Introduction
Methods
Results
Incidence of multiglandular disease in sporadic primary hyperparathyroidism
Reference (year) | Period, centre, operative strategy | Total number of patients | Double adenomas | Multigland hyperplasia |
---|---|---|---|---|
Alhefdhi et al. [11] | 2001–2013, University of Wisconsin, USA | 1402 | 124 (9 %) | 181 MGD (13 %) |
Vandenbulcke et al. [12] | 1993–2010, University Hospitals Leuven, Belgium, BNE | 698 | 46 (6.6 %) | 17 (2.4 %) |
Mazeh et al. [13] | 2001–2010, University of Wisconsin, USA, BNE | 1235 | 100 (8 %) | 135 (11 %) |
Schneider et al. [14] | University of Wisconsin, USA | 1049 overt PHPT | 148 (14.1 %) | |
388 mild PHPT | 133 (34.3 %) | |||
Hughes et al. [15] | Ann Arbor, USA, focused parathyroidectomy with MGD discovered intraoperatively | 1855 | 207 (11 %) | |
Cayo et al. [16] | 2000–2008, University of Wisconsin, USA | 755 | 163 (21.5 %) | |
Szabo et al. [17] | Uppsala University Hospital, Sweden, BNE | 659 | 77 (11.7 %) | 53 (8.0 %) |
Attie et al. [18] | Long Island Jewish Medical Centre, USA, BNE | 865 | 33 (3.8 %) | 46 (5.3 %) |
Ref | Centre | Total number of patients | Failure rate | Cause of failure |
---|---|---|---|---|
Lee et al. [19] | MD Anderson, USA | 357 | 19 (3.5 %) | 9 MGD |
Bagul et al. [20] | Sheffield, UK | 541 | 25 (5 %) | 13 MGD (2.5 %) |
Suliburk et al. [21] | University of Sydney, Australia | 1020 | 23 (2.2 %) | 10 DA, 3 MGD |
Pathogenesis of sporadic multiglandular disease
Definition of sporadic multiglandular disease
Double parathyroid adenomas
Lithium-associated hyperparathyroidism
Is sporadic multiglandular disease a synchronous or metachronous disease?
Risk factors of sporadic multiglandular disease
Age and gender
Radiation
Are there any other known risk factors for sporadic multiglandular disease?
Preoperative diagnosis of sporadic multiglandular disease
Can sporadic multiglandular disease be diagnosed preoperatively?
Can sestamibi distinguish single-gland from sporadic multiglandular disease?
Prelesion test characteristics for all patients | |||
---|---|---|---|
MGD lesions | SGD lesions | All lesion | |
Sensitivity | 61 %* (201/331) | 97 % (503/520) | 83 % (704/851) |
Specificity | 84 %* (163/193) | 93 % (1450/1560) | 92 % (1613/1753) |
Accuracy | 69 %* (364/524) | 94 % (1953/2080) | 89 % (2317/2604) |
Positive predictive value | 87 % (201/231) | 82 % (505/613) | 83 % (704/844) |
Negative predictive value | 56 %* (163/293) | 99 % (1450/1467) | 92 % (1613/1760) |
Effect of increasing lesion number per patient on test performance | ||||
---|---|---|---|---|
1 lesion | 2 lesions | 3 lesions | 4 lesions | |
Sensitivity | 97 % (503/520) | 68 %* (100/148) | 59 %* (79/135) | 46 %* (22/48) |
Specificity | 93 % (1450/1560) | 84 %* (124/148) | 87 %* (39/45) | |
Accuracy | 94 % (1953/2080) | 76 %* (224/296) | 66 %* (118/180) | 46 %* (22/48) |
Positive predictive value | 82 % (505/613) | 81 % (100/124) | 93 %* (79/85) | 100 % (22/22) |
Negative predictive value | 99 % (1450/1467) | 72 %* (124/172) | 41 %* (39/95) | 0 %* (0/26) |
What is the risk of sporadic multiglandular disease when a sestamibi scan is negative?
How accurate is the use concordant sestamibi scan and ultrasound for distinguishing single gland from sporadic multiglandular disease?
What is the accuracy of CT scan for distinguishing single-gland disease from sporadic multiglandular disease?
Sensitivity and specificity of imaging for localization of parathyroid tumours to side of the neck and quadrant of the neck | ||||
---|---|---|---|---|
Variable | Sensitivity (95 %) | 95 % CI | Specificity (%) | 95 % CI |
Side of the neck | ||||
4D-CT | 88 | 81–95 | 88 | 80–96 |
Ultrasonography | 57 | 47–67 | 94 | 88–99 |
Sestamibi | 65 | 55–75 | 88 | 80–96 |
Precise location in the neck | ||||
4D-CT | 70 | 59–81 | 89 | 85–93 |
Ultrasonography | 29 | 20–38 | 86 | 82–90 |
Sestamibi | 33 | 24–42 | 83 | 79–87 |
How accurate is SPECT imaging for distinguishing single gland from sporadic multiglandular disease?
SGD vs. MGD | |||||||
---|---|---|---|---|---|---|---|
Statistic and disease | Early images | Late images | Subtract on images | SPECT images | Early and late images | Planar images | All images |
Sensitivity (%) | |||||||
SGD | 74 (303/400)* | 87 (355/409)* | 88 (360/409)* | 90 (369/409)* | 90 (370/409)* | 96 (392/409)* | 90 (369/409)* |
MGD | 63 (79/125) | 65 (81/125) | 54 (68/125) | 59 (74/125) | 61 (76/125) | 63 (79/125) | 66 (82/125) |
Specificity (%) | |||||||
SGD | 93 (433/464) | 92 (427/464) | 94 (435/464) | 84 (390/464) | 90 (419/464) | 89 (410/464) | 98 (453/464)* |
MGD | 82 (9/11) | 82 (9/11) | 73 (8/11) | 82 (9/11) | 82 (9/11) | 64 (7/11) | 73 (8/11) |
Accuracy (%) | |||||||
SGD | 84 (736/873)* | 90 (782/873)* | 91 (795/873)* | 87 (759/873)* | 90 (789/873)* | 92 (802/873)* | 94 (822/873) |
MGD | 65 (88/136) | 66 (90/136) | 56 (76/136) | 61 (83/136) | 63 (85/136) | 63 (86/136) | 66 (90/136) |
Is genetic testing justified in patients with seemingly sporadic multiglandular disease under 40 years of age to rule out hereditary parathyroid disease?
Clinical manifestation of MEN-1 syndrome and indications for genetic screening | ||
---|---|---|
Major lesion (prevalence) | Minor lesions | Indications for genetic screening |
Hyperparathyroidism (90–97 %) | Adrenal adenomas |
Index case
|
Pituitary adenoma (33 %) | Facials angiofibromas | Clinically defined MEN-1 |
Tumours of endocrine pancreas (30–80 %) | Lipomas | (2 major lesions; 3 major and minor lesions) |
Neuroendocrine carcinoids | Clinically suspicious or atypical MEN-1 | |
Thyroid neoplasms | ||
Phaeochromocytomas | ||
Malignant melanomas |
Member of a MEN-1 family
| |
Testicular teratomas | All first degree relatives: a relative who shows signs or symptoms of MEN-1 |
Surgical treatment of sporadic multiglandular disease
Bilateral neck exploration for sporadic multiglandular disease
Is there a place for minimally invasive surgery in lithium-associated hyperparathyroidism?
Reference (year) | No of patients with LAH | IOPTH | Pathology (%) | Surgery (%) | p/rHPT (%) | Perm. HypoPT (%) | |||
---|---|---|---|---|---|---|---|---|---|
SA | DA | PH | BNE | Scan-directed | |||||
Wade et al. [100] | 19 | Yes | 68 | 32 (MGD) | 53 | 47 | 100 | 0 | |
Marti et al. [102] | 27 | Yes | 41 | 15 | 44 | 67 | 33 | 23 | 0 |
Skandarajah et al. [101] | 15 | Yes | 27 | 0 | 73 | 80 | 20 | 0 | 7 |
Järhult et al. [34] | 71 | N/A | 45 | 3 | 52 | 97 | 3 | 42 | 13 |
Carchman et al. [99] | 16 | Yes | 75 | 12.5 | 12.5 | 50 | 50 | 0 | 0 |
Is IOPTH monitoring helpful for the detection and postoperative outcome prediction in sporadic multiglandular disease?
Reference (year) | MGD/SA (%) | Criterion | PPV (%) | NPV (%) | Conclusion |
---|---|---|---|---|---|
Barczynski et al. [104] | 9/260 (3.5) | Halle | 100 | 14.2 | Miami criterion followed by the Vienna criterion is the best balanced among other criteria, with the highest accuracy in intraoperative prediction of cure. However, the Rome criterion followed by the Halle criterion is most useful in intraoperative detection of MGD. |
Miami | 99.6 | 70 | |||
Rome | 100 | 26.3 | |||
Vienna | 99.6 | 60.9 |
Is local anaesthesia with intravenous sedation feasible surgical treatment of sporadic MGD?
Long-term results of surgical treatment for sporadic multiglandular disease
Does cure rate of surgery for sporadic MGD differ from outcomes of surgery for solitary parathyroid adenoma?/prevalence of persistent sporadic MGD
Prevalence of recurrent sporadic multiglandular disease
Is more intense follow-up justified in sporadic multiglandular disease?
Redo operations in sporadic multiglandular disease
Summary
Recommendations
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Level V evidence supports that most single adenomas are monoclonal lesions arising from a single precursor, whereas sporadic MGD is polyclonal, hence a single parathyroid adenoma and MGD represent two different diseases.
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Levels IV and V evidence supports that the majority of cases with double parathyroid adenomas are synchronous. This notion is based on the observation that few patients have a recurrent disease after a successful parathyroidectomy.
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Levels III to V evidence supports an etiologic link between sustained lithium therapy and both hypercalcemia and increased PTH serum level.
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Levels IV and V evidence do not support any differences with respect to gender, age and preoperative serum calcium and PTH levels between a solitary adenoma and sporadic MGD.
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Level V evidence do not support any differences in prevalence of a solitary parathyroid adenoma and sporadic MGD among patients with radiation-induced vs. non-radiation-associated pHPT.
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Levels III to V evidence supports that negative preoperative localization studies in pHPT are highly predictive of a small-sized solitary adenoma or MGD.
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Levels I to IV evidence supports that sestamibi scanning and US have an unsatisfactory accuracy in predicting sporadic MGD, which is significantly inferior to a solitary parathyroid adenoma.
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Level V evidence supports that 4D-CT identifies more than a half of abnormal parathyroids in MGD missed by traditional imaging. However, taking into consideration that 4D-CT carries a huge radiation exposure, BNE remains the gold standard surgical approach having a high success rate in experienced hands in cases with negative or discordant sestamibi and ultrasound (grade C recommendation, GRADE: high, ‘⊕⊕⊕⊕’).
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Level V evidence supports that CT-MIBI-SPECT image fusion is superior to CT or MIBI-SPECT alone in preoperative localization of all pathologic glands in patients suffering from MGD (grade C recommendation, GRADE: high, ‘⊕⊕⊕⊕’).
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Levels III and IV evidence supports that genetic testing should be undertaken in patients with seemingly sporadic MGD under 40 years of age to rule out hereditary parathyroid disease (grade C recommendation, GRADE: high, ‘⊕⊕⊕⊕’).
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Levels III to V evidence supports that the presence of certain clinical risk factors for MGD should be taken into consideration in decision making which operative approach should be used for individual patient. Hence, BNE should beconsidered in MEN-1 syndrome, negative preoperative localization studies, and inadequate decrease of IOPTH level following removal of the image-indexed parathyroid lesion. All other clinical scenarios can be regarded as relative indications for BNE and include isolated familial PHPT, MEN-2 syndrome, history of lithium therapy, head and neck irradiation in anamnesis or discordant preoperative localization studies (grade C recommendation, GRADE: moderate, ⊕⊕⊕O).
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Levels IV and V evidence supports the use of preoperative parathyroid imaging if a unilateral/focused exploration is planned in case of suspicion of sporadic MGD (grade C recommendation, GRADE: moderate, ⊕⊕⊕O).
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Levels IV and V evidence supports the use of IOPTH monitoring to guide appropriate surgical therapy in sporadic MGD (grade C recommendation, GRADE: moderate, ⊕⊕⊕O).
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There is conflicting and equally weighted level V evidence supporting a routine preoperative plan of BNE vs. unilateral neck exploration for selected patients with MGD, e.g. LAH (no recommendation).
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There is conflicting or equally weighted levels IV to V evidence supporting that cure rates can be similar or worse for sporadic MGD than for single adenomas. Best outcomes can be expected if surgery is performed by an experienced parathyroid surgeon working in a high-volume parathyroid surgery centre (grade C recommendation, GRADE: high, ‘⊕⊕⊕⊕’).
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Levels IV and V evidence supports that recurrent and persistence pHPT occurs more frequently in patients with double adenomas. Hence, in situations where a double adenoma has been identified, the surgeon should have a high index of suspicion during surgery and postoperatively for the possibility of four-gland disease (grade C recommendation, GRADE: moderate, ⊕⊕⊕O).