Sociodemographic Factors in Pituitary Adenomas.

Pituitary adenomas have been increasingly detected in recent years, especially in the older population. Black patients have a higher incidence than other racial groups. In patients with functioning tumors, presentation and comorbidities are influenced by age and sex, whereas the impact of ethnoracial background is unclear. Active surveillance recommendation and surgery refusal disproportionally affect Black and older patients. The likelihood of surgery at high-volume centers is lower for patients of Black or Hispanic background, uninsured or with lower socioeconomic status. Multicentric studies are necessary to delineate the influence of sociodemographic factors according to the adenoma type and to address the causes of health care disparities.

The influence of race on outcomes following pituitary tumor resection.

OBJECTIVE: To assess the influence of race on short-term patient outcomes in a pituitary tumor surgery population. PATIENTS AND METHODS: Coarsened exact matching was used to retrospectively analyze consecutive patients (n = 567) undergoing pituitary tumor resection over a six-year period (June 07, 2013 to April 29, 2019) at a single, multi-hospital academic medical center. Black/African American and white patients were exact matched based on twenty-nine (29) patient, procedure, and hospital characteristics. Matching characteristics included surgical costs, American Society of Anesthesiologists grade, duration of surgery, and Charlson Comorbidity Index, amongst others. Outcomes studied included unplanned 90-day readmission, emergency room (ER) evaluation, and unplanned reoperation. RESULTS: Ninety-two (n = 92) patients were exact matched and analyzed. There was no significant difference in 90-day readmission (p = 0.267, OR (black/AA vs white) = 0.500, 95% CI = 0.131-1.653) or ER evaluation within 90 days (p = 0.092, OR = 3.000, 95% CI = 0.848-13.737) between the two cohorts. Furthermore, there was no significant difference in the rate of unplanned reoperation throughout the duration of the follow up period between matched black/African American and white patients (p = 0.607, OR = 0.750, 95% CI = 0.243-2.211). CONCLUSION: This study suggests that the effect of race on post-operative outcomes is largely mitigated when equal access is attained, and when race is effectively isolated from socioeconomic factors and comorbidities in a population undergoing pituitary tumor resection.

Pituitary germinomas: a multi-institutional study analyzing patient demographics and management patterns.

PURPOSE: Intracranial germinomas are exceedingly rare tumors found in the pineal and suprasellar regions. The extremely low incidence of pituitary germinoma has resulted in a significant gap in knowledge regarding its demographics, management, and treatment outcomes. We present the largest multicenter analysis of pituitary germinomas to date, focused on analyzing demographic and management patterns. METHODS: This study utilizes the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program (2004-2016) to study patients with a primary intracranial germinoma of the pituitary gland. We analyzed demographic information and management strategies among adult and pediatric populations and conducted a 20-year overall survival analysis using Kaplan-Meier curve for a descriptive evaluation of survival outcomes between age groups and treatment groups. RESULTS: 92 patients were included in the study, consisting of 58% pediatric patients and 42% adults, with overall 60% males. 82% patients received radiation as part of the treatment, with no significant difference between pediatric and adult groups. Chemotherapy was used significantly more in pediatrics (p = 0.0002) while surgery was significantly more common in adults (p = 0.0117). The most common treatment in pediatrics was radiation + chemotherapy (47%), while the most common treatment in adults was radiation + gross total resection + chemotherapy (23%) followed by radiation + gross total resection (19%). Younger age, radiotherapy, and chemotherapy were associated with increased 20-year survival on Kaplan-Meier curves. CONCLUSIONS: There exist significant differences in the management of pediatric and adult populations with pituitary germinomas. The low incidence of these tumors makes them challenging to study, but also highlights the importance of national cancer registries in amassing sufficient patient data from which to draw evidence-based conclusions.

Association between acromegaly and a single nucleotide polymorphism (rs2854744) in the IGFBP3 gene.

BACKGROUND: It has been reported that the single nucleotide polymorphism (SNP) rs2854744 at the - 202 locus of insulin-like growth factor binding protein-3 (IGFBP3) is associated with serum levels and a number of malignancies. However, the effect of IGFBP3 gene polymorphism on acromegaly is less clear. Therefore, in the current study, we aimed to investigate whether the -202A/C polymorphism of IGFBP3 constitutes a risk factor for acromegaly. METHODS: The study included 102 acromegalic patients and 143 control subjects in Beijing Tiantan Hospital. The genotyping of IGFBP3 was carried out using the MassARRAY method. Serum IGFBP3 concentrations were also determined. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the associations of genetic polymorphisms with the development of acromegaly and its different subtypes. RESULTS: The study revealed that the C allele of rs2854744 was associated with a reduced risk of acromegaly (OR 0.594, 95% CI 0.388-0.909), as well as with the female (OR 0.385, 95% CI 0.206-0.72), macroadenoma (OR 0.557, 95% CI 0.347-0.893) and monotherapy (OR 0.512, 95% CI 0.316-0.828) subgroups under the additive model. A higher serum IGFBP3 level was observed in patients with the AA genotype, but this difference was not significant (P = 0.331). CONCLUSION: This study is one of the first to show that the IGFBP3 polymorphism may have an influence on serum levels and that the C allele of rs2854744 is associated with a reduced risk of acromegaly. This correlation was more prominent in females, those with large tumours and those treated with monotherapy in a Chinese population. Genetic polymorphism of IGFBP3 may be involved in the development of acromegaly.

Occurrence of Endocrine and Thyroid Cancers Among Alaska Native People, 1969-2013.

BACKGROUND: Nationwide, the incidence of thyroid cancer is lower among American Indian/Alaska Native (AI/AN) people than among U.S. whites (USW). However, little is known about the incidence of thyroid or other endocrine cancers specifically among Alaska Native (AN) people. METHODS: Data were examined from the National Cancer Institute's Surveillance, Epidemiology, and End Results Alaska Native Tumor Registry on endocrine cancers diagnosed among AN people from 1969-2013, with a specific focus on thyroid cancers. Frequencies of endocrine cancers by site and also of thyroid cancers by histology, size, and stage at diagnosis were evaluated. Distributions were compared to USW (Surveillance, Epidemiology, and End Results 9 Registries) using the chi-square test. Five-year average annual age-adjusted incidence rates of thyroid cancers were calculated, stratified by histology, age, and five-year period of diagnosis, and compared to those observed among USW. Five-year cause-specific survival was evaluated using cause of death data from the National Death Index Plus from the National Center for Health Statistics. RESULTS: During the 45-year period (1969-2013), 224 endocrine cancers were diagnosed among AN people, of which 210 (94%) were thyroid cancers. Compared to USW, AN people were diagnosed at a slightly younger age, had a higher proportion of thyroid cancers diagnosed with a size of 20-40 mm, and a larger proportion of patients with regional metastases. More than 85% of AN thyroid cancers were of papillary histology. The incidence of thyroid cancers was similar between AN people and USW, and appeared to increase among AN people over the period of surveillance. Finally, five-year cause-specific survival rate was 100% for papillary carcinoma patients and 86.3% [confidence interval 54.7-96.5] for follicular thyroid cancer patients. CONCLUSIONS: This study is the first report of endocrine cancers and the first detailed examination of thyroid cancer among AN people. The incidence of thyroid cancer was similar among AN people and USW. However, compared to USW, AN people appear to be at risk for diagnosis at a younger age, larger size, and higher stage. Further research is needed to explore the causes of these differences.

Giant prolactinomas: clinical manifestations and outcomes of 16 Arab cases.

BACKGROUND: The management of giant prolactinomas remains a major challenge, despite dopamine agonists being the first line of treatment, owing to its efficacy to normalize prolactin levels and reduce tumor volume. The aim of this study is to characterize the therapeutic aspects, manifestations and outcomes of 16 cases of giant prolactinomas admitted at a single tertiary center in Riyadh, Saudi Arabia. METHODS: Retrospective data collection involving 16 Saudi patients diagnosed with giant prolactinoma at the Pituitary Clinic in King Fahad Medical City, Riyadh, Saudi Arabia between January 2006 and July 2012. RESULTS: A total of 16 patients (ten males; six females) with age of diagnosis between 21 and 55 years (mean 34.9 years) were included in the analysis. The most common presenting features include headache, visual defects and sexual dysfunction. Baseline mean serum prolactin level were extremely high for both sexes which eventually decreased by as much as 97% after cabergoline treatment. Serum prolactin concentrations completely normalized in six patients and significantly decreased in five patients 3-5 times that of normal range. Tumor volume also decreased by an average of 86% for males and 87% for females. Two patients had no tumor size change with cabergoline and required surgery. CONCLUSION: Findings indicate that cabergoline provides dramatic clinical improvements with excellent safety profile. Cabergoline should therefore be considered as the primary therapy for giant prolactinomas.

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

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. 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.

LRRC4 haplotypes are associated with pituitary adenoma in a Chinese population.

Pituitary adenoma results from accumulation of multiple genetic and/or epigenetic aberrations such as GNAS, MEN1, CNC, and FIPA. LRRC4 is relatively tissue-specific expressed gene in the normal brain and downregulated expression in glioma (87.5%), meningioma (80.9%), and pituitary adenoma (85.5%). It has been suggested that the aberrant expression of LRRC4 contributes to tumorigenesis in glioma. However, little is known yet about association between LRRC4 and risk of pituitary adenoma. In this study, we genotyped three LRRC4 haplotype-tagging SNPs (htSNP) by direct sequencing in case-control studies, which included 183 Han Chinese patients diagnosed with pituitary adenoma and 183 age-, gender-matched, and geographically matched Han Chinese controls. Haplotypes were reconstructed according to the genotyping data and linkage disequilibrium status of the htSNP. We observed statistically significant differences regarding the genotype TT + CT of rs6944446 in the NCA. Haplotype AC of rs3823994-rs6944446 is suggested to have a protective effect in the development of pituitary adenoma (OR 0.339; 95% CI 0.123-0.934). However, haplotype GT of rs3808058-rs6944446 (OR 1.575; 95% CI 1.048-2.368) and AGT of rs3823994-rs6944446-rs3808058 (OR 1.673; 95% CI 1.056-2.651) might be a risk factor for pituitary adenoma development. In a brief, the results support the hypothesis that polymorphisms or haplotypes in the LRRC4 may have important research significance and could be used to predict the risk of pituitary adenoma.

Disease control after reduced volume conformal and intensity modulated radiation therapy for childhood craniopharyngioma.

PURPOSE: To estimate the rate of disease control after conformal radiation therapy using reduced clinical target volume (CTV) margins and to determine factors that predict for tumor progression. METHODS AND MATERIALS: Eighty-eight children (median age, 8.5 years; range, 3.2-17.6 years) received conformal or intensity modulated radiation therapy between 1998 and 2009. The study group included those prospectively treated from 1998 to 2003, using a 10-mm CTV, defined as the margin surrounding the solid and cystic tumor targeted to receive the prescription dose of 54 Gy. The CTV margin was subsequently reduced after 2003, yielding 2 groups of patients: those treated with a CTV margin greater than 5 mm (n=26) and those treated with a CTV margin less than or equal to 5 mm (n=62). Disease progression was estimated on the basis of additional variables including sex, race, extent of resection, tumor interventions, target volume margins, and frequency of weekly surveillance magnetic resonance (MR) imaging during radiation therapy. Median follow-up was 5 years. RESULTS: There was no difference between progression-free survival rates based on CTV margins (>5 mm vs ≤5 mm) at 5 years (88.1% ± 6.3% vs 96.2% ± 4.4% [P=.6386]). There were no differences based on planning target volume (PTV) margins (or combined CTV plus PTV margins). The PTV was systematically reduced from 5 to 3 mm during the time period of the study. Factors predictive of superior progression-free survival included Caucasian race (P=.0175), no requirement for cerebrospinal fluid shunting (P=.0066), and number of surveillance imaging studies during treatment (P=.0216). Patients whose treatment protocol included a higher number of weekly surveillance MR imaging evaluations had a lower rate of tumor progression. CONCLUSIONS: These results suggest that targeted volume reductions for radiation therapy using smaller margins are feasible and safe but require careful monitoring. We are currently investigating the differences in outcome based on host factors to explain the results.

Demographic differences in incidence for pituitary adenoma.

Incidence estimates for pituitary adenomas vary widely, suggesting the effects of numerous risk factors or varying levels of tumor surveillance. We studied the epidemiology of pituitary adenomas using 2004-2007 data collected by 17 Surveillance, Epidemiology, and End Results Programs in the United States (N = 8,276). We observed that incidence rates generally increased with age and were higher in females in early life and higher in males in later life. Males are diagnosed with larger tumors on average than females. Diagnosis may be delayed for males, giving tumors a chance to grow larger before clinical detection. We also observed that American Blacks have higher incidence rates for pituitary adenomas compared with other ethnic groups. There are several potential explanations for this finding with some evidence that at least part of the effect may be due to differential diagnosis between races.

Prolactinoma and hyperprolactinaemia: a transcultural comparative study between Germany as a western, liberal, industrialised country and Syria as an oriental society with a strong Islamic tradition.

OBJECTIVE: Prolactinomas and hyperprolactinaemia cause hypogonadism and impairment of sexual and reproductive function. In this transcultural study, clinical characteristics of prolactinoma/hyperprolactinaemia were compared between a liberal, western, industrialised country and a more traditional, Islamic, oriental society. METHODS: Sixty-two Syrian patients with hyperprolactinaemia were compared to 62 German patients with hyperprolactinaemia. RESULTS: In Syria and Germany, prolactinoma and hyperprolactinaemia were more frequent in females than in males (Syria 87% females; Germany 63% females). Prolactinomas were larger in males, males were older at diagnosis in both countries. Recorded clinical symptoms were comparable, even if culturally determined differences in spontaneous reporting of and asking for symptoms might be considered. The average age of the Syrian patients at diagnosis of hyperprolactinaemia was more than 6 years lower than in the German cohort (33.4 ± 10.4 vs. 39.7 ± 17.6 years). In Germany, a variety of therapeutic regimens were applied. In Syria, bromocriptine was prescribed exclusively. DISCUSSION AND CONCLUSION: The differences may be attributed to culturally determined differences in sexual and reproductive behaviour, i.e. sexual intercourses of young, unmarried girls and women in association to the use of oral contraceptives regulating the menstrual cycle, maternal age at first delivery and birth frequency. Exclusive prescription of bromocriptine in Syria may be associated to limited resources and the safety of bromocriptine during pregnancy.

Complications and death among elderly patients undergoing pituitary tumour surgery.

BACKGROUND: Preoperative determinants of surgical risk in elderly patients with pituitary tumour are not fully defined. The aim of this study was to quantify operative risk for these patients. DESIGN AND METHODS: We performed a retrospective analysis of the Nationwide Inpatient Sample (1998-2005), a database containing discharge information from a stratified, random sample of 20% of all non-federal hospitals in 37 states. Patients >65 years old who underwent pituitary tumour resection were identified by ICD-9 coding. Primary outcome was inpatient death. Other outcomes included post-operative complications, length of stay (LOS) and total charges. RESULTS: A total of 8400 patients (53.7% male) were identified. Mean age was 72.2. Mean co-morbidity score was 5.3. A majority were white (82.0%) admitted to academic hospitals (69.5%) for elective procedures (55.7%). Inpatient mortality was 3.8%. The most common complication was fluid and electrolyte abnormalities (14.3%). Mean LOS was 8.5 days. In multivariate analysis, patients >80 years old had 30% greater odds of death, relative to 65-69 year old counterparts. Each complication increased LOS by an average of at least 4 days. These associations were statistically significant (P-values <0.05). CONCLUSIONS: New clinically relevant risk stratification information is now available to assist clinicians in operative decision-making for elderly patients with pituitary tumour considering operative intervention.

Variations in referral patterns for hypophysectomies among pediatric patients with sellar and parasellar tumors.

PURPOSE: It has been shown that patients admitted to high-volume hospitals for resection of sellar and parasellar lesions experience reduced mortality and morbidity. It remains unknown what preoperative factors influence admission to high-volume centers. We report a nationwide analysis of patients <18 years of age undergoing neurosurgical intervention for these lesions. METHODS: A retrospective analysis of the Nationwide Inpatient Sample was performed with additional factors from the Area Resource File. International Classification of Diseases, 9th Revision diagnosis/procedural codes were used to identify patients undergoing resection of tumors from the pituitary gland or related structures. Patients >or=18 years old were excluded. Covariates included age, gender, race, and insurance status. Multivariate analysis was performed using multiple logistic regression models. A p value <0.05 was considered statistically significant. RESULTS: In total, 1,063 patients were identified. Most (69.8%) were seen at low-volume centers. Mean (median) patient age was 13.7 (15) years. The majority of patients were female (54.8%), white (61.9%), and insured (90.3%). Hispanics were 44% less likely (odds ratio (OR) 0.56, 95% confidence interval (CI) 0.34-0.92, p < 0.05) to be seen at high-volume centers than their Caucasian counterparts. Each increase in 2-year patient age category was associated with greater access to high-volume centers (OR 1.12, 95% CI 1.03-1.23, p < 0.05), relative to 0-2 years old. Female gender, insurance status, county poverty, neurosurgeon density, and calendar year were not significantly associated with admission to high-volume centers. CONCLUSIONS: Age and racial disparities play a significant role in access neurosurgical care, affecting admission of pediatric patients to high-volume neurosurgical centers across the USA.

Molecular diagnosis of pituitary adenoma predisposition caused by aryl hydrocarbon receptor-interacting protein gene mutations.

Pituitary adenomas are common neoplasms of the anterior pituitary gland. Germ-line mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene cause pituitary adenoma predisposition (PAP), a recent discovery based on genetic studies in Northern Finland. In this population, a founder mutation explained a significant proportion of all acromegaly cases. Typically, PAP patients were of a young age at diagnosis but did not display a strong family history of pituitary adenomas. To evaluate the role of AIP in pituitary adenoma susceptibility in other populations and to gain insight into patient selection for molecular screening of the condition, we investigated the possible contribution of AIP mutations in pituitary tumorigenesis in patients from Europe and the United States. A total of 460 patients were investigated by AIP sequencing: young acromegaly patients, unselected acromegaly patients, unselected pituitary adenoma patients, and endocrine neoplasia-predisposition patients who were negative for MEN1 mutations. Nine AIP mutations were identified. Because many of the patients displayed no family history of pituitary adenomas, detection of the condition appears challenging. Feasibility of AIP immunohistochemistry (IHC) as a prescreening tool was tested in 50 adenomas: 12 AIP mutation-positive versus 38 mutation-negative pituitary tumors. AIP IHC staining levels proved to be a useful predictor of AIP status, with 75% sensitivity and 95% specificity for germ-line mutations. AIP contributes to PAP in all studied populations. AIP IHC, followed by genetic counseling and possible AIP mutation analysis in IHC-negative cases, a procedure similar to the diagnostics of the Lynch syndrome, appears feasible in identification of PAP.

Does the prevalence of gsp mutations in GH-secreting pituitary adenomas differ geographically or racially? Prevalence of gsp mutations in Japanese patients revisited.

OBJECTIVE: The prevalence of gsp mutations in GH-secreting pituitary adenomas was thought to differ geographically or racially, given its exceptionally lower incidence among Japanese patients (4.4-9.3%) compared to other regions (30-50%). However, this notion is now being challenged after a recent paper reported a 53.3% incidence among Japanese with acromegaly. We have since re-evaluated the prevalence of gsp mutations on a larger scale. PATIENTS: One hundred Japanese acromegaly patients with surgically confirmed GH-secreting pituitary adenomas were enrolled. METHODS: mRNAs from primary cultured adenomas were used for reverse transcriptase-polymerase chain reaction and direct sequencing of the Gsalpha subunit. Patient data were reviewed from medical charts. RESULTS: There were 53 gsp mutations (53%), consisting of 42 Arg201Cys, one Arg201His, one Arg201Ser, 8 Gln227Leu, and one Gln227Arg mutation. Age at operation, sex ratio, basal serum GH and IGF-I levels were no different with or without the mutations. In contrast, patients responded differently to most dynamic tests with statistical significance: serum GH levels in gsp-positive patients had blunted response to GHRH, were well suppressed by bromocriptine, and had higher rates of paradoxical response to TRH. Notably, paradoxical response to LHRH was observed exclusively in gsp-negative patients. Octreotide suppressed GH levels strongly regardless of gsp status. These clinical characteristics are similar to those of Caucasian patients. CONCLUSION: We conclude that the prevalence of gsp mutations in Japanese acromegaly patients is comparable to those of other reports from various regions. Therefore, Japanese patients do not stand as an example for geographical or racial difference in the prevalence of gsp mutations in GH-secreting pituitary adenomas.

Mapping the gene for hereditary hyperparathyroidism and prolactinoma (MEN1Burin) to chromosome 11q: evidence for a founder effect in patients from Newfoundland.

An autosomal dominant syndrome of prolactinomas, carcinoids, and hyperparathyroidism was described in four Newfoundland kindreds in 1980 and in one kindred from the Pacific Northwest in 1983. Because this syndrome shares many features with multiple endocrine neoplasia type 1, the gene for which maps to proximal chromosome 11q, we performed linkage studies with chromosome 11 markers in prolactinoma families to determine whether the two genes map to the same location. All proximal chromosome 11q markers gave positive LOD scores, and no recombinants were seen with PYGM (LOD score 15.25, recombination fraction .0). All affected individuals from Newfoundland shared the same PYGM allele, providing evidence for a founder effect. The disease in the Pacific Northwest kindred cosegregated with a different PYGM allele.

Ethnic distribution of primary central nervous system tumors in Washington, DC, 1971 to 1985.

An ethnic analysis was made of 8947 cases of primary central nervous system (CNS) tumors seen at the Armed Forces Institute of Pathology (AFIP), Washington, DC, from 1971 to 1985. Results showed a slightly higher frequency of primary CNS tumors in whites than in blacks with a white:black case ratio of 9:1 against the white:black population ratio in the United States of 7.4:1. Gliomas appeared to be twofold more frequent in whites than in blacks with a white:black case ratio of 12.1:1. However, meningiomas and pituitary adenomas were more common in blacks with a white:black case ratio of 6.7:1 and 4.2:1, respectively. When these results were compared with the results of a previous identical study using similar materials collected at AFIP from 1958 to 1970, the relative paucity of gliomas and higher frequency of meningiomas and pituitary adenomas in American blacks is again confirmed, thus re-emphasizing the importance of genetic factors in the genesis of primary CNS tumors. The remarkable decreasing white:black case ratio of primary CNS tumors as a whole (9:1 compared with 13.7:1) since 1970 probably reflects the socioeconomic improvement of American blacks during the same period.