Thyrotropin Alpha- and Beta-Subunit Responses to Thyrotropin-Releasing Hormone and Domperidone in Normal Subjects and in Patients with Microprolactinomas

Abstract

Microprolactinoma is a particular pathological situation characterized by the presence of increased hypothalamic dopaminergic tone reactive to tumoral hyperprolactinemia. Since dopamine (DA) is a physiological regulating factor of the secretion of thyroid-stimulating hormone (TSH), we investigated the responses of serum TSH (holo-TSH) and its subunits (α-subunit: α-sub, and TSH-β) to thyrotropin-releasing hormone (TRH) and domperidone (DOM; an antidopaminergic drug acting outside the blood-brain barrier) in 36 euthyroid subjects (20 controls and 16 patients with microprolactinoma) in order to evaluate the possible in vivo effects of DA excess on TSH subunit secretion. No significant difference in serum TSH increase after TRH (200 µg i.v.) was observed between patients with microprolactinoma and controls (TSH net incremental area under the curve, nAUC: 146 ± 9, mean ± SE, and 143 ± 7.7 µg/1/60 min, respectively), while serum α-sub and TSH-β responses were markedly reduced in patients with microprolactinoma as compared to those found in normals (α-sub nAUC: 3.0 ± 0.5 vs. 19.8 ± 2.2 µg/1/60 min, p < 0.001; TSH-β nAUC: 5.0 ± 0.8 vs. 9.5 ± 0.9 µg/1/60 min, p < 0.05). Serum TSH response to DOM administration (10 mg i.v.) was significantly higher in patients with microprolactinoma than in controls (TSH nAUC: 76 ± 12.7 vs. 28 ± 8.3 µg/1/90 min, p < 0.001), while serum α-sub increase was similar in the two groups (α-sub nAUC: 8.7 ± 4.8 and 10.2 ± 4.7 µg/1/90 min, p = NS), and serum TSH-β did not show any increase in patients with microprolactinoma (TSH-β nAUC: 0.2 ± 0.1 vs. 6.0 ± 3.3 µg/1/90 min, p < 0.001). The present findings show that in normal subjects, α-sub and TSH-β are cosecreted along with holo-TSH in response to both TRH and dopaminergic receptor blockade by DOM. On the contrary, in patients with microprolactinoma, α-sub and TSH-β responses to the above stimulatory agents are definitely impaired. Such an impairment is particularly evident after DOM administration which caused a holo-TSH release 3-fold higher than in controls. The discrepancy between the secretory response of holo-TSH and that of both α-sub and TSH-β in the condition of increased hypothalamic dopaminergic tone suggests a preferential secretion of holo-TSH molecules in order to overcome the chronic dopaminergic inhibition and maintain normal thyroid stimulation.