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Background

There are usually four parathyroid glands located alongside and sometimes within the thyroid gland.  However, sometimes during development, the parathyroid glands migrate may be found almost anywhere within the mediastinum.   There are basically two conditions which would prompt a removal of the glands, hyperplasia and neoplasia (adenoma or carcinoma).  The fact that there could be more than four glands and may be located anywhere within the mediastinum is an important issue for the surgeon removing these glands.  A frozen section is often performed intraoperatively to confirm that the tissue removed is indeed parathyroid tissue.

Parathyroid Adenoma
Parathyroid Carcinoma
Parathyroid Hyperplasia

LABORATORY/RADIOLOGIC/OTHER CHARACTERIZATION

The validity of quick intraoperative parathyroid hormone assay: an evaluation in seventy-two patients based on gross morphologic criteria.

Gordon LL, Snyder WH 3rd, Wians F Jr, Nwariaku F, Kim LT.

Department of Surgery, University of Texas Southwestern Medical Center, Dallas 75235-9156, USA.

Surgery 1999 Dec;126(6):1030-5 Abstract quote

BACKGROUND: Parathyroidectomy for primary hyperparathyroidism has conventionally required identification of all parathyroid glands with excision of grossly abnormal glands. Using this approach, cure rates exceed 95%. Directed cervical exploration has been advocated using quick intraoperative parathyroid hormone (QPTH) assay with preoperative localization. Adoption of this approach requires validation of the accuracy of QPTH assay.

METHODS: Patients with primary hyperparathyroidism undergoing bilateral neck exploration during a 31-month period were reviewed. Uniglandular (UGD) or multiglandular (MGD) disease was determined by gross morphologic criteria. QPTH assays were performed before skin incision and at 5, 10, and 20 minutes after excision of each abnormal gland. A 10-minute QPTH decrease of 50% from baseline levels indicated curative excision. These data were not used to guide extent of exploration or tissue resection.

RESULTS: Of 72 patients, 55 (76%) had UGD and 17 (24%) had MGD. QPTH assay accurately predicted the disease state in 89%. Four (7%) UGD patients did not have an appropriate QPTH decline at 10 minutes. Four (24%) MGD patients had an inappropriate QPTH decline at 10 minutes.

CONCLUSIONS: Using QPTH guided exploration, 6% (4 of 72) of patients would undergo unnecessary extended exploration and 6% (4 of 72) (95% CI, 1% to 13%) may require reoperation for unidentified MGD. These results validate the accuracy of QPTH assay.

Improved success rate in reoperative parathyroidectomy with intraoperative PTH assay.

Irvin GL 3rd, Molinari AS, Figueroa C, Carneiro DM.

Department of Surgery, University of Miami School of Medicine, Jackson Memorial and Veterans Affairs Medical Centers, Florida 33101, USA.

Ann Surg 1999 Jun;229(6):874-8; discussion 878-9 Abstract quote

OBJECTIVE: The clinical usefulness of preoperative localization and intraoperative PTH assay (QPTH) in primary hyperparathyroidism have been established. However, without the use of QPTH, the parathyroidectomy failure rate remains 5% to 10% in large reported series and is probably much higher in the hands of less experienced parathyroid surgeons. Persistent hypercalcemia requires another surgical procedure. The authors compared the outcomes in 50 consecutive patients undergoing more difficult secondary parathyroidectomy with and without the adjunctive support of QPTH.

METHODS: Two groups of similar patients underwent reoperative parathyroidectomy for failed surgery or recurrent disease. The successful return to normocalcemia in group I, with QPTH used to localize and confirm complete excision of all hyperfunctioning glands, was compared with group II, who did not have this intraoperative adjunct.

RESULTS: In 31/33 patients in group I, calcium levels returned to normal. With good preoperative localization studies, 17 patients underwent successful straightforward parathyroidectomies as predicted by QPTH. In the other 14 patients, QPTH assay proved extremely beneficial by facilitating localization with differential venous sampling; measuring the increase in hormone secretion after massage of specific areas; recognizing suspicious nonparathyroid tissue excised without a decrease in hormone levels, avoiding frozen-section delay; and correctly identifying the excision of abnormal tissue despite false-positive/false-negative sestamibi scans. In group II, who underwent surgery before QPTH was available, 4 of 17 patients (24%) remained hypercalcemic after extensive reexploration.

CONCLUSION: With the intraoperative hormone assay used to facilitate localization and confirm excision of all hyperfunctioning tissue, the success rate of reoperative parathyroidectomy has improved from 76% to 94%.

Intraoperative quick parathyroid hormone versus same-day parathyroid hormone testing for minimally invasive parathyroidectomy: A cost-effectiveness study.

Agarwal G, Barakate MS, Robinson B, Wilkinson M, Barraclough B, Reeve TS, Delbridge LW.

Endocrine Surgical Unit, Royal North Shore Hospital, University of Sydney, Sydney, Australia.

Surgery 2001 Dec;130(6):963-970 Abstract quote

Background
Intraoperative quick parathyroid hormone (QPTH) measurement is claimed to eliminate failures during minimally invasive parathyroidectomy. The cost-effectiveness of QPTH (ie, true cost of avoiding a failed operation) needs careful evaluation.

Methods
In 92 consecutive patients who underwent minimally invasive parathyroidectomy via a small lateral incision, QPTH was estimated preoperatively and at 5, 10, and 15 minutes postparathyroidectomy. QPTH results were subsequently compared with the procedure outcome. Cost-effectiveness analysis was performed for 3 subsequent theoretical management strategies: QPTH not performed, QPTH results available intraoperatively, and parathyroid hormone and serum calcium levels measured routinely with results made available the same day.

Results
With criteria for cure being a decrease in the QPTH measurement to less than 50% of preoperative levels and to within normal range, QPTH predictions were true positive in 78 patients; false-negative in 7; false-positive in 1; and true negative in 2. The true cost of using QPTH measurement to avoid a failed operation was US $19,801.19, with 7 patients undergoing unnecessary conversion. Routine same-day parathyroid hormone and calcium measurements significantly reduced this to $624.73. Sensitivity analysis with varying cost assumptions demonstrated cost-effectiveness analysis to be robust.

Conclusions
The fact that 97% of patients will be cured regardless of QPTH testing combined with its false-negative rates significantly reduces the cost-effectiveness of the test when compared with same-day parathyroid hormone testing.

A spike in parathyroid hormone during neck exploration may cause a false-negative intraoperative assay result.

Yang GP, Levine S, Weigel RJ.

Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA.

Arch Surg 2001 Aug;136(8):945-9 Abstract quote

HYPOTHESIS: We hypothesize that false-negative results using the rapid intraoperative parathyroid hormone (IOPTH) assay can be caused by spikes in the level of parathyroid hormone that occur during mobilization of the adenoma.

DESIGN: Retrospective analysis of a case series.

SETTING: University tertiary care center.

PATIENTS: Ten consecutive patients with primary hyperparathyroidism.

INTERVENTIONS: All patients underwent neck exploration with IOPTH monitoring. Using a sampling protocol described in the literature, IOPTH values were checked at the time of incision, during mobilization of the adenoma, and 10 minutes after resection of the adenoma.

MAIN OUTCOME MEASURES: Patients were evaluated for adequate parathyroid tissue excision as determined by IOPTH levels and examination of ipsilateral glands. All patients had normal serum calcium values documented postoperatively. Parathyroid hormone half-life was calculated assuming first-order kinetic decay.

RESULTS: Nine patients had an appropriate decline in IOPTH with a mean +/- SD parathyroid hormone half-life of 3.9 +/- 1.08 minutes. Mobilization of the adenoma resulted in a spike in the IOPTH value, with 1 patient's value increasing from a baseline of 95.5 pg/mL (10.1 pmol/L) to 751 pg/mL (79.1 pmol/L). Another patient who was confirmed to have a solitary adenoma had a false-negative postexcision value. A spike in IOPTH that occurred during neck dissection was not detected by the sampling protocol and explains the false-negative value. A literature review revealed that most protocols check baseline values early in the operation and are at risk for false-negative results due to a spike from mobilization of the adenoma.

CONCLUSIONS: These data demonstrate that false-negative IOPTH assay findings can result from a spike in parathyroid hormone level during exploration, which may go unrecognized if baseline values are measured during the early stages of mobilization of the adenoma. We have altered our assay protocol and have begun measuring IOPTH at the time of neck incision, at the time the adenoma is completely removed (time zero [t(0)]), and 10 minutes after excision.

Intraoperative parathyroid hormone monitoring fails to detect double parathyroid adenomas: A 2-institution experience.

Gauger PG, Agarwal G, England BG, Delbridge LW, Matz KA, Wilkinson M, Robinson BG, Thompson NW.

University of Michigan Departments of Surgery and Pathology, Ann Arbor, Mich.

Surgery 2001 Dec;130(6):1005-1010 Abstracty quote

Background. We hypothesized that intraoperative parathyroid hormone monitoring (IOPTH) reliably would detect double parathyroid adenomas.

Methods. This was a retrospective study of 20 patients undergoing conventional parathyroidectomy with resection of exactly 2 abnormal glands. Full exploration was performed regardless of IOPTH values, which were measured after anesthetic induction and 5 and 10 minutes following removal of the first abnormal parathyroid gland. Failure to fall below 50% of baseline value by 10 minutes following resection of the first gland indicated the presence of multiglandular disease.

Results. All patients were cured. All excised glands were hypercellular on histology. Mean IOPTH values in 9 of the 20 patients with true negative results (noncurative decrease, another gland present) were 66% +/- 7% at 5 minutes and 83% +/- 15% at 10 minutes. The IOPTH values in 11 of the 20 patients with false positive results (curative decrease, another gland present) were 28% +/- 4% at 5 minutes and 18% +/- 2% at 10 minutes. The false positive rate of IOPTH was 55%.

Conclusions. We found that IOPTH failed to reliably detect the presence of double parathyroid adenomas. These data suggest that caution should be exercised when terminating limited parathyroid exploration based on a curative fall in IOPTH values.

 

HISTOPATHOLOGICAL VARIANTS CHARACTERIZATION
CYTOLOGY  


Interpretative Problems and Preparative Technique Influence Reliability of Intraoperative Parathyroid Touch Imprints.

Yao DX, Hoda SA, Yin DY, Kuhel WI, Harigopal M, Resetkova E, DeLellis RA.

Departments of Pathology (Drs Yao, Hoda, Yin, Harigopal, and Resetkova) and Otorhinolaryngology (Dr Kuhel), New York Presbyterian Hospital-Weill Cornell Center, and Weill Medical College of Cornell University, New York, NY; and the Department of Pathology, Rhode Island Hospital, Providence, RI (Dr DeLellis).

 

Arch Pathol Lab Med 2003 Jan;127(1):64-67 Abstract quote

Context.-Identification of parathyroid tissue (PT) is crucial during parathyroid and thyroid surgery. Touch imprint preparation (TIP) examination is potentially a more time-effective and less labor-intensive approach than frozen section examination for identification of PT during intraoperative consultation. However, the reliability of PT-TIP remains controversial, and this fact has hindered its adoption as a replacement for frozen section examination. Objective.-To assess the factors contributing to the relative lack of reliability of TIP in a retrospective study.

Methods.-Fifty randomly selected, alcohol-fixed, hematoxylin-eosin- and/or Diff-Quik-stained TIPs of specimens that had been submitted to confirm PT during intraoperative consultation were retrospectively reviewed by 5 observers. The observers were blinded to the final interpretation (based on hematoxylin-eosin-stained permanent sections), which included PT in 39 (78%) of the 50 specimens, thyroid in 9 (18%), lymph node in 1 (2%), and adipose tissue 1 (2%). Cases in which a unanimous diagnosis was not attained were re-reviewed by 3 observers.

Results.-Of 50 TIPs reviewed, a unanimous diagnosis was rendered in 33 cases (66%), including 27 (69%) of 39 PT cases, 5 (56%) of 9 thyroid cases, and the 1 lymph node case. Cytologic features observed in the TIPs that were unanimously accepted as being diagnostic of PT included the presence of small uniform cells in isolation or in small groups, round to oval nuclei, salt-and-pepper chromatin, occasional naked nuclei, and delicate vacuoles both within the cytoplasm and in the background. Re-review of the 17 remaining TIPs cases, in which diagnostic unanimity was not achieved, demonstrated that factors hindering assessment of the TIPs included hypocellularity (n = 5 cases), air-drying effect (n = 4), hemorrhagic background (n = 4), and presence of PT cells in follicular (thyroid-like) arrangements (n = 4).

Conclusions.-The major factors influencing reliability of TIP of PT during intraoperative consultation are related primarily to interpretative problems and preparative technique. Awareness of interpretative problems and attention to preparation of TIPs may further enhance the accuracy of TIP during intraoperative consultation.

Intraoperative Cytology Increases the Diagnostic Accuracy of Frozen Sections for the Confirmation of Various Tissues in the Parathyroid Region


Vinod B. Shidham, MD, FIAC, MRCPath, Zeenat Asma, MD, R. Nagarjun Rao, MD, MRCPath, Ashwini Chavan, MD, Jinobya Machhi, MD, Urias Almagro, MD, and Richard A. Komorowski, MD

 

Am J Clin Pathol 2002;118:895-902 Abstract quote

The identification of parathyroid gland tissue and its distinction from adjacent structures such as thyroid gland, lymphoid, fibroadipose, and, rarely, thymic tissues on frozen section (FS) may be challenging owing to freezing artifact. Intraoperative cytology (IC) provides valuable complementary morphologic details.

We evaluated 72 specimens with IC alone (group 1), followed by interpretation with FS to reach a final interpretation using IC and FS together (group 2). An additional 105 specimens were evaluated by FS alone (group 3). Permanent section diagnosis was used as the "gold standard." Sensitivity and specificity were 100% for group 2, compared with lower values for group 1 (98% and 100%, respectively) and group 3 (94% and 94%, respectively).

IC is a valuable adjunct to FS during intraoperative consultation for evaluation of tissue in a parathyroid location.

VARIANTS  
Salivary Heterotopia, Cysts, and the Parathyroid Gland
Branchial Pouch Derivatives and Remnants

J. Aidan Carney, M.D., Ph.D., F.R.C.P.I.

From the Department of Laboratory Medicine and Pathology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, U.S.A.

Am J Surg Pathol 2000;24:837-845 Abstract quote

Five cases of periparathyroid salivary heterotopia associated with cysts were studied.

The specimens were obtained from three men and two women age 36 to 62 years who underwent surgery for primary hyperparathyroidism (four patients) and thyroid nodule (one patient). The heterotopia–cyst combination occurred with normal and abnormal parathyroid glands (four inferior and one of unknown location).

Review of histologic slides of all parathyroid glands excised from 258 patients during a 1-year period at the Mayo Clinic revealed two similar salivary gland–cyst units. Seven more cases featured one or more periparathyroid cysts, five with other nonsalivary-type epithelial accompaniments. One of the latter additionally had a focus of parathyroid cells in the cyst wall, and associated thyroid parenchyma with C cells, and cartilage.

Sternberg S. Diagnostic Surgical Pathology. Third Edition. Lipincott Williams and Wilkins 1999


Commonly Used Terms With Diseases of the Parathyroid Glands

Chief Cells-One of the main cell types predominately present in adenomas and hyperplasias.

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Last Updated 1/30/2003

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