Gender Affirming Hormone Replacement for the Adolescent and Young Adult Cancer Survivor with Hypogonadism.

Hypogonadism is a known late effect of cancer treatment. Hypogonadism requires replacement of sex steroids to ensure appropriate development of secondary sex characteristics, growth, and other beneficial health effects. We present a cancer survivor with hypogonadotropic hypogonadism and gender dysphoria. The patient received gender affirming care in our gender clinic with a multidisciplinary team that included an endocrinologist. This is not an isolated case at our institution. Survivorship oncologists must include a discussion about gender concurrently with conversations about survivors' development of puberty. Conversations should start early to ensure appropriate referrals and gender affirming hormone replacement.

Differential trajectories of neurocognitive functioning in females versus males following treatment for pediatric brain tumors.

BACKGROUND: Female and male trajectories of cerebellar and lobar brain structures are sexually dimorphic, making sex a potential candidate moderator of neurocognitive late effects from radiation treatment. We sought to evaluate longitudinal neurocognitive functioning in male versus female children treated for posterior fossa brain tumors. METHODS: Fifty-one female and 63 male survivors of posterior fossa tumors completed neuropsychological testing at 2 timepoints. We included patients treated with surgical resection, chemotherapy, and radiation therapy. Multilevel mixed modeling was used to predict IQ score as a function of patient sex following treatment (~2 or ~4 years post treatment). Effect sizes were used as a measure of clinical significance. RESULTS: Multilevel models resulted in a significant sex by time interaction (F = 6.69, P = 0.011). Females' cognitive scores were considerably higher compared with males at 4 years posttreatment. Females demonstrated an average improvement of 7.61 standard score IQ points compared with a decline of 2.97 points for males at 4 years follow-up. Effect sizes for female IQ compared with male IQ at 4 years posttreatment were between 0.8 and 0.9. CONCLUSION: Trajectories of neurocognitive functioning following posterior fossa tumor treatment differed between female and male children. Sexual dimorphism in radiation late effects may alter treatment decisions in children. Research into sex-specific neuroprotective mechanisms underlying neurocognitive development following pediatric brain tumor treatments is warranted.

Pediatric Central Diabetes Insipidus: Brain Malformations Are Common and Few Patients Have Idiopathic Disease.

CONTEXT: Pediatric cohorts of central diabetes insipidus (CDI) have shown varying prevalences for the different causes of CDI, including idiopathic. OBJECTIVE: The objective of the study was to determine the causes of CDI at a pediatric tertiary care center and to characterize their clinical outcomes. DESIGN AND SETTING: All patients with CDI at Seattle Children's Hospital were identified and retrospectively analyzed. PATIENTS: From 2000 to 2013, 147 patients with CDI were encountered (mean age 7 y at diagnosis, mean follow-up 6.2 y). OUTCOME MEASURES: The different causes of CDI were grouped, and age of diagnosis, anterior pituitary hormone deficiencies (APHDs), and presence of the posterior pituitary bright spot (PPBS) were analyzed. Patients with idiopathic CDI had infundibular thickening measured using a systematic method. RESULTS: Brain malformations caused 24% of CDI cases, and 12.2% were idiopathic. Four of 22 patients with initially idiopathic CDI were diagnosed with an underlying condition, none occurring later than 2.5 years from diagnosis. APHDs were as common in the brain malformation group as they were in the tumor/infiltrative group (72% vs 85%; P = .09). The PPBS was present in at least 13% of patients and in 19% of those with brain malformations. Patients with idiopathic CDI and stalk thickening on the initial magnetic resonance imaging were more likely to have an underlying diagnosis (40% vs 0%; P = .03). CONCLUSIONS: Brain malformations were a more common cause of pediatric CDI than previously reported. These patients have a high rate of APHDs, and many have persistence of the PPBS. Idiopathic CDI is an uncommon diagnosis, and none of our patients were diagnosed with Langerhans cell histiocytosis or germinoma for more than 3 years from CDI diagnosis. Providers can consider less frequent magnetic resonance imaging after this time point. A systematic method of infundibular measurement on the initial magnetic resonance imaging may predict an underlying germinoma or Langerhans cell histiocytosis.

Semiquantitative analysis of hypothalamic damage on MRI predicts risk for hypothalamic obesity.

OBJECTIVE: Excessive weight gain frequently occurs in patients with hypothalamic tumors and lesions leading to hypothalamic obesity (HO). METHODS: Digital brain magnetic resonance imaging (MRI) and clinical outcomes were studied retrospectively in a single center, including 45 children with postoperative lesions in the sellar region (41 craniopharyngiomas, 4 with Rathke's cleft cysts), ∼5 years post-surgery, mean age 13.9 years. Four standard sections covering hypothalamic areas critical to energy homeostasis were used to assess lesions and calculate a hypothalamic lesion score (HLS); the association with HO was examined. RESULTS: Compared to subjects who did not develop HO (n = 23), subjects with HO (n = 22) showed more frequently lesions affecting the third ventricular floor, mammillary bodies, and anterior, medial (all P < 0.05), and most importantly posterior hypothalamus (P < 0.01). The HLS correlated significantly with BMI z-score changes 12 and 30 months post-surgery, even after adjusting for potential confounders of gender, age at surgery, surgery date, surgery BMI z-score, hydrocephalus, and residual hypothalamic tumor (r = 0.34, P = 0.03; r = 0.40, P = 0.02, respectively). Diabetes insipidus was found to be an endocrine marker for HO risk. CONCLUSIONS: The extent of damage following surgery in the sellar region can be assessed by MRI using a novel scoring system for early HO risk assessment.

Association between glomerular filtration rate, free, total, and percent free prostate-specific antigen.

OBJECTIVES: To determine the relationship between glomerular filtration rate (GFR) and free prostate-specific antigen (fPSA), percent-free PSA (%fPSA), and total PSA (tPSA) in patients with diminished kidney function not on dialysis, using nationally representative data. METHODS: A total of 3782 men aged ≥ 40 years who participated in the National Health and Nutrition Examination Survey 2001-2006, and who met eligibility criteria for PSA testing were included in the final study population. GFR (mL/min/1.73 m(2)) was calculated using the Modification of Diet in Renal Disease equation 7 and categorized as ≥ 90, 60 to < 90, and 15 to < 60. Distribution of tPSA, fPSA, and %fPSA were estimated by GFR category and by age and race. Multivariate linear regression models were fit to determine the adjusted relationship between GFR and tPSA and %fPSA after adjusting for age, race, and body mass index. RESULTS: The multivariate linear regression analysis showed that GFR had a linear relationship with tPSA that was of borderline significance. There was a significant nonlinear relationship between GFR and %fPSA (P < .001): increased GFR was associated with a decrease in %fPSA for GFR levels below 90 [eg, change in %fPSA = -2.67 (95% CI -3.56, -1.77) for a GFR of 85 as compared with 65; P < .001]. The decline in %fPSA with increasing GFR was nonsignificant for GFR levels above 90. CONCLUSIONS: Our finding that renal function as measured by GFR is negatively associated with %fPSA has potential implications for use of this test in men with renal disease.

Learning amid controversy: prostate cancer knowledge and screening practices among US medical students.

BACKGROUND: No studies have examined medical students' recommendation and use of prostate-specific antigen (PSA) testing and digital rectal exam (DRE) to screen for prostate cancer. We hypothesized that students' race and extent of training on these techniques would be associated with their administration of them. METHODS: We analyzed multiinstitutional longitudinal data from a cohort of 2181 medical students in the class of 2003. We queried students' health behavior, their knowledge of prostate cancer racial disparities, their frequency of performing a PSA test or a DRE on a man 50 years of age or older (senior year only), the perceived relevance of such services to their future practice, and their training on PSA and DRE. We examined predictors of students' administering PSA and DRE tests to patients during the senior year and changes in the predictors over time. RESULTS: Respectively, 27% and 34% of students reported using the PSA and DRE "usually/always" during their senior year. Black students reported administering the PSA test more often than did students of other races, but race was not a significant predictor of PSA screening after controlling for personal healthy behavior. High perceived relevance to future practice and extensive training on PSA were most strongly associated with administration of PSA. CONCLUSIONS: The association between healthy personal behavior and PSA administration confounded the association between race and PSA screening. These results may help explain differences in prostate cancer screening among physicians and help medical educators tailor their curricula on prostate cancer screening.

Body composition and serum prostate-specific antigen: review and findings from Flint Men's Health Study.

Recent studies have suggested that obesity is associated with lower serum prostate-specific antigen levels, perhaps influencing the recommendation for prostate biopsy and potentially explaining part of the observed poorer prognosis among obese men. African-American men have the greatest rates of prostate cancer and are more likely to die of the disease, making early detection a priority in this group. We present findings from the Flint Men's Health Study, a study of African-American men, that are consistent with most studies suggesting that overweight men have prostate-specific antigen levels that are 0.15 to 0.30 ng/mL lower than those who are not overweight. We have coupled our results with a systematic review of publications in this area.

Prostate-specific antigen, sexual behavior, and sexually transmitted infections in US men 40-59 years old, 2001-2004: a cross-sectional study.

BACKGROUND: Sexually transmitted infections (STIs) are hypothesized to play a role in the development of prostate cancer, perhaps due to inflammation-induced oncogenesis. We assessed in a nationally representative population of middle-aged men whether sexual behavior indicators for an increased risk of genital infection were associated with serum prostate-specific antigen (PSA) concentration, a marker of prostatic disease and inflammation. RESULTS: The percentage of men between the ages of 40 and 59 with a PSA > or = 4.0 ng/ml was 2.6% (95% confidence interval [CI], 1.8% - 3.8%). The percentage of men between the ages of 40 and 59 self-reporting a past diagnosis of genital warts or genital herpes, or a recent diagnosis of gonorrhea or chlamydia is estimated to be 7.3% (95% CI, 6.2% - 8.6%). Men self-reporting that they had had sex without using a condom in the past month had a lower PSA concentration and higher %fPSA than those who did not. There were no associations between any of the other sexual activity or laboratory measures and PSA or %fPSA. CONCLUSION: In this nationally representative sample of middle-aged American men, we did not find consistent evidence for an association between sexual behavior or a history of STIs and PSA levels. Therefore, sexual factors are unlikely to lead to falsely elevated PSA tests in this population. We cannot rule out the role of these factors in causing false positive PSA tests in subgroups of the population that have a higher prevalence of high-risk sexual behavior, and more protracted or recent exposures to these agents.

Obesity is negatively associated with prostate-specific antigen in U.S. men, 2001-2004.

BACKGROUND: Recent studies have shown a negative association between body mass index (BMI) and prostate-specific antigen (PSA), a commonly used serum marker for the detection and diagnosis of prostate cancer. We have examined the association between several anthropometric measures and PSA in a nationally representative sample of men. METHODS: We analyzed data from the 2001-2004 National Health and Nutrition Examination Survey. Participants in this study were men ages >or=40 years without previously diagnosed prostate cancer who had PSA measured. Height, weight, waist circumference, BMI, triceps skinfold, subscapular skinfold, and calculated total body water were examined categorically by quintiles using multiple linear regression models. All tests of significance were two sided. RESULTS: Among white men, we report a trend for decreasing PSA with increasing weight, BMI, waist circumference, triceps skinfold thickness, and calculated total body water. Among Mexican American men, we found a trend for decreasing PSA with increasing BMI, and among black men we found a trend for decreasing PSA with increasing triceps thickness. None of the interaction terms between race/ethnicity and any of the anthropometric measures were statistically significant. Controlling for age and race/ethnicity in the multiple linear regression model, we found moderate declines in PSA with a 1 SD increase in BMI [5.9% decrease (95% confidence interval, -9.0% to -2.8%) in geometric mean PSA per 5.2-unit increase], weight [5.9% decline (-8.8% to -2.8%) per 17.7-kg increase], waist circumference [6.6% decline (-9.4% to -3.6%) per 13.4-cm increase], triceps skinfold [5.4% decline (-8.9% to -1.8%) per 6.4-mm increase], and calculated total body water [5.7% decline (-8.9% to -2.4%) per 6.5-liter increase]. CONCLUSION: Our population-based, nationally representative results expand the validity of previous studies on obesity and PSA. Higher weight, BMI, waist circumference, triceps skinfold, and total body water are associated with moderately lower PSA values. A prospective study is needed to verify whether this association affects the accuracy of the PSA test in obese men.

Prostate-specific antigen values in diabetic and nondiabetic US men, 2001-2002.

Recent studies have shown that diabetic men have a lower risk of prostate cancer and that this association may be related to time since diagnosis. The authors examined the association between diabetes and prostate-specific antigen (PSA) levels, controlling for potential confounders, in a nationally representative cross-sectional survey of the US population (National Health and Nutrition Examination Survey 2001-2002). Diabetes classification was self-reported, and undiagnosed diabetes was determined with fasting plasma glucose measurements. Controlling for age, men with self-reported diabetes had a 21.6% lower geometric mean PSA level than men without diabetes. The difference increased with years since diagnosis (>10 years: 27.5% lower geometric mean PSA level). Overweight men who had had diabetes for more than 10 years had a predicted geometric mean PSA level 40.8% lower than that of nondiabetic, normal-weight men. These results are consistent with the hypothesis that long-term diabetes is associated with a lower risk of prostate cancer. The mechanism of this association may involve the regulation of PSA by androgens, although the authors are unable to confirm this assertion. Better understanding of the determinants of PSA level is needed to make the distinction between factors affecting the PSA test's accuracy and those altering the risk of prostate cancer.