Intraoperative parathyroid hormone assay to guide completion of parathyroid surgery

S Shaju; Melvin Varghese; N Saran; A Mohamad Safwam

doi:10.4103/ksj.ksj_40_22

ORIGINAL ARTICLE

Year : 2022 | Volume : 28 | Issue : 2 | Page : 178-181

Intraoperative parathyroid hormone assay to guide completion of parathyroid surgery

S Shaju, Melvin Varghese, N Saran, A Mohamad Safwam
Department of General Surgery, KIMSHEALTH Hospital, Thiruvananthapuram, Kerala, India

Date of Submission	18-Nov-2022
Date of Decision	02-Dec-2022
Date of Acceptance	25-Dec-2022
Date of Web Publication	30-Jan-2023

Correspondence Address:
Dr. S Shaju
Department of General Surgery, KIMSHEALTH Hospital, Thiruvananthapuram - 695 029, Kerala
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ksj.ksj_40_22

Abstract

Introduction: Primary hyperparathyroidism (pHPT) is characterised by an autonomous production of parathyroid hormone (PTH), which causes hypercalcemia. It is classified into adenoma, glandular hyperplasia and carcinoma. The standard treatment for the pHPT has been bilateral neck exploration (BNE) and the visualisation of all parathyroid glands. However, the increasing sensitivity of pre-operative localisation methods such as 99Tc-sestamibi scanning and ultrasound in combination with intra-operative PTH monitoring (ioPTH) assay can be utilised to decrease the need of BNE and subsequent complications. The aim of the study was to determine the effectiveness of ioPTH during parathyroidectomy and to assess the effectiveness of ioPTH in surgery for pHPT. Materials and Methods: Thirty-one patients admitted to the general surgery department in our tertiary care centre with hyper-parathyroidism and underwent parathyroidectomy, whose ioPTH evaluation was done were considered for the study. Their pre-operative and post-excision (10 min after excision of suspicious gland) values of PTH were as noted. Reduction in ioPTH value, based on MIAMI criteria was considered as the eradication of hyper-functioning tissues and its effectiveness in confirming the success of pHPT-surgery in terms of post-operative serum calcium level, thereby evaluating MIAMI criteria. Results: Twenty-nine (90.6%) patients showed a reduction of more than 50% in PTH following excision of suspicious glands from pre-operative PTH which is statistically significant, whereas only 21 (65.6%) patient shows normal PTH value following excision of suspicious gland. However, all 31 patients showed decline in PTH value as compared to pre-excision value. Conclusion: When the abnormal parathyroid gland is excised, there will be the reduction of PTH more than 50% from their pre-excisional value. Hence, by utilising ioPTH assay to confirm the excision of pathological gland, we can reduce BNE.

Keywords: Hyperparathyroidism, Miami criteria, parathyroid adenoma, parathyroid hormone, parathyroidectomy

How to cite this article:
Shaju S, Varghese M, Saran N, Safwam A M. Intraoperative parathyroid hormone assay to guide completion of parathyroid surgery. Kerala Surg J 2022;28:178-81

How to cite this URL:
Shaju S, Varghese M, Saran N, Safwam A M. Intraoperative parathyroid hormone assay to guide completion of parathyroid surgery. Kerala Surg J [serial online] 2022 [cited 2023 Mar 24];28:178-81. Available from: http://www.keralasurgj.com/text.asp?2022/28/2/178/368597

Introduction

Primary hyperparathyroidism (pHPT) is a clinical condition characterised by an autonomous production of parathyroid hormone (PTH), which causes hypercalcaemia and hypophosphataemia. pHPT can have serious clinical manifestations. Nearly all patients with parathyroid problems have symptoms such as kidney stones, frequent headaches, fatigue and depression. Sometimes, the symptoms are not so obvious, like high blood pressure and the inability to concentrate.^[1],[2] pHPT is due to single gland disease in approximately 70%–95% of cases, gland hyperplasia responsible for 15%, double adenoma 4% or rarely caused by parathyroid carcinoma.^[3],[4] Associations include familial syndromes such as Type 1 and 2 multiple endocrine neoplasia (MEN). The only curative treatment for pHPT is surgical removal of the pathologic glands (one or more).^{[1],[2],[5],[6]}

The valid operative standard for the pHPT has been bilateral neck exploration (BNE) and the visualisation of all parathyroid glands.^[2] However, the increasing sensitivity of pre-operative localisation methods such as 99Tc-sestamibi scanning and ultrasound in combination with intra-operative parathyroid hormone (ioPTH) monitoring assay can be utilised to decreases the need of BNE and subsequent complications.^[2]

Nowadays, ioPTH is widely used in the majority of centres practicing parathyroid surgery. The most important advantage of ioPTH is the possibility to confirm, intraoperatively, the complete removal of hyper-functioning parathyroid tissue or to guide the surge onto perform BNE.^{[7],[8],[9],[10],[11],[12]} Success is defined as a fall in PTH levels of >50% at 10 min post-excision compared to baseline (Miami criteria) with an accuracy of 97%.^[9],[10] The main reasons for an inappropriate ioPTH drop are multiglandular disease and microadenomas.^[11],[12]

The main goal of our study was to confirm the usefulness of ioPTH assay to guide the completion of pHPT surgery in view of decreasing BNE and confirming eradication of hyperfunctioning tissue.

Materials and Methods

The aim of the study was to determine the effectiveness of ioPTH monitoring during parathyroid surgery and to assess the effectiveness of ioPTH in surgery for pHPT.

It was a descriptive study from July 2017 to June 2019 on all patients admitted to the general surgery department in our tertiary care centre with hyperparathyroidism and underwent parathyroid surgery, whom ioPTH evaluation is done were considered for the study.

The sample size was calculated expecting the cases with primary hyperparathyroid to be 44%,^[13] to determine this with 95% confidence interval (CI) and relative precision of 20% sample size of 31 patients will be recruited to the study. This is calculated by the following equation

Accordingly, at least 31 patients should be included in the study.

Patients with recurrent hyperparathyroidism and non-consenting patients were excluded from the study. Thirty-two patients were selected as cases, their pre-operative and post-excision (10 min after excision of suspicious gland) values of PTH value were detected. Electrochemiluminescence immunoassay was intended for the use of determining intact PTH. Serum collected using standard sampling tubes was used in our hospital and samples centrifuged before performing assay.

Reduction in ioPTH value, based on MIAMI Criteria (The MIAMI criterion was defined as 50% decline from the highest pre-incision or pre-excision PTH level obtained 10 min after excision of the hyper-secreting parathyroid gland) was considered as the eradication of hyper-functioning tissues and the effectiveness of this ioPTH value in confirming the successfulness of pHPT-surgery in terms of post-operative serum calcium level, thereby evaluating MIAMI criteria.

All the data were entered into MS Excel and analysed using the statistical software SPSS version 16.0. Mean and standard deviation were used for the continuous variables. The categorical variables were summarised as frequency and percentages. The comparison between pre- and post-excision variables was done using the paired t-test. P < 0.05 was considered statistically significant. Results on continuous measurements were represented as mean and SD. Distributions were examined using the histograms. Paired t-test was used to compare the pre- and postvariables. P < 0.05 obtained was considered as statistically significant.

Results

In our study, out of 32 patients selected, 20 (62.5%) were female and 10 (37.5%) were male. Twenty-nine (90.6) patients show a PTH reduction following excision of suspicious glands more than 50% from their pre-excision PTH value with mean 78.7, SD 18.3, 95% CI 72.1–85.3 and P < 0.001 which is statistically significant [Table 1].

Table 1: Statistical analysis of post-operative percentage of parathyroid hormone reduction

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Among study population, only 21 patients (65.6%) shows post excision normal serum PTH which statistically significant and 11 patients (34.4%) showed high PTH [Table 2].

Table 2: Pre-operative serum calcium versus post-operative serum calcium

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Out of 32 patients, 24 patients (75%) showed normal serum calcium following excision of suspicious parathyroid gland in the subsequent post-operative days (before discharge). All patients showed normal serum calcium in the follow-up period within 1 month.

Discussion

From our descriptive study conducted among 32 patients in our tertiary care centre, 29 (90.6%) patients show a reduction of more than 50% in PTH following excision of suspicious glands from pre-operative PTH which is statistically significant, whereas only 21 (65.6%) patients showed normal PTH value (normal PTH-10–65 pg/ml) following excision of the suspicious gland. However, all 32 patients showed decline in PTH value as compared to pre-excision values.

Out of 32 patients, immediate post-operative serum calcium showed normal range in 24 patients (75%) and remaining 8 patients showed above normal calcium value, but 32 patients showed reduction in calcium level from pre-excision value. We followed up for 1 month with serum calcium level of all the 32 patient shows normal range thus confirming the excision of pathological gland.

Thus, the study found that a reduction of more than 50% in PTH following excision of suspicious gland was able to confirm that surgery was successful and there is no need of bilateral exploration. Post-excision PTH value need not be in the normal range to confirm the excision of pathological gland and it can remain elevated depending upon the pre-excision PTH.

Irvin et al.^[14] conducted a study on PTH levels from whole blood samples taken 10 min after excision of hyperfunctioning parathyroid glands and compared with pre-operative and pre-excision samples in patients undergoing 63 parathyroidectomies and arrived at conclusion, PTH assay was especially helpful in predicting post-operative calcium levels when multiple excisions were necessary to remove all hyperfunctioning tissue or some normal parathyroid glands were not visualised.

Chiu et al.^[15] evaluated 6-month post-operative IOPTH values and serum calcium levels. The IOPTH values at baseline (pre-incision and pre-excision) and at 5 and 10 min after parathyroidectomy were reviewed according to the Miami criterion (>50% drop from highest baseline IOPTH level at 10 min after excision), criterion 1 (>50% drop from pre-incision IOPTH level at 10 min), criterion 2 (>50% drop from highest baseline IOPTH level at 10 min and final IOPTH level within the reference range), criterion 3 (>50% drop from highest baseline IOPTH level at 10 min and final IOPTH level less than the pre-incision value), criterion 4 (>50% drop from highest baseline IOPTH level at 5 min), and criterion 5 (>50% drop from pre-excision IOPTH level at 10 min) and arrived at conclusion: Satisfying criterion 2 had a high operative success but resulted in additional unnecessary surgical exploration. Criterion 1 was better at predicting post-operative normocalcemia than criterion 2.

Wharry et al.^[16] studied 1108 initial parathyroid operations for sporadic HPT using IOPTH monitoring from 1997 to 2011 stratified by final post-resection IOPTH level. All patients had adequate follow-up to verify cure and arrived at conclusion: Adjunctive ioPTH monitoring facilitates a high cure rate for initial surgery of sporadic pHPT. A final IOPTH level that is within the normal range and drops by >50% from baseline is a strong predictor of operative success. Patients with a final IOPTH level between 41 and 65 pg/mL should be followed beyond 6 months for long-term recurrence.

Westerdahl and Bergenfelz^[17] studied 269 consecutive patients with sporadic pHPT who underwent first-time parathyroid surgery with ioPTH measurement and followed up for as long as 10 years after surgery. With an average follow-up of 3.6 years (range, 6–120 months), the overall cure rate was 96%. The ioPTH level correctly predicted long-term outcome in 248 (92%) of 269 patients. Six patients had a false-positive ioPTH finding. Five of these patients were found to have germline mutations in the gene for MEN and arrived at conclusion: Intraoperative measurement of PTH level has a high overall accuracy with a mean follow-up of 3.6 years. However, among the late surgical failures with false-positive ioPTH findings, overlooked mutations in the MEN gene should be suspected, and therefore genetic analyses in these patients are of great importance.

The limitations of our study are, we included only the patients' in our hospital, hence the study population was limited to 32. This study required more number of patients from other hospitals to increase the study population and arrive at more accurate results. Determining PTH intra-operatively following the excision of suspicious glands may require fast actions since PTH has a half-life of 3–5 min. Delay in any step of specimen collection, preparation and transportation of the samples will interfere with results. Availability of ioPTH measurement was limited to a less number of hospitals.

Conclusion

We concluded that when the abnormal parathyroid glands are excised, there will be reduction of PTH more than 50% from their pre-excisional value. Hence, by utilising ioPTH assay to confirm the excision of pathological gland, we can reduce BNE.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Gasparri G, Camandona M, Palestini N. Primary, Secondary and Tertiary Hyperparathyroidism: Diagnostic and Therapeutic Updates. Gasparri G, Palestini N, Camandona M (eds), USA: Springer; 2015.
2.	Madkhali T, Alhefdhi A, Chen H, Elfenbein D. Primary hyperparathyroidism. Turk J Surg 2016;915:58-66.
3.	Reiher AE, Schaefer S, Chen H, Sippel RS. Does the final intraoperative PTH level really have to fall into the normal range to signify cure? Ann Surg Oncol 2012;19:1862-7.
4.	Taubman ML, Goldfarb M, Lew JI. Role of SPECT and SPECT/CT in the surgical treatment of primary hyperparathyroidism. Int J Mol Imaging 2011;2011:141593.
5.	Marcocci C, Cianferotti L, Cetani F. Bone disease in primary hyperparathyrodism. Ther Adv Musculoskelet Dis 2012;4:357-68.
6.	Barczynski M, Golkowski F, Konturek A, Buziak-Bereza M, Cichon S, Hubalewska-Dydejczyk A, et al. Technetium-99m-sestamibi subtraction scintigraphy versus ultrasonography combined with a rapid parathyroid hormone assay in parathyroid aspirates in preoperative localization of parathyroid adenomas and in directing surgical approach. Clin Endocrinol (Oxf) 2006;65:106-13.
7.	Hughes DT, Miller BS, Doherty GM, Gauger PG. Intraoperative parathyroid hormone monitoring in patients with recognized multiglandular primary hyperparathyroidism. World J Surg 2011;35:336-41.
8.	Grant CS, Thompson G, Farley D, van Heerden J. Primary hyperparathyroidism surgical management since the introduction of minimally invasive parathyroidectomy: Mayo clinic experience. Arch Surg 2005;140:472-8.
9.	Barczynski M. Minimally invasive parathyroidectomy without intraoperative parathyroid hormone monitoring: When and why? J Postgrad Med 2009;55:239-40. [PUBMED] [Full text]
10.	Sokoll LJ, Wians FH Jr., Remaley AT. Rapid intraoperative immunoassay of parathyroid hormone and other hormones: A new paradigm for point-of-care testing. Clin Chem 2004;50:1126-35.
11.	Barczynski M, Konturek A, Cichon S, Hubalewska-Dydejczyk A, Golkowski F, Huszno B. Intraoperative parathyroid hormone assay improves outcomes of minimally invasive parathyroidectomy mainly in patients with a presumed solitary parathyroid adenoma and missing concordance of preoperative imaging. Clin Endocrinol (Oxf) 2007;66:878-85.
12.	Khan AA, Khatun Y, Walker A, Jimeno J, Hubbard JG. Role of intraoperative PTH monitoring and surgical approach in primary hyperparathyroidism. Ann Med Surg (Lond) 2015;4:301-5
13.	Jortay AM, Verougstraete G, Wittersheim E, Hooghe L, Bisschop P, Bergmann P. Intraoperative measurement of parathyroid hormone in minimally invasive surgery for parathyroid adenoma. Acta Otorhinolaryngol Belg 2004;58:125-8.
14.	Irvin GL 3^rd, Dembrow VD, Prudhomme DL. Clinical usefulness of an intraoperative “quick parathyroid hormone” assay. Surgery 1993;114:1019-22.
15.	Chiu B, Sturgeon C, Angelos P. Which intraoperative parathyroid hormone assay criterion best predicts operative success? A study of 352 consecutive patients. Arch Surg 2006;141:483-7.
16.	Wharry LI, Yip L, Armstrong MJ, Virji MA, Stang MT, Carty SE, et al. The final intraoperative parathyroid hormone level: How low should it go? World J Surg 2014;38:558-63.
17.	Westerdahl J, Bergenfelz A. Parathyroid surgical failures with sufficient decline of intraoperative parathyroid hormone levels: Unobserved multiple endocrine neoplasia as an explanation. Arch Surg 2006;141:589-94.