Avital Harari

Incidence and Prevalence of Primary Hyperparathyroidism in a Racially Mixed Population

CONTEXT The epidemiology of primary hyperparathyroidism (PHPT) has generally been studied in Caucasian populations. OBJECTIVE The aim was to examine the incidence and prevalence of PHPT within a racially mixed population. DESIGN A descriptive epidemiologic study was performed. PATIENTS/SETTING The study population included 3.5 million enrollees within Kaiser Permanente Southern California. METHODS All patients with at least one elevated serum calcium level (>10.5 mg/dL, 2.6 mmol/L) between 1995 and 2010 were included. Cases of PHPT were identified by electronic query of laboratory values using biochemical criteria, after exclusion of secondary or renal and tertiary hyperparathyroidism cases. The incidence and prevalence rates of PHPT were calculated according to sex, race, age group by decade, and year. RESULTS Initial case finding identified 15,234 patients with chronic hypercalcemia, 13,327 (87%) of which had PHPT as defined by elevated or inappropriately normal parathyroid hormone levels. The incidence of PHPT fluctuated from 34 to 120 per 100,000 person-years (mean 66) among women, and from 13 to 36 (mean 25) among men. With advancing age, incidence increased and sex differences became pronounced (incidence 12-24 per 100,000 for both sexes younger than 50 y; 80 and 36 per 100,000 for women and men aged 50-59 y, respectively; and 196 and 95 for women and men aged 70-79 y, respectively). The incidence of PHPT was highest among blacks (92 women; 46 men, P < .0001), followed by whites (81 women; 29 men), with rates for Asians (52 women, 28 men), Hispanics (49 women, 17 men), and other races (25 women, 6 men) being lower than that for whites (P < .0001). The prevalence of PHPT tripled during the study period, increasing from 76 to 233 per 100,000 women and from 30 to 85 per 100 000 men. Racial differences in prevalence mirrored those found in incidence. CONCLUSIONS PHPT is the predominant cause of hypercalcemia and is increasingly prevalent. Substantial differences are found in the incidence and prevalence of PHPT between races.

Parathyroid Carcinoma: Update and Guidelines for Management

Opinion statementParathyroid carcinoma is one of the rarest known malignancies that may occur sporadically or as a part of a genetic syndrome. It accounts for approximately 1% of patients with primary hyperparathyroidism. The majority (90%) of parathyroid cancer tumors are hormonally functional and hypersecrete parathyroid hormone (PTH). Thus, most patients exhibit strong symptomatology of hypercalcemia at presentation. Sometimes, it can be difficult to diagnose parathyroid cancer preoperatively due to clinical features shared with benign causes of hyperparathyroidism. Imaging techniques such as neck ultrasound and 99mTc sestamibi scan can help localize disease, but they are not useful in the assessment of malignancy potential. Fine needle aspiration (FNA) prior to initial operation is not recommended due to technical difficulty in differentiating benign and malignant disease on cytology specimens and the possible associated risk of tumor seeding from the needle track. Complete surgical resection with microscopically negative margins is the recommended treatment and offers the best chance of cure. Persistent or recurrent disease occurs in more than 50% of patients with parathyroid carcinoma. Surgical resection is also the primary mode of therapy for recurrence since it can offer significant palliation for the metabolic derangement caused by hyperparathyroidism and allows hypercalcemia to become more medically manageable. However, reoperation is rarely curative and eventual relapse is likely. Chemotherapy and external beam radiation treatments have been generally ineffective in the treatment of parathyroid carcinoma. Typically, these patients require repeated operations that predispose them to accumulated surgical risks with each intervention. In inoperable cases, few palliative treatment options exist, although treatment with calcimimetics can effectively control hypercalcemia in some patients. Most patients ultimately succumb to complications of hypercalcemia rather than from tumor burden or infiltration.

Parathyroid Carcinoma: A 43-Year Outcome and Survival Analysis

CONTEXT Parathyroid carcinoma is a rare but ominous cause of primary hyperparathyroidism. OBJECTIVES AND MAIN OUTCOME MEASURES: The objective of the study was to review the outcomes of parathyroid cancer patients and to evaluate the factors associated with mortality. DESIGN, SETTING, AND PATIENTS This was a retrospective review performed on 37 patients with parathyroid cancer treated at a single university tertiary care center between 1966 and 2009. RESULTS The average age at cancer diagnosis was 53 yr (range 23-75 yr), and 23 patients (62%) were men. Eighteen patients (49%) recurred after their initial cancer operation. The average number of neck dissections done for cancer was three (range 1-11). After initial diagnosis, 22 patients (60%) eventually developed complications, including unilateral (n = 11) or bilateral (n = 3) vocal cord paralysis (38%). Eight patients (22%) had, at some point, an associated benign parathyroid adenoma. Median overall survival was 14.3 yr (range 10.5-25.7 yr) from the date of diagnosis. Factors associated with increased mortality included lymph node or distant metastases, number of recurrences, higher calcium level at recurrence, and a high number of calcium-lowering medications. Factors not associated with mortality included age, race, tumor size, time to first recurrence, and extent of initial operation. Initial operations done at our center had improved survival (P = 0.037) and decreased complication rates (P < 0.001) vs. those done elsewhere. CONCLUSION Parathyroid cancer patients typically have a long survival, which often includes multiple reoperations for recurrence and thus a high rate of surgical complications. Patients in whom there is a high index of suspicion for parathyroid cancer should be referred to a dedicated endocrine surgery center for their initial operation.

Malignant pheochromocytoma: a review

BACKGROUND Pheochromocytomas are rare catecholamine-secreting tumors. Approximately 10 percent of pheochromocytomas are malignant. Traditionally, there has been no reliable method available to predict the malignant potential of pheochromocytoma. However, recent research has increased focus on differentiating at the time of surgery/diagnosis those pheochromocytoma tumors which have malignant potential. In this review, we discuss the current information known of malignant pheochromocytomas. DATA SOURCES The PubMed database was searched for articles on malignant pheochromocytoma published between 1993 and 2010. CONCLUSIONS The difficult task of predicting the malignant potential of a pheochromocytoma has yet to be answered definitively. However, all the studies presented give an idea of what we may look for in these tumors at the time of diagnosis. We have provided an algorithm based on the most current information known. A much larger study should be performed to test many of these theories with enough power to determine a standard of care.

Racial and Socioeconomic Disparities in Presentation and Outcomes of Well-Differentiated Thyroid Cancer

CONTEXT Racial/ethnic minorities suffer disproportionate morbidity and mortality from chronic diseases. OBJECTIVE Our objective was to assess racial and socioeconomic status (SES) disparities in well-differentiated thyroid cancer (WDTC) patients. DESIGN AND PARTICIPANTS We conducted a retrospective cohort study on 25 945 patients with WDTC (1999-2008) from the California Cancer Registry (57% white, 4% black, 24% Hispanic, and 15% Asian-Pacific Islander [API]). MAIN OUTCOMES We evaluated effect of race and SES variables on stage of cancer presentation and overall/disease-specific survival. RESULTS Significant differences in stage of presentation between all racial groups were found (P<.001), with minority groups presenting with a higher percentage of metastatic disease as compared with white patients (black, odds ratio [OR]=1.36 with confidence interval [CI] 1.01-1.84; Hispanic, OR=1.89 [CI, 1.62-2.21], API, OR=1.82 [CI, 1.54-2.15]). Hispanic (OR=1.59, [CI, 1.48-1.72]) and API (OR=1.32 [1.22-1.44]) patients also presented with higher odds of regional disease. Patients with the lowest SES presented with metastatic disease more often than those with the highest SES (OR=1.45 [CI, 1.16-1.82]). Those that were poor/uninsured and/or with Medicaid insurance had higher odds of presenting with metastatic disease as compared with those with private insurance (OR=2.41, [CI, 2.10-2.77]). Unadjusted overall survival rates were higher among API and Hispanic patients and lower among black patients (P<.001 vs white patients). Adjusted overall survival also showed a survival disadvantage for black patients (hazard ratio=1.4, [CI, 1.10-1.73]) and survival advantage for API patients (hazard ratio=0.83, [CI, 0.71-0.97]). In disease-specific survival analyses, when only those patients with metastatic disease were analyzed separately, black patients again had the lowest survival rates, and Hispanic/API patients had the highest survival rates (P<.04). CONCLUSION Black patients and those with low SES have worse outcomes for thyroid cancer. API and Hispanic patients may have a protective effect on survival despite presenting with more advanced disease.

Effect of reoperation on outcomes in papillary thyroid cancer

BACKGROUND The influence of lymph node recurrences of papillary thyroid carcinoma (PTC) on overall prognosis is uncertain. We performed a population-based, longitudinal analysis to evaluate the impact of reoperation on mortality. METHODS Patients who underwent initial operation for PTC >1 cm were abstracted from the California Cancer Registry database (1999-2008). Reoperation was defined as any lymph node dissection after total or near-total thyroidectomy. RESULTS Of the 11,986 patients included in the study, 222 (1.9%) underwent one or more reoperations. The median time to reoperation was 8.7 months, with 58.6% and 83.8% of reoperations being performed within 1 and 2 years of initial thyroidectomy, respectively. The mortality rate from PTC was 2.3% (271 patients). After we adjusted for age, sex, tumor size, stage, and radioactive iodine treatment, we found that reoperation was associated with an increased risk of all-cause mortality in patients ≥45 years of age (hazard ratio [HR] 1.51, P < .05). Reoperation was associated with an increased risk of disease-specific mortality in both patients <45 (HR 6.22, P < .01) and ≥45 (HR 2.49, P < .001). CONCLUSION Reoperation is independently associated with mortality in PTC. Most reoperations are performed soon after initial thyroidectomy and likely reflect persistent rather than recurrent disease.

Trends in the frequency and quality of parathyroid surgery: analysis of 17,082 cases over 10 years.

OBJECTIVE To examine trends in the frequency and quality of surgery for primary hyperparathyroidism (PHPT) in California during the period of 1999 to 2008. BACKGROUND The quality of surgery for PHPT can be measured by the complication rate and the success rate of surgery. A fraction of patients with failed initial surgery undergo reoperation. METHODS Data on patients undergoing parathyroidectomy (PTx) were obtained from the California Office of Statewide Health Planning and Development. Renal transplant recipients and dialysis patients were excluded. Hospitals were categorized by case volume: Very low: 1 to 4 operations annually; Low: 5 to 9; Medium, 10 to 19; High: 20 to 49; Very high: 50 or more. Complication rates and the percentage of cases requiring reoperation were analyzed. RESULTS A total of 17,082 cases were studied. Annual case volume grew from 990 to 2746 (177% increase) over the study period, corresponding to a 147% increase in the per capita PTx rate. The proportion of cases performed by very high-volume hospitals increased from 6.4% to 20.5% (P < 0.001). The overall complication rate declined from 8.7% to 3.8% (P < 0.001). Complication rates were inversely related to hospital volume (very high volume, 3.9% vs very low volume, 5.2%, P < 0.05). Reoperation was performed in 363 patients (2.1%). The reoperation rate increased from 0.91% to 2.73% during the study period (P < 0.01). The reoperation rate was inversely and nonlinearly related to hospital volume, as described by the equation % reoperation = 100/(total hospital case volume). CONCLUSIONS Surgery for PHPT has grown safer and more common over time. High-volume centers have lower rates of complication and reoperation.

Successful localization of recurrent thyroid cancer in reoperative neck surgery using ultrasound-guided methylene blue dye injection

BACKGROUND Reoperation in the neck can be challenging and is associated with increased complication rates and operative times. Here we analyze our methylene blue dye injection method to localize reoperative neck pathology in patients with thyroid cancer and lymph node metastases. STUDY DESIGN We retrospectively reviewed the records of all patients at a single university tertiary care center who had reoperative neck surgery for recurrent thyroid cancer between 2004 and 2009, and who also underwent intraoperative methylene blue dye injection. Outcomes measured were efficacy and safety of the injection technique as well as complication rates. RESULTS Fifty-three operations were performed in 44 patients (average age, 51.2 years [range 16 to 83 years]). Ninety-one percent (48 of 53) of the operations resulted in successful resection of recurrent disease. Of these, 96% (46 of 48) were guided successfully by blue dye injection. Thyroglobulin became undetectable in 42% (11 of 26) of patients. Neck pathology included the following thyroid cancers: papillary (48 of 53), follicular (2 of 53), medullary (2 of 53), and tall cell variant (1 of 53). Among these patients, there were a total of 26 central and 38 lateral neck dissections. The average number of previous neck dissections was 2 (range 1 to 5). The mean intraoperative ultrasound/injection time was 21.3 min (n = 13). Median operative time was 90 minutes (range 40 to 300 minutes). Complications included 2 permanent vocal cord paralyses, 1 instance of permanent hypocalcemia, and 3 instances of temporary hypocalcemia. There were no complications related to the dye injection. CONCLUSIONS Intraoperative, ultrasound-guided, methylene blue dye injection is a safe and effective technique. It facilitates tumor localization and removal especially in patients requiring reoperative neck surgery.

Adrenal incidentaloma: Does an adequate workup rule out surprises?

BACKGROUND Adrenal incidentaloma remains a diagnostic challenge. Despite well-established management guidelines, the long-term results of following these guidelines are unknown. We sought to determine how accurately these guidelines identify functioning incidentalomas and how often these guidelines result in adrenalectomy for benign tumors. METHODS We catalogued adrenal incidentalomas from a retrospective review of 500 consecutive adrenalectomies at a single institution. The outcome measures studied were patient demographics, preoperative biochemical analysis, imaging characteristics, tumor size, type of operation performed, and postoperative histologic diagnosis. RESULTS Eighty-one of the 500 adrenalectomies performed were for incidentalomas. Size was the only significant characteristic that distinguished cortical cancers from benign adenomas. Only 1 out of 26 functioning tumors was incorrectly identified on preoperative workup. We also found that 25% of cortisol-secreting incidentalomas were cystic, and that benign adenomas accounted for 42% of all tumors resected. CONCLUSION Current guidelines accurately predict the functional status of adrenal incidentalomas. Some cystic lesions may be functioning and should therefore be screened for hormonal hypersecretion. However, even with the most up-to-date diagnostic tools available, most adrenal incidentalomas resected are benign tumors.

Surgery is associated with improved survival for adrenocortical cancer, even in metastatic disease

BACKGROUND Adrenocortical carcinoma (ACC) is a rare but lethal tumor. Predictors of survival include earlier stage at presentation and complete operative resection. We assessed effect of treatment and demographic variables on survival. METHODS ACC cases were abstracted from the California Cancer Registry and Office of Statewide Health Planning and Development (1999-2008). Predictors included patient demographics, comorbidities, tumor size, stage, and treatment (none, surgery, chemotherapy and/or radiation [CRT], and surgery plus CRT). RESULTS We studied 367 patients with median tumor size of 10 cm. At presentation, 37% had localized, 17% had regional, and 46% had metastatic disease. Median survival was 1.7 years (7.4 years local, 2.6 years regional, and 0.3 years metastatic, P < .0001). One-year and 5-year survival was: 92%/62% (local); 73%/39% (regional); and 24%/7% (metastatic). Increased age (hazard ratio [HR] 1.16) and Cushings syndrome (HR 1.66) worsened survival (P < .05). Low socioeconomic status worsened survival in local and regional disease (P < .05). In multivariable regression, both surgery (regional HR 0.13; metastatic HR 0.52) and surgery plus CRT (regional HR 0.15; metastatic HR 0.31) improved survival compared with no treatment (P < .02). CONCLUSION In ACC, surgery is associated with improved survival, even in metastatic disease. Surgery should be considered for select patients as part of multimodality treatment.