From the Guidelines
Hypothyroidism causes hyperprolactinemia primarily through the increased production of thyrotropin-releasing hormone (TRH) and compensatory pituitary hyperplasia, as reported in a recent consensus guideline published in 2024 1. This mechanism is supported by the fact that severe primary hypothyroidism can be accompanied by hyperprolactinemia, probably due to compensatory TRH hypersecretion and pituitary hyperplasia 1. Some key points to consider in this context include:
- Hyperprolactinemia is reported in 43% of women and 40% of men presenting with frank primary hypothyroidism, and in 36% of women and 32% of men with subclinical hypothyroidism 1.
- The prevalence of hyperprolactinemia in patients with hypothyroidism highlights the importance of assessing thyroid function in patients with elevated prolactin levels.
- Treating the underlying hypothyroidism with levothyroxine at appropriate doses will normalize prolactin levels without requiring specific anti-prolactin medications. The relationship between hypothyroidism and hyperprolactinemia is well-established, and evaluating thyroid function is essential in patients with hyperprolactinemia, as treating the underlying hypothyroidism can resolve the hyperprolactinemia 1.
From the Research
Hypothyroidism and Hyperprolactinemia
- Hypothyroidism can cause hyperprolactinemia, as seen in a case study where a 30-year-old female with primary hypothyroidism had a prolactin level of 323 ng/mL 2.
- The degree of hyperprolactinemia in hypothyroidism is generally modest, but rare cases can have exceptionally high prolactin levels, exceeding 100 ng/mL 2.
- A study found that basal and thyrotropin-releasing hormone (TRH)-induced prolactin values are significantly increased in primary hypothyroidism compared to an age- and sex-matched group 3.
Pathogenesis of Hyperprolactinemia in Hypothyroidism
- The exact mechanism of hyperprolactinemia in hypothyroidism is not fully understood, but it is thought to be related to the increased levels of thyrotropin-releasing hormone (TRH) which can stimulate prolactin release 3.
- A systematic review found a positive correlation between higher serum TSH levels and higher serum prolactin levels, suggesting a possible link between the two hormones 4.
- Macroprolactinemia, a condition where prolactin is bound to IgG antibodies, can also contribute to hyperprolactinemia in hypothyroidism, as seen in a case study where 76% of the total prolactin was macroprolactin 2.
Treatment and Outcomes
- Treatment of hypothyroidism with levothyroxine can lead to resolution of hyperprolactinemia and pituitary enlargement in the majority of patients 4.
- However, macroprolactinemia can attenuate the impact of levothyroxine on hypothalamic-pituitary-thyroid axis activity and thyroid autoimmunity, as seen in a study where women with macroprolactinemia had a less pronounced response to levothyroxine treatment 5.
- A study found that hyperprolactinemia is not an important feature in patients with newly diagnosed hypothyroidism, and menstrual irregularities do not relate to hyperprolactinemia in hypothyroidism 6.