Intraoperative monitoring of intact PTH during surgery for primary hyperparathyroidism

The intraoperative differential diagnosis between adenoma and hyperplasia during surgery for primary hyperparathyroidism (pHPT) is sometimes difficult. Several methods have been proposed to aid the surgeon in deciding on the amount of parathyroid tissue to be resected. We examined the use of intraoperative monitoring of intact PTH in 47 patients operated upon for pHPT. The highly sensitive assay for intact PTH was modified to permit a total turn-around time from gland excision to obtained result of about 60 min. The correlation (r) between the results of the modified and the conventional method; which requires 24 h of incubation, was 0.98. At 15 min after removal of the parathyroid adenoma the levels of intact PTH had decreased by [mean (SD)] 85 (11)%. A decrease of 63% in intact PTH in patients with parathyroid adenoma predicted with 95% confidence the 4 patients with primary hyperplasia as not having parathyroid adenoma. We conclude that intraoperative measurement of intact PTH could be a valuable adjunct to surgical skill, especially for reoperative parathyroid surgery.

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Intraoperatives monitoring der intakten PTH-sekretion bei eingriffen wegen primärem Hyperparathyreoidismus

Zusammenfassung Die intraoperative Differentialdiagnose zwischen Adenom und Hyperplasie bereitet bei Eingriffen wegen primarem Hyperparathyreoidismus (pHPT) gelegentlich Schwierigkeiten. Es wurden verschiedene Methoden vorgeschlagen, nach denen der Chirurg entscheiden kann, wieviel parathyreoides Gewebe zu resezieren ist. Wir untersuchten bei 47 Patienten, die wegen pHPT operiert wurden, die Anwendung des intraoperativen Monitoring der intakten PTH-Sekretion. Der entsprechende hochsensitive PTH-Assay wurde modifiziert, damit ein komplettes Resultat von der Exzision an über 60 min zu erzielen war. Die Korrelation r zwischen den Ergebnissen nach modifizierter und konventioneller Methode (die eine 24-h-Inkubation erfordert) betrug 0,98. Die intakte PTH-Sekretion verringerte sich 15 min nach Entfernung des parathyreoiden Adenoms um 85 (11)% [Mittelwert (SD)]. Die Patienten mit parathyreoidem Adenom wiesen eine PTH-Verringerung von 63% auf; dies ließ bei den 4 Patienten mit primärer Hyperplasie zu 95% zuverlässig erkennen, daß sie kein parathyreoides Adenom hatten. Wir folgern daraus, daß die intraoperative Messung der PTH-Sekretion ein wichtiges chirurgisches Hilfsmittel (insbesondere bei Reoperationen) sein kann.

This study was supported by grants from the Medical Faculty, Lund University, Lund, Sweden     

Predictive value of intact parathyroid hormone measurement during surgery for renal hyperparathyroidism

Background and aims In contrast to that in patients with primary hyperparathyroidism, the value of intraoperative intact parathyroid hormone (iPTH) measurement is still unclear in patients with renal hyperparathyroidism and was, therefore, evaluated in a large cohort of patients.Patients Intraoperative iPTH measurement was performed in 153 patients with renal hyperparathyroidism (129 with terminal renal failure and 24 with functioning kidney graft). Subtotal and total parathyroidectomy were performed in 123 and 13 patients, respectively, during initial surgery. In patients with recurrent disease (17), the respective hyperfunctioning tissue was removed. Intraoperative blood samples were obtained by puncture of the internal jugular vein before preparation of the parathyroids (PTH₀) and 15 min after parathyroidectomy (PTH₁₅). iPTH was measured with the Elecsys 2010 system. Postoperative iPTH levels (PTH_post) were determined at postoperative days 1 to 3 and at week 2. Patients were arbitrarily divided in four groups according to the postoperative iPTH values: 0–25 pg/ml (group 1), 26–65 pg/ml (group 2), 66–150 pg/ml (group 3) and more than 150 pg/ml (group 4).Results The mean PTH₀ value was 869±57 pg/ml, which decreased to 167±15 pg/ml at PTH₁₅. The mean relative PTH₁₅ value was 21.6±1.7%. Postoperatively, iPTH decreased to 42±9 pg/ml. The postoperative iPTH value of the 129 patients with terminal renal failure was 25 pg/ml or less in 99 patients, 26–65 pg/ml in 11 patients, 66–150 pg/ml in eight patients and higher than 150 pg/ml in 11 patients. Two successive criteria of iPTH decrease were used: first, a PTH₁₅ of 150 pg/ml or, second, a relative PTH₁₅ of 30% less was used. Fifteen patients did not fulfil both criteria. In 13 of them (86.7%) iPTH_post was higher than 65 pg (true failure to decline). Of 114 patients who fulfilled the criteria, 108 (94.7%) had normal postoperative iPTH values (true decline). Absolute PTH₁₅ values of less than 150 pg/ml predicted normal postoperative iPTH levels in 77 of 78 patients.Conclusion A PTH₁₅ value of 150 pg/ml or less predicts operative success in patients with renal failure in 98.7% of cases, independently of the relative decay. In contrast, if the relative PTH₁₅ is higher than 30%, high postoperative PTH values are predicted with a probability of 86.7%. Although there remain some borderline cases, intraoperative iPTH measurement is accurate and also can be useful in patients with renal hyperparathyroidism.The paper was presented at the first constitutive meeting of the European Society of Endocrine Surgeons (ESES) in Pisa, Italy, on 14–15 May 2004     

Intraoperative parathyroid hormone monitoring during parathyroidectomy for hyperparathyroidism in waiting list and kidney transplant patients

This report describes the use of the intraoperative parathyroid hormone (ioPTH) assay during parathyroidectomy in waiting list and transplanted patients. ioPTH levels were determined in 40 patients on the waiting list for kidney transplantation with secondary hyperparathyroidism who underwent subtotal parathyroidectomy and 9 transplanted patients with tertiary hyperparathyroidism who underwent removal of hyperplasic glands. Rapid PTH levels decreased significantly at each time period; the percentage decrease in rapid PTH levels was 61.3% among patients with IPT II and 70.2% in patients with IPT III at 10 minutes and 86.5% in patients with IPT II and 91% in patients with IPT III at 15 minutes after excision of hypersecreting parathyroid tissue. A decrease of 50% or more from baseline PTH levels at 10 minutes and/or a decrease of 85% or more at 15 minutes predicted successful removal of abnormal parathyroid glands. The application of this technique during subtotal parathyroidectomy has proved useful for correct excision of parathyroid glands among waiting list patients with IPT II, while in kidney transplant patients with IPT III it allowed removal of only the pathological glands with a limited surgical approach.     

The role of parathyroid hormone measurements after surgery for primary hyperparathyroidism

BACKGROUND: During parathyroidectomy for primary hyperparathyroidism (pHPT), intraoperative parathyroid hormone (IOPTH) levels are used to confirm removal of all hyperfunctioning parathyroid tissue. The phenomenon of elevated parathyroid hormone (PTH) levels with normocalcemia after curative parathyroidectomy, seen in up to 40% of patients, continues to be an unexpected and unexplained finding. We therefore investigated whether postoperative PTH levels are as reliable as IOPTH levels in predicting cure after surgery for pHPT. METHODS: We reviewed our prospective database of consecutive patients undergoing surgery for pHPT between December 1999 and November 2004. Curative parathyroidectomy was defined as normocalcemia 6 months or longer postoperatively. RESULTS: A total of 328 patients who underwent 330 operations for pHPT had IOPTH measurements and serum follow-up calcium levels at 6 months or longer. Surgery was curative in 315 (95.5%) operations. IOPTH levels correctly predicted operative success in 98.2% (positive predictive value [PPV]. Postoperatively, the PPV of a normal PTH level at 1 week, 3 months, and 6 months was 97.1%, 97.3%, and 96.5%, respectively. Of all patients with an elevated postoperative PTH level at 1 week, 3 months, or 6 months, only 13.7%, 14.3%, and 14%, respectively, were not cured. CONCLUSIONS: Normal postoperative PTH levels reliably predict operative success. However, they do not improve upon results predicted by IOPTH levels. Elevated postoperative PTH levels do not predict operative failure in most patients. We propose that PTH measurements after surgery for pHPT may be misleading, costly, and not indicated in normocalcemic patients.     

Reassessment of parathyroid hormone monitoring during parathyroidectomy for primary hyperparathyroidism after 2 preoperative localization studies

HYPOTHESIS: For patients with primary hyperparathyroidism and patients with 2 localization studies showing the same single location of parathyroid disease, use of intraoperative parathyroid hormone (IOPTH) measurement does not significantly increase the success of minimally invasive parathyroidectomy. DESIGN: Retrospective cohort study. SETTING: Experience of 2 academic centers over 5 years (at Brigham and Women's Hospital, Boston, Mass) and almost 4 years (at Rhode Island Hospital, Providence). PATIENTS: A total of 569 patients with primary hyperparathyroidism who underwent technetium Tc 99m sestamibi (MIBI) parathyroid imaging and neck ultrasonography (US). MAIN OUTCOME MEASURES: Incidence of correct prediction of location and extent of disease. RESULTS: In 322 patients (57%), MIBI and US imaging identified the same single site of disease. In 319 (99%) of these 322 patients, surgical exploration confirmed a parathyroid adenoma at that site, and the IOPTH levels normalized on removal. In 3 (1%) of the 322 patients, IOPTH measurement identified unsuspected additional disease. In 3 (1%) of the remaining 319 patients, IOPTH-guided removal of a single adenoma failed to correct hypercalcemia. Therefore, the failure rate of surgery in patients with positive MIBI and positive US imaging was 1% with IOPTH measurement and 2% without IOPTH measurement (P = .50). In 201 (35%) of the 569 patients, only 1 of the 2 studies recognized an abnormality or the studies disagreed on location. In these cases, either MIBI imaging or US imaging (if MIBI imaging was negative) failed to predict the correct site or extent of disease in 76 (38%) of the 201 patients (P<.001 vs concordant studies). CONCLUSIONS: In primary hyperparathyroidism, concordant preoperative localization with MIBI and US imaging is highly accurate. Use of IOPTH measurement in these cases adds only marginal benefit. When only 1 of the 2 studies identifies disease or the studies conflict, however, IOPTH measurement remains essential during minimally invasive parathyroidectomy.     

Pitfalls of intraoperative quick parathyroid hormone monitoring and gamma probe localization in surgery for primary hyperparathyroidism

HYPOTHESIS: Intraoperative quick parathyroid hormone (qPTH) monitoring and gamma probe (GP) localization greatly aid the surgeon. DESIGN: Prospective case series of patients undergoing parathyroidectomy (PTX) with preoperative localization studies, operative data (including intraoperative qPTH values and GP localization), and outcomes. Follow-up was complete (mean, 4.2 months). SETTING: University teaching hospital. PATIENTS: We studied 57 consecutive patients with primary hyperparathyroidism from December 1, 1999, through November 30, 2000. Of these, 51 underwent first-time PTX, and 6, reoperative PTX (rePTX). MAIN OUTCOME MEASURES: Cure rate and morbidity after PTX or rePTX; sensitivity and accuracy of preoperative localization studies; prediction of cure from results of qPTH monitoring (comparing Nichols [>50% fall from the highest baseline level and lower than the lowest baseline] or normal-limit [>50% fall from first baseline level and lower than upper limit of the reference range] criteria); and value of GP localization. RESULTS: Patients were cured in 50 (98%) of 51 PTX and 6 (100%) of 6 rePTX for single adenomas (n = 49), double adenomas (n = 4), and multigland hyperplasia (n = 3). Nichols criteria for qPTH monitoring correctly categorized 45 (92%) of 49 cured single adenomas 10 minutes after excision. Only 35 (71%) of these adenomas were correctly categorized as cured by means of the normal-limit criteria. In double adenomas, both sets of criteria in the 10-minute samples indicated unresected glands in only 2 of 4 cases. Preoperative sestamibi parathyroid scans correctly localized 38 (76%) of 50 single adenomas. The GP was used in 54 of 57 cases. All adenomas measured greater than 20% of background ex vivo, but 6 thyroid nodules also measured greater than 20% ex vivo. In double adenomas, the GP helped locate the second adenoma in only 1 of 4 cases. The GP was graded as crucial in 2 cases with dense scar (both rePTX), helpful in 12 (22%) of 54 cases (particularly in retroesophageal glands), confirmatory in 32 (59%), and not helpful in 8 (15%). The GP helped localize 3 (43%) of 7 glands not seen on sestamibi parathyroid scans. CONCLUSIONS: Intraoperative qPTH monitoring confirmed cure in most cases. For single adenomas, use of the Nichols criteria for qPTH assessment allowed more accurate and faster confirmation than the normal-limit criteria. The GP was less useful but was crucial in 2 rePTX cases; it was not specific for parathyroid tissue. Both techniques have potential pitfalls that could result in surgical failure.     

Intraoperative measurement of intact parathyroid hormone in renal hyperparathyroidism by an inexpensive routine assay

Although the kinetics of intraoperative intact parathyroid hormone (iPTH) are well characterised in primary hyperparathyroidism, no data are available for patients with renal hyperparathyroidism and renal insufficiency, partially because of the high costs of intraoperative quick iPTH measurement. Therefore we evaluated an inexpensive laboratory test with a duration of 18 min for intraoperative use and measured iPTH intraoperatively in 34 patients with renal hyperparathyroidism. Samples were taken before and 5 min and 15 min after parathyroid resection. Blood samples were put on ice immediately and sent to the hospital central laboratory via a pneumatic tube system. The first 76 probes were measured in parallel using three assays: the Nichols Quick PTH, the Roche Elecsys and the Biermann Immulite assay. The subsequent samples were only measured using the Elecsys assay. Determination of iPTH from 76 samples showed a correlation coefficient of 0.997 between the Immulite and Elecsys assay and a correlation coefficient of 0.987 for the Nichols Quick PTH and the Elecsys test. In renal hyperparathyroidism the mean iPTH was 26+/-2% of the starting value 5 min after subtotal parathyroidectomy and 18+/-2% after 15 min. Renal function influenced absolute iPTH values in patients with renal hyperparathyroidism but not relative changes. In patients with terminal renal insufficiency iPTH decreased from 615+/-57 pg/m before preparation to 109+/-13 pg/ml 15 min after subtotal resection. In contrast in patients after kidney transplantation iPTH decreased from a lower starting value of 341+/-94 pg/ml to 58+/-9 pg/ml after 15 min. The iPTH kinetics showed a biphasic clearance of iPTH with an initial dominant half-life of 3.2 min and a terminal half-life of 29.2 min. Half-life did not correlate with renal function. All operations were successful as indicated by an adequate drop in PTH (from 709+/-92 pg/ml preoperatively to 22+/-6 pg/ml at discharge) and calcium (from 2.57+/-0.04 mmol/l to 2.32+/-0.04 mmol/l). In conclusion, intraoperative measurement of iPTH is also reliable in patients with renal hyperparathyroidism. Elimination kinetics are similar to that in patients with primary disease. However, the half-life was not influenced by renal function. The availability of a quick, inexpensive, routine iPTH test might expand its use to renal hyperparathyroidism, specifically for surgical decisions in problem cases.     

原发性甲状旁腺机能亢进患者术中监测甲状旁腺激素的临床意义

目的：探讨原发性甲状旁腺机能亢进症（PHPT）患者术中动态监测甲状旁腺激素（IOPTH）的临床价值。 方法：回顾性分析1998年1月—2012年1月行手术治疗的36例PHPT患者的临床资料,其中2005年以后术中行IOPTH监测患者22例（IOPTH组）,2005年以前术中未行IOPTH监测的患者14例（常规组）,比较两组的术中情况与治疗效果。 结果：与常规组比较,IOPTH组手术时间明显缩短[（72.95±24.34）min vs.（81.86±29.46）min,P=0.000],术后短期（1个月内）甲状旁腺功能恢复患者比例增加（90.9% vs. 57.1%,P=0.018）,永久性甲状旁腺功能减退发生率明显减少（4.5% vs. 28.6%,P=0.042）。IOPTH监测对于判断高功能病灶完全切除与否的敏感度为100%,准确率为95.5%。 结论：PHPT手术中,在术前定位基础上联合IOPTH,有助于判断功能亢进腺体是否全部切除,避免遗漏多发病变腺体及不必要的双侧探查,缩短手术时间,疗效确切。     

Influence of concurrent chronic kidney disease on intraoperative parathyroid hormone monitoring during parathyroidectomy for primary hyperparathyroidism

Background

The influence of chronic kidney disease on intraoperative parathyroid hormone monitoring during parathyroidectomy for primary hyperparathyroidism has not been well-established. We hypothesize that chronic kidney disease influences intraoperative parathyroid hormone degradation kinetics during parathyroidectomy.

Comparison of parathyroid hormone levels from the intact and whole parathyroid hormone assays after parathyroidectomy for primary and secondary hyperparathyroidism

BACKGROUND: Most commercial intact parathyroid hormone (intact PTH) assays cross-react with non-(1-84) PTH (likely 7-84 PTH). Using a whole-molecule PTH (whole PTH) assay that specifically measured only 1-84 PTH, we compared the kinetics of whole PTH and intact PTH after parathyroidectomy in patients with primary hyperparathyroidism (HPT) and secondary HPT. METHODS: This study comprised 74 patients with primary HPT caused by a single adenoma and 18 patients with secondary HPT who underwent parathyroidectomy. Blood samples were drawn after anesthesia, just before excision of a single adenoma in primary HPT, and just before excision of the last parathyroid gland in secondary HPT, and at 5, 10, and 15 minutes after excision. The 7-84 PTH level was calculated by subtracting the whole PTH value from the intact PTH value. RESULTS: There was a difference between the percentage of 7-84 PTH/intact PTH in plasma samples from patients with primary HPT and secondary HPT (28%+/-12% vs 35%+/-9%; P<.05). Plasma whole PTH decreased more rapidly than intact PTH after parathyroidectomy in patients in both the primary HPT (P<.0001) and secondary HPT groups (P<.0001). Decline of intact PTH was slower in patients with secondary HPT than in patients with primary HPT; however, there was no significant difference in the decline of whole PTH between the 2 groups. CONCLUSIONS: The quick intact PTH assay is not used frequently during surgery in patients with secondary HPT; however, our results suggest that a quick whole PTH assay may be a more useful adjunct to parathyroidectomy in both secondary HPT and primary HPT.     

Intraoperative adjuncts in surgery for primary hyperparathyroidism

Purpose  This paper is a review of the evidence base to produce recommendations for the use of intraoperative parathyroid hormone (PTH), radioguided parathyroidectomy (RGP), methylene blue (MB), frozen section, and intraoperative neuromonitoring during surgery for primary hyperparathyroidism (PHPT). Materials and methods  A Medline keyword search of English-language articles led to the production of a draft document, subsequently revised by committee, containing levels of evidence and the grading of recommendations as proposed by the Agency for Healthcare Research and Quality. Results  Literature review provides the basis for clear recommendations on the use of intraoperative PTH at surgery for PHPT. There is little evidence to support the use of RGP, MB, routine frozen section, and intraoperative neuromonitoring.     

Intact parathyroid hormone in primary hyperparathyroidism

In 49 patients with primary hyperparathyroidism, intact parathyroid hormone (PTH) was measured with a recently developed immunoradiometric assay, and midregional PTH fragments (sequence 44-68) were measured with an established radioimmunoassay technique. In 47 normal subjects, the concentration of intact PTH ranged from 2.0 to 6.8 pmol/l, and in 49 patients with primary hyperparathyroidism it ranged from 6.4 to 80.0 pmol/l. In contrast, midregional PTH fragments were normal in seven of 49 patients with primary hyperparathyroidism. In five healthy controls and in 12 patients with surgically confirmed primary hyperparathyroidism and serum calcium levels below 3.0 mmol/l, a rapid calcium loading test was performed. In healthy controls, intact PTH was in the low normal to subnormal range within 2.5-5.0 min, and had recovered within 15 min of calcium infusion. In patients with primary hyperparathyroidism, the calcium infusion also led to a 30-50 per cent decrease in intact PTH levels within 5.0-7.5 min after injection, with a slow recovery after 10-15 min. In six of the patients with only slightly elevated basal intact PTH, a suppression to the normal range was observed. In 24 patients (16 patients with a solitary adenoma and eight patients with four-gland hyperplasia) the intact PTH levels were followed intraoperatively during parathyroidectomy, revealing a significantly different rate of decline for single adenomas compared with hyperplasia during the first 15 min after removal of the primary enlarged gland. Intact PTH values remained constantly elevated in one patient with primary hyperparathyroidism and an unsuccessful neck exploration. These results confirm that (a) the measurement of intact PTH in patients with primary hyperparathyroidism is superior to the measurement of midregional fragments; (b) PTH secretion in primary hyperparathyroidism is not totally autonomous; and (c) intraoperative monitoring of intact PTH values could be used to monitor the success of surgery.     

Intraoperative parathyroid hormone measurement in patients with secondary hyperparathyroidism

HYPOTHESIS: Secondary hyperparathyroidism decreases renal clearance of parathyroid hormone (PTH). OBJECTIVE: To determine whether rapid PTH assays can be used to predict the success of a total parathyroidectomy to treat symptomatic secondary hyperparathyroidism. DESIGN: Case series from August 1 to December 31, 2000. SETTING: Tertiary referral center. PARTICIPANTS: Patients with symptomatic secondary hyperparathyroidism (n = 24) who underwent total parathyroidectomy and autotransplantation were included in the study. INTERVENTIONS: Blood samples for rapid PTH analyses were drawn from an indwelling catheter at the induction of anesthesia (baseline) and before (0 minutes), 10 minutes, and 30 minutes after the removal of the last parathyroid gland. Regular intact PTH (iPTH) assays were conducted later. MAIN OUTCOME MEASURE: If a patient's regular iPTH levels were below 65 pg/mL at 1 week or 3 months postoperatively, the operation was considered successful. RESULTS: All 24 patients had successful operations. Rapid PTH and regular iPTH correlated significantly at 0, 10, and 30 minutes. Rapid PTH levels decreased significantly at each time period and were 176 +/- 40.9 pg/mL (mean +/- SE) at 10 minutes. The percentage decrease in rapid PTH levels was 39.5% +/- 12.7% at 0 minutes, 75.1% +/- 6.2% at 10 minutes, and 91.0% +/- 0.1% at 30 minutes (mean +/- SE). A decrease of 60% or more from baseline PTH levels at 10 minutes and/or a decrease of 85% or more at 30 minutes predicted the successful removal of all parathyroid glands. CONCLUSIONS: A drop in PTH levels is delayed until 30 minutes after total parathyroidectomy; however, a rapid PTH assay 10 minutes after the removal of the last parathyroid gland is as accurate as an assay performed at 30 minutes postoperatively. Intraoperative PTH monitoring demonstrates relevant decreases in rapid PTH levels after parathyroidectomy that are similar to those previously documented in patients with primary hyperparathyroidism.     

Disturbance of basal and stimulated serum levels of intact parathyroid hormone in primary hyperparathyroidism

In patients with primary hyperparathyroidism, measurements were made of basal and stimulated levels of intact parathyroid hormone (PTH). The basal PTH values were elevated in all but six of 89 patients and provided clear separation towards normal individuals (n = 75) and patients with hypercalcemia of other origin (n = 34). The PTH value correlated with the serum calcium concentration in hyperparathyroidism and with the weight of excised parathyroid adenomas but not with that of chief cell hyperplasias. A constant ethylenediaminetetraacetic acid infusion during 60 minutes of induced essentially linear reductions of plasma-ionized calcium concentrations, averaging 0.02 mmol/L/10 minutes, which were associated with swift, curvilinear, elevations of PTH levels that reached a plateau after 10 to 20 minutes. The increment in serum PTH level correlated with the basal PTH value both in patients with hyperparathyroidism and controls. However, in proportion to the much greater glandular mass in the patients with hyperparathyroidism, the secretion of PTH was relatively reduced. The findings support the value of the intact PTH assay in the differential diagnosis of hypercalcemia and show that PTH secretion in vivo is extremely sensitive to hypocalcemic stimulation, that the pathological parathyroid tissue in hyperparathyroidism is characterized by a reduction of hormone release per unit weight, and that the hormone secretion in hyperparathyroidism operates closer to its maximal capacity than under normal circumstances.     

Intraoperative monitoring of kinetic total serum calcium levels in primary hyperparathyroidism surgery

BACKGROUND: In the setting of minimal approach Sestamibi-guided parathyroid surgery for primary hyperparathyroidism we evaluated if total serum calcium level monitoring is as valuable as intraoperative parathyroid hormone (iPTH) monitoring. STUDY DESIGN: Prospective open single-blinded efficacy trial of two intraoperative diagnostic monitoring methods (iPTH and total serum calcium level) on a cohort of surgical patients. All patients (n = 35) were undergoing parathyroid surgery at the Department of General Surgery at B Cruces' Hospital, Vizcaya, Spain, between October 1999 and March 2001. Kinetics of serum levels of Ca and iPTH during surgery and time of prediction of cure for each method (measured in the clinic, admission, and intraoperatively, such as induction of anesthesia, and every 5 minutes after removal of adenoma) were analyzed. RESULTS: Hypercalcemia and iPTH levels became corrected in 34 patients. Average serum calcium levels dropped from pathologic 11.07 +/- 0.41 mg/dL (mean +/- standard deviation) to normal values 9.7 +/- 0.82 mg/dL during the first intraoperative determination (minute 5), but mean iPTH decreased from pathologic (192 +/- 98 pg/mL) to normal values (39.93 +/- 25.12 pg/mL) during the third intraoperative determination (minute 15). Serum calcium level at 5 minutes after removal decreased by 100% in 34 patients, but iPTH only showed a similar drop during the third determination at 15 minutes. Frozen sections were conclusive for parathyroid tissue (20.56 +/- 10.3 minutes after removal). CONCLUSIONS: Intraoperative measurement of total calcium level might be an easier and less expensive method than iPTH measurement in the prediction of cure during surgery for primary hyperparathyroidism resulting from adenoma.     

Dynamics of parathyroid hormone release and serum calcium regulation after surgery for primary hyperparathyroidism

Analysis of 14 patients with primary hyperparathyroidism (HPT) prior to and during the first year after parathyroid surgery disclosed that the operation was associated with rapid reductions of intact serum parathyroid hormone (PTH) and total serum and ionized plasma calcium values. A decreased urinary calcium excretion, a gradual elevation of renal calcium reabsorption, a transient reduction of serum calcitriol, and a late increase in 25-hydroxycholecalciferol values were also noted. Dynamic tests of parathyroid function by EDTA infusion and an oral calcium load revealed a sigmoidal relationship between serum PTH and calcium levels, and that parathyroid surgery induced considerable changes in both the position and slope of the dose-response curve. It was also apparent that PTH release was submaximally stimulated event at periods of hypocalcemia. The findings substantiate that adjustments of PTH release to acute alterations of serum calcium occur along the prevailing dose-response relationship, while stimuli being maintained for longer periods of time induce compensatory shifts in the position and slope of this curve. It is further suggested that unknown factors with PTH-like function may participate in the calcium regulation after surgery for primary HPT.

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Resumen El análisis de 14 pacientes con hiperparatiroidismo primario (HPT) realizado antes y durante el primer año siguiente a cirugía paratiroidea demostró que la operación estuvo asociada con una reducción rápida del nivel sérico de la hormona paratiroidea intacta (PTH) y de los valores séricos de calcio total y de calcio ionizado. También se observó una disminución en la excreción urinaria de calcio, una elevación gradual de la reabsorción renal de calcio, una reducción transitoria del calcitriol sérico y un incremento tardío de los valores de 25-hidroxicolecalciferol. Las pruebas dinámicas de función paratiroidea mediante la infusión de EDTA y una carga oral de calcio revelaron una relación que se expresa como curva sigmoidea entre los niveles séricos de PTH y los de calcio, y que la cirugía paratiroidea indujo cambios considerables tanto en la posición como en la inclinación de la curva dosis-dependiente. También resultó aparente que la liberación de PTH aparecía submáximamente estimulada aun en periodos de hipocalcemia. Los hallazgos confirman que los ajustes en la liberación de PTH, ante alteraciones agudas, en el nivel de calcio sérico se producen según la relación dosis-dependiente, en tanto que los estímulos sostenidos por más prolongados periodos de tiempo inducen cambios compensatorios en la posición y en la inclinación de la curva. Además, sugieren que otros factores desconocidos con funcíones similares a las de la PTH pueden tener participación en la regulación del calcio después de efectuada la cirugía para HPT primario.

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Résumé L'étude de 14 patients atteints d'hyperparathyroïdie primaire (HPT) avant et durant la première année suivant la chirurgie a mis en évidence que l'intervention s'accompagnait d'une rapide diminution de la parathormone sérique (PTH) et des taux de calcium total et calcium ionisé plasmatiques. Une diminution de la calciurie, une élèvation progressive de la réabsorption rénale du calcium, une réduction transitoire du calcitriol sérique et une élèvation retardée du 25 hydroxycholecalciférol ont été également notées. Des tests dynamiques de la fonction parathyroïdienne par perfusion d'EDTA et charge orale en calcium ont montré une relation sigmoïde entre la PTH sérique et la calcémie. La chirurgie parathyroïdienne induit des modifications notables à la fois de la position et de la pente de la courbe dose-réponse. Il est également apparu que la libération de PTH était stimulée de façon sous maximale même en cas d'hypocalcémie. Ces résultats établissent que l'adjustement de la libération de PTH à des modifications brusques de la calcémie se fait selon la prévalence de la relation dose-réponse, tandis que des stimuli persistent sur de longues périodes induisent des changements de position et de pente de cette courbe. Il est de plus suggéré que des facteurs inconnus ayant une fonction PTH libre peuvent participer à la régulation du calcium après la chirurgie pour HPT primaire.

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Presented at the International Association of Endocrine Surgeons in Stockholm, Sweden, August, 1991.