Hemoglobin decline as a signal for hyperprolactinemia onset prior to prolactinoma diagnosis in hypogonadal men

Abstract

BackgroundMen harboring prolactinomas frequently suffer from central hypogonadism with secondary anemia. They present insidious and nonspecific symptoms of hypogonadism, making it difficult to diagnose the disease and determine its duration. The result is a delay in diagnosis, which may have harmful hormonal and metabolic consequences. We hypothesized that a decrease in hemoglobin (HB) levels prior to prolactinoma diagnosis, may signal hyperprolactinemia onset and estimate disease duration.MethodsWe retrospectively evaluated the prediagnosis temporal trends in HB levels of 70 males with prolactinoma, diagnosed from January 2010 to July 2022. Men without hypogonadism, patients that received testosterone, and those with unrelated anemia were excluded.ResultsSixty‐one of seventy men (87%) with prolactinoma presented with hypogonadism, and forty men (57%) had HB levels ≤13.5 g/dL at diagnosis. We identified 25 patients with “informative” HB curves (mean age, 46.1±14.9 years; median prolactin, 952 ng/mL; median follow‐up, 14.0 years), demonstrating an obvious prediagnosis HB decrease (greater than 1.0 g/dL), from a prediagnosis baseline HB of 14.4 ± 0.3 to 12.9 ± 0.5 g/dL at diagnosis. The median “low‐HB duration” (from the first low HB measurement to hyperprolactinemia diagnosis) was 6.1 years (IQR, 3.3–8.8 years). In symptomatic patients, we identified a correlation between “low‐HB duration” and patient‐reported sexual dysfunction duration (n = 17, R = 0.502, p = 0.04). The “low‐HB duration” was significantly longer than the reported sexual dysfunction duration (7.0 ± 4.5 vs. 2.9 ± 2.5 years, p = 0.01).ConclusionsIn our cohort of men with prolactinomas and hypogonadism, we found a marked decrease in HB levels that preceded prolactinoma diagnosis by a median of 6.1 years, with a mean delay of 4.1 years between HB decrease and hypogonadal symptoms appearance. These results suggest that HB decline prior to prolactinoma diagnosis may serve as a marker for hyperprolactinemia onset in a subset of hypogonadal men and allow a more accurate assessment of disease duration.

Prolactin-secreting pituitary adenomas: male-specific differences in pathogenesis, clinical presentation and treatment

“…In another study by Shimon et al, anemia was diagnosed in almost all subjects and improved in line with a reduction in PRL concentrations and an increase in testosterone levels (19). In the recently published study by Rudman et al it has been shown that marked decrease in hemoglobin levels in men preceded PRLoma diagnosis by a median of 6.1 years, with a mean delay of 4.1 years between hemoglobin decrease and HH symptoms onset (147).…”