Unanticipated thyroid cancer in patients with substernal goiters: are we underestimating the risk?

BACKGROUND: The rate of unexpected thyroid cancers found at the time of thyroidectomy is thought to be similar in patients with cervical and substernal multinodular goiters (MNGs). METHODS: The objective of this study was to compare the prevalence of undiagnosed cancer found in patients undergoing a thyroidectomy for a cervical or substernal MNG. We conducted a review of patients with a preoperative diagnosis of an MNG (both cervical and substernal) at a tertiary referral center between 2005 and 2012. RESULTS: We identified 538 patients who underwent thyroidectomy for an MNG (144 with substernal MNGs and 394 with cervical MNGs). Patients with substernal MNGs were older (59.6 vs. 52.3; p < 0.001), more likely to be men (34 vs. 11.1 %; p < 0.001), and less likely to have a history of radiation exposure to the neck (2.1 vs. 12.4 %; p < 0.001). Thyroid cancer (>1 cm) was found in 13.7 % of substernal MNG specimens and in 6.3 % of cervical MNG specimens (p = 0.003). On multivariate analysis, substernal location [odds ratio (OR) = 2.360; confidence interval (CI), 1.201-4.638] was the only variable independently associated with an unexpected thyroid cancer on surgical pathology. CONCLUSION: The rate of postoperatively discovered thyroid cancer is significant in patients with substernal MNGs and is increased when compared to patients with cervical MNGs. Surgeons should counsel their patients regarding the possibility of this unexpected result.

The underestimated risk of cancer in patients with multinodular goiters after a benign fine needle aspiration.

IMPORTANCE: Ultrasound-guided fine needle aspiration (FNA) is an excellent tool for evaluating patients with solitary thyroid nodules, with a false-negative malignancy rate of <3%. The utility of FNA in patients with a cervical multinodular goiter (MNG) is unknown, because biopsy and surveillance of thyroids with numerous nodules may be impractical. OBJECTIVE: To evaluate the incidence and risk factors for unsuspected thyroid cancer on final pathology in patients with a non-functional, cervical MNG who had a benign preoperative FNA and underwent thyroidectomy. DESIGN, SETTING AND PARTICIPANTS: Retrospective review of patients with non-functional, cervical MNG at a high-volume tertiary referral center between 2005 and 2012. MAIN OUTCOME MEASURE(S): Incidence of thyroid cancer on surgical pathology. RESULTS: Of the 134 patients included in the study, 31 (23.1%) were found to have thyroid cancer on final pathology. Twenty-one (15.7%) patients had a microscopic papillary cancer (<1 cm) and 10 (7.5%) patients had other forms of thyroid cancer [five follicular, four papillary (>1 cm), and one patient with a papillary and follicular cancer]. On univariate analysis, male gender had a near-significant association with non-micropapillary thyroid cancer (p = 0.06). On multivariate analysis, male gender (OR = 10.2, 95% CI 1.35-76.8) and FNA cytology not reviewed at our institution (OR = 6.0, 95% CI 1.2-30) were independently associated with non-micropapillary thyroid cancer. CONCLUSIONS AND RELEVANCE: The incidence of thyroid cancer in patients with MNG and benign FNA is significant. Men and patients in whom the FNA cytology is not reviewed by an experienced cytopathologist may be at an increased risk for an undetected thyroid cancer.

Ultrasound-guided methylene blue dye injection for parathyroid localization in the reoperative neck.

BACKGROUND: The goal of this study was to review a single institution's experience using intraoperative ultrasound-guided (ioUSG) methylene blue dye injection for the localization and removal of enlarged parathyroid glands in patients with primary hyperparathyroidism and a history of previous neck surgery. METHODS: We performed a retrospective review of nine consecutive patients who underwent reoperative parathyroidectomy using ioUSG methylene blue dye injection. RESULTS: All patients had successful resolution of their hyperparathyroidism, with at least a 50 % decrease in intraoperative parathyroid hormone level after resection. One patient had transient recurrent laryngeal nerve paresis. There were no permanent recurrent laryngeal nerve injuries or cases of permanent hypoparathyroidism. CONCLUSIONS: Blue dye injection is a safe and effective method of localizing diseased parathyroid glands in the reoperative neck.

Controversies in familial thyroid cancer 2014.

Thyroid cancer is the sixth most common cancer in women, and the majority of patients with thyroid cancer has sporadic disease. However, about 25% of patients with medullary thyroid cancer and 5% with papillary thyroid cancer have familial tumors. Currently, there are numerous controversies regarding the mode of inheritance, tumor behavior, extent of surgical resection for optimal results, coexisting thyroid pathology, risk of other cancers, and extent of postoperative treatment of patients with familial thyroid cancer. This review aimed to give insight to surgeons on this interesting topic.

New evidence about thyroid cancer prevalence: prevalence of thyroid cancer in younger and middle-aged Japanese population.

We have made a cross-sectional investigation of men in the Japanese military for the presence of thyroid abnormalities and thyroid cancer to document the prevalence of thyroid disease in these persons. Six thousand, four hundred and twenty-two Japanese military men and women were screened for thyroid disease by history, physical examination and ultrasound examination. Among them, 6,182 were men 50 years of age, 47 were women 50 years of age, and 149 were men 40 years of age and 44 were women 40 years of age. Among the 50 years old men, thyroid nodules were found in 924 men (14.9%): Nineteen individuals (0.31%) had thyroid cancers ranging from 1 mm to 30 mm in diameter (12.5 mm in mean), pathological TNM staging revealed 7 cases of stage I, 2 cases of stage II and 9 cases of stage III. There was a significant increase in thyroid nodules in 50 years old men compared to that in 40 year old men, but there was no significant difference between men and women (p>0.05). Our data document that the detection rate of thyroid cancer in 50 years old men was 0.31%, and the rate of thyroid nodules increased with age in men, but the frequency of thyroid nodules were similar in men and women of the same age.

MicroRNA expression profiling is a potential diagnostic tool for thyroid cancer.

BACKGROUND: Approximately 30% of fine-needle aspiration (FNA) biopsies of thyroid nodules are indeterminate or nondiagnostic. Recent studies suggest microRNA (miRNA, miR) is differentially expressed in malignant tumors and may have a role in carcinogenesis, including thyroid cancer. The authors therefore tested the hypothesis that miRNA expression analysis would identify putative markers that could distinguish benign from malignant thyroid neoplasms that are often indeterminate on FNA biopsy. METHODS: A miRNA array was used to identify differentially expressed genes (5-fold higher or lower) in pooled normal, malignant, and benign thyroid tissue samples. Real-time quantitative polymerase chain reaction was used to confirm miRNA array expression data in 104 tissue samples (7 normal thyroid, 14 hyperplastic nodule, 12 follicular variant of papillary thyroid cancer, 8 papillary thyroid cancer, 15 follicular adenoma, 12 follicular carcinoma, 12 Hurthle cell adenoma, 20 Hurthle cell carcinoma, and 4 anaplastic carcinoma cases), and 125 indeterminate clinical FNA samples. The diagnostic accuracy of differentially expressed genes was determined by analyzing receiver operating characteristics. RESULTS: Ten miRNAs showed >5-fold expression difference between benign and malignant thyroid neoplasms on miRNA array analysis. Four of the 10 miRNAs were validated to be significantly differentially expressed between benign and malignant thyroid neoplasms by quantitative polymerase chain reaction (P < .002): miR-100, miR-125b, miR-138, and miR-768-3p were overexpressed in malignant samples of follicular origin (P < .001), and in Hurthle cell carcinoma samples alone (P < .01). Only miR-125b was significantly overexpressed in follicular carcinoma samples (P < .05). The accuracy for distinguishing benign from malignant thyroid neoplasms was 79% overall, 98% for Hurthle cell neoplasms, and 71% for follicular neoplasms. The miR-138 was overexpressed in the FNA samples (P = .04) that were malignant on final pathology with an accuracy of 75%. CONCLUSIONS: MicroRNA expression differs for normal, benign, and malignant thyroid tissue. Expression analysis of differentially expressed miRNA could help distinguish benign from malignant thyroid neoplasms that are indeterminate on thyroid FNA biopsy.

Neuroendocrine tumors.

Neuroendocrine tumors comprise a broad family of tumors, the most common of which are carcinoid and pancreatic neuroendocrine tumors. The NCCN Neuroendocrine Tumors Guidelines discuss the diagnosis and management of both sporadic and hereditary neuroendocrine tumors. Most of the recommendations pertain to well-differentiated, low- to intermediate-grade tumors. This updated version of the NCCN Guidelines includes a new section on pathology for diagnosis and reporting and revised recommendations for the surgical management of neuroendocrine tumors of the pancreas.

Fluorodeoxyglucose-positron emission tomography scan-positive recurrent papillary thyroid cancer and the prognosis and implications for surgical management.

BACKGROUND: To compare outcomes for patients with recurrent or persistent papillary thyroid cancer (PTC) who had metastatic tumors that were fluorodeoxyglucose-positron emission tomography (FDG-PET) positive or negative, and to determine whether the FDG-PET scan findings changed the outcome of medical and surgical management. METHODS: From a prospective thyroid cancer database, we retrospectively identified patients with recurrent or persistent PTC and reviewed data on demographics, initial stage, location and extent of persistent or recurrent disease, clinical management, disease-free survival and outcome. We further identified subsets of patients who had an FDG-PET scan or an FDG-PET/CT scan and whole-body radioactive iodine scans and categorized them by whether they had one or more FDG-PET-avid (PET-positive) lesions or PET-negative lesions. The medical and surgical treatments and outcome of these patients were compared. RESULTS: Between 1984 and 2008, 41 of 141 patients who had recurrent or persistent PTC underwent FDG-PET (n = 11) or FDG-PET/CT scans (n = 30); 22 patients (54%) had one or more PET-positive lesion(s), 17 (41%) had PET-negative lesions, and two had indeterminate lesions. Most PET-positive lesions were located in the neck (55%). Patients who had a PET-positive lesion had a significantly higher TNM stage (P = 0.01), higher age (P = 0.03), and higher thyroglobulin (P = 0.024). Only patients who had PET-positive lesions died (5/22 vs. 0/17 for PET-negative lesions; P = 0.04). In two of the seven patients who underwent surgical resection of their PET-positive lesions, loco-regional control was obtained without evidence of residual disease. CONCLUSION: Patients with recurrent or persistent PTC and FDG-PET-positive lesions have a worse prognosis. In some patients loco-regional control can be obtained without evidence of residual disease by reoperation if the lesion is localized in the neck or mediastinum.

Identification of differentially expressed microRNA in parathyroid tumors.

BACKGROUND: The molecular factors that control parathyroid tumorigenesis are poorly understood. In the absence of local invasion or metastasis, distinguishing benign from malignant parathyroid neoplasm is difficult on histologic examination. We studied the microRNA (miRNA) profile in normal, hyperplastic, and benign and malignant parathyroid tumors to better understand the molecular factors that may play a role in parathyroid tumorigenesis and that may serve as diagnostic markers for parathyroid carcinoma. METHODS: miRNA arrays containing 825 human microRNAs with four duplicate probes per miRNA were used to profile parathyroid tumor (12 adenomas, 9 carcinomas, and 15 hyperplastic) samples normalized to four reference normal parathyroid glands. Differentially expressed miRNA were validated by real-time quantitative TaqMan polymerase chain reaction (PCR). RESULTS: One hundred fifty-six miRNAs in parathyroid hyperplasia, 277 microRNAs in parathyroid adenoma, and 167 microRNAs in parathyroid carcinomas were significantly dysregulated as compared with normal parathyroid glands [false discovery rate (FDR) < 0.05]. By supervised clustering analysis, all parathyroid carcinomas clustered together. Three miRNAs (miR-26b, miR-30b, and miR-126*) were significantly dysregulated between parathyroid carcinoma and parathyroid adenoma. Receiver-operating characteristic curve analysis showed mir-126* was the best diagnostic marker, with area under the curve of 0.776. CONCLUSIONS: Most miRNAs are downregulated in parathyroid carcinoma, while in parathyroid hyperplasia most miRNAs are upregulated. miRNA profiling shows distinct differentially expressed miRNAs by tumor type which may serve as helpful adjunct to distinguish parathyroid adenoma from carcinoma.

Prospective randomized trial of ligasure versus harmonic hemostasis technique in thyroidectomy.

BACKGROUND: Two surgical devices have become popular in thyroid surgery: a bipolar energy sealing system (B) and ultrasonic coagulation (UC). Retrospective and prospective studies have demonstrated that the use of these surgical devices for thyroidectomy compared with conventional thyroidectomy (clamp-and-tie) techniques reduces operative time and cost. We conducted a prospective randomized clinical trial to determine if there is any difference in operative time and cost between B and UC. MATERIALS AND METHODS: A single-blinded prospective randomized controlled trial was conducted at a tertiary referral center. A total of 90 patients who required a thyroidectomy for thyroid cancer, thyroid nodules, or hyperthyroidism were randomized to either B or UC during thyroidectomy. The operative time and cost of thyroidectomy were compared between the two groups. RESULTS: There was no statistically significant difference in patient age, gender, body mass index, indication for thyroidectomy and thyroid gland weight between the two groups. There was no statistically significant difference in operating room cost or total cost for thyroidectomy between the B and UC groups. There was also no statistically significant difference in the operative time between the B and UC groups (187.6 vs. 184.2 min, P = 0.48) or in postoperative complication rates. The only statistically significant difference in total cost was between surgeons independent of the device used (P < 0.01). CONCLUSIONS: In thyroid surgery, total cost and operative time were similar between the two surgical devices used.

Thyroid cancer and lymph node metastases.

There is considerable controversy about the prognostic implications of lymph node metastases in patients with papillary thyroid cancer and whether patients with papillary thyroid cancer should have a prophylactic or selective central (level VI) neck dissection. Some experts report that a prophylactic ipsilateral neck dissection results in fewer patients having elevated thyroglobulin levels but others do not agree. A comprehensive review of the literature suggests that the presence of macroscopic metastases of papillary thyroid cancer in cervical lymph nodes results in a higher recurrence rate and increased death rate, especially in patients 45 years of age or older, whereas microscopic nodal metastases do not appear to adversely influence survival. Until more information is available we recommend preoperative ultrasonography and a selective ipsilateral neck dissection for patients with papillary thyroid cancer.

Unique patterns of metastases in common and rare types of malignancy.

This review on the unique patterns of metastases by common and rare types of cancer addresses regional lymphatic metastases but also demonstrates general principles by consideration of vital organ metastases. These general features of successfully treated metastases are relationships to basic biological behavior as illustrated by disease-free interval, organ-specific behavior, oligo-metastatic presentation, genetic control of the metastatic pattern, careful selection of patients for surgical resection, and the necessity of complete resection of the few patients eligible for long-term survival after resection of vital organ metastasis. Lymph node metastases, while illustrating these general features, are not related to overall survival because lymph node metastases themselves do not destroy a vital organ function, and therefore have no causal relationship to overall survival. When a cancer cell spreads to a regional lymph node, does it also simultaneously spread to the systemic site or sites? Alternatively, does the cancer spread to the regional lymph node first and then it subsequently spreads to the distant site(s) after an incubation period of growth in the lymph node? Of course, if the cancer is in its incubation stage in the lymph node, then removal of the lymph node in the majority of cases with cancer cells may be curative. The data from the sentinel lymph node era, particularly in melanoma and breast cancer, is consistent with the spectrum theory of cancer progression to the sentinel lymph node in the majority of cases prior to distant metastasis. Perhaps, different subsets of cancer may be better defined with relevant biomarkers so that mechanisms of metastasis can be more accurately defined on a molecular and genomic level.

Prospective evaluation of the rate and impact of hemolysis on intraoperative parathyroid hormone (IOPTH) assay results.

BACKGROUND: Intraoperative parathyroid hormone (IOPTH) is commonly used during minimally invasive parathyroidectomy. Retrospective evidence suggested that hemolysis may artificially lower IOPTH results. Falsely decreased IOPTH measurements could result in either failed parathyroidectomy or unnecessary bilateral neck exploration. METHODS: A total of 130 IOPTH specimens from 30 patients were assayed before and after induction of mechanical hemolysis using a vortex and inert sterile glass beads. Free hemoglobin (Hg) was measured as a surrogate for extent of hemolysis. Paired sample t test was used for comparison of matched prehemolysis and posthemolysis specimens. RESULTS: Of the samples, 16.9% were hemolyzed at the baseline (11 of 72 pre-excision, 11 of 55 postexcision). We successfully induced moderate hemolysis (ΔHg 0.1-1.0 mg/DL) in 66 samples that had minimal hemolysis at baseline. In these, mechanical hemolysis increased free Hg by an average of 0.37 mg/DL (533%; mean posthemolysis free Hg = 0.43; moderate hemolysis) and lowered PTH values by an average of 39% (median = 36%, SD = 11%; P = .002). The decrease in PTH was related to the extent of hemolysis induced (r = 0.51; P < .001), but was unrelated to the specimen's baseline (true) PTH (P = .24). In 12 of 30 patients, the experimentally hemolyzed pre-excision PTH value would have reduced the 50% threshold sufficiently to cause a false-negative result. In 6 of the 30 parathyroidectomies, a hemolyzed postexcision PTH value would have decreased PTH value sufficiently to cause a false-positive result. CONCLUSIONS: Hemolysis of IOPTH specimens occurs commonly and falsely reduces PTH results. In 18 of 30 patients, this effect was sufficient to have contributed to either a false-positive or false-negative IOPTH result.

Multiple genetic alterations in papillary thyroid cancer are associated with younger age at presentation.

BACKGROUND: There is a significant gender and age disparity in thyroid cancer incidence and outcome. The molecular basis for these divergent clinical presentations and outcome are essentially unknown. METHODS: The primary tumor genotype in 217 patients with papillary thyroid cancer was determined for six common somatic genetic alterations (RET/PTC1, RET/PTC3, and NTRK1 rearrangements, and BRAF V600E, KRAS, and NRAS hotspot mutations) by PCR and direct sequencing, and nested PCR. Univariate and multivariate analyses were performed to determine the association of genetic changes and age, gender, and other clinicopathologic factors. RESULTS: One hundred twenty-one of the 190 conventional papillary thyroid carcinoma samples (63.7%) had at least one genetic alteration, and 27 of the samples (14.2%) had more than one alteration. In the follicular variant of papillary thyroid carcinomas, 13 of the 27 samples (48.1%) had at least one genetic alteration and three of the 27 samples (11.1%) had more than one. The presence of multiple genetic alterations was associated with younger age at diagnosis (P=0.034), mean difference of 8 y earlier. We found no significant association with the number or type of genetic alterations present by gender, tumor size, extent of tumor differentiation, multicentricity, lymph node metastasis, distant metastases, TNM stage, and the AMES risk group. The association of multiple genetic alterations and younger age were independent of tumor size, lymph node or distant metastasis, TNM stage, or AMES risk group. CONCLUSIONS: Multiple genetic alterations are more common in younger patients with papillary thyroid cancer, but there is no difference in the type or number of genetic alterations by gender. Our findings suggest that multiple genetic alterations in thyroid cancer may be associated with earlier disease initiation and or progression.

Molecular testing for somatic mutations improves the accuracy of thyroid fine-needle aspiration biopsy.

BACKGROUND: Thyroid fine-needle aspiration (FNA) biopsy is indeterminate or suspicious in up to 30% of cases and these patients are commonly subjected to at least a diagnostic hemithyroidectomy. If malignant on histology, a completion thyroidectomy is usually performed, which may be associated with higher morbidity. To determine the clinical utility of genetic testing in thyroid FNA biopsy, we conducted a prospective clinical trial. METHODS: Four hundred seventeen patients with 455 thyroid nodules were enrolled and had genetic testing for common somatic mutations (BRAF, NRAS, KRAS) and gene rearrangements (RET/PTC1, RET/PTC3, RAS, TRK1) by PCR and direct sequencing and by nested PCR, respectively. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of genetic testing in thyroid FNA biopsy were determined based on the histologic diagnosis. RESULTS: One hundred twenty-five of 455 thyroid nodule FNA biopsies were indeterminate or suspicious on cytologic examination. Overall, 50 mutations were identified (23 BRAF, 4 RET/PTC1, 2 RET/PTC3, 21 NRAS) in the thyroid FNA biopsies. There were significantly more mutations detected in malignant thyroid nodules than in benign (P = 0.0001). For thyroid FNA biopsies that were indeterminate or suspicious, genetic testing had a sensitivity of 12%, specificity of 98%, PPV of 38%, and NPV of 65%. CONCLUSIONS: Genetic testing for somatic mutations in thyroid FNA biopsy samples is feasible and identifies a subset of malignant thyroid neoplasms that are indeterminate or suspicious on FNA biopsy. Genetic testing for common somatic genetic alterations thus could allow for more definitive initial thyroidectomy in those with positive results.

Surgery for asymptomatic primary hyperparathyroidism: proceedings of the third international workshop.

CONTEXT: An international workshop on primary hyperparathyroidism (PHPT) was convened on May 13, 2008, to review and update the previous summary statement on the management of asymptomatic PHPT published in 2002. EVIDENCE ACQUISITION: Electronic literature sources were systematically reviewed, addressing critical aspects of the surgical issues pertaining to the indications, imaging, surgical treatment, and cost-effective management of patients with PHPT. EVIDENCE SYNTHESIS: The surgical group concluded that many patients with "asymptomatic" PHPT have neurocognitive symptoms that may be unmasked after successful parathyroidectomy. Furthermore, reduced bone density and increased fracture risk can be improved with parathyroidectomy. When PHPT is symptomatic, it may be associated with nephrolithiasis, increased cardiovascular disease, and decreased survival. Preoperative imaging studies should only be performed to help plan the operation, and negative imaging should never preclude surgical referral. Noninvasive localization studies including ultrasound and sestamibi scans are often employed, especially in anticipation of focused explorations. Invasive localization studies should be reserved for remedial explorations where noninvasive imaging has been unsuccessful. CONCLUSIONS: When performed by expert parathyroid surgeons, parathyroid surgery is safe, cost-effective, and associated with very low perioperative morbidity. Minimally invasive approaches to parathyroid surgery appear to be as effective as the classic bilateral cervical exploration approach.

Candidate genes associated with malignant pheochromocytomas by genome-wide expression profiling.

OBJECTIVE: To improve our understanding of the molecular mechanisms involved in malignant pheochromocytoma by examining differences in the gene expression profile between benign and malignant tumors. BACKGROUND: The molecular events involved in the malignant transformation of pheochromocytoma are poorly understood. There are also no reliable and uniformly accepted histopathologic criteria to distinguish benign from malignant pheochromocytoma. METHODS: We performed genome-wide expression profiling of 58 pheochromocytomas (29 benign and sporadic, 16 benign and hereditary, 13 malignant) with technical and biologic replication. RESULTS: Unsupervised cluster analysis showed 3 main clusters of tumors that did not have complete concordance with the clinical and pathologic groupings of pheochromocytomas. Supervised cluster analysis showed almost completely separate clustering between benign and malignant tumors. The differentially expressed genes with known function belonged to 8 biologic process categories; signal transduction, transcription, protein transport, protein synthesis, smooth muscle contraction, ion transport, chemotaxis, and electron transport. Gene set enrichment analysis revealed significant correlation between the microarray profiles of malignant pheochromocytomas and several known molecular pathways associated with carcinogenesis and dedifferentiation. Ten differentially expressed genes had high diagnostic accuracy, and 5 of these genes (CFC1, FAM62B, HOMER1, LRRN3, TBX3, ADAMTS) in combination had an area under the receiver operating characteristic (ROC) curve of 0.96 for distinguishing benign versus malignant tumors. CONCLUSIONS: Differentially expressed genes between benign and malignant pheochromocytomas distinguish between these tumors with high diagnostic accuracy. Our findings provide new insight into the genes and molecular pathways that may be involved in malignant pheochromocytomas.

Diagnostic markers and prognostic factors in thyroid cancer.

There has been considerable progress identifying biomarkers in thyroid tumors that improve the accuracy of fine-needle aspiration biopsy and also help predict tumor aggressiveness or behavior. In this review we address both the clinical potential of molecular biomarkers and their usefulness, based on the most recent literature. We describe the current best clinical staging systems and the common somatic mutations in thyroid cancer. The BRAF mutation is the most common mutation in papillary thyroid cancer and has recently been reported to be associated with disease aggressiveness; it is also an independent predictor of tumor behavior. Combined testing of RET/PTC, NTRK, RAS and PAX8-PPARgamma, which are mutually exclusive mutations, helps improve the accuracy of fine-needle aspiration biopsy. Gene-expression profiling studies have identified a variety of potential molecular markers to help distinguish benign from malignant thyroid neoplasms. Expression analysis of differentially expressed microRNAs also appears to be a promising diagnostic approach for distinguishing benign from malignant thyroid neoplasm. It is especially useful for indeterminate nodules by fine-needle aspiration biopsy.

Surgical treatment of persistent hyperparathyroidism after renal transplantation.

OBJECTIVE: To provide a review on current knowledge about the pathogenesis, epidemiology, and clinical complications of persistent hyperparathyroidism after kidney transplantation (3HPT) and to discuss the surgical approaches. BACKGROUND: 3HPT usually regresses within the first months after transplantation. Parathyroidectomy for 3HPT is therefore not usually needed. Consequently, few studies have been published regarding the best medical management for 3HPT and indications for parathyroidectomy. METHODS: Medical literature databases were searched for studies on the surgical treatment of 3HPT published in English. RESULTS: Forty-one studies were identified and included in this review. CONCLUSIONS: 3HPT most commonly occurs in patients who have severe secondary hyperparathyroidism at the time of transplantation. Indications for parathyroidectomy in patients with 3HPT include persistent severe hypercalcemia, defined as a serum calcium level greater than 11.5 mg/dl, unexplained renal function deterioration, or progressive bone mineral density loss. Published studies suggest that the best surgical approach for patients with 3HPT is subtotal parathyroidectomy or total parathyroidectomy with autotransplantation. 3HPT poses important health risks, particularly concerning bone density and the cardiovascular system. Because spontaneous improvement of parathyroid function is uncommon after 3 months of transplantation, waiting for more than 6 months before parathyroidectomy should be discouraged.