Hyperprolactinemia unrelated to pregnancy occurs in approximately 0.1 to 0.3% of the general population and may result in infertility, hypogonadism, and galactorrhea. Such nonphysiologic hyperprolactinemia is caused mainly by drugs or by tumors in the anterior pituitary gland, ... Hyperprolactinemia unrelated to pregnancy occurs in approximately 0.1 to 0.3% of the general population and may result in infertility, hypogonadism, and galactorrhea. Such nonphysiologic hyperprolactinemia is caused mainly by drugs or by tumors in the anterior pituitary gland, primarily prolactinomas (see 600634). However, 10 to 60% of patients with hyperprolactinemia who undergo MRI have normal findings (summary by Newey et al., 2013).
Newey et al. (2013) studied 3 sisters with familial idiopathic hyperprolactinemia. The proband was a 41-year-old woman with a 2-year history of oligomenorrhea and menorrhagia who was found to have hyperprolactinemia. Between age 18 and 31 years, she ... Newey et al. (2013) studied 3 sisters with familial idiopathic hyperprolactinemia. The proband was a 41-year-old woman with a 2-year history of oligomenorrhea and menorrhagia who was found to have hyperprolactinemia. Between age 18 and 31 years, she gave birth to 4 children, and at the cessation of breastfeeding after each pregnancy, she required dopamine agonist therapy to terminate persistent galactorrhea. She had no clinical features of hypopituitarism and was taking no medication; MRI of the pituitary was normal. A 38-year-old sister with a 3-year history of primary infertility and a 43-year-old sister with longstanding oligomenorrhea were both also found to have persistent hyperprolactinemia with a normal MRI of the pituitary gland. In addition, the proband's father and son were found to have persistent hyperprolactinemia. None of the affected family members had immunologic abnormalities.
In the proband of a 3-generation family segregating autosomal dominant hyperprolactinemia, who was known to be negative for mutation in the MEN1 (613733), AIP (605555), and PRL (176760) genes, Newey et al. (2013) identified heterozygosity for a missense ... In the proband of a 3-generation family segregating autosomal dominant hyperprolactinemia, who was known to be negative for mutation in the MEN1 (613733), AIP (605555), and PRL (176760) genes, Newey et al. (2013) identified heterozygosity for a missense mutation in the PRLR gene (H188R; 176761.0002). The mutation segregated with disease in the family and was not found in 110 ethnically matched controls or in more than 13,000 alleles from the NHLBI GO Exome Sequencing Project. The proband's 13-year-old prepubertal daughter, who carried the mutation but did not have hyperprolactinemia, was thought to represent age-related penetrance for the disease. Studies in transfected HEK293 cells demonstrated that H188R is a loss-of-function mutation.