A 28-year-old woman comes to the office due to a 4-month history of amenorrhea. She has also had a whitish nipple discharge from both breasts. The patient has taken several pregnancy tests at home that have been negative. She has also had increased fatigue, depressed mood, and weight gain over this time. The patient has had no headaches or vision changes. She has no prior medical problems and takes no medications. On physical examination, there is thinning of the outer third of the eyebrows. The thyroid is enlarged and nontender to palpation. Abdominal and pelvic examinations are normal. The skin appears dry. Laboratory results are as follows:
| Beta-hCG, serum | negative |
| Thyroxine (T4) | 2.5 µg/dL |
| TSH | 11.0 µU/mL |
| Prolactin | 30 ng/mL (<20 ng/mL) |
| Antithyroid peroxidase antibodies | positive |
Which of the following is the most likely mechanism causing this patient's elevated prolactin level?
Show Explanatory Sources
This patient has symptoms of hypothyroidism (eg, fatigue, weight gain, goiter, thinning of outer eyebrow edges). Her low thyroxine (T4), elevated TSH, and antithyroid peroxidase antibodies are further indicative of primary hypothyroidism from chronic autoimmune (Hashimoto) thyroiditis. In patients with primary hypothyroidism, there is a compensatory increase in hypothalamic thyrotropin-releasing hormone (TRH) production as thyroid hormone levels fall, stimulating increased secretion of TSH by the pituitary.
Prolactin is regulated primarily by the inhibitory effects of dopaminergic neurons from the hypothalamus. However, lactotroph cells express TRH receptors, and TRH stimulates synthesis and release of prolactin. The elevated TRH levels in the pituitary in patients with primary hypothyroidism can therefore increase prolactin secretion and lead to hyperprolactinemia.
In premenopausal women, hyperprolactinemia can cause galactorrhea. Prolactin suppresses GnRH secretion from the hypothalamus, leading to reduced secretion of LH (and to a lesser extent FSH) and subsequent hypogonadism, anovulation, and amenorrhea. Symptoms in men are often nonspecific, but can include infertility, decreased libido, and impotence.
(Choices A and B) The most common cause of primary hypothyroidism is chronic autoimmune (Hashimoto) thyroiditis. Most patients with Hashimoto thyroiditis produce thyroid peroxidase autoantibodies, but it is TRH (not the autoantibodies) that triggers prolactin release.
(Choice C) Antidopaminergic drugs (eg, antipsychotics, metoclopramide) can reduce the inhibitory effect of dopamine on prolactin secretion and lead to hyperprolactinemia, but TSH has little effect on dopamine pathways.
(Choice E) The stimulatory effect of TRH on pituitary lactotrophs is mediated by TRH receptors on lactotroph cells, not by effects on dopaminergic pathways. Overproduction of dopamine would inhibit lactotroph activity.
(Choice F) Effects of the hypothalamic-pituitary-thyroid axis on prolactin secretion are mediated primarily by TRH, not TSH.
Educational objective:
Prolactin production is regulated primarily by inhibitory effects of hypothalamic dopaminergic pathways. However, prolactin secretion is stimulated by thyrotropin-releasing hormone (TRH). In patients with primary hypothyroidism, the increased production of TRH by the hypothalamus can lead to hyperprolactinemia.