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

Abstract

Men 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. We 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. Sixty-one of seventy men (87%) with prolactinoma presented with hypogonadism, and forty men (57%) had HB levels ≤13.5g/dL at diagnosis. We identified 25 patients with "informative" HB curves (mean age, 46.1±14.9years;median prolactin, 952ng/mL; median follow-up, 14.0 years), demonstrating an obvious prediagnosis HB decrease (greater than 1.0g/dL), from a prediagnosis baseline HB of 14.4 ± 0.3to 12.9 ± 0.5g/dLat 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 ± 4.5vs.2.9 ± 2.5years, p=0.01). In 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.