A postoperative parathyroid hormone-based algorithm to reduce symptomatic hypocalcemia following completion/total thyroidectomy: A retrospective analysis of 591 patients.

BACKGROUND: An institutional protocol for selective calcium/calcitriol supplementation after completion/total thyroidectomy was established based on the 4-hour postoperative parathyroid hormone level. The aim of this study was to evaluate the outcomes of this protocol 5 years after implementation. METHODS: All patients who underwent completion/total thyroidectomy from January 2012 to December 2016 were reviewed. Predictors of a 4-hour parathyroid hormone level <10 pg/mL and symptomatic hypocalcemia were assessed. RESULTS: Of 591 patients, 448 (76%) had a 4-hour parathyroid hormone ≥10, 72 (12%) had a 4-hour parathyroid hormone of 5-10, and 71 (12%) had a 4-hour parathyroid hormone <5. Hypocalcemic symptoms were infrequent (30/448, 7%) if the 4-hour parathyroid hormone was ≥10; 56% (40/71) of those with a 4-hour parathyroid hormone <5 reported symptoms. With 4-hour parathyroid hormone of 5-10, symptoms were reported in 32 of 72 (44%) patients; supplementation at discharge included calcium (n = 55, 76%), calcium and calcitriol (n = 12, 17%), or none (n = 5, 7%). Ten patients subsequently received calcitriol for persistent symptoms. On multivariate analysis, predictors of 4-hour parathyroid hormone <10 included incidental parathyroidectomy, malignancy, and thyroiditis; predictors of hypocalcemic symptoms included age <55 and 4-hour parathyroid hormone <10. CONCLUSION: After completion/total thyroidectomy, patients with a 4-hour parathyroid hormone ≥10 can be safely discharged without routine supplementation. The addition of calcitriol to calcium supplementation should be strongly considered for patients with a 4-hour parathyroid hormone of 5-10.

The role and timing of parathyroid hormone determination after total thyroidectomy.

Postoperative hypocalcemia is a common complication of total thyroidectomy resulting from manipulation, resection, or devascularization of the parathyroid glands. Parathyroid hormone (PTH) levels assessed in the perioperative period have been used to predict development of hypocalcemia. Articles examining the role of PTH measurement in the perioperative period following total or completion thyroidectomy are reviewed. Focus is placed on the timing of PTH measurement and the ability to predict which patients will develop hypocalcemia requiring supplementation. Postoperative PTH determination is highly accurate in predicting the development of hypocalcemia. Studies have examined PTH levels drawn at differing time points, ranging from intraoperatively until postoperative day 1 (POD1) with similar accuracy. This data is used to guide postoperative selective calcium and calcitriol supplementation in patients at highest risk for hypocalcemia. When evaluated within the first 4 hours postoperatively, predictive accuracy is maintained but can allow for earlier discharge for those patients at lower risk. Alternatively, some authors argue for routine supplementation, which can reduce the rate of postoperative hypocalcemia but increases the rate of unnecessary supplementation and potential risks associated with hypercalcemia. PTH determination at four hours after total thyroidectomy is an accurate predictor of hypocalcemia and can guide selective calcium supplementation for those at high risk, as well as facilitate a safe earlier hospital discharge for those at low risk of developing postoperative hypocalcemia.

The American Association of Endocrine Surgeons Guidelines for Definitive Management of Primary Hyperparathyroidism.

Importance: Primary hyperparathyroidism (pHPT) is a common clinical problem for which the only definitive management is surgery. Surgical management has evolved considerably during the last several decades. Objective: To develop evidence-based guidelines to enhance the appropriate, safe, and effective practice of parathyroidectomy. Evidence Review: A multidisciplinary panel used PubMed to review the medical literature from January 1, 1985, to July 1, 2015. Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. Findings: Initial evaluation should include 25-hydroxyvitamin D measurement, 24-hour urine calcium measurement, dual-energy x-ray absorptiometry, and supplementation for vitamin D deficiency. Parathyroidectomy is indicated for all symptomatic patients, should be considered for most asymptomatic patients, and is more cost-effective than observation or pharmacologic therapy. Cervical ultrasonography or other high-resolution imaging is recommended for operative planning. Patients with nonlocalizing imaging remain surgical candidates. Preoperative parathyroid biopsy should be avoided. Surgeons who perform a high volume of operations have better outcomes. The possibility of multigland disease should be routinely considered. Both focused, image-guided surgery (minimally invasive parathyroidectomy) and bilateral exploration are appropriate operations that achieve high cure rates. For minimally invasive parathyroidectomy, intraoperative parathyroid hormone monitoring via a reliable protocol is recommended. Minimally invasive parathyroidectomy is not routinely recommended for known or suspected multigland disease. Ex vivo aspiration of resected parathyroid tissue may be used to confirm parathyroid tissue intraoperatively. Clinically relevant thyroid disease should be assessed preoperatively and managed during parathyroidectomy. Devascularized normal parathyroid tissue should be autotransplanted. Patients should be observed postoperatively for hematoma, evaluated for hypocalcemia and symptoms of hypocalcemia, and followed up to assess for cure defined as eucalcemia at more than 6 months. Calcium supplementation may be indicated postoperatively. Familial pHPT, reoperative parathyroidectomy, and parathyroid carcinoma are challenging entities that require special consideration and expertise. Conclusions and Relevance: Evidence-based recommendations were created to assist clinicians in the optimal treatment of patients with pHPT.

A single parathyroid hormone level obtained 4 hours after total thyroidectomy predicts the need for postoperative calcium supplementation.

BACKGROUND: Parathyroid hormone (PTH) levels after total thyroidectomy have been shown to predict the development of symptomatic hypocalcemia and the need for calcium supplementation. This study aimed to determine whether a PTH level drawn 4 hours postoperatively is as effective as a level drawn on postoperative day 1 (POD1) in predicting this need. STUDY DESIGN: This is a single-institution retrospective review of 4-hour and POD1 PTH levels in patients who underwent total thyroidectomy from January 2012 to September 2012. If POD1 PTH was ≥10 pg/mL, patients did not routinely receive supplementation; if PTH was <10 pg/mL, patients received oral calcium with or without calcitriol. RESULTS: Of 77 patients, 20 (26%) had a 4-hour PTH <10 pg/mL; 18 (90%) of these patients had a POD1 PTH <10 pg/mL. No patient with a 4-hour PTH ≥10 pg/mL had a POD1 PTH <10 pg/mL. All 18 patients with POD1 PTH <10 pg/mL received calcium supplementation. Three additional patients received supplementation due to reported symptoms or surgeon preference. A 4-hour PTH ≥10 pg/mL compared with a POD1 PTH had a similar ability to predict which patients would not need calcium supplementation; sensitivity was 98% vs 98%, specificity was 90% vs 86%, and and negative predictive value was 95% vs 95%. Of 21 patients who received supplementation, 13 (62%) also received calcitriol, including 9 patients (69%) with a 4-hour PTH <6 pg/mL. CONCLUSIONS: A single PTH level obtained 4 hours after total thyroidectomy that is ≥10 pg/mL accurately identifies patients who do not need calcium supplementation or additional monitoring of serum calcium levels. Same-day discharge, if deemed safe, can be accomplished with or without calcium supplementation based on the 4-hour PTH level. Greater consideration should be given to calcitriol supplementation in patients with a 4-hour PTH <6 pg/mL.

Papillary thyroid microcarcinoma: an over-treated malignancy?

BACKGROUND: The clinical importance of papillary thyroid microcarcinoma (PTMC) remains controversial, with current guidelines suggesting that thyroid lobectomy alone is sufficient. The purpose of this study was to identify population-level treatment patterns in the USA for PTMC. METHODS: Patients with PTMC in SEER (1998-2010) were included; demographic, clinical (extent of surgery, administration of post-operative radioactive iodine [RAI]), and pathologic characteristics were examined. Outcomes of interest were 5- and 10-year overall survival (OS) and disease-specific survival (DSS). RESULTS: The cohort consisted of 29,512 patients. Mean age at diagnosis was 48.5 years; mean tumor size was 0.53 cm. Overall, 73.4 % of patients underwent total thyroidectomy, and RAI was administered to 31.3 %. In multivariate analysis, total thyroidectomy was more frequently performed in patients with multifocal (odds ratio [OR] 2.55), 'regional', or 'distant' PTMC (OR 2.90 and 2.59). Non-operative management was associated with male patients (OR 4.24) and those aged ≥65 years (OR 6.31). Post-operative RAI was associated with multifocal PTMC (OR 2.57). Overall, 5- and 10-year DSS was 99.6 and 99.3 %, respectively, with no difference in DSS between patients who underwent partial versus total thyroidectomy. OS of patients with PTMC who underwent any thyroid operation was similar to that of the general population of the USA. CONCLUSIONS: An increasing number of patients are undergoing total thyroidectomy and RAI for PTMC. While there may be a subset of patients for whom more aggressive therapy is indicated, many patients with PTMC may be over-treated, with no demonstrable benefit to survival.

Persistent elevation in serum parathyroid hormone levels in normocalcemic patients after parathyroidectomy: does it matter?

BACKGROUND: The clinical importance of elevated serum parathyroid hormone (PTH) levels in patients with normocalcemia after curative parathyroidectomy (PTX) for primary hyperparathyroidism (pHPT) is unclear. This study sought to determine whether these patients, when compared with those with normal PTH levels, differ in preoperative and pathologic factors and are at increased risk of recurrent pHPT. METHODS: A chart review was performed of sporadic pHPT patients who underwent PTX between December 1999 and July 2011. RESULTS: Of 1,037 patients who underwent PTX, 310 had 6-month serum calcium, vitamin D, and PTH levels evaluated. PTX was curative (normocalcemia at ≥6 months) in 97%. At 6 months, 62 (21%) had elevated serum PTH levels. Compared with patients with normal postoperative PTH levels, patients with elevated PTH levels had greater BMI (P < .0001), greater PTH levels (P < .0001), and lesser vitamin D levels (P = .014) preoperatively and lesser vitamin D levels at 6 months (P = .05). At ≥1 year follow-up, 38 (61%) patients had calcium levels checked; all remained normocalcemic. PTH levels were available for 32 patients; 17 had persistently increased PTH levels. CONCLUSION: Patients with elevated PTH levels after curative PTX do not have greater rates of recurrence than patients with normal PTH levels. The greater PTH levels and lesser vitamin D levels support postoperative vitamin D supplementation in these patients.

Predicting the need for calcium and calcitriol supplementation after total thyroidectomy: results of a prospective, randomized study.

BACKGROUND: The optimal protocol for the detection and treatment of postthyroidectomy hypoparathyroidism is unknown. We sought to identify and treat patients at risk for symptomatic hypocalcemia on the basis of a single parathyroid hormone (PTH) obtained the morning after surgery (POD1). METHODS: We performed a prospective, randomized study of total thyroidectomy patients who had POD1 calcium and PTH (pg/mL) levels. Randomization was determined by POD1 PTH: if ≥ 10, patients received no supplementation unless symptomatic; if <10, patients were randomized to calcium, calcium and calcitriol, or no supplementation. RESULTS: Of 143 patients, 112 (78%) had a POD1 PTH ≥ 10. Hypocalcemic symptoms were transiently reported in 11 (10%) and managed with outpatient calcium. Of 31 patients with PTH <10, 15 (48%) developed symptoms, including 5 who required intravenous calcium. On multivariate logistic regression analysis, when we adjusted for postoperative calcium level and performance of central neck dissection, we found that predictors of hypocalcemic symptoms were younger age (odds ratio 1.59, 95% confidence interval 1.07-2.32) and a PTH <10 (odds ratio 1.08, 95% confidence interval 1.04-1.12). There were no patient or treatment-related factors that predicted a POD1 PTH <10. CONCLUSION: A single POD1 PTH level <10 can accurately identify those patients at risk for clinically significant hypocalcemia. All total thyroidectomy patients with a postoperative PTH ≥ 10 can be safely discharged without supplementation. Given the small number of patients with PTH <10, it is unclear whether both calcium and calcitriol are needed for these higher-risk patients.

Effect of prophylactic central compartment neck dissection on serum thyroglobulin and recommendations for adjuvant radioactive iodine in patients with differentiated thyroid cancer.

BACKGROUND: Controversy exists in the management of patients with differentiated thyroid cancer (DTC). The purpose of this study was to examine the effect of prophylactic central compartment neck dissection (CCND) on serum thyroglobulin (Tg) levels and recommendations for adjuvant radioactive iodine (RAI). METHODS: The records of 103 patients who underwent completion/total thyroidectomy for DTC between January 2009 and November 2010 were reviewed. Prophylactic CCND was defined as removal of central compartment lymph nodes with no preoperative or intraoperative evidence of lymphadenopathy. Institutional protocol included a diagnostic whole-body scan before RAI; patients with a negative scan and Tg < 2.0 did not receive adjuvant RAI. RESULTS: Among the 103 patients, therapeutic CCND was performed in 17 (17 %) and prophylactic CCND in 49 (48 %). Of the 49 patients, 20 (41 %) had positive cervical lymph nodes. Positive lymph nodes changed American Joint Committee on Cancer tumor, node, metastasis staging in 17 patients and recommendations for RAI in 14. At a median follow-up of 21 months, there was no difference in Tg level based on the application of CCND; however, 92 % of patients with M0 disease had an undetectable Tg. One patient had recurrent DTC based on serum Tg only. CONCLUSIONS: Prophylactic CCND resulted in detection of unsuspected metastatic lymphadenopathy in 20 (41 %) of 49 patients and changed RAI recommendations in 14 (33 %). To date, most patients have an undetectable Tg. Longer follow-up is needed to detect potential differences in recurrent disease based on the use of CCND or long-term effects of RAI.

Postoperative calcium supplementation in patients undergoing thyroidectomy.

PURPOSE OF REVIEW: Postoperative hypocalcemia is one of the most common complications following thyroidectomy. This review examines recent literature on predictive factors for hypocalcemia, measurement of serum calcium and parathyroid hormone (PTH) levels, and algorithms for supplementation with calcium and/or vitamin D. RECENT FINDINGS: Risk factors for developing postthyroidectomy hypocalcemia include hyperthyroidism, vitamin D deficiency, female sex, substernal thyroid disease, and thyroid cancer, necessitating central neck lymphadenectomy. Several studies have shown that routine postoperative oral calcium and calcitriol supplementation results in lower rates of tetany. Recent studies have focused on the predictive value of intraoperative and postoperative serum PTH levels for the development of symptomatic hypocalcemia. Although the exact timing and serum levels of PTH have been variable, studies have confirmed that patients with very low postoperative PTH levels require oral calcitriol and calcium supplementation. A societal-level cost-utility analysis examining the use of routine vs. selective oral calcium and calcitriol supplementation found that routine supplementation is more cost-effective, and is associated with improved quality of life, irrespective of the surgeons' specific rates of hypocalcemia. SUMMARY: Although some clinicians favor routine supplementation postoperatively, others advocate selective supplementation, guided by postoperative PTH levels. The optimal algorithm is unknown, although a recent cost-analysis study suggests that routine supplementation may be favored at the societal level.

The value of postoperative parathyroid hormone levels in predicting the need for long-term vitamin D supplementation after total thyroidectomy.

BACKGROUND: Few studies have examined the need for vitamin D supplementation after total thyroidectomy. This study examines the role of postoperative day (POD) 1 serum calcium and parathyroid hormone (PTH) levels in predicting the need for long-term vitamin D supplementation after total thyroidectomy. METHODS: A retrospective, single institutional study of patients who underwent total thyroidectomy between January 2007 and December 2008 was performed. Data collected included extent of surgery, final pathology, postoperative calcium (mg/dl) and PTH (pg/ml) values, and duration of vitamin D supplementation. Patients were divided into 4 groups based on POD1 PTH values: group 1 (<5.0); group 2 (5.0-10); group 3 (10.1-20); and group 4 (>20). RESULTS: Of the 104 patients, 26 were in group 1, 12 in group 2, 18 in group 3, and 48 in group 4, with median PTH values of <2.5, 8.2, 14.1, and 30 pg/ml, respectively. All 7 (7%) patients who required vitamin D supplementation >1 month were in group 1. The positive predictive value of POD1 PTH <5.0 in predicting supplementation >1 month was 27% (sensitivity 100%, specificity 80%). Seventy-eight patients had a POD1 PTH level ≥5, and none required vitamin D supplementation >1 month (100% negative predictive value). The positive predictive value of various POD1 calcium thresholds (<7.5, <8.0, and <8.5 mg/dl) was 17, 14, and 15%, respectively. CONCLUSIONS: Postoperative PTH levels better predict long-term hypocalcemia requiring vitamin D supplementation than serum calcium levels. A PTH level ≥5.0 may identify patients who can be safely discharged without routine vitamin D supplementation.

To supplement or not to supplement: a cost-utility analysis of calcium and vitamin D repletion in patients after thyroidectomy.

BACKGROUND: Postoperative hypocalcemia is the most common complication after thyroidectomy; prevention and treatment remain areas of ongoing debate. The purpose of this study was to determine the incremental cost utility of routine versus selective calcium and vitamin D supplementation after total or completion thyroidectomy. METHODS: A cost-utility analysis using a Markov decision model was performed for a hypothetical cohort of adult patients after thyroidectomy. Routine or selective supplementation of oral calcium carbonate, vitamin D (calcitriol), and intravenous calcium gluconate, when required, was used. Selective supplementation was determined by serum intact parathyroid hormone levels. The incremental cost utility, measured in U.S. dollars per quality-adjusted life-year (QALY), was calculated. RESULTS: In the base-case analysis, the cost of routine supplementation was $102 versus $164 for selective supplementation. Patients in the routine arm gained 0.002 QALYs compared to patients in the selective arm (0.95936 QALYs vs. 0.95725 QALYs). At the population level, this translates into a savings of $29,365/QALY (95% confidence interval, -$66,650 to -$1,772) for routine supplementation. Sensitivity analyses demonstrated that the model was most sensitive to the utility of the hypocalcemic state, postoperative rates of hypocalcemia, and cost of serum parathyroid hormone testing. CONCLUSIONS: Routine oral calcium and calcitriol supplementation in patients after thyroidectomy seems to be less expensive and results in higher patient utility than selective supplementation. Surgeons who have very low rates of hypocalcemia in their patients may benefit less from routine supplementation.

Subtotal parathyroidectomy for primary hyperparathyroidism.

OBJECTIVE: To discuss the etiology of multiple gland disease in the context of primary hyperparathyroidism, as well as indications for surgery, operative management and technical considerations of subtotal parathyroidectomy, and postoperative/long-term management. METHODS: We conducted a systematic review of the literature using evidence-based criteria. RESULTS: Approximately 15% of patients with primary hyperparathyroidism have multiple gland disease, and a small subset of these cases is due to a familial syndrome. Subtotal parathyroidectomy is one operative approach to the management of multiple gland disease. Subtotal parathyroidectomy for multiple gland disease results in normocalcemia in at least 95% of cases. Intraoperative parathyroid hormone monitoring can help guide the extent of the operation and determine the need to perform a concurrent autograft. After subtotal parathyroidectomy, most patients develop postoperative hypocalcemia and require calcium and possibly calcitriol supplementation; approximately 10% to 15% develop permanent hypoparathyroidism. All patients after parathyroidectomy, especially those with familial primary hyperparathyroidism, should undergo long-term follow-up for surveillance of recurrent primary hyperparathyroidism. If persistent or recurrent primary hyperparathyroidism occurs after subtotal parathyroidectomy, completion total parathyroidectomy and parathyroid autotransplant should be performed. CONCLUSIONS: Subtotal parathyroidectomy is an excellent surgical approach for patients with primary hyperparathyroidism due to multiple gland disease from either sporadic or familial causes.