Diabetes and Prostate Cancer Outcomes in Obese and Nonobese Men After Radical Prostatectomy.

Background: The link between diabetes and prostate cancer progression is poorly understood and complicated by obesity. We investigated associations between diabetes and prostate cancer-specific mortality (PCSM), castrate-resistant prostate cancer (CRPC), and metastases in obese and nonobese men undergoing radical prostatectomy (RP). Methods: We included 4688 men from the Shared Equal Access Regional Cancer Hospital cohort of men undergoing RP from 1988 to 2017. Diabetes prior to RP, anthropometric, and clinical data were abstracted from 6 Veterans Affairs Medical Centers electronic medical records. Primary and secondary outcomes were PCSM and metastases and CRPC, respectively. Multivariable-adjusted hazard ratios (adj-HRs) and 95% confidence intervals (CIs) were estimated for diabetes and PCSM, CRPC, and metastases. Adjusted hazard ratios were also estimated in analyses stratified by obesity (body mass index: nonobese <30 kg/m2; obese ≥30 kg/m2). All statistical tests were 2-sided. Results: Diabetes was not associated with PCSM (adj-HR = 1.38, 95% CI = 0.86 to 2.24), CRPC (adj-HR = 1.05, 95% CI = 0.67 to 1.64), or metastases (adj-HR = 1.01, 95% CI = 0.70 to 1.46), among all men. Interaction terms for diabetes and obesity were statistically significant in multivariable models for PCSM, CRPC, and metastases (P ≤ .04). In stratified analyses, in obese men, diabetes was associated with PCSM (adj-HR = 3.06, 95% CI = 1.40 to 6.69), CRPC (adj-HR = 2.14, 95% CI = 1.11 to 4.15), and metastases (adj-HR = 1.57, 95% CI = 0.88 to 2.78), though not statistically significant for metastases. In nonobese men, inverse associations were suggested for diabetes and prostate cancer outcomes without reaching statistical significance. Conclusions: Diabetes was associated with increased risks of prostate cancer progression and mortality among obese men but not among nonobese men, highlighting the importance of aggressively curtailing the increasing prevalence of obesity in prostate cancer survivors.

Poorly controlled diabetes increases the risk of metastases and castration-resistant prostate cancer in men undergoing radical prostatectomy: Results from the SEARCH database.

BACKGROUND: Although diabetes is inversely related to prostate cancer (PC) risk, to the authors' knowledge the impact of glycemic control on PC progression is unknown. In the current study, the authors tested the association between hemoglobin A1c (HbA1c) and long-term PC outcomes among diabetic men undergoing radical prostatectomy (RP). METHODS: The authors retrospectively reviewed data regarding men undergoing RP from 2000 to 2017 at 8 Veterans Affairs hospitals. Diabetic patients were identified using International Classification of Diseases, Ninth Revision (ICD-9) codes (250.x) or by an HbA1c value >6.5% at any time before RP. Cox models tested the association between HbA1c and biochemical disease recurrence (BCR), castration-resistant PC (CRPC), metastases, PC-specific mortality, and all-cause mortality. The model for BCR was adjusted for multiple variables. Due to limited events, models for long-term outcomes were adjusted for biopsy grade and prostate-specific antigen only. RESULTS: A total of 1409 men comprised the study population. Of these, 699 patients (50%) had an HbA1c value <6.5%, 631 (45%) had an HbA1c value of 6.5% to 7.9%, and 79 (6%) had an HbA1c value ≥8.0%. Men with an HbA1c value ≥8.0% were younger (P < .001) and more likely to be black (P = .013). The median follow-up after RP was 6.8 years (interquartile range, 3.7-10.6 years). On multivariable analysis, HbA1c was not found to be associated with BCR. However, a higher HbA1c value was associated with metastasis (hazard ratio [HR], 1.21; 95% CI, 1.02-1.44 [P = .031]) and CRPC (HR, 1.27; 95% CI, 1.03-1.56 [P = .023]). Although not statistically significant, there were trends between higher HbA1c and risk of PC-specific mortality (HR, 1.24; 95% CI, 0.99-1.56 [P = .067]) and all-cause mortality (HR, 1.09; 95% CI, 0.99-1.19 [P = .058]). CONCLUSIONS: Among diabetic men undergoing RP, a higher HbA1c value was associated with metastases and CRPC. If validated in larger studies with longer follow-up, future research should test whether better glycemic control improves long-term PC outcomes.

MULTIPLE PITUITARY ADENOMAS WITH FUNCTIONAL FOLLICLE-STIMULATING HORMONE SECRETION LEADING TO OVARIAN HYPERSTIMULATION SYNDROME.

OBJECTIVE: To present a rare case of multiple pituitary adenomas with a functional follicle-stimulating hormone component leading to ovarian hyperstimulation syndrome. METHODS: We present the clinical, laboratory, imaging, and pathologic findings along with a review of the literature. RESULTS: A 28-year-old female presented with 5 months of amenorrhea and abdominal pain. Physical exam was unremarkable. Labs revealed elevated prolactin (94 ng/mL), elevated estradiol (608 pg/mL), inappropriately normal follicle-stimulating hormone (10.2 mIU/mL), and suppressed luteinizing hormone (0.36 mIU/mL). Transvaginal ultrasound showed numerous large ovarian cysts bilaterally. Brain magnetic resonance imaging showed a 1.2-cm sellar mass. Various medical therapies were not tolerated due to side effects and the patient underwent gross total resection of the sellar mass with marked improvement in her symptoms and blood hormone levels, resumption of menstruation, and shrinkage of the ovarian cysts. Histologic examination revealed 3 separate staining patterns consistent with multiple pituitary adenomas. CONCLUSION: Functioning gonadotroph adenomas are rare and often difficult to diagnose, though in premenopausal women they can lead to the distinct clinical presentation of spontaneous ovarian hyperstimulation syndrome. The favored treatment approach is surgical as it has the highest reported success rate. Recurrence is not uncommon and long-term surveillance is recommended. Given limited data on long-term follow-up, the role of available therapies is not well defined, and further research is needed. To our knowledge, this is the first reported case of multiple pituitary adenomas that included a functional gonadotroph component.

Treatment-related neuroendocrine prostate cancer resulting in Cushing's syndrome.

Here we present, to the best of our knowledge, the first case of a paraneoplastic Cushing's syndrome (hypercortisolism) resulting from treatment-related neuroendocrine prostate cancer - a highly aggressive and difficult disease to treat. A 51-year-old man was started on androgen deprivation therapy after presenting with metastatic prostate cancer, characterized by diffuse osseous metastasis. Shortly thereafter, he developed progressive disease with biopsy proven neuroendocrine prostate cancer as well as symptoms of increased skin pigmentation, hypokalemia, hypertension, hyperglycemia and profound weakness, consistent with ectopic Cushing's syndrome. Molecular analysis of the patient's tumor through RNA sequencing showed high expression of several genes including CHGA, ASCL1, CALCA, HES6, PCSK1, CALCB and INSM1 confirming his neuroendocrine phenotype; elevated POMC expression was found, supporting the diagnosis of ectopic Cushing's syndrome.