Descriptive epidemiology of pituitary tumors in the United States, 2004–2009

Clinical article

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Object

Pituitary tumors are abnormal growths that develop in the pituitary gland. The Central Brain Tumor Registry of the United States (CBTRUS) contains the largest aggregation of population-based data on the incidence of primary CNS tumors in the US. These data were used to determine the incidence of tumors of the pituitary and associated trends between 2004 and 2009.

Methods

Using incidence data from 49 population-based state cancer registries, 2004–2009, age-adjusted incidence rates per 100,000 population for pituitary tumors with ICD-O-3 (International Classification of Diseases for Oncology, Third Edition) histology codes 8040, 8140, 8146, 8246, 8260, 8270, 8271, 8272, 8280, 8281, 8290, 8300, 8310, 8323, 9492 (site C75.1 only), and 9582 were calculated overall and by patient sex, race, Hispanic ethnicity, and age at diagnosis. Corresponding annual percent change (APC) scores and 95% confidence intervals were also calculated using Joinpoint to characterize trends in incidence rates over time. Diagnostic confirmation by subregion of the US was also examined.

Results

The overall annual incidence rate increased from 2.52 (95% CI 2.46–2.58) in 2004 to 3.13 (95% CI 3.07–3.20) in 2009. Associated time trend yielded an APC of 4.25% (95% CI 2.91%–5.61%). When stratifying by patient sex, the annual incidence rate increased from 2.42 (95% CI 2.33–2.50) to 2.94 (95% CI 2.85–3.03) in men and 2.70 (95% CI 2.62–2.79) to 3.40 (95% CI 3.31–3.49) in women, with APCs of 4.35% (95% CI 3.21%–5.51%) and 4.34% (95% CI 2.23%–6.49%), respectively. When stratifying by race, the annual incidence rate increased from 2.31 (95% CI 2.25–2.37) to 2.81 (95% CI 2.74–2.88) in whites, 3.99 (95% CI 3.77–4.23) to 5.31 (95% CI 5.06–5.56) in blacks, 1.77 (95% CI 1.26–2.42) to 2.52 (95% CI 1.96–3.19) in American Indians or Alaska Natives, and 1.86 (95% CI 1.62–2.13) to 2.03 (95% CI 1.80–2.28) in Asians or Pacific Islanders, with APCs of 3.91% (95% CI 2.88%–4.95%), 5.25% (95% CI 3.19%–7.36%), 5.31% (95% CI –0.11% to 11.03%), and 2.40% (95% CI –3.20% to 8.31%), respectively. When stratifying by Hispanic ethnicity, the annual incidence rate increased from 2.46 (95% CI 2.40–2.52) to 3.03 (95% CI 2.97–3.10) in non-Hispanics and 3.12 (95% CI 2.91–3.34) to 4.01 (95% CI 3.80–4.24) in Hispanics, with APCs of 4.15% (95% CI 2.67%–5.65%) and 5.01% (95% CI 4.42%–5.60%), respectively. When stratifying by age at diagnosis, the incidence of pituitary tumor was highest for those 65–74 years old and lowest for those 15–24 years old, with corresponding overall age-adjusted incidence rates of 6.39 (95% CI 6.24–6.54) and 1.56 (95% CI 1.51–1.61), respectively.

Conclusions

In this large patient cohort, the incidence of pituitary tumors reported between 2004 and 2009 was found to increase. Possible explanations for this increase include changes in documentation, changes in the diagnosis and registration of these tumors, improved diagnostics, improved data collection, increased awareness of pituitary diseases among physicians and the public, longer life expectancies, and/or an actual increase in the incidence of these tumors in the US population.

Abbreviations used in this paper:AIAN = American Indian or Alaska Native; APC = annual percentage change; API = Asian or Pacific Islander; CBTRUS = Central Brain Tumor Registry of the United States; CDC = Centers for Disease Control and Prevention; ICD-O-3 = International Classification of Diseases for Oncology, Third Edition; NPCR = National Program of Cancer Registries; SEER = Surveillance, Epidemiology, and End Results.

Object

Pituitary tumors are abnormal growths that develop in the pituitary gland. The Central Brain Tumor Registry of the United States (CBTRUS) contains the largest aggregation of population-based data on the incidence of primary CNS tumors in the US. These data were used to determine the incidence of tumors of the pituitary and associated trends between 2004 and 2009.

Methods

Using incidence data from 49 population-based state cancer registries, 2004–2009, age-adjusted incidence rates per 100,000 population for pituitary tumors with ICD-O-3 (International Classification of Diseases for Oncology, Third Edition) histology codes 8040, 8140, 8146, 8246, 8260, 8270, 8271, 8272, 8280, 8281, 8290, 8300, 8310, 8323, 9492 (site C75.1 only), and 9582 were calculated overall and by patient sex, race, Hispanic ethnicity, and age at diagnosis. Corresponding annual percent change (APC) scores and 95% confidence intervals were also calculated using Joinpoint to characterize trends in incidence rates over time. Diagnostic confirmation by subregion of the US was also examined.

Results

The overall annual incidence rate increased from 2.52 (95% CI 2.46–2.58) in 2004 to 3.13 (95% CI 3.07–3.20) in 2009. Associated time trend yielded an APC of 4.25% (95% CI 2.91%–5.61%). When stratifying by patient sex, the annual incidence rate increased from 2.42 (95% CI 2.33–2.50) to 2.94 (95% CI 2.85–3.03) in men and 2.70 (95% CI 2.62–2.79) to 3.40 (95% CI 3.31–3.49) in women, with APCs of 4.35% (95% CI 3.21%–5.51%) and 4.34% (95% CI 2.23%–6.49%), respectively. When stratifying by race, the annual incidence rate increased from 2.31 (95% CI 2.25–2.37) to 2.81 (95% CI 2.74–2.88) in whites, 3.99 (95% CI 3.77–4.23) to 5.31 (95% CI 5.06–5.56) in blacks, 1.77 (95% CI 1.26–2.42) to 2.52 (95% CI 1.96–3.19) in American Indians or Alaska Natives, and 1.86 (95% CI 1.62–2.13) to 2.03 (95% CI 1.80–2.28) in Asians or Pacific Islanders, with APCs of 3.91% (95% CI 2.88%–4.95%), 5.25% (95% CI 3.19%–7.36%), 5.31% (95% CI –0.11% to 11.03%), and 2.40% (95% CI –3.20% to 8.31%), respectively. When stratifying by Hispanic ethnicity, the annual incidence rate increased from 2.46 (95% CI 2.40–2.52) to 3.03 (95% CI 2.97–3.10) in non-Hispanics and 3.12 (95% CI 2.91–3.34) to 4.01 (95% CI 3.80–4.24) in Hispanics, with APCs of 4.15% (95% CI 2.67%–5.65%) and 5.01% (95% CI 4.42%–5.60%), respectively. When stratifying by age at diagnosis, the incidence of pituitary tumor was highest for those 65–74 years old and lowest for those 15–24 years old, with corresponding overall age-adjusted incidence rates of 6.39 (95% CI 6.24–6.54) and 1.56 (95% CI 1.51–1.61), respectively.

Conclusions

In this large patient cohort, the incidence of pituitary tumors reported between 2004 and 2009 was found to increase. Possible explanations for this increase include changes in documentation, changes in the diagnosis and registration of these tumors, improved diagnostics, improved data collection, increased awareness of pituitary diseases among physicians and the public, longer life expectancies, and/or an actual increase in the incidence of these tumors in the US population.

Abbreviations used in this paper:AIAN = American Indian or Alaska Native; APC = annual percentage change; API = Asian or Pacific Islander; CBTRUS = Central Brain Tumor Registry of the United States; CDC = Centers for Disease Control and Prevention; ICD-O-3 = International Classification of Diseases for Oncology, Third Edition; NPCR = National Program of Cancer Registries; SEER = Surveillance, Epidemiology, and End Results.

Pituitary tumors are abnormal growths that develop in the pituitary gland and are generally benign slow-growing tumors. Although most are not symptomatic, they can cause a wide array of symptoms depending on their hormonal activity. Even those that are not hormone secreting can cause symptoms as a result of intracranial mass effect. Tumor growth appears to be promoted by hormones that modulate normal pituitary activity and by growth factors that have been implicated in normal fetal pituitary development.1 More specifically, tumors of the pituitary seem to arise from the expansion of single precursor cells that possess a unique proliferative advantage.9 At least one-third of pituitary tumors can cause health complications that may include mood disorders, sexual dysfunction, infertility, obesity and disfigurement, visual disturbances, hypertension, diabetes mellitus, and accelerated heart disease.1

The overall age-adjusted incidence rate of pituitary tumors has been reported by the Central Brain Tumor Registry of the United States (CBTRUS) as 2.94 cases per 100,000 persons.4 After gliomas and meningiomas, tumors of the pituitary are the third most common brain tumor, accounting for 10%–15% of all primary brain tumors.15 A comprehensive meta-analysis of data from autopsy and radiological studies suggested that pituitary tumors may be present in as many as 1 in every 6 persons.3,5 More specifically, Ezzat et al. reported that pituitary adenomas occurred with a frequency of 14.4% in pooled autopsy series and 22.5% in radiological series.5 In the present report we describe the epidemiology of pituitary tumors, focusing on incidence rates by patient sex, race, Hispanic ethnicity, and age at diagnosis as well as diagnostic confirmation by subregion of the US by using data from two population-based cancer registries that include cases of malignant and nonmalignant primary brain and CNS tumors.

Methods

Data Collection

We used population-based registry data on cases diagnosed with pituitary tumors between 2004 and 2009. The CBTRUS contains incidence data from 49 central cancer registries (Centers for Disease Control and Prevention's [CDC's] 44 National Program of Cancer Registries [NPCR] and 5 Surveillance, Epidemiology, and End Results [SEER] registries) and captures the incidence of primary brain tumors for over 97% of the US population (CBTRUS 2012). The Benign Brain Tumor Cancer Registries Amendment Act, which mandated registration of benign brain tumors in the US, went into effect in 2004; hence, we conducted all analyses using 2004–2009 data to allow for the most complete data set. Our analysis includes newly diagnosed malignant and nonmalignant tumors with International Classification of Diseases for Oncology, Third Edition (ICD-O-3) histology codes 8040, 8140, 8146, 8246, 8260, 8270, 8271, 8272, 8280, 8281, 8290, 8300, 8310, 8323, 9492 (site C75.1 only), and 9582 (Table 1).

TABLE 1:

Brain and CNS tumors of the pituitary gland (CBTRUS, 2004–2009)*

ICD-O Topography Code & Histology GroupingICD-O-3 Histology CodeSpecific Histology Classification
C75.1 & C75.2
 tumorlet8040tumorlet, benign; tumorlet, NOS
 adenocarcinoma, NOS8140adenoma, NOS; atypical adenoma; adenocarcinoma in situ; adenocarcinoma, NOS
8146monomorphic adenoma
 neuroendocrine carcinoma, NOS8246neuroendocrine carcinoma, NOS
 papillary adenoma, NOS8260papillary adenoma, NOS
 chromophobe carcinoma8270chromophobe adenoma; chromophobe carcinoma
 prolactinoma8271prolactinoma
 pituitary adenoma & carcinoma8272pituitary adenoma, NOS; pituitary carcinoma, NOS
 acidophil carcinoma8280acidophil adenoma; acidophil carcinoma
8281mixed acidophil-basophil adenoma; mixed acidophil-basophil carcinoma
 oxyphilic adenocarcinoma8290oxyphilic adenoma; oxyphilic adenocarcinoma
 basophil carcinoma8300basophil adenoma; basophil carcinoma
 clear cell adenocarcinoma, NOS8310clear cell adenoma; clear cell adenocarcinoma, NOS
 granular cell carcinoma8323mixed cell adenoma; mixed cell adenocarcinoma
C75.1 only
 ganglioneuroblastoma9492gangliocytoma
C75.1 & C75.2
 granular cell tumors9582granular cell tumor of sellar region

NOS = not otherwise specified.

Population data for each region were obtained from the National Cancer Institute's SEER program (http://seer.cancer.gov) and were made available by the US Census Bureau.

Statistical Analysis

SEER*Stat (http://seer.cancer.gov/seerstat/) was used to calculate frequencies and incidence rates overall and by patient sex, race, Hispanic ethnicity, selected age groups, and year of diagnosis. The standard population used to calculate the age-adjusted incidence rates is an estimate of the 2000 US population. Frequency of diagnostic confirmation by subregion of the US was calculated with SEER*Stat as well, using the North American Association of Central Cancer Registries (NAACCR) regional scheme (http://faststats.naaccr.org). Diagnostic confirmation records the best method used to confirm the presence of the cancer being reported. The best method could be used at any time throughout the entire course of the disease; it is not limited to confirmation at the time of initial diagnosis. Joinpoint regression software was used to identify sharp changes in incidence during the time period included in this analysis (http://surveillance.cancer.gov/joinpoint/). This statistical software takes trend data and fits the simplest Joinpoint model that the data allow.

Results

Average Annual Incidence Trends

The CBTRUS data set included 51,125 cases of pituitary tumors diagnosed from 2004 to 2009. The distribution of benign versus malignant tumors was 99.7% versus 0.3%. All age-adjusted incidence rates were reported per 100,000 population. The overall age-adjusted incidence of pituitary tumor was 2.87 (Table 2). When stratifying by patient sex, the overall age-adjusted incidence of pituitary tumor was 2.71 for males and 3.11 for females (Table 3). When stratifying by race, the overall age-adjusted incidence of pituitary tumor was 2.59 for whites, 4.76 for blacks, 2.28 for American Indians or Alaska Natives (AIANs), and 2.13 for Asian or Pacific Islanders (APIs; Table 4). When stratifying by Hispanic ethnicity, the overall age-adjusted incidence of pituitary tumor was 2.79 for non–Spanish-Hispanic-Latinos and 3.55 for Spanish-Hispanic-Latinos (Table 5). When stratifying by age at diagnosis, the incidence of pituitary tumor was highest for those 65–74 years of age and lowest for those 15–24 years of age, with corresponding overall age-adjusted incidence rates of 6.39 and 1.56, respectively (Table 6).

TABLE 2:

Age-adjusted incidence rates and APC in incidence of pituitary tumors (CBTRUS, 2004–2009)*

YearNo. of CasesAAIR95% CIAPC (95% CI)
overall51,1252.872.85–2.904.25 (2.91–5.61)
200472432.522.46–2.58
200578112.692.63–2.75
200684852.882.82–2.94
200787222.922.86–2.98
200892663.073.01–3.14
200995983.133.07–3.20

AAIR = age-adjusted incidence rate.

Values expressed as percent.

TABLE 3:

Age-adjusted incidence rates and APCs in incidence of pituitary tumors, by patient sex (CBTRUS, 2004–2009)

YearNo. of CasesAAIR95% CIAPC (95% CI)*
male
 overall22,9932.712.68–2.754.35 (3.21–5.51)
 200432652.422.33–2.50
 200534762.532.45–2.62
 200636902.642.55–2.73
 200739662.782.70–2.87
 200842612.952.86–3.04
 200943352.942.85–3.03
female
 overall28,1323.113.07–3.144.34 (2.23–6.49)
 200439782.702.62–2.79
 200543352.922.83–3.00
 200647953.203.11–3.29
 200747563.143.05–3.23
 200850053.283.18–3.37
 200952633.403.31–3.49

Values expressed as percent.

TABLE 4:

Age-adjusted incidence rates and APCs in incidence of pituitary tumors, by race (CBTRUS, 2004–2009)

YearsNo. of CasesAAIR95% CIAPC (95% CI)*
white
 overall38,1212.592.56–2.613.91 (2.88–4.95)
 200455312.312.25–2.37
 200558562.432.36–2.49
 200663202.592.52–2.65
 200764912.632.56–2.69
 200868492.752.68–2.82
 200970742.812.74–2.88
black
 overall92944.764.66–4.865.25 (3.19–7.36)
 200412383.993.77–4.23
 200513904.444.20–4.69
 200615534.814.57–5.06
 200715954.864.62–5.11
 200816885.094.84–5.34
 200918305.315.06–5.56
AIAN
 overall3962.282.05–2.545.31 (−0.11 to 11.03)
 2004451.771.26–2.42
 2005672.271.73–2.92
 2006662.371.80–3.06
 2007692.241.73–2.87
 2008732.541.95–3.23
 2009762.521.96–3.19
API
 overall17002.132.02–2.232.40 (−3.20 to 8.31)
 20042271.861.62–2.13
 20052562.051.80–2.33
 20062852.191.94–2.47
 20073062.262.00–2.53
 20083312.372.12–2.65
 20092952.031.80–2.28

Values expressed as percent.

TABLE 5:

Age-adjusted incidence rates and APCs in incidence of pituitary tumors, by Hispanic ethnicity (CBTRUS, 2004–2009)

YearNo. of CasesAAIR95% CIAPC (95% CI)*
non–Spanish-Hispanic-Latino
 overall43,8802.792.77–2.824.15 (2.67–5.65)
 200462872.462.40–2.52
 200567422.622.55–2.68
 200673142.812.74–2.87
 200774962.852.78–2.91
 200879263.002.93–3.06
 200981153.032.97–3.10
Spanish-Hispanic-Latino
 overall72453.553.47–3.645.01 (4.42–5.60)
 20049563.122.91–3.34
 200510693.283.07–3.51
 200611713.453.24–3.67
 200712263.573.35–3.79
 200813403.763.55–3.99
 200914834.013.80–4.24

Values expressed as percent.

TABLE 6:

Age-adjusted incidence rates and APCs in incidence of pituitary tumors, by age at diagnosis (CBTRUS, 2004–2009)

YearsNo. of CasesAAIR95% CIAPC (95% CI)*
ages 15–24 yrs
 overall39051.56(1.51–1.61)3.56 (0.57–6.65)
 20045661.37(1.26–1.49)
 20056291.52(1.40–1.64)
 20066631.59(1.47–1.72)
 20076571.56(1.44–1.68)
 20086501.55(1.43–1.67)
 20097401.74(1.62–1.87)
ages 25–34 yrs
 overall65762.82(2.75–2.89)4.14 (1.85–6.47)
 20049502.47(2.32–2.64)
 20059982.61(2.45–2.77)
 200611202.91(2.74–3.09)
 200711112.86(2.69–3.03)
 200811793.00(2.83–3.18)
 200912183.04(2.87–3.21)
ages 35–44 yrs
 overall84123.36(3.29–3.44)6.22 (4.53–7.95)
 200412022.81(2.66–2.98)
 200513213.12(2.95–3.29)
 200613833.28(3.11–3.46)
 200714213.41(3.24–3.59)
 200815423.76(3.58–3.95)
 200915433.81(3.63–4.01)
ages 45–54 yrs
 overall97773.87(3.79–3.95)4.34 (3.77–4.92)
 200413823.43(3.26–3.62)
 200514983.64(3.45–3.83)
 200615983.81(3.63–4.00)
 200716773.93(3.75–4.13)
 200817654.08(3.90–4.28)
200918574.29(4.09–4.49)
ages 55–64 yrs
 overall87964.72(4.62–4.82)3.62 (2.09–5.18)
 200412034.29(4.05–4.54)
 200512684.33(4.09–4.57)
 200614664.79(4.54–5.04)
 200715254.80(4.56–5.04)
 200816104.94(4.70–5.19)
 200917245.10(4.86–5.35)
ages 65–74 yrs
 overall72206.39(6.24–6.54)2.99 (0.30–5.76)
 200410175.66(5.31–6.02)
 200511026.07(5.72–6.44)
 200612126.60(6.24–6.99)
 200712416.61(6.25–6.99)
 200813076.73(6.36–7.10)
 200913416.62(6.27–6.99)
ages 75–84 yrs
 overall46326.05(5.88–6.23)4.55 (2.99–6.13)
 20046875.41(5.02–5.83)
 20057175.62(5.21–6.04)
 20067625.95(5.53–6.39)
 20077676.02(5.60–6.47)
 20088546.66(6.22–7.12)
 20098456.65(6.21–7.12)
ages ≥85 yrs
 overall11753.90(3.68–4.13)6.05 (−0.51 to 13.05)
 20041362.99(2.50–3.53)
 20051793.79(3.25–4.38)
 20061763.57(3.07–4.14)
 20072234.35(3.80–4.96)
 20082354.43(3.88–5.03)
 20092264.12(3.60–4.70)

Values expressed as percent.

Time Trends

In the period from 2004 to 2009, the overall annual percentage change (APC) was 4.25% (95% CI 2.91%–5.61%), and the annual age-adjusted incidence rates for pituitary tumor ranged from 2.52 to 3.13 (Fig. 1 and Table 2). When stratifying by patient sex, the APC was 4.35% (95% CI 3.21%–5.51%) for males and 4.34% (95% CI 2.23%–6.49%) for females (Fig. 2 and Table 3). The annual age-adjusted incidence rates for pituitary tumor ranged from 2.42 to 2.94 in males and 2.70 to 3.40 in females. When stratifying by race, the APC was 3.91% (95% CI 2.88%–4.95%) for whites, 5.25% (95% CI 3.19%–7.36%) for blacks, 5.31% (95% CI –0.11% to 11.03%) for AIANs, and 2.40% (–3.20% to 8.31%) for APIs (Table 4). The annual age-adjusted rates for pituitary tumor ranged from 2.31 to 2.81 in whites, 3.99 to 5.31 in blacks, 1.77 to 2.52 in AIANs, and 1.86 to 2.03 in APIs. When stratifying by Hispanic ethnicity, the APC was 4.15% (95% CI 2.67%–5.65%) for non–Spanish-Hispanic-Latinos and 5.01% (95% CI 4.42%–5.60%) for Spanish-Hispanic-Latinos (Table 5). The annual age-adjusted rates for pituitary tumor ranged from 2.46 to 3.03 in non–Spanish-Hispanic-Latinos and 3.12 to 4.01 in Spanish-Hispanic-Latinos. When stratifying by age at diagnosis, the APC was 3.56% (95% CI 0.57%–6.65%) for 15- to 24-year-olds, 4.14% (95% CI 1.85%–6.47%) for 25- to 34-year-olds, 6.22% (95% CI 4.53%–7.95%) for 35- to 44-year-olds, 4.34% (95% CI 3.77%–4.92%) for 45- to 54-year-olds, 3.62% (95% CI 2.09%–5.18%) for 55- to 64-year-olds, 2.99% (95% CI 0.30%–5.76%) for 65- to 74-year-olds, 4.55% (95% CI 2.99%–6.13%) for 75- to 84-year-olds, and 6.05% (95% CI –0.51% to 13.05%) for those 85 years and older (Table 6). The annual age-adjusted rates for pituitary tumor ranged from 1.37 to 1.74 in the 15- to 24-year-olds, from 2.47 to 3.04 in the 25- to 34-year-olds, from 2.81 to 3.81 in the 35- to 44-year-olds, from 3.43 to 4.29 in the 45- to 54-yearolds, from 4.29 to 5.10 in the 55- to 64-year-olds, from 5.66 to 6.73 in the 65- to 74-year-olds, from 5.41 to 6.66 in the 75- to 84-year-olds, and from 2.99 to 4.43 in those 85 years and older .

Fig. 1.
Fig. 1.

Overall average annual age-adjusted time trend of pituitary tumors (CBTRUS, 2004–2009).

Fig. 2.
Fig. 2.

Average annual age-adjusted incidence rates of pituitary tumors, by patient sex (CBTRUS, 2004–2009).

Incidence by Age at Diagnosis and Patient Sex

When stratifying by age at diagnosis and patient sex, females had a greater incidence of pituitary tumors from ages 0 to 50 years (Fig. 3). From ages 50 to 54 years, the incidence rates were similar between males (4.25) and females (3.99; Table 7). After age 54 years, males had a greater incidence of pituitary tumors.

Fig. 3.
Fig. 3.

Average age-adjusted incidence rates of pituitary tumors, by age at diagnosis and patient sex (CBTRUS, 2004–2009).

TABLE 7:

Average age-adjusted incidence rates of pituitary tumors, by age at diagnosis and patient sex (CBTRUS, 2004–2009)

Age (yrs)MaleFemale
No. of CasesAAIR95% CINo. of CasesAAIR95% CI
0–142370.130.11–0.153950.230.20–0.25
15–193830.600.54–0.6612001.981.87–2.10
20–245080.790.72–0.8618143.002.87–3.14
25–297801.281.19–1.3722783.883.73–4.05
30–3410361.781.67–1.8924824.374.20–4.55
35–3914152.312.19–2.4425394.214.05–4.38
40–4417972.802.67–2.9326614.143.98–4.30
45–4921483.293.16–3.4426714.013.86–4.17
50–5425184.254.09–4.4224403.993.83–4.15
55–5925485.014.81–5.2121143.933.76–4.10
60–6423766.095.84–6.3417584.123.93–4.31
65–6922347.657.34–7.9716124.844.60–5.08
70–7419268.438.06–8.8214485.194.93–5.47
75–7915638.468.04–8.8911804.734.46–5.01
80–849917.627.16–8.118984.394.11–4.69
≥855335.725.24–6.226423.092.85–3.34

Diagnostic Confirmation

Across the US, the majority of pituitary tumors were microscopically confirmed (Fig. 4), which include those tumors with a positive histology or positive cytology. The biggest difference in diagnostic confirmation was in the New England subregion, where 75% were microscopically confirmed and 25% were radiographically confirmed. Tumors that were radiographically confirmed involved radiology and other imaging techniques without microscopic confirmation. The smallest difference in diagnostic confirmation was in the West South Central subregion, where 54% were microscopically confirmed and 46% were radiographically confirmed.

Fig. 4.
Fig. 4.

Diagnostic confirmation of pituitary tumors, by US subregion. Frequencies are listed inside the bars (CBTRUS, 2004–2009).

Discussion

Pituitary tumors are relatively common in the US, with an average incidence of 2.9 per 100,000 population between 2004 and 2009, and this incidence is rising with an overall APC of 4.25%. This increase supports results found in other population-based studies. In a cohort study conducted in northern Finland, the incidence of pituitary adenomas increased from 3.8 to 4.2 cases per 100,000 population in 1992–1999 to 2000–2007.14 The increase in incidence was attributable to the rise in incidentally discovered pituitary adenomas from 0.59 to 1.6 cases per 100,000 population.14 In Sweden, a cohort study utilizing their nationwide cancer registry revealed that the age-standardized incidence of pituitary adenoma increased from approximately 6 to 11 cases per million inhabitants from 1958 to 1991.11 Rises in incidence have generally been attributed to improvements in diagnostic technology that have increased sensitivity for detecting pituitary tumors.7 In addition, the greater use of imaging, particularly for indications such as sinusitis, trauma, and headache, may lead to the increased detection of incidental pituitary tumors. In fact, the prevalence of asymptomatic incidental pituitary tumors in the general population has been estimated between 0.15% and 0.3%.10,16 Furthermore, greater accuracy and improved documentation of pituitary tumors in cancer registries may be responsible for the observed increase in incidence. Nonetheless, these results may also represent a true increase in pituitary tumor incidence. Our analysis demonstrated an increased risk for pituitary tumor as one ages, with the peak incidence occurring between 65 and 74 years old.

Incidence was slightly higher in females than in males. The male/female incidence rate ratio was 0.87, with incidence peaks of 4.37 and 5.19 in females at ages 30–34 and 70–74 years, respectively (Fig. 3; Table 7). In males, one large incidence peak of 8.46 at ages 75–79 years was found. This difference was attributable to prolactinomas, the most commonly diagnosed pituitary tumor, which occur more frequently in women than in men and at earlier ages in women than in men.2,6,7 Moreover, females tend to present earlier because of an increased symptom burden from hyperprolactinemia, such as a disruption in the menstrual period and hypogonadism.2 Additionally, pituitary tumors were detected more frequently in women than in men.12,13 These factors may account for females having a peak incidence at a significantly younger age than that in males.7

An analysis of SEER data by McDowell and colleagues revealed that the age-adjusted incidence rate of pituitary adenomas per 100,000 population in blacks was 4.4, which was much higher than in AIANs, APIs, and whites, whose incidence rates were 1.9, 2.3, and 2.5, respectively (p < 0.001).8 This finding is consistent with current findings; that is, the average incidence for whites and blacks was 2.6 and 4.8, respectively. Reasons for this disparity include a natural difference in incidence as well as the fact that blacks may present with different symptoms or present with symptoms at different timings.8

The NPCR and SEER have provided a rich source of data to CBTRUS that has allowed us to document robust phenomena and explore several potential explanations. However, epidemiological studies are limited by their dependence on population-specific registries.5 In addition, the SEER programs mainly collect information from patient medical records. Thus, variables that are not reliably reported in medical records will not be useful from an analytical perspective.8 Moreover, bias from regional influences, such as diagnostic practices, reporting patterns, and case definition, should be considered.5 Lastly, SEER and NPCR do not provide data on whether the pituitary tumors are hormone releasing or non–hormone releasing.

Conclusions

In the present study we give current incidence rates of and time trends for pituitary tumors in the US. Although our methods provide reasonable estimates of the true incidence of pituitary tumors in the era of modern diagnostic tools, the true geographic variations in the epidemiology of pituitary tumors remain uncertain.14 Given the passage of the Benign Brain Tumor Cancer Registries Amendment Act in 2004, it will be several years before comprehensive data on pituitary tumor incidence are available from major cancer registries. In our large patient cohort with pituitary tumors reported between 2004 and 2009, the incidence of pituitary tumors was found to increase. Possible explanations for the increase include changes in documentation, changes in the diagnosis and registration of these tumors, improved diagnostics, improved data collection, increased awareness of pituitary diseases among physicians and the public, longer life expectancies, and/or an actual increase in the incidence of these tumors in the US population. Future analyses will need to compare our findings with theirs to see if this incidence is still on the rise.

Disclosure

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. Dr. Selman owns stock in Osteoplastics II and has stock options in Surgical Theater. Dr. Barnholtz-Sloan was funded in part by the Case Comprehensive Cancer Center Support Grant (NCI P30 CA043703). Support for the CBTRUS in 2013 was provided by the National Brain Tumor Society (www.braintumor.org), the Pediatric Brain Tumor Foundation (www.curethekids.org), other private donations, and the CDC under Cooperative Agreement 5U58DP003831-02. The contents in this report are solely the responsibility of the authors and do not necessarily represent the official view of the CDC.

Author contributions to the study and manuscript preparation include the following. Conception and design: Barnholtz-Sloan, Gittleman, Ostrom, Kruchko. Acquisition of data: Barnholtz-Sloan, Kruchko. Analysis and interpretation of data: Barnholtz-Sloan, Gittleman. Drafting the article: Barnholtz-Sloan, Gittleman, Ostrom, Farah, Ondracek, Kruchko. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Barnholtz-Sloan. Statistical analysis: Gittleman, Ostrom. Administrative/technical/material support: Wolinsky, Kruchko. Study supervision: Barnholtz-Sloan.

This article contains some figures that are displayed in color online but in black-and-white in the print edition.
Portions of this work were presented in poster form at the 4th Quadrennial Meeting of the World Federation of Neuro-Oncology held in San Francisco, California, on November 23, 2013.

References

  • 1

    Asa SLEzzat S: The pathogenesis of pituitary tumours. Nat Rev Cancer 2:8368492002

  • 2

    Ciccarelli ADaly AFBeckers A: The epidemiology of prolactinomas. Pituitary 8:362005

  • 3

    Daly AFRixhon MAdam CDempegioti ATichomirowa MABeckers A: High prevalence of pituitary adenomas: a cross-sectional study in the province of Liege, Belgium. J Clin Endocrinol Metab 91:476947752006

    • Search Google Scholar
    • Export Citation
  • 4

    Dolecek TAPropp JMStroup NEKruchko C: CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005–2009. Neuro Oncol 14:Suppl 5v1v492012. (Erratum in Neuro Oncol 15:646–647 2013)

    • Search Google Scholar
    • Export Citation
  • 5

    Ezzat SAsa SLCouldwell WTBarr CEDodge WEVance ML: The prevalence of pituitary adenomas: a systematic review. Cancer 101:6136192004

    • Search Google Scholar
    • Export Citation
  • 6

    Fernandez AKaravitaki NWass JAH: Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxfordshire, UK). Clin Endocrinol (Oxf) 72:3773822010

    • Search Google Scholar
    • Export Citation
  • 7

    Hemminki KFörsti AJi J: Incidence and familial risks in pituitary adenoma and associated tumors. Endocr Relat Cancer 14:1031092007

    • Search Google Scholar
    • Export Citation
  • 8

    McDowell BDWallace RBCarnahan RMChrischilles EALynch CFSchlechte JA: Demographic differences in incidence for pituitary adenoma. Pituitary 14:23302011

    • Search Google Scholar
    • Export Citation
  • 9

    Melmed S: Pathogenesis of pituitary tumors. Nat Rev Endocrinol 7:2572662011

  • 10

    Morris ZWhiteley WNLongstreth WT JrWeber FLee YCTsushima Y: Incidental findings on brain magnetic resonance imaging: systematic review and meta-analysis. BMJ 339:b30162009

    • Search Google Scholar
    • Export Citation
  • 11

    Nilsson BGustavasson-Kadaka EBengtsson BAJonsson B: Pituitary adenomas in Sweden between 1958 and 1991: incidence, survival, and mortality. J Clin Endocrinol Metab 85:142014252000

    • Search Google Scholar
    • Export Citation
  • 12

    Ónnestam LBerinder KBurman PDahlqvist PEngström BEWahlberg J: National incidence and prevalence of TSH-secreting pituitary adenomas in Sweden. J Clin Endocrinol Metab 98:6266352013

    • Search Google Scholar
    • Export Citation
  • 13

    Popovic VDamjanovic SMicic DNesovic MDjurovic MPetakov M: Increased incidence of neoplasia in patients with pituitary adenomas. Clin Endocrinol (Oxf) 49:4414451998

    • Search Google Scholar
    • Export Citation
  • 14

    Raappana AKoivukangas JEbeling TPirilä T: Incidence of pituitary adenomas in Northern Finland in 1992–2007. J Clin Endocrinol Metab 95:426842752010

    • Search Google Scholar
    • Export Citation
  • 15

    Sivakumar WChamoun RNguyen VCouldwell WT: Incidental pituitary adenomas. Neurosurg Focus 31:6E182011

  • 16

    Vernooij MWIkram MATanghe HLVincent AJHofman AKrestin GP: Incidental findings on brain MRI in the general population. N Engl J Med 357:182118282007

    • Search Google Scholar
    • Export Citation

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Article Information

Contributor Notes

Address correspondence to: Jill Barnholtz-Sloan, Ph.D., Case Comprehensive Cancer Center, CWRU School of Medicine, 11100 Euclid Ave., Wearn 152, Cleveland, OH 44106-5065. email: jsb42@case.edu.Please include this information when citing this paper: published online June 13, 2014; DOI: 10.3171/2014.5.JNS131819.
Headings
Figures
  • View in gallery

    Overall average annual age-adjusted time trend of pituitary tumors (CBTRUS, 2004–2009).

  • View in gallery

    Average annual age-adjusted incidence rates of pituitary tumors, by patient sex (CBTRUS, 2004–2009).

  • View in gallery

    Average age-adjusted incidence rates of pituitary tumors, by age at diagnosis and patient sex (CBTRUS, 2004–2009).

  • View in gallery

    Diagnostic confirmation of pituitary tumors, by US subregion. Frequencies are listed inside the bars (CBTRUS, 2004–2009).

References
  • 1

    Asa SLEzzat S: The pathogenesis of pituitary tumours. Nat Rev Cancer 2:8368492002

  • 2

    Ciccarelli ADaly AFBeckers A: The epidemiology of prolactinomas. Pituitary 8:362005

  • 3

    Daly AFRixhon MAdam CDempegioti ATichomirowa MABeckers A: High prevalence of pituitary adenomas: a cross-sectional study in the province of Liege, Belgium. J Clin Endocrinol Metab 91:476947752006

    • Search Google Scholar
    • Export Citation
  • 4

    Dolecek TAPropp JMStroup NEKruchko C: CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005–2009. Neuro Oncol 14:Suppl 5v1v492012. (Erratum in Neuro Oncol 15:646–647 2013)

    • Search Google Scholar
    • Export Citation
  • 5

    Ezzat SAsa SLCouldwell WTBarr CEDodge WEVance ML: The prevalence of pituitary adenomas: a systematic review. Cancer 101:6136192004

    • Search Google Scholar
    • Export Citation
  • 6

    Fernandez AKaravitaki NWass JAH: Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxfordshire, UK). Clin Endocrinol (Oxf) 72:3773822010

    • Search Google Scholar
    • Export Citation
  • 7

    Hemminki KFörsti AJi J: Incidence and familial risks in pituitary adenoma and associated tumors. Endocr Relat Cancer 14:1031092007

    • Search Google Scholar
    • Export Citation
  • 8

    McDowell BDWallace RBCarnahan RMChrischilles EALynch CFSchlechte JA: Demographic differences in incidence for pituitary adenoma. Pituitary 14:23302011

    • Search Google Scholar
    • Export Citation
  • 9

    Melmed S: Pathogenesis of pituitary tumors. Nat Rev Endocrinol 7:2572662011

  • 10

    Morris ZWhiteley WNLongstreth WT JrWeber FLee YCTsushima Y: Incidental findings on brain magnetic resonance imaging: systematic review and meta-analysis. BMJ 339:b30162009

    • Search Google Scholar
    • Export Citation
  • 11

    Nilsson BGustavasson-Kadaka EBengtsson BAJonsson B: Pituitary adenomas in Sweden between 1958 and 1991: incidence, survival, and mortality. J Clin Endocrinol Metab 85:142014252000

    • Search Google Scholar
    • Export Citation
  • 12

    Ónnestam LBerinder KBurman PDahlqvist PEngström BEWahlberg J: National incidence and prevalence of TSH-secreting pituitary adenomas in Sweden. J Clin Endocrinol Metab 98:6266352013

    • Search Google Scholar
    • Export Citation
  • 13

    Popovic VDamjanovic SMicic DNesovic MDjurovic MPetakov M: Increased incidence of neoplasia in patients with pituitary adenomas. Clin Endocrinol (Oxf) 49:4414451998

    • Search Google Scholar
    • Export Citation
  • 14

    Raappana AKoivukangas JEbeling TPirilä T: Incidence of pituitary adenomas in Northern Finland in 1992–2007. J Clin Endocrinol Metab 95:426842752010

    • Search Google Scholar
    • Export Citation
  • 15

    Sivakumar WChamoun RNguyen VCouldwell WT: Incidental pituitary adenomas. Neurosurg Focus 31:6E182011

  • 16

    Vernooij MWIkram MATanghe HLVincent AJHofman AKrestin GP: Incidental findings on brain MRI in the general population. N Engl J Med 357:182118282007

    • Search Google Scholar
    • Export Citation
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