Incidental Solitary Adrenal Metastasis as the Initial Manifestation of a Solid Variant of Papillary Thyroid Carcinoma, With Emphasis on Pathologic Diagnosis and Clinical Management.

Objective: Distant metastases from papillary thyroid carcinoma (PTC) are relatively rare and may be associated with a poor prognosis. The adrenal gland is a highly unusual site of metastasis in the natural course of PTC. Herein, we describe a case of an incidentally detected metastatic solid variant of PTC in the adrenal gland of an asymptomatic patient as the initial presentation. Case Report: A 67-year-old male patient was evaluated for a 4.7-cm adrenal incidentaloma discovered during a workup for nephrolithiasis. Biochemical evaluation revealed a nonfunctioning adrenal mass. The patient underwent adrenalectomy, which revealed metastatic PTC. A subsequent thyroid ultrasound revealed an isthmic nodule. Fine needle aspiration of the nodule was cytologically suspicious for a follicular neoplasm, and gene expression analysis revealed an HRAS c.182A>G sequence variation. The patient subsequently underwent total thyroidectomy, which revealed a 1.2-cm solid variant of PTC in the thyroid isthmus. Postoperatively, the patient underwent radioactive iodine ablation. Discussion: Our case illustrates an exceedingly rare and challenging situation-a metastatic solid variant of PTC in the adrenal gland of a patient with no prior history of PTC. When confronted with a PTC in the adrenal gland in the absence of a previously identified primary tumor, our experience suggests that the next step in management should be total thyroidectomy followed by radioactive iodine ablation. Conclusion: A solid variant of PTC is a rare cause of an incidentally detected adrenal lesion. Multidisciplinary care team coordination is essential for accurate diagnosis and treatment plan formulation.

Rapid Relief: Thyroidectomy is a Quicker Cure than Radioactive Iodine Ablation (RAI) in Patients with Hyperthyroidism.

BACKGROUND: Time to hormonal control after definitive management of hyperthyroidism is unknown but may influence patient and physician decision making when choosing between treatment options. The hypothesis is that the euthyroid state is achieved faster after thyroidectomy than RAI ablation. METHODS: A retrospective review of all patients undergoing definitive therapy for hyperthyroidism was performed. Outcomes after thyroidectomy were compared to RAI. RESULTS: Over 3 years, 217 patients underwent definitive therapy for hyperthyroidism at a county hospital: 121 patients received RAI, and 96 patients underwent thyroidectomy. Age was equivalent (p = 0.72). More males underwent RAI (25% vs 15%, p = 0.05). Endocrinologists referred for both treatments equally (p = 0.82). Both treatments were offered after a minimum 1-year trial of medical management (p = 0.15). RAI patients mostly had Graves (93%), versus 73% of thyroidectomy patients (p < 0.001). Thyroidectomy patients more frequently had eye symptoms (35% vs 13%, p < 0.001), compressive symptoms (74% vs 15%, p < 0.001), or were pregnant/nursing (14% vs 0, p < 0.001). While the thyroidectomy patients had a documented discussion of all treatment modalities, 79% of RAI patients did not have a documented discussion regarding the option of surgical management (p < 0.001). Both treatment groups achieved an euthyroid state (71% vs 65%, p = 0.39). Thyroidectomy patients became euthyroid faster [3 months (2-7 months) versus 9 months (4-14 months); p < 0.001]. CONCLUSIONS: Thyroidectomy for hyperthyroidism renders a patient to an euthyroid state faster than RAI. This finding may be important for patients and clinicians considering definitive options for hyperthyroidism.

Early endocrine attending surgeon presence increases operating room efficiency.

BACKGROUND: Preincision operating room (OR) preparation varies greatly. Cases requiring exacting preoperative setup may be more sensitive to inconsistent team members and trainees. Leadership and oversight by the surgeon may facilitate a timely start. The study hypothesized that early attending presence in the OR expedites surgery start time, improving efficiency, and decreasing cost. METHODS: Prospective data collection of endocrine surgery cases at an urban teaching hospital was performed. Time points recorded in minutes. Cost/min of OR time was $54. Patients classified as in the OR ≤10 min before attending arrival or >10 min before attending arrival. RESULTS: A total of 227 cases (166 thyroid, 54 parathyroid, 10 adrenal) were performed over 14 mo. Of the patients, 128 were in the OR ≤10 min before attending arrival, and 99 patients were >10 min (3 ± 3 min versus 35 ± 14 min, P < 0.01). The ≤10 min procedures started sooner after patient arrival in OR (40 ± 11 versus 63 ± 19, P < 0.01) which equated to $1202 of savings before incision. Although attending time in the OR before incision was equivalent between groups for adrenal and parathyroid, time to incision was shorter in the ≤10 min groups, saving $2416 ± 477 and $1458 ± 244, respectively (P < 0.01). Attending time in OR before thyroidectomy was 13 min longer in ≤10 min than >10 min (P < 0.01), but incisions were made 20 min sooner (P < 0.01) equating to $1076 ± 120 in savings. CONCLUSIONS: Early attending presence in the OR shortens time to incision. For parathyroid and adrenal cases, this does not require additional surgeon time. In ORs without consistent teams, early attending presence in the OR improves efficiency and yields significant cost savings.

The relationship between chronic lymphocytic thyroiditis and central neck lymph node metastasis in North American patients with papillary thyroid carcinoma.

BACKGROUND: Several studies have reported that concurrent chronic lymphocytic thyroiditis (CLT) with papillary thyroid carcinoma (PTC) is associated with improved prognosis of the PTC, including decreased lymph node metastasis. We sought to assess the incidence of central nodal metastasis (CNM) in patients with PTC and concurrent CLT. METHODS: We studied 495 consecutive patients who underwent thyroidectomy with nodal excision for PTC. Pathology reports identified the presence of CLT and the extent of CNM. RESULTS: There were 226 patients (46%) with CLT and 220 (44%) with CNM. Patients with CLT were more often female (88% vs. 71%; P < .001) and had a younger median age (43 vs. 47 years; P = .03), a lesser incidence of CNM (35% vs. 52.4%; P < .001), and a greater incidence of pT1a (40% vs. 25%; P < .001) and pT1b (38% vs. 29%; P < .001) tumors. Multivariate analysis showed that the presence of CLT was associated with a 39% decreased odds of CNM after adjusting for age, gender, tumor size, PTC histopathologic subtype, and presence of lymphovascular invasion (odds ratio, 0.61; 95% confidence interval, 0.38-0.99; P = .046). Predicted probability modeling showed that all females with CLT and no suspicious nodal findings on ultrasonography had a 9-11% risk of CNM with pT1a tumors. CONCLUSION: Female patients of all ages with CLT and small PTCs have the least incidence of CNM.

Serendipity in the diagnosis of pheochromocytoma.

OBJECTIVES: Pheochromocytomas are increasingly being discovered incidentally on imaging studies performed without clinical suspicion of the existence of an adrenal lesion. We aimed to determine the rate of diagnosis of adrenal pheochromocytoma as an incidental finding during a recent 7-year period. METHODS: We obtained the Department of Pathology database to study all the patients at our institution with newly diagnosed pheochromocytomas in the 7-year period from 2005 to 2011 to determine the clinical presentation and the means of diagnosis. RESULTS: In 40 (70.2%) of the 57 patients, an adrenal pheochromocytoma was detected in an imaging study performed without suspicion of an adrenal lesion. There were 13 chest computed tomography studies-8 to evaluate for possible pulmonary emboli. Other indications included abdominal pain or discomfort (n = 8), trauma (n = 3), abnormal liver function tests (n = 3), suspect renal artery stenosis (n = 3), hematuria (n = 2), colitis (n = 2), and 4 miscellaneous indications. DISCUSSION: Our study documents that the commonest current means of initial detection of pheochromocytoma is by serendipitous discovery. In 16 of our 40 patients with serendipitously discovered pheochromocytomas, there were no clinical symptoms of pheochromocytoma; these were true incidentalomas. More than two thirds of the new cases of pheochromocytoma were detected by serendipity (found during studies not performed to evaluate for pheochromocytoma), approximately one third were true incidentalomas (pheochromocytomas in patients without symptoms). CONCLUSIONS: In a 7-year period at a single institution, 40 patients, 70% of new cases of surgically proven pheochromocytoma, were initially detected by serendipity. Sixteen patients, 40% of those incidentally discovered represented true examples of "incidentalomas."

Intrathyroidal parathyroid glands: small, but mighty (a Napoleon phenomenon).

BACKGROUND: Intrathyroidal parathyroid adenomas (ITPAs) are a rare entity. The aim of this study is to describe the experience of 2 endocrine surgery centers and to distinguish characteristics of intrathyroidal parathyroid adenoma and nonintrathyroidal parathyroid adenomas. METHODS: We included patients who had undergone operations for primary hyperparathyroidism who had intrathyroidal parathyroid adenomas. Patients with single intrathyroidal parathyroid adenomas were also compared to age- and sex-matched controls with nonintrathyroidal parathyroid adenomas. RESULTS: Of 4,868 patients who underwent parathyroidectomy between January 2002 and June 2011, we identified 53 (1%) patients with intrathyroidal parathyroid adenoma. Sestamibi and ultrasound scans correctly identified the adenoma in 35 (70%) and 11 (61%) cases, respectively. Single adenomas were identified in 44 (83%) patients, double adenomas in 4 (8%) patients, and hyperplasia in 5 (9%) patients. Lobectomy was performed in 17 (32%) patients; enucleation was used in 36 (68%) patients. Cure was achieved in all patients and no patients experienced a recurrence. Patients with single intrathyroidal parathyroid adenomas had significantly smaller glands than patients with nonintrathyroidal parathyroid adenomas (325 ± 47 vs 772 ± 61 mg; P < .0001); however, no significant difference was identified between the groups with regard to demographics, symptoms, preoperative laboratory values, or outcomes. CONCLUSION: Single intrathyroidal parathyroid adenomas are smaller than nonintrathyroidal parathyroid adenomas, but patients with intrathyroidal parathyroid adenomas present with similar laboratory values and symptoms. Recognition of this rare entity can lead to a successful surgical outcome.

Three-gene molecular diagnostic model for thyroid cancer.

BACKGROUND: The preoperative diagnosis of thyroid nodules primarily depends upon fine needle aspiration (FNA) cytology. However, up to 25% of FNA samples have associated "suspicious or indeterminate", but not diagnostic cytologic reports, resulting in difficulty deciding appropriate clinical management for these patients. We hypothesize that the use of molecular markers as an adjunct to FNA cytology can improve the distinction of benign from malignant nodules that have associated suspicious or indeterminate cytology. METHODS: Using microarray analysis, we previously identified and reported on 75 genes useful in the distinction of benign versus malignant thyroid nodules. In the present study, we have further validated the expression of 14 of these markers in a large number of thyroid samples by immunohistochemistry (IHC) analysis of 154 thyroid tumors and quantitative real-time RT-PCR (QRT-PCR) analysis of 95 FNA samples. Of the 154 tumors analyzed by IHC, 44 samples (29%) had associated suspicious or indeterminate FNA cytology. RESULTS: Receiver operating characteristic using three-gene model, (HMGA2, MRC2, and SFN) analysis for the detection of malignant nodules resulted in areas under the curve (AUCs) of≥0.95 (80% sensitivity; 100% specificity) and≥0.84 (71% sensitivity; 84% specificity) for the IHC data in tumors, and QRT-PCR data in FNA samples, respectively. CONCLUSIONS: Our results suggest that a three-gene model for the cytological diagnosis of indeterminate thyroid nodules is both feasible and promising. Implementation of this as an adjunct to thyroid cytology may significantly impact the clinical management of patients with suspicious or indeterminate thyroid FNA nodules.

Preoperative thyroid ultrasound is indicated in patients undergoing parathyroidectomy for primary hyperparathyroidism.

BACKGROUND: Primary hyperaparathyroidism (pHPT) is often accompanied by underlying thyroid pathology that can confound preoperative parathyroid localization studies and complicate intra-operative decision making. The aim of this study was to examine the utility of preoperative thyroid ultrasonography (US) in patients prior to undergoing parathyroidectomy for pHPT. METHODS: An Institutional Review Board approved prospective study was undertaken from January 2005 through July 2008. All patients with pHPT meeting inclusion criteria (n=94) underwent preoperative thyroid ultrasound in addition to standard (99m)Tc-sestamibi scintigraphy for parathyroid localization. Demographics, operative management and final pathology were examined in all cases. RESULTS: Fifty-four of the 94 patients (57%) were noted to have a thyroid nodule on preoperative US, of which 30 (56%) underwent further examination with fine needle aspiration biopsy. Alteration of the operative plan attributable to underlying thyroid pathology occurred in 16 patients (17%), with patients undergoing either total thyroidectomy (n=9) or thyroid lobectomy (n=7). Thyroid cancer was noted in 33% of patients undergoing thyroid resection, and 6% of all patients with HPT. CONCLUSIONS: The routine utilization of preoperative thyroid ultrasound in patients prior to undergoing parathyroid surgery for pHPT is indicated. The added information from this non-invasive modality facilitates timely management of co-incidental, and sometimes malignant, thyroid pathology.

Long-term outcome in patients with primary hyperparathyroidism who underwent minimally invasive parathyroidectomy.

BACKGROUND: Minimally invasive parathyroidectomy (MIP) has become a well-accepted treatment for selected patients with primary hyperparathyroidism (PHPT). However, few studies have evaluated long-term outcomes for this operative approach. We therefore chose to examine both the long-term symptom resolution and biochemical cure following MIP for PHPT. METHODS: A total of 460 PHPT patients who underwent a MIP between 2004 and 2009 were successfully mailed a questionnaire that assessed preoperative and postoperative Parathyroidectomy Assessment of Symptoms (PAS) scores, most recent calcium and parathyroid hormone (PTH) levels, and information about any reoperation for PHPT. Long-term evaluation of symptomatic and biochemical cure was performed. RESULTS: A total of 200 patients (43.5%) responded to our correspondence. The mean age of the patients was 58.7 ± 11.9 years, 74.5% were female, and 78.5% were Caucasian. The mean follow-up was 37 ± 19 months. The mean PAS scores fell by 117 ± 14 at long-term follow-up after MIP (P < 0.0001). All 13 symptoms comprising the PAS score diminished, of which ten did so significantly (P < 0.01). There was a significant drop in the mean serum calcium (preop. 11.1 mg/dl, postop. 9.6 mg/dl; P < 0.0001) and PTH (preop. 130.9 pg/ml, postop. 45.7 pg/ml; P < 0.0001) at long-term follow-up. Five patients (2.5%) developed recurrent disease (calcium > 10.5 mg/dl), and one (0.5%) underwent a reoperation for persistent disease and was subsequently cured. CONCLUSIONS: This study demonstrates that MIP has long-term benefits in terms of excellent symptom resolution and a high biochemical cure rate (97%) in selected patients who have PHPT, preoperative localization with sestamibi scans, and assessment of intraoperative PTH level.

Predictive factors of malignancy in pediatric thyroid nodules.

BACKGROUND: Studies suggest that while most pediatric thyroid nodules are benign, there is a higher rate of malignancy than in adults. We investigate clinical factors that may predict malignancy in pediatric thyroid nodules. METHODS: A retrospective review of 207 pediatric thyroidectomies was conducted over 15 years at 2 tertiary hospitals. Analyses examined predictive values of 16 clinicopathologic factors associated with cancer. Positive predictive values (PPVs) of fine-needle aspiration biopsy specimens (FNABs) were analyzed independently. RESULTS: Malignancy occurred in 41% of patients. After excluding missing data, malignancy was more likely with family history of thyroid cancer (34.2% vs 17.7%; P = .111), palpable lymphadenopathy (34.2% vs 2.9%; P = .001), and hypoechoic nodules (52.2% vs 19.2%; P = .016). Palpable lymphadenopathy indicated greater than 2-fold increased risk for malignancy (relative risk, 2.18; 95% confidence interval, 1.56-3.05). PPVs of FNAB results were 0.94 for malignancy, 0.63 for suspicious for malignancy, and 0.55 for indeterminate lesions. PPV for benign FNAB to be benign on final pathology was 0.71. CONCLUSION: While malignancy is associated with family history of thyroid cancer and hypoechoic lesions, palpable lymphadenopathy had the greatest risk. When compared to adults, a benign FNAB in children is not as accurate and the likelihood that an indeterminate nodule is cancer is greater.

Profile of patients with completion thyroidectomy and assessment of their suitability for outpatient surgery.

OBJECTIVE: Outpatient thyroid surgery for thyroid lobectomy has been shown to be safe and feasible. The safety of outpatient completion thyroidectomy in patients who have previously undergone thyroid lobectomy has not been extensively evaluated in the medical literature to date. The authors sought to evaluate postoperative complications associated with completion thyroidectomy in their institution to determine if it would be safe and feasible to perform as an outpatient procedure. STUDY DESIGN: Case series with chart review. SETTING: Tertiary care teaching hospital. SUBJECTS AND METHODS: Two hundred four consecutive patients, who underwent completion thyroidectomy after previous thyroid lobectomy from January 2000 to June 2010, comprised the study population. Medical records were reviewed for preoperative and postoperative serum calcium levels, preoperative and postoperative fiber-optic laryngoscopic examination of vocal fold mobility, associated comorbidities, length of hospital stay, drain use, seroma or hematoma formation, final thyroid pathology, and postoperative follow-up. RESULTS: Overall, 9 patients (4.4%) developed postoperative complications, including transient symptomatic hypocalcemia in 4 patients (2.0%), transient laboratory hypocalcemia in 3 patients (1.5%), seroma formation in 1 patient (0.5%), and hematoma development in 1 patient (0.5%). There were no cases with permanent or temporary vocal fold paralysis. No significant difference was found in the overall complication rate before and after 4 hours of observation (P = .50). CONCLUSION: Selected patients who undergo completion thyroidectomy after previous thyroid lobectomy can be safely discharged after 4 hours of postoperative observation with appropriate instructions.

Tumor size and presence of calcifications on ultrasonography are pre-operative predictors of lymph node metastases in patients with papillary thyroid cancer.

BACKGROUND AND OBJECTIVES: Lymph node metastases in papillary thyroid cancer (PTC) are common and their presence can significantly alter the treatment for patients with PTC. We therefore sought to identify pre-operative predictors of lymph node metastases in patients with PTC. METHODS: A thyroid tumor database was queried to identify patients with a pre-operative diagnosis of PTC and underwent thyroidectomy between January 2006 and August 2009. One hundred and three patients who had a pre-operative ultrasound and had lymph nodes surgically resected were identified. Clinical factors and tumor ultrasound characteristics were recorded. The pre-operative ultrasound results, type of operation, and final pathology results were also recorded. RESULTS: Of the 103 patients, 74 (72%) were women and 29 (28%) were men with an age range of 15-78 years (median age of 43). Of the ultrasound characteristics evaluated only calcifications (P = 0.007) and size (P = 0.003) were statistically associated with positive cervical lymph nodes. None of the other demographic or clinical factors were significantly associated with lymph node metastases. CONCLUSIONS: Thyroid nodule size and presence of calcifications on ultrasound were found to have a statistically significant association with lymph node metastases in patients with PTC. This information could be used to guide the surgical management of these patients.

A profile of patients with hyperparathyroidism undergoing lithium therapy for affective psychiatric disorders.

BACKGROUND: Our objective was to evaluate whether lithium-induced hyperparathyroidism (LIHPT) is caused by single-gland versus multigland disease. METHODS: Medical records of 7 patients who underwent parathyroidectomy for LIHPT were reviewed. RESULTS: The mean preoperative calcium was 11.1 ± 0.7 mg/dL. Six of 7 patients were rendered eucalcemic with surgery. Of the 6 patients successfully treated with surgery, 4 had single-gland disease, 1 had double adenomas, and 1 had 4-gland hyperplasia. Intraoperative intact serum parathyroid hormone (iPTH) accurately predicted resolution of hyperparathyroidism in 6 of 7 patients. One patient then subsequently developed persistent hyperparathyroidism refractory to further surgery. Localization studies defined the extent of disease in 5 of 7 patients. CONCLUSION: LIHPT presents with a spectrum of disease ranging from single-gland to multigland disease. The utility of preoperative localization studies and intraoperative iPTH in this population is uncertain. Bilateral exploration may be best to achieve a resolution of LIHPT.

Role of preoperative intact parathyroid hormone levels in predicting the likelihood of multiglandular disease in primary hyperparathyroidism.

BACKGROUND: Minimally invasive parathyroidectomy has become increasingly popular for the treatment of primary hyperparathyroidism, but is not a feasible option for multiglandular disease. It has been suggested that preoperative intact parathyroid hormone (iPTH) levels may predict multiglandular disease. We examined this hypothesis in patients who underwent surgical intervention for primary hyperparathyroidism at Johns Hopkins Medical Institutions. METHODS: We retrospectively reviewed 502 consecutive patients with primary hyperparathyroidism who underwent parathyroidectomy. Multivariable logistic regression analysis assessed preoperative iPTH levels as a predictor of multiglandular disease and a positive sestamibi scan, after adjustment for age, sex, and race. RESULTS: Preoperative iPTH levels were not significantly associated with a greater likelihood of multiglandular disease. However, sestamibi scan positivity was significantly more likely in patients with higher preoperative iPTH levels. CONCLUSION: Preoperative iPTH levels are not helpful in predicting multiglandular disease and should not be used to exclude a minimally invasive parathyroidecotomy for patients with primary hyperparathyroidism. © 2010 Wiley Periodicals, Inc. Head Neck, 2011.

Survival implications of cervical lymphadenectomy in patients with medullary thyroid cancer.

BACKGROUND: The relationship between extent of cervical lymphadenectomy along with the number of involved lymph nodes (LNs) removed and overall survival has not been well documented in patients with medullary thyroid carcinoma (MTC). This study investigates whether the overall number of LNs removed and the number of metastatic LNs are independent prognostic factors for overall survival. METHODS: Data from patients with MTC in the Surveillance, Epidemiology, and End Results (SEER) registry database were examined. After categorizing the study population based on the number of overall LNs examined and the number of metastatic LNs, survival estimates were compared. The total number of examined LNs and their histopathological status were analyzed for their prognostic value in estimating overall survival. RESULTS: 593 patients were included in this study. Those with all negative LNs had the best overall survival; those with LNs examined and at least one positive LN had worst overall survival (p < 0.0001). The total number of examined LNs for both groups with negative and positive LNs was not associated with improved survival outcome (p = 0.41). In node-positive patients, each additional positive LN was significantly associated with an increase in overall mortality [hazard ratio (HR) = 1.05, 95% confidence interval (CI) = 1.02-1.08]. CONCLUSIONS: Cervical LN metastases conferred an independent risk for worse survival rate in MTC. Cervical lymphadenectomy is important for staging and regional disease control, however the extent of lymph node dissection, the overall number of lymph nodes removed along with removal of an increased number of involved lymph nodes do not confer a survival advantage. Future prospective studies are needed.

Postoperative hypocalcemia after thyroidectomy for Graves' disease.

BACKGROUND: It is believed that patients who undergo thyroidectomy for Graves' disease are more likely to experience postoperative hypocalcemia than patients undergoing total thyroidectomy for other indications. However, no study has directly compared these two groups of patients. The aim of this study was to determine whether there was an increased incidence or severity of postoperative hypocalcemia in patients who underwent thyroidectomy for Graves' disease. METHODS: An institutional review board-approved database was created of all patients who underwent thyroidectomy from 1998 to 2009 at the Johns Hopkins Hospital. There were a total of 68 patients with Graves' disease who underwent surgery. Fifty-five patients who underwent total thyroidectomy were randomly selected and served as control subjects. An analysis was conducted that examined potential covariates for postoperative hypocalcemia, including age, gender, ethnicity, preoperative alkaline phosphatase level, size of goiter, whether parathyroid tissue or glands were present in the specimen, and the reason the patient underwent surgery. Specific outcomes examined were calcium levels on postoperative day 1, whether or not patients experienced symptoms of hypocalcemia, whether or not Rocaltrol was required, the number of calcium tablets prescribed upon discharge, whether or not postoperative tetany occurred, and calcium levels 1 month after discharge. RESULTS: Each outcome was analyzed using a logistic regression. Graves' disease patients had a significantly (p-value < 0.001) higher odds of greater number of calcium tablets prescribed upon discharge. Further, 6 of 68 patients with Graves' disease and no patient in the control group were readmitted with tetany (p = 0.033). There was a trend, though not significant, toward patients with Graves' disease having a higher prevalence of hypocalcemia the day after thyroidectomy and 1 month later. CONCLUSIONS: Patients with Graves' disease are more likely to require increased dosages of calcium as well as experience tetany postoperatively than patients undergoing total thyroidectomy for other indications. This suggests that patients operated upon for Graves' disease warrant close followup as both inpatients and outpatients for signs and symptoms of hypocalcemia.