Robustness of the male lactotropic axis to the hyperprolactinemic stimulus of primary thyroidal failure

Primary hypothyroidism is a presumptive proximate basis for increased serum PRL concentrations. However, most studies to date have been performed in females and do not address the possible effect of sex differences. In the present study we investigated the 24-h patterns of pulsatile PRL release in 10 hypothyroid men (24-h mean ± SEM: total T₄, 35 ± 8 nmol/ L; TSH, 55 ± 10 mU/L) by sampling blood at 10-min intervals for 24 h. The study was repeated in 5 men, 5-7 months and again 14-36 months after treatment with levothyroxine. The control group consisted of 7 normal age-matched euthyroid men. The mean 24-h serum PRL concentration of 4.9 ± 0.6 μg/L in 10 hypothyroid men was not significantly different from the value of 4.9 ± 0.5 μg/L found in the normal group (P > 0.5). Pulsatile features of PRL release were evaluated by Cluster analysis, which revealed normal mean PRL peak frequency (12.6 ± 0.7 vs. 13.4 ± 0.6 pulses/24 h; P > 0.5), maximal peak amplitude (6.1 ± 0.7 vs. 6.7 ± 0.6 μg/L; P > 0.5), peak increment (2.2 ± 0.3 vs. 2.6 ± 0.3 μg/L; P = 0.3), mean valley (4.2 ±0.6 vs. 4.4 ± 0.4 μg/L; P > 0.5), and prepeak nadir (3.6 ± 0.5 vs. 3.6 ± 0.4 μg/L; P > 0.5) PRL concentrations. Five to 7 months of T₄ therapy in 5 hypothyroid men caused significant decreases in the mean 24-h (2.9 ± 0.5 vs. 6.1 ± 1.2 μg/L; P < 0.05), interpulse valley (2.5 ± 0.4 vs. 5.2 ± 1.1 μg/L; P < 0.05), and prepeak nadir (2.3 ± 0.3 vs. 4.6 ± 1.0 μg/L; P < 0.05) PRL concentrations. These values returned to normal after 14-36 months of treatment. Cosinor analysis revealed preserved circadian PRL rhythmicity during hypothyroidism, with a normal circadian mesor (mean), amplitude, and acrophase. In summary, we have demonstrated normal mean 24-h serum PRL concentrations as well as normal pulsatile and circadian patterns of PRL release in men with primary hypothyroidism. These results stand in contrast to previous reports of increased serum PRL concentrations observed predominantly in hypothyroid premenopausal women. The foregoing disparity suggests the possibility of a role for estrogen in enhancing the effect of hypothyroidism on PRL release. Decreased serum PRL concentrations after 5-7 months of T₄ replacement, but not at later follow-up, indicate one or more transient alterations in the secretion and/or clearance of PRL during the early phases of thyroid hormone replacement.