Cost Effectiveness of Routine Laryngoscopy in the Surgical Treatment of Differentiated Thyroid Cancer.

BACKGROUND: Some surgeons perform flexible fiberoptic laryngoscopy (FFL) in all patients prior to thyroid cancer operations. Given the low likelihood of recurrent laryngeal nerve (RLN) or aerodigestive invasion in clinically low-risk thyroid cancers, the value of routine FFL in this group is controversial. We hypothesized that routine preoperative FFL would not be cost effective in low-risk differentiated thyroid cancer (DTC). METHODS: A decision model was constructed comparing preoperative FFL versus surgery without FFL in a clinical stage T2 N0 DTC patient without voice symptoms. Total thyroidectomy and definitive hemithyroidectomy were both modeled as possible initial surgical approaches. Outcome probabilities and their corresponding utilities were estimated via literature review, and costs were estimated using Medicare reimbursement data. Sensitivity analysis was conducted to examine the uncertainty of cost, probability, and utility estimates in the model. RESULTS: When the initial surgical strategy was total thyroidectomy, routine preoperative FFL produced an incremental cost of $183 and an incremental effectiveness of 0.000126 quality-adjusted life-years (QALYs). The incremental cost-effectiveness ratio (ICER) for routine FFL prior to total thyroidectomy was $1.45 million/QALY, exceeding the $100,000/QALY threshold for cost effectiveness. Routine FFL became cost effective if the preoperative probability of asymptomatic vocal cord paralysis increased from 1.0% to 4.9%, or if the cost of preoperative FFL decreased from $128 to $27. Changing the extent of initial surgery to hemithyroidectomy produced a higher ICER for routine FFL of $1.7 million/QALY. CONCLUSION: Routine preoperative FFL is not cost effective in asymptomatic patients with sonographically low-risk DTC, regardless of the initial planned extent of surgery.

Thyroid cancer is more likely to be detected incidentally on imaging in private hospital patients.

BACKGROUND: The incidence of well-differentiated thyroid cancer (WDTC) is increasing. Patients with higher socioeconomic status have higher rates of WDTC, possibly due to increased imaging and overdiagnosis. We compared methods of WDTC diagnosis in patients treated at a public and an adjacent private university hospital. MATERIALS AND METHODS: Patients with WDTC at the two hospitals between 2004 and 2010 were included. Patients were categorized into having their WDTC discovered on physical examination or on unrelated imaging. Demographic and pathologic data were collected. T-test was used for quantitative variables, and chi-squared test was used for categorical values. Binomial logistic regression was used to asses for confounding. RESULTS: Among 473 patients, 402 (85%) were from the university hospital, and 71 (15%) were from the public hospital. Patients from the university hospital were older (mean age: 49 versus 44, P = 0.02) and had a different racial composition compared to those from the public hospital. The patients at the public hospital had larger tumors (23 versus 18 mm, P = 0.04). Patients from the university hospital were more likely to have WDTC detected by imaging than patients in the public hospital (46% versus 28%, P < 0.01) on univariate analysis. CONCLUSIONS: This study demonstrates that patients with WDTC treated at a university hospital are more likely to have their tumor detected on unrelated imaging than those treated at a public hospital. These data may support the hypothesis that patients with improved insurance are more likely to have WDTC detected by imaging.

Method of Detection of Well-Differentiated Thyroid Cancers in Obese and Non-Obese Patients.

BACKGROUND: The incidence of well-differentiated thyroid cancer (WDTC) is increasing rapidly. Many authors feel that this increase is due to over-diagnosis and that one of the contributing factors is the increasing use of various imaging studies. The rate of obesity has also been increasing in the United States. It has been suggested that patients with an increased body mass index (BMI kg/m2) have a higher incidence of WDTC than patients with normal BMI. One might hypothesize that thyroid nodules are more difficult to palpate in obese patients and that as more cancers are detected by imaging the apparent rate of increase in WDTC in obese patients would appear to be greater than in non-obese patients. This study was undertaken to evaluate this hypothesis by determining if there is any difference in the way thyroid cancers are initially detected in obese and non-obese patients. METHODS: The medical records of all 519 patients with a postoperative diagnosis of WDTC who underwent thyroidectomy at NYU Langone Medical Center from January 1, 2007 through August 31, 2010 by the three members of NYU Endocrine Surgery Associates were reviewed. Patients were divided into Non-obese (BMI<30 kg/m2) and Obese (BMI≥30 kg/m2) groups. Patients were also divided by the initial method of detection of their tumor into Palpation, Imaging, and Incidental groups. RESULTS: The final study group contained 270 patients, 181(67%) of whom were in the Non-obese Group and 89(33%) were in the Obese Group. In the Non-obese group, 81(45%) of tumors were found by palpation, 72(40%) were found by imaging, and 28(16%) were found incidentally. In the Obese group, 40(45%) were found by palpation, 38(43%) were found by imaging, and 11(12%) were found incidentally. These differences were not statistically significant (p-value 0.769). CONCLUSION: We show that BMI does not play a role in the method of initial detection in patients with WDTC. This suggests that the prevalence of WDTC detected by imaging is not an artifact caused by an increasingly obese population and that any association of WDTC and obesity is not related to the way in which these tumors are detected.

Management of recurrent/persistent nodal disease in patients with differentiated thyroid cancer: a critical review of the risks and benefits of surgical intervention versus active surveillance.

BACKGROUND: The primary goals of this interdisciplinary consensus statement are to define the eligibility criteria for management of recurrent and persistent cervical nodal disease in patients with differentiated thyroid cancer (DTC) and to review the risks and benefits of surgical intervention versus active surveillance. METHODS: A writing group was convened by the Surgical Affairs Committee of the American Thyroid Association and was tasked with identifying the important clinical elements to consider when managing recurrent/persistent nodal disease in patients with DTC based on the available evidence in the literature and the group's collective experience. SUMMARY: The decision on how best to manage individual patients with suspected recurrent/persistent nodal disease is challenging and requires the consideration of a significant number of variables outlined by the members of the interdisciplinary team. Here we report on the consensus opinions that were reached by the writing group regarding the technical and clinical issues encountered in this patient population. CONCLUSIONS: Identification of recurrent/persistent disease requires a team decision-making process that includes the patient and physicians as to what, if any, intervention should be performed to best control the disease while minimizing morbidity. Several management principles and variables involved in the decision making for surgery versus active surveillance were developed that should be taken into account when deciding how best to manage a patient with DTC and suspected recurrent or persistent cervical nodal disease.

Thyroid cancers detected by imaging are not necessarily small or early stage.

BACKGROUND: The incidence of well-differentiated thyroid cancer (WDTC) in the United States is increasing rapidly. Much of this increase is due to the detection by imaging of small, nonpalpable tumors. The incidence of advanced WDTC is also increasing, suggesting a true increase in the incidence of WDTC. This study was performed to determine how WDTCs of all sizes and stages are initially detected. METHODS: A retrospective chart review of 519 patients who underwent surgery for WDTC from January 1, 2007, through August 31, 2010, was performed. A total of 473 patients suitable for inclusion in this study were divided into three groups based upon the method by which the tumor was initially detected: tumors detected by an imaging study (184 patients-39%), those detected because a mass was felt in the neck (218 patients-46%), and those detected incidentally on pathological study of the surgical specimen (71 patients-15%). Method of detection was correlated with age and sex of the patient, and size, stage, and nodal status of the tumor. RESULTS: Patients in the Palpation group were more likely to be female (79% vs. 67% vs. 74%), younger (46 vs. 51 vs. 52), and to have larger tumors than those in the Imaging or Incidental groups. In the Imaging group, the tumor was detected on thyroid sonogram in 98 (53%), computed tomography in 38 (21%), magnetic resonance imaging in 19 (10%), carotid duplex scan in 14 (8%), and positron-emission tomography or other imaging studies in 15 (8%). Thirty-three percent of tumors <1 cm, 51% 1-2 cm, 29% 2-4 cm, and 38% >4 cm were first detected on an imaging study. Forty-seven percent of Stage III and IV cancers in patients aged ≥45 years and 39% of patients with positive central nodes were in the Imaging group. CONCLUSION: This study demonstrates that while most tumors discovered by imaging were small and early stage, almost half of advanced (Stage III and IV) WDTCs were initially discovered by imaging studies. These findings are consistent with the hypothesis that the frequent use of imaging studies may explain not only the increasing incidence of early WDTC, but more advanced thyroid cancers as well.

Clinical and therapeutic implications of Sprouty2 feedback dysregulation in BRAF V600E-mutation-positive papillary thyroid cancer.

BACKGROUND: The BRAF V600E (BRAF+) mutation activates the mitogen-activated protein kinase (MAPK/ERK) pathway and may confer an aggressive phenotype in papillary thyroid cancer (PTC). Clinically, the behavior of BRAF+ PTC, however, varies from an indolent to an aggressive course. SPRY2 is a negative feedback regulator of the MAPK/ERK pathway. We hypothesize that the level of SPRY2 expression contributes to MAPK/ERK pathway output and accounts for BRAF+ and clinical heterogeneity. METHODS: A tissue microarray with BRAF-positive PTCs (BRAF+ PTCs) was constructed and analyzed for SPRY2 expression and MAPK/ERK output. Data were studied in the context of clinicopathologic factors to develop a risk stratification system predictive of tumor biology. SPRY2 function was studied by silencing SPRY2 in BRAF+ PTC cells. These cells were treated with MAPK/ERK pathway inhibitors and assessed for growth effects. RESULTS: BRAF+ PTCs with an intact MAPK/ERK feedback pathway do not exhibit lymph node metastases. BRAF+ PTCs with dysregulated feedback pathways have nodal metastasis. When SPRY2 is silenced, the BRAF+ PTC cells are significantly more sensitive to MAPK/ERK inhibition. CONCLUSION: PTC behavior likely is dependent on both the driver of the MAPK/ERK pathway and its regulatory feedback. When the feedback pathway is intact, the tumor phenotype seems to be less aggressive. This observation has direct and important clinical implications and may alter our treatment strategies.

Clinical utility of immunohistochemistry for the detection of the BRAF v600e mutation in papillary thyroid carcinoma.

BACKGROUND: BRAF V600E mutation is the most common genetic alteration in papillary thyroid cancer (PTC). We used a mutation-specific antibody for immunohistochemical (IHC) detection of the BRAF V600E mutation and correlated expression with clinicopathologic features. The study was designed to validate the accuracy and determine the clinical importance of IHC detection of the BRAF V600E mutation in PTC. METHODS: Direct sequencing and IHC for BRAF V600E mutation was performed in 37 consecutive patients with PTCs. IHC was scored on an intensity proportion scale. IHC positive tumors were stratified into intensity categories. The categories were assessed for clinicopathologic variables, including age, extrathyroidal extension, lymphovascular invasion, and lymph node metastases. RESULTS: A total of 25 PTCs were BRAF V600E-positive and 12 were BRAF mutation-negative on IHC. The BRAF V600E mutation-specific antibody had a sensitivity of 89% and specificity of 100% for detecting the mutation. Tumors with high-intensity staining were more likely to have extrathyroidal extension. CONCLUSION: IHC is an accurate method for the detection of the BRAF V600E mutation in PTC, and its ability to quantify the mutation expression may serve as a better predictor of tumor behavior than molecular sequencing. It provides a potentially rapid, easily applicable, and economic alternative to current techniques.

The prognostic significance of nodal metastases from papillary thyroid carcinoma can be stratified based on the size and number of metastatic lymph nodes, as well as the presence of extranodal extension.

BACKGROUND: Ultrasound and prophylactic dissections have facilitated identification of small-volume cervical lymph node (LN) metastases in patients with papillary thyroid carcinoma (PTC). Since most staging systems do not stratify risk based on size or number of LN metastases, even a single-microscopic LN metastasis can upstage a patient with low-risk papillary thyroid microcarcinoma (PMC) to an intermediate risk of recurrence in the American Thyroid Association (ATA) system and to an increased risk of death in the American Joint Committee on Cancer (AJCC) staging system (stage III if the metastatic node is in the central neck or stage IVA if the microscopic LN metastasis is identified in the lateral neck). Such microscopic upstaging may lead to potentially unnecessary or additional treatments and follow-up studies. The goal of this review is to determine if the literature supports the concept that specific characteristics (clinically apparent size, number, and extranodal extension) of LN metastases can be used to stratify the risk of recurrence in PTC. SUMMARY: In patients with pathological proven cervical LN metastases (pathological N1 disease; pN1), the median risk of loco-regional LN recurrence varies markedly by clinical staging, with recurrence rates for patients who are initially clinically N0 (clinical N0 disease; cN0) of 2% (range 0%-9%) versus rates of recurrence for patients who are initially clinically N-positive (clinical N1 disease; cN1) of 22% (range 10%-42%). Furthermore, the median risk of recurrence in pN1 patients varies markedly by the number of positive nodes, <5 nodes (4%, range 3%-8%) vs. >5 nodes (19%, range 7%-21%). Additionally, the presence of extranodal extension was associated with a median risk of recurrence of 24% (range 15%-32%) and possibly a worse disease-specific survival. CONCLUSION: Our previous paradigm assigned the same magnitude of risk for all patients with N1 disease. However, small-volume subclinical microscopic N1 disease clearly conveys a much smaller risk of recurrence than large-volume, macroscopic clinically apparent loco-regional metastases. Armed with this information, clinicians will be better able to tailor initial treatment and follow-up recommendations. Implications of N1 stratification for PTC into small-volume microscopic disease versus clinically apparent macroscopic disease importantly relate to issues of prophylactic neck dissection utility, need for pathologic nodal size description, and suggest potential modifications to the AJCC TNM (tumor, nodal disease, and distant metastasis) and ATA risk recurrence staging systems.

Surgical approach and outcomes in patients with lithium-associated hyperparathyroidism.

BACKGROUND: Patients receiving lithium therapy are at elevated risk of developing hyperparathyroidism. In lithium-associated hyperparathyroidism (LAH), the incidence of multiglandular disease (MGD) is unclear, and the need for routine bilateral cervical exploration remains controversial. Therefore, in LAH patients, surgical approaches, pathologic findings, cure rates, and factors associated with persistent or recurrent disease were investigated. METHODS: Retrospective analysis of 27 patients with LAH undergoing parathyroidectomy with the intraoperative parathyroid hormone (PTH) assay. RESULTS: The median postoperative follow-up was 7 months; 17 patients had >6 months follow-up. Cervical exploration was unilateral in 9, bilateral in 18 (3 were converted from unilateral). Sixteen patients (62%) had MGD, 12 with four-gland hyperplasia and 4 with double adenomas. Ten patients (38%) had a single adenoma. Twenty-five (93%) of 27 patients had initially successful surgery. Of the 17 patients with >6 months follow-up, two had persistent disease and two experienced recurrent disease. All patients with a single adenoma remain free of disease. Three (75%) of four patients with persistent/recurrent disease had MGD and were receiving lithium at the time of surgery. Patients with persistent/recurrent disease were older (p = 0.01) and had experienced a longer duration of hypercalcemia (p = 0.04). CONCLUSIONS: LAH patients have a high incidence of MGD, and bilateral exploration is frequently necessary. With access to the intraoperative PTH assay, it is reasonable to initiate a unilateral approach because many patients will harbor single adenomas and can be reliably rendered normocalcemic. Patients with MGD remain at higher risk of persistent/recurrent disease.

Follicular variant of papillary thyroid cancer: encapsulated, nonencapsulated, and diffuse: distinct biologic and clinical entities.

OBJECTIVE: To examine genotypic and clinical differences between encapsulated, nonencapsulated, and diffuse follicular variant of papillary thyroid carcinoma (EFVPTC, NFVPTC, and diffuse FVPTC, respectively), to characterize the entities and identify predictors of their behavior. DESIGN: Retrospective medical chart review and molecular analysis. SETTING: Referral center of a university hospital. PATIENTS: The pathologic characteristics of 484 consecutive patients with differentiated thyroid cancer who underwent surgery by the 3 members of the New York University Endocrine Surgery Associates from January 1, 2007, to August 1, 2010, were reviewed. Forty-five patients with FVPTC and in whom at least 1 central compartment lymph node was removed were included. MAIN OUTCOME MEASURES: Patients with FVPTC were compared in terms of age, sex, tumor size, encapsulation, extrathyroid extension, vascular invasion, central nodal metastases, and the presence or absence of mutations in BRAF, H-RAS 12/13, K-RAS 12/13, N-RAS 12/13, H-RAS 61, K-RAS 61, N-RAS 61, and RET/PTC1. RESULTS: No patient with EFVPTC had central lymph node metastasis, and in this group, 1 patient (4.5%) had a BRAF V600E mutation and 2 patients (9%) had RAS mutations. Of the patients with NFVPTC, none had central lymph node metastasis (P > .99) and 2 (11%) had a BRAF V600E mutation (P = .59). Of the patients with diffuse FVPTC, all had central lymph node metastasis (P < .001), and 2 (50%) had a BRAF V600E mutation (P = .06). CONCLUSIONS: FVPTC consists of several distinct subtypes. Diffuse FVPTC seems to present and behave in a more aggressive fashion. It has a higher rate of central nodal metastasis and BRAF V600E mutation in comparison with EFVPTC and NFVPTC. Both EFVPTC and NFVPTC behave in a similar fashion. The diffuse infiltrative pattern and not just presence or absence of encapsulation seems to determine the tumor phenotype. Understanding the different subtypes of FVPTC will help guide appropriate treatment strategies.

Importance of intraoperative parathyroid hormone measurement in the diagnosis of parathyroid lipoadenoma.

BACKGROUND: Parathyroid lipoadenoma is an uncommon tumor that may be difficult to diagnose on intraoperative frozen section. Intraoperative parathyroid hormone (PTH) measurement is useful in assessing the adequacy of parathyroidectomy. This case demonstrates the value of intraoperative PTH measurement in recognizing a parathyroid lipoadenoma. METHODS AND RESULTS: A case of a 62-year-old woman with primary hyperparathyroidism in which intraoperative PTH measurement helped confirm the diagnosis of parathyroid lipoadenoma is presented. CONCLUSIONS: In patients with primary hyperparathyroidism, a significant decrease in intraoperative PTH confirms that an enlarged parathyroid with normal to low cellularity containing abundant fat is a lipoadenoma and that further exploration is not necessary.

Impact of the 2009 American Thyroid Association guidelines on the choice of operation for well-differentiated thyroid microcarcinomas.

BACKGROUND: The 2009 ATA Guidelines state "lobectomy alone may be sufficient treatment for small (< 1 cm), low risk, unifocal, intrathyroidal papillary carcinomas in the absence of . . . nodal metastases." We determined how often these criteria are satisfied, and whether tumor size alone can dictate operative management. METHODS: Medical records of 346 patients with well-differentiated thyroid cancer (WDTC) who underwent thyroidectomy from January 1, 2007 to November 10, 2009, were reviewed. There were 130 patients with tumors ≤ 1 cm and negative lateral nodes. Pathology reports were reviewed to identify adverse features including multifocality, extrathyroidal extension, vascular invasion, and central node metastases. RESULTS: Eighty-four percent underwent total thyroidectomy and 16% central node dissection. All but 2 patients had papillary cancer. Sixty-one percent with cancers 6-10 mm (group 1) had adverse pathologic features compared with 32% with cancers < 6 mm (group 2). Multifocality was most common: 55% in group 1 versus 32% in group 2 (P = .004). Positive central nodes were identified in 23% of group 1 versus 4% of group 2 (P = .004). Of patients in group 1, 88% had positive or suspicious fine-needle aspiration biopsy (FNAB) preoperatively. CONCLUSION: We recommend that total thyroidectomy be considered as the initial operation for thyroid tumors 6-10 mm in size in which the preoperative FNAB is diagnostic or suspicious for WDTC.

Relation of final intraoperative parathyroid hormone level and outcome following parathyroidectomy.

OBJECTIVE: To determine if final intraoperative parathyroid hormone (IOPTH) level predicts those at risk for recurrence after parathyroidectomy. Minimally invasive parathyroid exploration guided by preoperative imaging and IOPTH level is an accepted alternative to bilateral exploration for the treatment of primary hyperparathyroidism (HPT). However, additional enlarged, hypercellular parathyroid glands are present in some patients in whom IOPTH levels fall to normal after excision of a single adenoma. At least 15% of patients are normocalcemic with elevated PTH levels (PPTH) after parathyroidectomy. In these patients, a higher risk of recurrent HPT has been found. DESIGN: Retrospective review of medical records. SETTING: University teaching hospital. PATIENTS: The records of all 194 patients who underwent successful initial parathyroidectomy for nonfamilial HPT in 2007 and 2008 by 1 surgeon were reviewed. MAIN OUTCOME MEASURES: Intraoperative PTH level was measured prior to incision (baseline); at excision of the abnormal gland; at 5, 10, 15, and 20 minutes after excision; and at various additional times as needed. Of the patients, 71% underwent minimally invasive parathyroid exploration. Calcium, PTH, and 25-hydroxyvitamin D levels were measured during the first month after surgery in all patients and after 3 months or more in 80%. Patients were divided into 5 groups depending on the following final IOPTH levels: lower than 10 pg/mL (group l) (to convert PTH to nanograms per liter, multiply by 1.0); 10 to 19 pg/mL (group 2); 20 to 29 pg/mL (group 3); 30 to 39 pg/mL (group 4); and 40 pg/mL or higher (group 5). RESULTS: Of the patients, 82% had a single adenoma, 9% had double adenomas, and 9% had 3 or more abnormal glands. The final IOPTH/baseline IOPTH value in groups 1 to 5 was 7%, 11%, 16%, 23%, and 26%, respectively. There was no significant difference in the preoperative calcium among the groups. All 3 patients with persistent HPT and 5 patients with PPTH were in group 5. One of the 96 patients in groups 1 and 2 and 5 of the 72 patients in groups 3 and 4 had PPTH at the last evaluation. CONCLUSION: Patients with a final IOPTH level of 40 pg/mL or higher are at higher risk of having persistent HPT and should be followed up closely and indefinitely following parathyroidectomy.

Preoperative parathyroid scintigraphic lesion localization: accuracy of various types of readings.

PURPOSE: To retrospectively compare the accuracy of various parathyroid scintigraphy readings for single-gland disease (SGD) and multigland disease (MGD) in patients with primary hyperparathyroidism, with histologic analysis as the reference standard. MATERIALS AND METHODS: Institutional review board approval was obtained for this HIPAA-compliant study. Records of 462 patients with primary hyperparathyroidism who underwent preoperative imaging with a technetium 99m ((99m)Tc) sestamibi and (99m)TcO4- protocol that consisted of early and late pinhole (99m)Tc sestamibi, pinhole thyroid imaging, image subtraction, and single photon emission computed tomography (SPECT) were retrospectively reviewed. An experienced nuclear medicine physician without knowledge of other test results or of the final diagnoses graded images on a scale from 0 (definitely normal) to 4 (definitely abnormal). Early pinhole (99m)Tc sestamibi images, late pinhole (99m)Tc sestamibi images, subtraction images, SPECT images, early and late pinhole (99m)Tc sestamibi images, all planar images, and all images--including SPECT images--were read in seven sessions. Receiver operating characteristic curves were generated for each session and were used to calculate sensitivity, specificity, and accuracy. RESULTS: A total of 534 parathyroid lesions were excised. Of the 462 patients, 409 had one lesion, whereas 53 had multiple lesions. Reading all images together was more accurate (89%, P = .001) than was reading early (79%), late (85%), subtraction (86%), and SPECT (83%) images separately; however, it was not significantly more accurate than reading planar images (88%) or early and late images together (87%). Reading all images was significantly less sensitive in the detection of lesions with a median weight of 600 mg or less than in the detection of lesions with a median weight of more than 600 mg (86% vs 94%, P = .004). Per-lesion sensitivity for reading all images was significantly higher for SGD than for MGD (90% vs 66%, P < .001). Sensitivity of reading all images together in the identification of patients with MGD was 62%. CONCLUSION: Reviewing early, late, and subtraction pinhole images together with SPECT images maximizes parathyroid lesion detection accuracy. Test sensitivity is adversely affected by decreasing lesion weight and MGD.

Warthin-like tumor of the thyroid gland: an uncommon variant of papillary thyroid cancer.

Several variants of papillary thyroid cancer have been described, including, most recently, Warthin-like tumor of the thyroid gland. To bring attention to this uncommon variant, we review previous reports on this entity and we add 5 new cases to the literature. We retrospectively reviewed the records of all patients who had undergone thyroidectomy at our institution during a 7-year period. Among these cases, we identified 5 patients who had had a Warthin-like tumor of the thyroid. From their charts, we compiled data on age, sex, lymphadenopathy, distant spread, and treatment. Pathologic specimens were reviewed for tumor size, capsular invasion, and vascular invasion. All 5 patients were women (mean age: 51.6 yr). Tumor size ranged from 0.9 to 2.0 cm. Multifocality was seen in 1 of the 5 patients; this patient was also the only one who experienced capsular and vascular invasion. No patient had lymph node spread or distant metastasis. Because the follow-up period among these patients was still short, we were unable to analyze long-term survival data.

Persistently elevated parathyroid hormone levels after parathyroid surgery.

BACKGROUND: Persistent elevation of serum parathyroid hormone (PTH), despite normocalcemia, occurs in 8% to 40% of patients after parathyroidectomy. Explanations have included hypocalcemia owing to vitamin D deficiency or bone remineralization, and persistent hyperparathyroidism. METHODS: A retrospective chart review of 816 consecutive patients who underwent surgery for primary hyperparathyroidism was conducted. RESULTS: One hundred fourteen patients (15%) had persistently elevated PTH levels (PPTH). Patients with PPTH had higher preoperative PTH levels than those with normal PTH levels postoperatively. They also had lower postoperative Ca(++) and vitamin D levels. Multiple gland enlargement was identified in fewer patients with PPTH than in those with normal postoperative PTH levels. In patients with PPTH and a postoperative Ca(++) less than 9.6 mg/dL (group I), there was a greater decrease in IOPTH, a higher initial postoperative PTH level, and a lower postoperative vitamin D level than in PPTH patients whose postoperative Ca(++) was > or =9.6 mg/dL (group II). Postoperative Ca(++) and vitamin D levels were also lower in patients whose PPTH did not ultimately resolve. Three patients in group II had recurrent disease. CONCLUSIONS: Persistent elevation of postoperative serum PTH levels in normocalcemic patients is associated with mild hypocalcemia, probably owing to vitamin D deficiency. In some patients it may also be indicative of mild persistent hyperparathyroidism.