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.     

Primärer Hyperparathyreoidismus

Introduction

Normocalcemic hyperparathyrinemia, i.e. elevated parathyroid hormone (PTH) levels after parathyroidectomy in patients with primary hyperparathyroidism (pHPT) may occur in the course of postoperative recovery without the development of persistence or relapse.

Materials, methods and results

Intraoperative and long-term (7 year) postoperative PTH and calcium levels after curative parathyroidectomy are demonstrated on the basis of a case report of a 62-year-old female patient with severe pHPT and pronounced osseous and renal manifestations. The intraoperative PTH gradient displayed a decrease from 1072 pg/ml to 13 pg/ml (normal range 11–67 pg/ml) followed by an increase of up to 287pg/ml. The hyperparathyoid values decline to subnormal levels on administration of calcium and vitamin D and increase again after tapering these medications. The inverse calcium/PTH correlation in the course of the 7-year observation period suggests an intact feed-back mechanism. Preoperative PTH screening was performed in 316 consecutive normocalcemic thyroid patients to evaluate the rate of incidental hyperparathyroidism in patients with normal serum calcium levels. Of these patients 31 (9.8%) with normocalcemia (average 2.28 mmol/l, normal range 2.1–2.7 mmol/l) exhibited increased PTH levels averaging 84.2 pg/ml. A parathyroid adenoma was found intraoperatively as the cause for normocalcemic pHPT in only 1 of these 31 patients.

Discussion and conclusions

A review of the literature revealed that late postoperative elevated parathyroid hormone levels after successful pHPT surgery occur in 21.5%. Multiple causes are discussed, e.g. reactive hyperparathyroidism in cases of relative hypocalcemia, hungry bone syndrome, vitamin D deficiency, renal dysfunction and ethnic or lifestyle differences. In mild cases of postoperative hyperparathyrinemia observation of the patient may be sufficient. In cases of reactive hyperparathyroidism due to hypocalcemia, administration of calcium is indicated, in symptomatic patients, additional administration of vitamin D or calcitriol is necessary. Vitamin D deficiency per se needs adequate substitution. In cases of ongoing hyperparathyrinemia an interdisciplinary diagnostic and therapeutic approach is required.     

Decrease of serum calcium concentration and lost influence of calcium on parathyroid hormone release in a patient with primary hyperparathyroidism after treatment with diphosphonates

Summary Prolonged decrease of elevated serum calcium levels after treatment with diphosphonates in patients with primary hyperparathyroidism (pHPT) is very rare. A patient with water clear cell hyperplasia and five enlarged glands is presented who received diphosphonates (day 1 through day 8 dichloromethylene diphosphonate orally and a single dose of 60 mg pamidronate on day 8 intravenously) leading to a significant fall in serum calcium levels. Surprisingly, there was no reactive increase in intact parathyroid hormone (PTH) in the following 18 days. Patients with missing PTH regulation to hypocalcemia after diphosphonates who need a period of stabilization prior to parathyroid surgery might benefit most from this therapy.     

Applicability of intraoperative parathyroid hormone assay during thyroidectomy

OBJECTIVE: To evaluate the applicability of intraoperative parathyroid hormone (quick PTH) assay to monitor parathyroid function and to identify clinically significant hypocalcemia compared with postoperative serum calcium monitoring. SUMMARY BACKGROUND DATA: Close monitoring of serum calcium levels is a standard of care to identify post-thyroidectomy hypocalcemia due to parathyroid insufficiency. METHODS: Quick PTH assay was performed before and after thyroidectomy for 100 patients at risk of postoperative hypocalcemia and 20 control patients who underwent unilateral lobectomy. Postoperative serum calcium levels were closely monitored. RESULTS: Control patients had a normal but 38.9 +/- 5.9% (mean +/- SEM) decline in quick PTH after thyroidectomy. Eleven of 100 at-risk patients (11%) developed postoperative hypocalcemia. Hypocalcemic patients had significantly lower quick PTH values after thyroidectomy compared with that of normocalcemic patients. Serum calcium was significantly lower in hypocalcemic patients the morning after operation but not early after the operation (within 6 hours). A normal or less than 75% decline in quick PTH after thyroidectomy can accurately identify normocalcemic patients during surgery as compared to more than 24 hours by serum calcium monitoring. CONCLUSIONS: The quick PTH assay can monitor parathyroid function during thyroidectomy and identify patients at risk of clinically significant hypocalcemia much earlier than serum calcium monitoring. It may facilitate early discharge and the use of parathyroid autotransplantation during thyroidectomy.     

原发性甲状旁腺功能亢进症的外科治疗

目的　总结原发性甲状旁腺功能亢进症的外科治疗经验。方法　回顾性分析 1985～2 0 0 2年在我科行外科手术治疗的 5 5例原发性甲状旁腺功能亢进症患者的临床资料。全组病例均行甲状旁腺切除术。结果　 5 5例患者中无症状者 8例 ,骨、关节病变 2 4例 ,泌尿系结石病变 10例 ,骨和泌尿系结石病变 13例 ,病理性骨折 16例。全组血钙均升高 ,在 2 7～ 3 9mmol/L之间 ,平均 (3 1± 0 4 )mmol/L。 5 0例患者术前测定甲状旁腺激素升高在 10 2～ 2 0 0 0pg/ml之间 ,平均 (489 2±6 9 2 ) pg/ml。联合B超、CT、核素扫描术前定位诊断率达 90 9%。术后全组均随访 6个月～ 2年 ,术后临床表现缓解 ,骨质疏松改善 ,骨折愈合 ,有 39例患者出现短期低血钙 ,37例出现面部、手足麻木 ,10例出现手足抽搐。术后有 15例患者血钙正常 ,1例略高于正常值 ,低血钙者经骨化三醇和钙剂治疗 1～ 3周均可改善 ,血钙恢复正常。术后 4 7例患者甲状旁腺激素均在 2个月内恢复到正常 ,3例略高于正常值。结论　甲状旁腺切除术是治疗原发性甲状旁腺功能亢进症的有效方法。经术前影像学定位后行小范围、小创伤的甲状旁腺切除术是可行的手术方法。及时将原发性甲状旁腺功能亢进症患者转入内分泌外科治疗可达到早期治疗、减少骨关节和泌     

Reelevation of parathyroid hormone level after parathyroidectomy in patients with primary hyperparathyroidism: importance of decreased renal parathyroid hormone sensitivity

BACKGROUND: We hypothesized that impaired peripheral sensitivity to parathyroid hormone (PTH) may play a role in reelevation of PTH after successful operation for primary hyperparathyroidism (pHPT). METHODS: Factors affecting reelevation of PTH were determined in 90 patients who underwent parathyroidectomy for pHPT. PTH/nephrogenous cyclic adenosine monophosphate ratio, as an index of renal resistance to PTH, was examined in relation to factors shown to influence reelevation of PTH. RESULTS: Serum PTH levels were elevated above the upper limit of normal in 23 patients (26%) at 1 week and in 39 patients (43%) at 1 month after parathyroidectomy. These 39 normocalcemic patients with elevated serum PTH at 1 month after parathyroidectomy had a higher preoperative serum level of PTH and lower serum phosphate and 25-hydroxyvitamin D (25OHD) concentrations than those with normal PTH (n = 59). Elevated PTH and low 25OHD were shown by multivariate analysis to be significant predictors of reelevation of PTH. Renal resistance to PTH was higher in patients with vitamin D deficiency or renal insufficiency than in patients with normal serum vitamin D concentrations or normal renal function, and it increased according to increases in levels of PTH. CONCLUSIONS: The mechanism of PTH reelevation in patients with pHPT after successful parathyroidectomy appears to be renal resistance to PTH.     

Low parathyroid hormone levels after thyroid surgery: a feasible predictor of hypocalcemia

BACKGROUND: Selecting patients with a low risk of hypocalcemia is mandatory if patients are to be discharged on the first day after bilateral thyroidectomy. This study investigated the predictive value of intraoperative parathyroid hormone (PTH). METHODS: Thirty-eight patients underwent total or near-total thyroidectomy. Patients with or without biochemical and symptomatic hypocalcemia were compared regarding intraoperative PTH levels and previously suggested risk factors. The accuracy of intraoperative PTH to predict patients at risk for postoperative hypocalcemia was compared with a calcium concentration of less than 2.00 mmol/L (8.0 mg/dL) on the first postoperative day. RESULTS: PTH levels after resection of the second lobe, age, and number of parathyroid glands identified intraoperatively were independently associated with the reduction in serum calcium concentration measured at nadir on the first or second postoperative day. PTH levels after resection of the second lobe were lower among patients who developed biochemical (P <.001) and symptomatic hypocalcemia (P <.01) compared with those who did not. Low levels of intraoperative PTH identified the 3 patients who required intravenous calcium during the first 24 postoperative hours. An intraoperative PTH level below reference range and a calcium concentration of less than 2.00 mmol/L measured 1 day postoperatively both predicted biochemical hypocalcemia with a similar sensitivity (90% vs 90%) and specificity (75% vs 82%). Intraoperative PTH was slightly better than a serum calcium concentration of less than 2.00 mmol/L on postoperative day 1 to predict symptomatic hypocalcemia, with a sensitivity of 71% vs 52% and a specificity of 81% vs 76%, respectively. CONCLUSIONS: Parathyroid gland insufficiency is the main determinant of transient hypocalcemia after bilateral thyroid surgery. Low intraoperative PTH levels during thyroid surgery are therefore a feasible predictor of postoperative hypocalcemia.     

Long-term Follow-up of Patients with Elevated PTH Levels following Successful Exploration for Primary Hyperparathyroidism

Several studies have documented elevated parathyroid hormone (PTH) levels after seemingly successful exploration for primary hyperparathyroidism (pHPT). It is not known if this is a transient phenomenon after pHPT surgery or if it predisposes to recurrent disease. A series of 99 consecutive patients with pHPT who had solitary parathyroid adenomas were followed for 5 years. Serum levels of PTH and biochemical variables reflecting PTH activity were measured before operation, at 8 weeks postoperatively, and then yearly for 5 years. All patients were normocalcemic after exploration. At 8 weeks after operation 28% of the patients had elevated serum PTH levels; at 5 years this figure decreased to 16%. During the 5-year follow-up one group of patients normalized their PTH levels, another groups PTH levels fluctuated, and still another group had consistently normal PTH levels. Patients with fluctuating PTH levels had increased levels of serum calcium and phosphate. Some of these patients (15%) showed signs of impaired renal function. Two patients with consistently elevated PTH levels showed signs of mild renal dysfunction, and one of them developed recurrent HPT. Elevated PTH levels after successful parathyroid surgery is not a transient phenomenon. An increased risk for recurrent disease is postulated for some of the patients who do not normalize their PTH levels postoperatively, and long-term surveillance of these patients is suggested.     

Normal PTH Levels in Primary Hyperparathyroidism: Still the Same Disease?

Purpose  

Previous studies have suggested that primary hyperparathyroidism (pHPT) with only normal parathyroid hormone (PTH) levels is a milder, less symptomatic form of pHPT. This study investigates symptoms, laboratory values, imaging, and outcomes of sporadic pHPT patients with normal PTH values.     

Preoperative Normal Level of Parathyroid Hormone Signifies an Early and Mild Form of Primary Hyperparathyroidism

Abstract Contemporary patients are often diagnosed with mild or intermittent hypercalcemia. In addition, most studies demonstrate patients with parathyroid (PTH) levels in the upper normal range. The aim of the present investigation was to define subgroups of patients with mild primary hyperparathyroidism (pHPT), which could be of importance in the decision for or against surgical treatment. Two-hundred and eleven patients, operated for pHPT were investigated with biochemical variables known to reflect PTH activity, renal function, and bone mineral content. The preoperative diagnosis of pHPT was based on the presence of hypercalcemia combined with an inappropriate serum concentration of PTH. The mean age of the patients was 64 ± 14 years and the mean serum level of calcium was 2.78 ± 0.19 mmol/L. One hundred and sixty-two patients (77%) had raised levels of calcium and PTH the day before surgery (overt pHPT), 25 patients (12%) had a normal level of calcium and a raised PTH level (normal calcium group), and 20 patients (9%) had a raised level of calcium and a normal level of PTH (normal PTH group). In four patients the level of calcium and PTH was normal. Between-group analysis demonstrated no major difference in symptom and signs of pHPT. Except for lower adenoma weight, patients in the normal calcium group did not essentially differ from the patients in the overt pHPT group. However, patients in the normal PTH group were a decade younger, and had better renal function, lower bone turnover, and a preserved bone density compared with patients in the overt pHPT group. In conclusion, the data from the present investigation show that pHPT patients with a preoperative normal PTH level have an early and mild form of the disease. Furthermore, the serum calcium concentration does not reflect disease severity in pHPT.     

Postoperative Elevated Serum Levels of Intact Parathyroid Hormone after Surgery for Parathyroid Adenoma: Sign of Bone Remineralization and Decreased Calcium Absorption

Increased levels of intact parathyroid hormone (PTH) have been documented after surgery for primary hyperparathyroidism (pHPT) despite normocalcemia. The pathogenesis remains to be elucidated. Seventeen consecutive patients operated on for solitary parathyroid adenoma were investigated before and at 8 weeks and 1 year after surgery with serum levels of intact PTH, biochemical variables known to reflect PTH activity, and bone mineral content (BMC). In addition, an oral calcium loading test was performed 8 weeks after the operation. All patients had low or normal serum calcium levels during follow-up. Eight weeks after operation six patients (35%) had an increased serum PTH level. These patients (group I) preoperatively had higher serum levels of PTH and alkaline phosphatase than patients with normal PTH levels (group II). They also had lower BMC and larger parathyroid adenomas. They did not differ in renal function. At 8 weeks after operation group I showed higher mean serum levels of osteocalcin and propeptide of type I procollagen but lower urinary calcium excretion. In contrast to patients in group II, they also showed a lower calciuric response and a trend to a lower calcemic response during the oral calcium load. The two groups showed similar parathyroid sensitivity for calcium. Patients in group I demonstrated a significant increase in BMC the first year after the operation. Increased serum PTH 8 weeks after surgery for sporadic parathyroid adenoma was not due to persistent pHPT or impaired renal function. Instead, the results imply there is diminished calcium absorption and increased bone turnover with cortical bone remineralization.     

Role of cyclase activating parathyroid hormone (1-84 PTH) measurements during parathyroid surgery: potential improvement of intraoperative PTH assay

SUMMARY BACKGROUND DATA: Quick intraoperative parathyroid hormone assays are widely used as a guide to the adequacy of resection during parathyroid surgery. However, some authors have reported a 15% error rate of these assays because of the presence of false-positive and false-negative results. Recently the authors have found that most commercial intact PTH (iPTH) assays cross-react with non-(1-84) PTH (likely 7-84 PTH) and that the proportional levels of non-(1-84) PTH in patients were variable in a much wider range, accounting mostly for 20% to 60% of the immunoreactivity in samples obtained from hyperparathyroid patients. A cyclase activating PTH (CAP) measured by a novel immunoradiometric assay was shown to measure specifically 1-84 PTH. Using a CAP assay, the authors studied the rate of decline of CAP after parathyroidectomy and compared it with iPTH as measured by the Nichols intact PTH immunoradiometric assay. METHODS: This study comprised 29 patients with primary hyperparathyroidism (pHPT) caused by a single adenoma and 7 patients with secondary hyperparathyroidism (secondary HPT) who underwent parathyroidectomy. Blood samples were drawn after anesthesia, before excision of one enlarged parathyroid gland in pHPT and of the last gland in secondary HPT, and at 5, 10, and 15 minutes after excision. The 7-84 PTH level was calculated by subtracting the CAP value from the iPTH value. RESULTS: The percentage of 7-84 PTH in iPTH in plasma samples was 27.5 +/- 14.4% in pHPT and 39.6 +/- 15.1% in secondary HPT. In pHPT patients the plasma CAP and iPTH value decreased to 23.4 +/- 10.8 and 32.0 +/- 11.3% of the preexcision level at 5 minutes, 10.6 +/- 7.7 and 21.1 +/- 8.8% at 10 minutes, and 8.5 +/- 4.9 and 16.1 +/- 6.8% at 15 minutes after removal of the enlarged gland, respectively. At 5 minutes, CAP levels of all 29 pHPT patients had decreased to less than 40% of the preparathyroidectomy level; however, 7 (24%) patients still had an iPTH level of more than 40%. In secondary HPT patients, CAP and iPTH values had dropped to 43.3 +/- 20.2 and 66.1 +/- 19.7% at 5 minutes, 28.6 +/- 16.6 and 53.6 +/- 18.1% at 10 minutes, and 14.2 +/- 9.0 and 41.0 +/- 12.9% at 15 minutes after removal of the last enlarged gland, respectively. At 10 minutes, CAP levels of all seven secondary HPT patients had decreased to less than 50% of the preexcision level; however, three (43%) patients still had an iPTH level of more than 50%. In pHPT and secondary HPT, the 7-84 PTH level had dropped to 57.4 +/- 85.9 and 62.1 +/- 84.9%, respectively, of the preexcision value 15 minutes after removal of the enlarged gland or glands. CONCLUSIONS: The percentage of 7-84 PTH in iPTH in plasma samples varies substantially between patients with HPT. In both pHPT and secondary HPT, the plasma CAP value decreased more rapidly than iPTH after parathyroidectomy, depending on the amount of 7-84 PTH in circulation. These results suggest that the CAP assay may be a more useful adjunct to parathyroidectomy than the currently used iPTH assay.     

PTHrP enhances the secretory response of PTH to a hypocalcemic stimulus in rat parathyroid glands

BACKGROUND: The secretion of parathyroid hormone (PTH) from the parathyroid glands might be regulated by autocrine/paracrine factors, and a feedback regulatory mechanism of PTH on the secretion of PTH has been suggested. Because of the existence of a common receptor between PTH and PTH-related peptide (PTHrP), the aim of the present study was to examine the possible effects of PTHrP 1-40 and 1-86 on PTH secretion in rats. METHODS: In vivo, the effect of PTHrP on Ca++-regulated PTH secretion was examined by the induction of hypocalcemia and hypercalcemia by an infusion of EGTA and Ca++, with and without PTHrP. The eventual effects of PTHrP on the peripheral metabolism of PTH were examined by infusion of human PTH (hPTH) with and without PTHrP. hPTH was measured by an intact hPTH assay not cross reacting with rat PTH or PTHrP. To examine whether near physiological levels of circulating PTH have an autoregulatory effect in vivo on PTH secretion from the parathyroid gland, an acute reduction of the circulating PTH was induced by an acute unilateral parathyroidectomy (UPTX). PTH secretion from the remaining parathyroid gland was followed in response to EGTA-induced hypocalcemia. In vitro investigations on the effect of PTHrP 1-40 on PTH secretion from whole rat parathyroid glands incubated in media containing a calcium concentration of 0.6 or 1.35 mmol/L were performed to confirm whether the effect of PTHrP was directly on the gland. The rat PTH assay was examined for cross reaction with PTHrP. RESULTS: In vivo, the same rate of decrease of plasma Ca++ was induced in the experimental groups. The maximal response of PTH to hypocalcemia (218 +/- 16 pg/mL, N = 6) was significantly enhanced by PTHrP 1-40 (525 +/- 79 pg/mL, N = 6) and by PTHrP 1-86 (465 +/- 29 pg/mL, N = 6, P < 0.001). No effect of PTHrP on PTH secretion was found during normocalcemia or hypercalcemia. UPTX resulted in a 50% reduction of PTH secretion, and no compensatory increase of PTH was observed. PTHrP had no effect on the metabolism of PTH. In vitro, low-Ca++-induced PTH secretion was significantly augmented by 300% (P < 0.01) when the medium contained PTHrP 1-40. PTHrP did not cross react with the PTH assay. CONCLUSIONS: PTHrP significantly enhanced the low-Ca++-stimulated PTH secretion in vivo and in vitro. An autocrine/paracrine role of PTHrP in the parathyroid glands is suggested. An autoregulatory effect of circulating PTH on the PTH secretion from parathyroid glands seems unlikely. The "maximal secretory capacity" of the parathyroid glands induced by hypocalcemia in vivo and in vitro is not the maximum, as PTH secretion can be increased even further, by several-fold.     

Parathyroid hormone 7-84 induces hypocalcemia and inhibits the parathyroid hormone 1-84 secretory response to hypocalcemia in rats with intact parathyroid glands

Biologic effects of large C-terminal parathyroid hormone (PTH) fragments, opposite to those of N-terminal PTH, have been demonstrated. C-terminal PTH fragments are co-secreted with N-terminal PTH from the parathyroids. The aim of our study was to examine whether C-terminal PTH 7-84 regulates secretion of PTH 1-84 and affects the expression of genes of relevance for parathyroid function, PTH, calcium-sensing receptor (CaR), PTH type 1 receptor (PTHR1), and PTH-related peptide (PTHrP) genes in rat parathyroid glands. PTH 7-84 induced a significant decrease in plasma Ca2+ in rats with intact parathyroid glands. Despite the reduction of plasma Ca2+, no stimulation of PTH 1-84 secretion took place. Furthermore, the PTH 1-84 secretory response to EGTA-induced acute and severe hypocalcemia was significantly inhibited by PTH 7-84. During recovery from hypocalcemia, plasma Ca2+ levels were significantly lower in the PTH 7-84-treated group, as compared with the vehicle group, and at the same time plasma PTH 1-84 levels were significantly suppressed. The expression of PTH, CaR, PTHR1, and PTHrP genes in the rat parathyroid glands was not affected by PTH 7-84. The peripheral metabolism of PTH 1-84 was not affected by PTH 7-84. PTH 7-84 did not cross-react with the rat bioactive PTH 1-84 assay. In normal rats with intact parathyroid glands, PTH 7-84 inhibited the PTH 1-84 secretory response to hypocalcemia and induced a significant decrease in plasma Ca2+. These effects of PTH 7-84 on PTH 1-84 secretion and on plasma Ca2+ levels were not associated with significant changes in PTH, PTHR1, CaR, and PTHrP gene expressions in the rat parathyroid glands. It is hypothesized that PTH 7-84 regulates PTH secretion via an autocrine/paracrine regulatory mechanism.     

Parathyroid hormone: A sensitive predictor of hypocalcemia following total thyroidectomy

OBJECTIVE: To investigate whether monitoring parathyroid hormone (PTH) could predict hypocalcemia following total thyroidectomy or other bilateral thyroid manipulations. STUDY DESIGN AND SETTING: Forty patients undergoing total thyroidectomy as well as other bilateral thyroid procedures were prospectively enrolled. PTH levels were measured preoperatively and 30 minutes postoperatively. Calcium levels were measured preoperatively and every 8-12 hours for the first 72 postoperative hours. Changes in PTH levels as well as symptoms of hypocalcemia were correlated with postoperative hypocalcemia. RESULTS: Hypocalcemia developed in 13/40 patients (32.5%), mainly those patients undergoing total thyroidectomy in conjunction with paratracheal neck dissections. The respective sensitivity and specificity of a drop in PTH for detecting hypocalcemia was 92% and 66% (50% drop), 23% and 75% (75% drop), and 46% and 100% (drop below normal range). CONCLUSIONS: A 50% drop in PTH levels 30 minutes following bilateral thyroid procedures is a sensitive predictor of hypocalcemia. A drop of 75% is a highly specific indicator of postoperative hypocalcemia, though not highly sensitive. EBM RATING: C-4.     

Intraoperative parathyroid hormone assay for management of patients undergoing total thyroidectomy

BACKGROUND: Rapid parathyroid hormone (PTH) assay has been applied to predict hypocalcemia after thyroidectomy compared with conventional close monitoring of serum calcium levels. We evaluated the reliability of intraoperative intact PTH (ioPTH) assay to predict hypocalcemia after total thyroidectomy and sought to develop an algorithm for the management of postthyroidectomy patients. METHODS: Rapid PTH assays were performed before and after thyroidectomy for 92 new patients receiving total thyroidectomy. Preoperative and postoperative serum calcium and standard PTH levels were serially obtained to 6 months after surgery RESULTS: Postoperative hypocalcemia developed in 34 of 92 patients (37%), who showed significantly lower ioPTH values compared with those of normocalcemic patients (mean 9.2 pg/mL vs 31.3 pg/mL). The ioPTH levels were significantly correlated with standard PTH levels (p < .001, r > 0.62), but not with early serum calcium levels within 8 hours after the operation. Sensitivity and specificity of ioPTH levels of <15.0 pg/mL for the prediction of postoperative hypocalcemia were 85% and 84%, respectively. A value of >15.0 pg/mL and <70% decline in ioPTH after thyroidectomy can reliably identify normocalcemic patients during thyroidectomy or patients requiring close monitoring and early calcium supplement CONCLUSIONS: Rapid ioPTH assay can reliably monitor parathyroid function after thyroidectomy and predict postoperative hypocalcemia. The proposed algorithm based on rapid PTH levels will lead to improved prediction of normocalcemic patients.     

Utility of Intraoperative Parathyroid Hormone Monitoring in Patients with Multiple Endocrine Neoplasia Type 1-Associated Primary Hyperparathyroidism Undergoing Initial Parathyroidectomy

Background

Intraoperative parathyroid hormone monitoring (IOPTH) is a widely used adjunct for primary hyperparathyroidism (pHPT). However, the benefit of IOPTH in familial pHPT, such as in multiple endocrine neoplasia type I (MEN1), remains unclear.

Methods

We performed a retrospective analysis of 52 patients with MEN1-associated pHPT undergoing initial parathyroidectomy with IOPTH monitoring at our institution. Parathyroid hormone (PTH) levels were measured before skin incision and 10 min after resection of the last parathyroid gland. Variables analyzed included percent drop of PTH from baseline and the final PTH level compared to the normal reference range (RR).

Results

A total of 52 patients underwent initial subtotal parathyroidectomy with IOPTH. An IOPTH decrease cutoff of ≥75 % from baseline had the highest biochemical cure rate (87 %). In the remaining 13 % who met this cutoff, all had persistent pHPT, with ≥90 % drop of PTH from baseline. The remaining patients, who did not meet the ≥75 % cutoff, were cured. Follow-up was available for three of four patients with final IOPTH levels above the RR: one had persistent pHPT, two had hypoparathyroidism (50 %). When a postresection PTH level was within the RR, 88 % of patients were cured. While considered cured from pHPT, 7 % of patients in this group developed permanent hypoparathyroidism. When the final PTH level dropped below the RR, 28 % developed permanent hypoparathyroidism.

Conclusions

A cutoff in IOPTH decrease of ≥75 % from baseline has the highest biochemically cure rate in patients with pHPT associated with MEN1. However, a 75 % cutoff in IOPTH decrease does not exclude persistent pHPT. The absolute IOPTH value does not accurately predict postoperative hypoparathyroidism.     

In Vitro Parathyroid Hormone Release in Patients with Secondary Hyperparathyroidism

Background: The purpose of this study was to determine the precise endocrim. characteristics of parathyroid function in secondary hyperparathyroidism (sHPT).
Methods: We examined the effects of extracellular ionized calcium (Ca²⁺) varying from 0.5 to 2.0 mM on parathyroid hormone (PTH) release in parathyroid cell suspensions using a mid-regional PTH assay. Cells were obtained from 26 patients with sHPT who were divided into two groups according to the type of hyperplasia they exhibited, either nodular (n=16) or diffuse [n= 10). For compdrison, we also analyzed data from nine patients with primary hyperparathyroidism (pHPT; adenomas).
Results: Significant in vitro suppression of PTH release by Ca²⁺ was observed in the majority of subjects, regardless of the histologic abnormality. The pHPT group exhibited no significant relationship between clinical and in vitro data. In contrast, in the sHPT group (taken as a whole), suppression of PTH release by Ca²⁺ exhibited a plateau at a total serum calcium concentration of 2.5 mmol/L, and a parathyroid gland weight of 2 g.
Conclusions: These findings suggest that there is a curvilinear relationship in sHPT, but not pHPT, between the in vitro calcium sensitivity of parathyroid cells and total serum calcium, as well as gland weight. The in vitro calcium sensitivity in sHPT remains constant when the total serum calcium concentration exceeds 2.5 mmol/L, or when the gland weight exceeds 2 g.     

Super-selective venous sampling in conjunction with quickPTH for patients with persistent primary hyperparathyroidism: report of five cases

Selective venous sampling (SVS) helps to interpret imaging results in patients with persistent primary hyperparathyroidism (pHPT). However, one of the drawbacks of conventional SVS may be low "spatial resolution", depending on the sample size. We modified SVS in the following way: first, patients underwent conventional SVS with up to 11 parathyroid hormone (PTH) samples taken. The quickPTH assay was used to measure PTH levels. The patients subsequently underwent super-selective venous sampling (super-SVS) in the region with the highest quickPTH level in the same session. The subjects were five consecutive patients with persistent pHPT investigated by various imaging techniques, none of which was considered conclusive. Therefore, all five patients underwent super-SVS, which was done successfully in four. Re-evaluation of the imaging results of these four patients resulted in localization of the parathyroid adenoma. Curative surgery was performed successfully in all four patients during the study period. Super-SVS increases the "spatial resolution" of conventional SVS and may have advantages when imaging results of patients with persistent pHPT are interpreted. Its true value must be analyzed in larger studies.