Amenorrhea-galactorrhea-sterility triad

Introduction The typical symptom of prolactinoma is amenorrhea-milk-infertility triad. Prolactinoma refers to a tumor in which the pituitary gland secretes PRL, and the incidence of pituitary functional (secreted) tumors is the highest. The clinical manifestations of typical prolactinoma are amenorrhea, galactorrhea, infertility (fertility), hyperprolactinemia, and pituitary changes.

Cause

There are many reasons for high PRL. In addition to physiological high PRL, there are pathological and drug-induced causes. Unexplained causes are called idiopathic high PRL.

1. Pathologically high PRL: pathologically high PRL is more common in hypothalamic-pituitary diseases, with PRL tumors being the most common. In addition to PRL tumors (or mixed tumors containing PRL tumors), other hypothalamic-pituitary tumors, invasive or inflammatory diseases, sarcoidosis, granuloma, and trauma, radiation damage, etc. are due to obstruction or obstruction of dopamine in the hypothalamus. The blood flow to the pituitary gland causes the prolactin release inhibitor (PIF) such as dopamine to fail to reach the pituitary gland. The condition of high PRL caused by increased prolactin release factor (PRF) is seen in primary hypothyroidism, stress stimulation, and neurogenic stimulation. Patients with chronic renal failure have high PRL due to glomerular filtration to clear PRL disorders. Patients with cirrhosis have elevated PRL due to inactivation of estrogen and PRL in the liver. Some rheumatic diseases such as systemic lupus erythematosus (SLE), Sjogren's syndrome, systemic sclerosis can also have high PRL, but no correlation with disease activity and serological abnormalities, autoimmune disease with high The cause of PRL is unknown. Hyperprolactinemia may or may not be accompanied by galactorrhea.

2. Drug-induced high PRL: a number of drugs that cause high PRL, including dopamine receptor antagonists, oral contraceptives containing estrogen, certain antihypertensives, opiates and H2 blockers (such as cimetidine) and so on. Among them, dopamine receptor antagonists are some drugs with stability, sedative or antiemetic effects as well as antidepressants and antipsychotics. Blood PRL generally does not exceed 100 g/L at the usual doses. After 5 to 7 days of oral administration of domperidone, the level of high PRL was between 35 and 70 g/L, which was significantly elevated and was misdiagnosed as PRL. Because chlorpromazine and metoclopramide (mesopressin) have the strongest effect, 25mg chlorpromazine can increase the serum PRL level of normal people by 5-7 times, so it is often used in the dynamic test of PRL to assist the diagnosis of PRL tumor. .

3. PRL tumors: There have been several hypotheses about the pathogenesis of PRL tumors. It has been thought that long-term administration of estrogen may be the cause of PRL neoplasia, but large-scale studies have shown that oral contraceptives, especially low-dose estrogens, are not associated with the formation of PRL tumors. It is now believed that the pituitary self-defect is the starting cause of PRL tumor formation, and the hypothalamic regulatory disorder only plays a role of allowing and promoting. Some candidate genes have been found in human pituitary tumors by molecular biology techniques. The tumor activation genes associated with PRL tumors are heparin binding secretory transforming gene (HST) and pituitary tumor transforming gene. , PTTG). Tumor suppressor genes include the CDKN2A gene and the MENI gene, which are found in familial multiple endocrine neoplasia syndrome-type I patients. Due to the mutation of these genes, the growth inhibition state of pituitary stem cells is released, and it is transformed into one or several pituitary cells, and monoclonal proliferation occurs. In the hypothalamic hormone regulation disorder, local formation of tumors in the glandular pituitary leads to the autonomous synthesis and secretion of one or several pituitary hormones.

The discovery of specific tumor molecular markers contributes to the early diagnosis and treatment of microadenomas, and provides a basis for selecting appropriate follow-up protocols. Family screening of familial MEN-I is also possible.

an examination

Related inspection

Infertility check thyroid hormone releasing hormone thyroid hormone releasing hormone excitatory test prolactin (PRL) secretion inhibition test prolactin (PRL) excitatory test

Auxiliary inspection:

(1) Determination of blood PRL: normal human fasting serum PRL is less than 20g / L, prolactinoma patients serum PRL more than 100g / L, more than 300g / L almost certainly exist in prolactinoma.

(2) Sphenoidal positive and lateral radiographs of pituitary CT or magnetic resonance imaging: the presence of tumors can be confirmed. Visual inspection can assist with diagnosis.

(3) Serum FSH, LH, and estradiol (E2) values can be reduced.

(4) If necessary, TRH stimulation test, metoclopramide test, have a certain reference value for the diagnosis of prolactinoma.

(5) for related examinations to exclude primary hypothyroidism and hypothalamus, pituitary and other endocrine diseases, except for brain and breast diseases.

Differential diagnosis

The patients had amenorrhea-lactation, male sexual dysfunction or infertility, serum PRL levels were significantly elevated, and pituitary tumors were present in CT or MRI imaging. The diagnosis of PRL tumors was mostly difficult. What needs to be identified are those with a slight increase in PRL levels, with or without saddle-occupying lesions. Clinically, the diagnosis is based on the exclusion of other pituitary adenomas. The differential diagnosis of PRL tumors is mainly centered on high PRL. When serum PIL is mild to moderately elevated (not reaching 200 nmol/L), it must be differentiated from idiopathic high PRL, pituitary non-PRL tumor, hypothalamic tumor or saddle area tumor.

1. Pituitary non-prolactinoma: blood PRL is generally less than 200nmol / L, MRI or CT examination can find a lesion in the glandular body, expanding the compression of the pituitary stalk to the saddle to prevent PIF from reaching the pituitary gland. Pituitary hormone test found that in addition to increased PRL, there is another hormone increase (no functional adenoma is not), but other pituitary hormones are reduced. After treatment with bromocriptine, PRL decreased to normal, but the size of pituitary tumors rarely changed. Clinically, this situation should consider the possibility of pituitary non-PPL tumors, and it is common for non-functional pituitary adenomas and GH tumors.

2. Hypothalamic tumor or saddle area pharyngeal tumor: There are many types of tumors, the common point is that serum PRL is often less than 100nmol/L; MRI or CT examination shows no lesions in the pituitary; the mass is not associated with the pituitary gland, close to The pituitary stalk region and the compression of the pituitary stalk cause portal blood flow disorders, or the synthesis and secretion of dopamine in the hypothalamus. In general, patients have symptoms such as cranial nerve compression, increased intracranial pressure, and diabetes insipidus. Usually the MRI or high-resolution CT examination of the hypothalamic-pituitary area can be distinguished from PRL tumors.

3. Primary hypothyroidism: In general, it is easy to distinguish it from PRL tumors. In a few cases, it not only causes high PRL blood, but also causes the pituitary gland to enlarge, making MRI and other tests mistaken for pituitary adenomas. . In recent years, MRI examination of multiple patients with primary hypothyroidism has revealed pituitary tumors, and laboratory tests have high PRL. Although clinical symptoms of hypothyroidism are not obvious, thyroid function tests indicate primary hypothyroidism. Symptoms, cured with thyroid hormone replacement therapy.

4. Idiopathic hyperprolactinemia: The cause is unknown and may be caused by hypothalamic lesions (undetected lesions). Idiopathic hyper-PRL must be diagnosed by excluding pharmacological, pathological, and physiologically high PRL. There was no abnormality in CT or MRI, and the serum PRL was only slightly elevated (more than 100 nmol/L). A small number of patients can later evolve into PRL tumors. Treatment with bromocriptine can prevent the formation of PRL tumors and should be followed up regularly.

5. Milky hyperprolactinemia: Lactation is a physiological phenomenon in humans and even all mammals, while galactorrhea refers to pathological lactation in non-physiological conditions or non-pregnancy lactation. Men have milk secretion almost all pathological conditions. Foreign countries report that some women of normal reproductive age are in non-pregnancy lactation, and can also squeeze a small amount of milk, which may be physiological. In general, women who are more likely to have lactation during non-pregnancy lactation or who have amenorrhea at the same time should be considered abnormal.

In conclusion, the diagnosis of patients with galactorrhea or amenorrhea should first consider the possibility of hyperprolactinemia. If the blood PRL is not elevated or the elevation is not obvious, further PRL stimulation test or necessary imaging examination should be performed.

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