Hyperprolactinemia and Galactorrhea: Spontaneous Versus Iatrogenic Hypothyroidism*

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Abstract
Although hyperprolactinemia and galactorrhea occur in primary hypothyroidism, factors influencing their presence are not well established. To further define these factors, the duration of illness and serum levels of PRL and TSH were investigated in a group of 50 patients with spontaneous (27 females and 7 males) and iatrogenic (16 females) primary hypothyroidism. To test the hypothesis of reduced hypothalamic dopamine content in overt long-standing primary hypothyroidism, the percent increase in serum PRL after the administration of metoclopramide, a dopamine blocker (2.5 mg, iv bolus), was studied in 13 women with spontaneous primary hypothyroidism and compared with that in 10 euthyroid women. While 88.2% of the patients with spontaneous primary hypothyroidism were hyperprolactinemic, only 31% of those with iatrogenic disease had elevated PRL levels. Women with spontaneous primary hypothyroidism had a longer duration of illness (72 ± 12 vs. 6.7 ± 1.8 months; P < 0.001) and higher serum TSH (189 ± 32 vs. 68 ± 14 μU/ml; P < 0.01) and PRL levels (49.8 ± 5.6 vs. 20.9 ± 0.8 ng/ml; P < 0.001) than women with iatrogenic hypothyroidism. A linear correlation existed between PRL and duration of illness (r = 0.53; P < 0.001), while a logarithmic correlation was found between PRL and TSH levels (r = 0.44; P < 0.01). Even though the duration of illness and TSH levels were similar in women with spontaneous disease with (n = 7) or without (n = 20) galactorrhea, the former were significantly younger (39.3 ± 1.8 vs. 56.6 ± 3 yr; P < 0.001), and their PRL levels were significantly higher (69.3 ± 8.9 vs. 42.9 ± 2.2 ng/ml; P < 0.001). The PRL response to metoclopramide in women with spontaneous disease was significantly smaller than that in controls (194 ± 39% vs. 446 ± 40%; P < 0.001) and inversely correlated with basal PRL levels (r = -0.55; P < 0.05). These data indicate that in primary hypothyroidism 1) the duration of illness is important in the development of hyperprolactinemia, 2) galactorrhea is more common in young women with spontaneous disease and high PRL levels, and 3) hypothalamic dopamine appears reduced in spontaneous disease.