Hyperprolactinemia
Classification & external resources

ICD-10	E22.1
ICD-9	253.1
DiseasesDB	6314
eMedicine	med/1098
MeSH	D006966

Hyperprolactinaemia (BrE) or hyperprolactinemia (AmE) is the presence of abnormally high levels of prolactin in the blood. Normal levels are less than 580 mIU/L for women, and less than 450 mIU/L for men.

The hormone prolactin is downregulated by dopamine and is upregulated by estrogen. A falsely high measurement may occur due to the presence of the biologically inactive macroprolactin in the serum. This can show up as high prolactin in some types of tests, but is asymptomatic.

Causes

Hyperprolactinaemia may be caused by either disinhibition (e.g. compression of the pituitary stalk or reduced dopamine levels) or excess production from a prolactinoma (a pituitary gland adenoma tumour). A prolactin level of 1000–5000mIU/L could be from either mechanism, but >5000mIU/L is likely due to an adenoma with macroadenomas (large tumours over 10 mm diameter) having levels of up to 100,000mIU/L. Hyperprolactinemia inhibits gonadotropin-releasing hormone (GnRH) by increasing the release of dopamine from the arcuate nucleus of the hypothalamus (dopamine inhibits GnRH secretion), thus inhibiting gonadal steroidogenesis, which is the cause of many of the symptoms described below:

There is a suspicion that Minoxidil, a potassium channel opener, may be related to the development of this disease. A two year test with Minoxidil, under normal dosing parameters, was carried out on rats which caused pheochromocytomas in both males and females, and preputial gland adenomas in males^[1].

Physiological causes

Physiological causes (i.e. as result of normal body functioning): pregnancy, breastfeeding, stress, sleep.

Prescription drugs

Use of prescription drugs are the most common cause of hyperprolactinaemia. Prolactin secretion in the pituitary is normally suppressed by the brain chemical, dopamine. Drugs that block the effects of dopamine at the pituitary or deplete dopamine stores in the brain may cause the pituitary to secrete prolactin. These drugs include the major tranquilizers (phenothiazines), trifluoperazine (Stelazine), ,and haloperidol (Haldol); some antipsychotic medications; metoclopramide (Reglan), used to treat gastroesophageal reflux and the nausea caused by certain cancer drugs; and less often, alpha-methyldopa and reserpine, used to control hypertension. Finally oestrogens and TRH.

Diseases

Prolactinoma or other tumors arising in or near the pituitary—such as those that cause acromegaly or Cushing's syndrome—may block the flow of dopamine from the brain to the prolactin-secreting cells, likewise division of the pituitary stalk or hypothalamic disease. Other causes include chronic renal failure, hypothyroidism and sarcoidosis. Some women with polycystic ovary syndrome may have mildly elevated prolactin levels.

Apart from diagnosing hyperprolactinaemia and hypopituitarism, prolactin levels are often determined by physicians in patients who have suffered a seizure, when there is doubt whether this was an epileptic seizure or a non-epileptic seizure. Shortly after epileptic seizures, prolactin levels often rise, while they are normal in non-epileptic seizures.

Idiopathic

In many patients elevated levels remain unexplained and may represent a form of hypothalamic-pituitary dysregulation.

Symptoms

In women, a high blood level of prolactin often causes hypoestrogenism with anovulatory infertility and a decrease in menstruation. In some women, menstruation may disappear altogether (amenorrhea). In others, menstruation may become irregular or menstrual flow may change. Women who are not pregnant or nursing may begin producing breast milk. Some women may experience a loss of libido (interest in sex). Intercourse may become painful because of vaginal dryness.

In men, the most common symptoms of hyperprolactinemia are impotence, decreased libido, erectile dysfunction, and infertility. Because men have no reliable indicator such as menstruation to signal a problem, many men with hyperprolactinemia being caused by an adenoma may delay going to the doctor until they have headaches or eye problems caused by the enlarged pituitary pressing against nearby eye nerves. They may not recognize a gradual loss of sexual function or libido. Only after treatment do some men realize they had a problem with sexual function.

Because of hypoestrogenism, hyperprolactinaemia can lead to osteoporosis.

Diagnosis

A doctor will test for prolactin blood levels in women with unexplained milk secretion (galactorrhea) or irregular menses or infertility, and in men with impaired sexual function and, in rare cases, milk secretion. If prolactin is high, a doctor will test thyroid function and ask first about other conditions and medications known to raise prolactin secretion. Whilst a plain X-ray of the bones surrounding the pituitary may reveal the presence of a large macro-adenoma, the small micro-adenoma will not be apparent. Magnetic resonance imaging (MRI) is the most sensitive test for detecting pituitary tumors and determining their size. MRI scans may be repeated periodically to assess tumor progression and the effects of therapy. Computed Tomography (CT scan) also gives an image of the pituitary, but it is less sensitive than the MRI.

In addition to assessing the size of the pituitary tumor, doctors also look for damage to surrounding tissues, and perform tests to assess whether production of other pituitary hormones is normal. Depending on the size of the tumor, the doctor may request an eye exam with measurement of visual fields.

Historical eponyms

On occasion the following eponyms may be encountered:

1. Ahumada-DelCastillo Syndrome, refers to the association of galactorrhea and amenorrhea.
2. Chiari-Frommel Syndrome, refers to extended postpartum galactorrhea and amenorrhea.
3. Forbes-Albright Syndrome, refers to galactorrhea-amenorrhea associated with a pituitary tumor.

These eponyms were established before prolactin measurements could be done reliably in the clinical setting.

References

•  • [ e] Endocrine pathology: endocrine diseases (, )
Thyroid	Hypothyroidism (Iodine deficiency, Cretinism, Congenital hypothyroidism, Goitre, Myxedema) - Hyperthyroidism (Graves disease, Toxic multinodular goitre, Teratoma with thyroid tissue or Struma ovarii) - Thyroiditis (De Quervain's thyroiditis, Hashimoto's thyroiditis, Riedel's thyroiditis) - Euthyroid sick syndrome
Pancreas	Diabetes mellitus (type 1, type 2, coma, angiopathy, ketoacidosis, nephropathy, neuropathy, retinopathy) - Hypoglycemia - Hyperinsulinism - Zollinger-Ellison syndrome
Parathyroid	Hypoparathyroidism (Pseudohypoparathyroidism) - Hyperparathyroidism (Primary, Secondary, Tertiary)
Pituitary	hyperfunction (Acromegaly, Hyperprolactinaemia, Syndrome of inappropriate antidiuretic hormone) - Hypopituitarism (Sheehan's syndrome, Kallmann syndrome, Simmonds' disease, Growth hormone deficiency) - Diabetes insipidus - Hypothalamic-pituitary dysfunction
Adrenal	Cushing's syndrome (Nelson's syndrome, Pseudo-Cushing's syndrome) - Congenital adrenal hyperplasia (due to 21-hydroxylase deficiency) - Hyperaldosteronism (Conn syndrome, Bartter syndrome) - Adrenal insufficiency (Addison's disease) - Hypoaldosteronism
Gonads	Polycystic ovary syndrome - 5-alpha-reductase deficiency - Hypogonadism - Delayed puberty - Precocious puberty
Other	Autoimmune polyendocrine syndrome - Carcinoid syndrome - Laron syndrome - Multiple endocrine neoplasia - Psychogenic dwarfism - Androgen insensitivity syndrome - Progeria