Long-term assessment of patients with macroprolactinemia.

Three patients presenting with hyperprolactinemia associated with normal menses, retained fertility, and minimal lactation were followed for a period of 5 to 7 years. All had associated thyroid autoimmune disorders (one with chronic thyroiditis and two with Graves' disease). Their major form of circulating prolactin (PRL) was in the large-molecular weight (150K) form (macroprolactinemia). Whereas normal serum content of 150K PRL is less than 10% of the total, these three patients had 150K PRL fractions of 97%, 96%, and 67%. The retention of normal menses and fertility of these subjects suggested that the 150K PRL had diminished biologic activity as patients with elevations of 22K PRL will have amenorrhea and infertility. Over time, the serum PRL levels of these three patients decreased with a coincident fall in the percentage of 150K PRL. Although serum thyroid concentrations usually influence serum PRL levels, no such effects were seen in these patients whether they were hypothyroid or hyperthyroid, neither was a causal relationship between the macroprolactinemia and autoimmune thyroid disease established. Macroprolactinemia cannot be considered to be a completely benign condition as occasionally it may be associated with infertility and osteopenia.