9%) were identified intraoperatively.Tc-PS positive/weak glands were heavier than nonlocalizedglands. Tc-PS contributed to successful surgery in fourpatients with a single difficult gland each (three retrievedfrom the neck and one—fifth gland—requiring mediast-inotomy). There was one persistence (3%) because of amissed fourth undescended inferior parathyroid gland. Tworecurrences 2 years after surgery were due to a fifth thoracicgland not shown in the preoperative Tc-PS.Conclusions Preoperative Tc-PS helped in the intraoperativeidentification of moderate or major ectopias in 4/33 patients

but was not useful to prevent recurrences from highlyectopic glands not visualized before first-time surgery.

Keywords Secondary hyperparathyroidism .

Parathyroid scintigraphy . Ectopias

Introduction

Parathyroid scintigraphy (Tc-PS) has become a routineimaging technique in the preoperative assessment ofpatients undergoing parathyroidectomy for primary hyper-parathyroidism. Its role in predicting parathyroid position,in detecting ectopias, and preventing recurrences in patientswith secondary renal hyperplasia is controversial [1, 2].Because these patients always require a bilateral parathy-roid exploration, it has been generally assumed that Tc-PSdoes not have a significant role in planning the surgicalintervention. Few studies, however, and with a limitednumber of patients, have addressed this issue prospectively.

The hypothesis of the present study is that preoperative Tc-PS may have a role in secondary hyperparathyroidism as themore common causes of failure of parathyroidectomy in thissetting are identification of less than four glands and glandswith major ectopias [3–5]. These surgical failures couldtheoretically be prevented, or at least minimized, by preoper-ative imaging. We report our experience on preoperative Tc-PS imaging in hemodialysis patients undergoing first-timeparathyroidectomy for secondary renal hyperparathyroidism.

Patients and methods

Consecutive patients referred for parathyroidectomy forrenal hyperparathyroidism between 1998 and 2005 were

Langenbecks Arch Surg (2008) 393:21–24DOI 10.1007/s00423-007-0151-z

Presented at the 2nd Biennial Congress of the ESES, May 2006,Krakow, Poland.

A. de la Rosa : J. Jimeno : E. Membrilla : J. J. Sancho :J. A. Pereira :A. Sitges-Serra (*)Department of Surgery, Endocrine Surgery Unit, Hospital del Mar,Paseo Marítimo 25-29,08003 Barcelona, Spaine-mail: asitges@imas.imim.es

prospectively investigated. In addition to conventionalpreoperative biochemical assessment, all of them under-went a dual-phase parathyroid Tc-PS in frontal planarprojection (20 mCi of 99 mTc-Sestamibi) with detection at10 min and 2 h after isotope injection. No single photonemission computed tomography (SPECT) was performed.Images of the neck and upper thorax were obtained inplanar anterior incidence with the patient in a supineposition with the neck hyperextended. Subsequently athyroid scintigraphy with 4 mCi of 99 mTc-pertechnectatewas obtained. The number and position of visualized glandswere recorded. According to the Tc-PS, glands wereclassified as clearly identified, weakly marked, or non-visualized and, also, as normal in position, minor ectopia(accessible through a standard central small cervicotomy),or major ectopia. The correlation between parathyroidweight and histology (diffuse vs nodular hyperplasia) andidentification on the Tc-PS was investigated after surgery.Usefulness of Tc-PS was assessed according to the numberof ectopias identified and the potential prevention ofpersistent disease. All patients were followed for aminimum of 1 year. Statistical analysis was done with theStatview 4.0 Package (Cupertino, CA). Two-tailed Stu-dent’s t test was used to compare means of continuousvariables with a normal distribution and the chi-square testfor analysis of discrete variables. Statistical significancewas set at P<0.05. Data are presented as SD±SEM.

Results

There were 33 patients included in the study (20 men, 13women) with a mean age of 52 years (range 27–78 years).None of these patients had undergone previous necksurgery. They had been on regular hemodialysis for a meanof 59±7 months, and their preoperative biochemicalassessment was as follows: parathyroid hormone (PTH)1,343±122 pg/ml, Ca 10.1±0.2, P 5.7±0.5 pg/ml andalkaline phosphatase 482±60 U/l.

Preoperative and intraoperative parathyroid identification Of132 potential glands, 48 (35%) were localized preopera-tively by Tc-PS, and 128 (96.9%) were identified intra-operatively. Four glands were missed. Mean weight perresected gland was 569±57 mg. There were weightdifferences between localized/weak glands and not local-ized glands in the Tc-PS (798±116 vs 431±53 mg; P=0.003). Glands with nodular hyperplasia were not identifiedmore often than those with diffuse hyperplasia (nodular39% vs diffuse 49%). Glands missed by the Tc-PS weremore often superior glands (70 vs 57%; P=0.1), despitethere were no weight differences between superior andinferior glands (533 vs 617 mg).

Benefits of Tc-PS Parathyroid scintigraphy was deemed tohave substantially contributed to successful surgery bypreventing missing a diseased gland in two patients withlow-lying inferior thymic parathyroid glands (retrievedfrom the neck), in one patient with a low paraesophagealsuperior descended gland (retrieved from the neck) and inone patient with a fifth mediastinal gland and four normalglands identified intraoperatively in the neck (Fig. 1).During follow-up, we identified one persistence and tworecurrences. The single persistence (3%) was due to amissed fourth undescended inferior parathyroid gland(parathymus) not shown in the Tc-PS frontal projectionbut identified 6 months later on an oblique view of arepeated Tc-PS (Fig. 2). Two recurrences were observed amean of 2 years after surgery. Both were due to a fifththoracic gland in the aortopulmonary window that did notshow up in the preoperative Tc-PS. Thus, of three surgical

Fig. 1 A parathyroid adenoma identified by preoperative Tc-PS in a49-year old patient on hemodialysis for 5 years. Four normal glandswere identified at neck exploration, and anterior mediastinotomy wascarried during the same intervention

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failures, one could have been prevented if the undescendedparathymus had been looked for initially by performing anoblique scintigraphic or a SPECT view.

Discussion

Complete parathyroid identification is mandatory inpatients undergoing parathyroidectomy for renal hyperpara-thyroidism. When less than four glands are found, theincidence of persistence is close to 50%. Hibi et al. [6]investigated 21 patients with less than four glands foundintraoperatively. Of these, five patients had the missinggland identified by the pathologist. In 8 of the remaining 16patients, high PTH levels persisted after the initial opera-tion, including three patients who underwent neck reexplo-ration. Kinnaert et al. [7] observed persistence in at least5/15 patients in whom less than four glands were identifiedat surgery. We missed four glands in 33 patients, and one ofthem (parathymus) did cause a persistence. Thus, completeparathyroid identification should be the main goal ofparathyroidectomy for renal disease independently onwhether total or subtotal resection is contemplated.

Whether preoperative Tc-PS can be helpful to achievetotal parathyroid identification in renal hyperparathyroidismis controversial, and no comparative studies have beenperformed. The sensitivity of Tc-PS to identify hyperplasticglands was 35% in our study. Piga et al. [8] performed Tc-PS in nine patients undergoing parathyroidectomy andidentified 13/28 potential glands (44%). Custodio et al. [9]found a sensitivity of 50% in 18 patients, and Perie et al.

found a sensitivity of 66% in patients referred forparathyroidectomy. The higher sensitivity found in thesestudies compared to the present one could be due totechnical reasons, differences in severity of disease, or acombination of both. In general, mean gland weight andpreoperative PTH concentrations in our series were lowerthan those in the quoted studies.

Gland weight differences between localized and non-localized glands were found in the present and many otherstudies [2, 9–12] leaving no doubt that glands localized byTc-PS are larger—mean weight ranging between 500 and900 mg—than those not identified (mean weight rangingbetween 250 and 400 mg). Other factors reported tofacilitate nonvisualization [12] are superior position, ectopia,and diffuse hyperplasia (vs nodular). Thus, althoughsome functional characteristics such as cell-cycle [13] orproliferation indexes [14, 15] may influence tracer uptake,gland weight is a crucial determinant of the sensitivity ofTc-PS. The fact that in ours and in others’ studies [10, 12]superior glands were missed more often despite having asimilar weight than the inferior glands is most probablyrelated to their retrothyroidal position that may weaken theradionuclide signal, particularly, if patients have, and oftenhave, a hyperplastic thyroid. The correlation betweentracer uptake and parathyroid gland nodularity is morecontroversial. According to our data, nodular glands didnot show up more often in the Tc-PS. In other studies[12, 14, 15], however, Tc-PS was clearly superior indetecting nodular glands than diffuse glands althoughsensitivity of imaging techniques was similar, suggestingthat tracer uptake by nodular glands is greater despite asimilar size/weight.

Fig. 2 A left parathymus thatwas initially missed in a planarview despite a clear asymmetrybetween both “salivary glands”.PTH persisted elevated, and anoblique Tc-PS performed6 months later revealed theectopic left lower hyperplasticundescended gland

Langenbecks Arch Surg (2008) 393:21–24 23

Little information is given on the potential benefits of Tc-PSto achieve complete intraoperative parathyroid identification inthe studies published so far. Even in the extensive case reviewby Guillem et al. [12], there is little surgical information onwhich patients did benefit or could have benefited from PS.In the present study, at least one reintervention in a patientwith a fifth mediastinal gland was spared thanks topreoperative imaging. In three other patients with low lyingsuperior or inferior glands, it was deemed to have substan-tially contributed to complete parathyroid identification. It didnot, however, prevent one persistence due to a parathymus(which could have been detected in an oblique or SPECTview) and two late recurrences both due to supernumeraryglands in the aortopulmonary window. In the study of Piga etal. [8], five ectopic glands were identified in 5/38 (13%)patients, a prevalence similar to ours (4/33=12%). In theirstudy, there were two mediastinal and three lateral-jugularglands detected by Tc-PS, which could have been missed orat least would have been difficult to identify intraoperatively.In the study of 20 preoperative patients by Perie et al. [10],the authors state that no supernumerary or ectopic glandswere identified. There was, however, one persistence due to amissed low-lying inferior enlarged parathyroid (1,150 mg),visible in the scan but nevertheless missed by the surgeon.Thus, 1/20 (5%) patients could have been spared areintervention as happened in at least one of our patientswith a major mediastinal ectopia. These authors conclude thatpreoperative identification of hyperplastic glands by means ofTc-PS plus ultrasonography is helpful for the surgeon. Fusteret al. [1] claim that a high recurrence rate (19%) within 1 yearafter subtotal parathyroidectomy was due to the surgeon(blinded for Tc-PS information!) leaving remnantscorresponding to Tc-PS positive glands. This is at variancewith most surgeons’ experience that points to missed glandsor supernumerary glands as the most common causes ofpersistence or early recurrence. As this paper does not reporton the causes of all recurrences, it is difficult to agree with theauthors’ suggestion that remnants of Tc-PS positive glandsare particularly prone to produce a relapse. In fact, in theirstudy, at least two of the nine recurrences were due to missedglands that were found at reoperation. At least one of thesecould have been prevented if the surgeon would have beengiven the Tc-PS information. In addition, there was anotherrecurrence related to the growth of a remnant of a Tc-PSnegative gland. Our findings do not support the contentionthat scan-positive glands are particularly hyperactive or thattheir remnants after subtotal parathyroidectomy carry a higherrisk of relapse.

In summary, Tc-PS will detect between 35–65% ofhyperplastic glands in secondary hyperparathyroidism andidentify moderate or major ectopias in no less that 5–10%of cases, suggesting that it has a role in the preoperativeassessment of such patients.

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