• Chapter 1: Management
• Chapter 2: Transcutaneous Bilirubin Testing
• Chapter 3: Use of Cardiac Biomarkers for Acute Coronary Syndromes
• Chapter 4: Coagulation
• Chapter 5: Critical care
• Chapter 6: Diagnosis and Management of Diabetes Mellitus
• Chapter 7: Drugs and Ethanol
• Chapter 8: Infectious Disease
• Chapter 9: Occult Blood
• Chapter 11: pH Testing
• Chapter 12: Renal Function Testing
• Chapter 13: Reproductive Testing

Primary Hyperparathyroidism

Does the addition of intraoperative parathyroid hormone (PTH) measurements to surgery for parathyroid disease improve the accuracy of identifying multiglandular disease compared to bilateral exploratory surgery? Does the addition of intraoperative PTH measurements to surgery for parathyroid disease improve the adequacy of resection or cure rate compared to bilateral exploratory surgery alone in patients with primary hyperparathyroidism? Does the addition of intraoperative PTH measurements to surgery for parathyroid disease improve morbidity or complication rate compared to bilateral exploratory surgery alone in patients with primary hyperparathyroidism? Does the use of intraoperative PTH measurements alone or in combination with a unilateral or minimally invasive surgical procedure for primary hyperparathyroidism improve use of local or regional anesthesia or extent of exploration (unilateral versus bilateral) compared to standard bilateral exploration? Does the use of intraoperative PTH measurements alone or in combination with a unilateral or minimally invasive surgical procedure for primary hyperparathyroidism improve use of frozen sections compared to standard bilateral exploration? Does the use of intraoperative PTH measurements alone or in combination with a unilateral or minimally invasive surgical procedure for primary hyperparathyroidism improve operating room time, operating room fees, overall hospital costs, or length of stay compared to standard bilateral exploration? Does the use of intraoperative PTH measurements alone or in combination with a unilateral or minimally invasive surgical procedure for primary hyperparathyroidism improve incision size/cosmetic result or patient satisfaction/pain compared to standard bilateral exploration?

Guideline 141. According to evidence for improved patient health and operational and economic outcomes, the guideline developers recommend routine use of intraoperative PTH testing for patients undergoing surgery for primary hyperparathyroidism and strongly recommend routine use in minimally invasive or directed procedures.
Strength/consensus of recommendation: A/B
Level of evidence: I, II, and III (randomized controlled trials, controlled trials, cohort study, case series, models and simulations, opinion)

Other Parathyroid Diseases

Does the addition of intraoperative PTH measurements to surgery for parathyroid disease improve the adequacy of resection or cure rate compared to bilateral exploratory surgery alone in patients with secondary or tertiary hyperparathyroidism? (Literature Search 68 - Refer to Appendix B - see the "Availability of Companion Documents" field)

Guideline 142. Numerous case series suggest a role for intraoperative PTH in secondary or tertiary hyperparathyroidism, yet no studies compared outcomes to surgical procedures in which intraoperative PTH testing was not used. In addition, criteria for expected changes in PTH concentrations after total or subtotal parathyroidectomy require further study. Therefore, the guideline developers make no recommendation for or against routinely providing intraoperative PTH testing for this application.
Strength/consensus of recommendation: I
Level of evidence: III (multiple case series, opinion)

Does the addition of intraoperative PTH measurements to surgery for parathyroid disease improve the adequacy of resection or cure rate compared to bilateral exploratory surgery alone in patients with reoperative disease? (Literature Search 69 - Refer to Appendix B - see the "Availability of Companion Documents" field)

Guideline 143. Evidence with respect to successful surgical outcome shows utility of intraoperative PTH in patients undergoing reoperation, and therefore we recommend that the assay be used routinely in this patient population.
Strength/consensus of recommendation: B
Level of evidence: II and III (controlled trials, multiple case series)

Does the addition of intraoperative PTH measurements to surgery for parathyroid disease improve the adequacy of resection or cure rate compared to bilateral exploratory surgery alone in patients with multiple endocrine neoplasia (MEN) I? (Literature Search 70 - Refer to Appendix B - see the "Availability of Companion Documents" field)

Guideline 144. The guideline developers make no recommendation for use of intraoperative PTH testing in patients with MEN I. Results were positive in several case studies and several larger retrospective series; however, the studies lacked control groups.
Strength/consensus of recommendation: I
Level of evidence: III (multiple case series)

Does the addition of intraoperative PTH measurements to surgery for parathyroid disease improve the adequacy of resection or cure rate compared to bilateral exploratory surgery alone in patients with parathyroid cancer? (Literature Search 71 - Refer to Appendix B - see the "Availability of Companion Documents" field)

Guideline 145. The guideline developers conclude that the evidence is insufficient to recommend for or against use of intraoperative PTH measurements in patients with parathyroid cancer.
Strength/consensus of recommendation: I
Level of evidence: III (multiple case series)

Localization

Does performing intraoperative PTH measurements in the angiography suite aid in identifying PTH gradients and result in a diagnostic study during venous localization compared to performing PTH measurements in the central laboratory? (Literature Search 72 - Refer to Appendix B - see the "Availability of Companion Documents" field)

Guideline 146. Despite limited evidence, the guideline developers recommend that intraoperative PTH measurements be considered as a replacement for traditional laboratory measurements of PTH during venous localization to provide real-time results to the angiography team to guide sampling.
Strength/consensus of recommendation: B
Level of evidence: III (case reports and series, and opinion)

Guideline 147. The guideline developers make no recommendation for use of rapid PTH tests in the operating suite for tumor localization because of conflicting studies. Although this may be a promising application for the rapid assay, additional studies are needed to determine whether this approach is better than more current and improved preoperative scanning techniques and the most appropriate population for use, such as reoperative cases, because routine use is not justified.
Strength/consensus of recommendation: I
Level of evidence: III (case series)

Secondary Questions

Is there evidence to support use of a specific assay? (Literature Search 73 - Refer to Appendix B - see the "Availability of Companion Documents" field)

Guideline 148. There is no evidence to suggest superiority of an intraoperative intact PTH assay from a particular manufacturer compared to available assays. The guideline developers do not recommend the use of a specific assay for intraoperative PTH monitoring. Additional studies comparing bio-intact or whole PTH rapid intraoperative assays to intact rapid intraoperative assays need to be performed to determine whether improved benefit exists.
Strength/consensus of recommendation: I
Level of evidence: III (comparative studies)

Is there evidence to support a recommended sampling protocol with respect to timing and number of samples or recommended criteria for interpretation of intraoperative PTH values? (Literature Search 74 - Refer to Appendix B - see the "Availability of Companion Documents" field)

Guideline 149. The guideline developers recommend in patients undergoing parathyroidectomy for primary hyperparathyroidism that baseline samples be obtained at preoperation/exploration and preexcision of the suspected hyperfunctioning gland. Specimens for PTH should be drawn at 5 and 10 min postresection, with a 50% reduction in PTH concentrations from the highest baseline as a criterion. Additional samples may be necessary. Kinetic analyses appear promising; however, more work needs to done to confirm their utility.
Strength/consensus of recommendation: A
Level of evidence: III (comparative studies and opinion)

Does performing intraoperative PTH measurements in or adjacent to the operating suite improve turnaround and operative times compared to performing intraoperative PTH measurements in the central laboratory with specimens transported via pneumatic tube or messenger? (Literature Search 75 - Refer to Appendix B - see the "Availability of Companion Documents" field)

Guideline 150. Evidence is lacking to recommend the location of intraoperative PTH testing either in or adjacent to the operating room or in the central laboratory. Important considerations such as interaction with the surgical team must be weighed in concert with costs and staffing issues. Studies to evaluate turnaround and operative times related to different locations have not been explicitly performed. Regardless of specific evidence, external validity may limit applicability to individual institutions.
Strength/consensus of recommendation: I
Level of evidence: III (comparative reports and series, and opinion)

Summary

In summary, according to strong impressions from relatively few controlled studies, intraoperative PTH is recommended for routine use in patients undergoing surgery for primary hyperparathyroidism, particularly in directed surgical approaches (see the Table below). This recommendation is based on evidence for improved patient/health, operational, and economic outcomes and applies to initial surgeries and in patients undergoing reoperative procedures. In contrast to the setting of primary hyperparathyroidism, further studies are needed to define the role of intraoperative PTH testing in patients with secondary/tertiary hyperparathyroidism, multiple endocrine neoplasia I, and parathyroid cancer. The number of commercial assays available for rapid PTH speaks to the interest in this point-of-care application. However, none of these assays was deemed superior, nor was there a recommendation for testing location. Future studies may serve to refine assay format and specificity, testing location, sampling protocols, and test interpretation, although standardization of some of these aspects of intraoperative PTH testing will be limited by institution-specific conditions. In addition to intraoperative monitoring during surgical resection, rapid PTH assays have potential applications in diagnostic localization. The assay is recommended for use in the angiography suite; however, additional studies are needed to determine whether or not the assay proves useful in the operating suite. Rapid PTH testing has spawned interest in using other rapid hormone tests intraoperatively and for tumor localization. Thus, the future is promising for rapid hormones in nonparathyroid disease applications, following in the footsteps of the rapid PTH model.

Table. Summary of Recommendations for Intraoperative PTH

Definitions:

Levels of Evidence

1. Evidence includes consistent results from well-designed, well-conducted studies in representative populations.
2. Evidence is sufficient to determine effects, but the strength of the evidence is limited by the number, quality, or consistency of the individual studies; generalizability to routine practice; or indirect nature of the evidence.
3. Evidence is insufficient to assess the effects on health outcomes because of limited number or power of studies, important flaws in their design or conduct, gaps in the chain of evidence, or lack of information.

Strength of Recommendations

A - The National Academy of Clinical Biochemistry (NACB) strongly recommends adoption; there is good evidence that it improves important health outcomes and concludes that benefits substantially outweigh harms.

B - The NACB recommends adoption; there is at least fair evidence that it improves important health outcomes and concludes that benefits outweigh harms.

C - The NACB recommends against adoption; there is evidence that it is ineffective or that harms outweigh benefits.

I - The NACB concludes that the evidence is insufficient to make recommendations; evidence that it is effective is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined.

Electronic copies: Available in Portable Document Format (PDF) from the National Academy of Clinical Biochemistry (NACB) Web site.

Print copies: National Academy of Clinical Biochemistry publications are available through American Association for Clinical Chemistry (AACC) Press. To make a purchase or request a catalog, contact AACC Customer Service at 202-857-0717 or custserv@aacc.org.

Electronic copies: Available in Portable Document Format (PDF) from the National Academy of Clinical Biochemistry (NACB) Web site.

Print copies: National Academy of Clinical Biochemistry publications are available through American Association for Clinical Chemistry (AACC) Press. To make a purchase or request a catalog, contact AACC Customer Service at 202-857-0717 or custserv@aacc.org.

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