• Prolactin (PRL) has 199 amino acids and is similar in effectiveness to growth hormone and hPL. PRL is released from lactotroph cells in the anterior pituitary. Small prolactin is mostly found in the circulation in the monomeric form (23 kd), and the clinically active form is monomeric prolactin. Since total prolactin is often measured in laboratories, the correlation between prolactin level and galactorrhea is quite weak.
• The main effect of prolactin is the initiation and maintenance of lactation. Its normal level is 5-27 ng/ml. PRL is released in a certain pattern for 24 hours. It has a diurnal rhythm during the day. While its lowest level is observed in the middle of the day, it starts to rise in the afternoon and continues to increase after sleep, reaching its highest level at midnight and towards the morning. The half-life is approximately 20 minutes. While dopamine (prolactin inhibitory factor) and dopamine agonists inhibit PRL release, metoclopramide, a dopamine antagonist, increases PRL release.
• Inhibitory Factors:
► Dopamine
► GABA
► Diketopiperazine
► Pyroglutamic acid
► Somatostatin
• Stimulatory Factors
► Endogenous opiates
► 17 B-Estradiol
► GnRH
► TRH
► Histamine, serotonin
► Substance P, VIP
In particular, TRH, VIP and GnRH are also known as "prolactin releasing factors".
etiology
1. Physiological factors
• idiopathic
• Coitus
• Newborn
• Nipple
• Pregnancy
• Postpartum
• Puerperium
• Sleep
• Stress
• Exercise
• Surgery
2. CNS Factors
• Empty sella syndrome
• Pituitary adenoma
• Hypothyroidism
•Acromegaly
• Craniopharyngioma
• Arachnoid cyst
• Cystic glioma
• Cysticercosis
• Dermoid cyst
• Histiocytosis
• Neurotuberculosis
• Pineal tumors
• Pseudotumor cerebri
• Sarcoidosis
• Suprasellar cyst
• Lymphoid hypophysitis
• Metastatic tumor
• Heavy operation
3. Metabolic disorders
• Hypernephroma
• Bronchogenic sarcoma
• Nelson's syndrome
• MEN-1
• Chronic renal failure
• Addison's disease1
• Cushing's syndrome
• Cirrhosis
4. Medicines
• Antidepressants
- amocapine
- Imipramine
- Amitriptyline
• Anesthetics
• Alpha methyldopa
• Dopamine antagonists
- Piperazine
- Thioxanthine
- Buterphenon
- Piperidine
- Dibenzoxapine
- Dihydrondolone
- Procanamide
- Metoclopramide
• Estrogen and POPs
• Verapamil
• Reserpine
• Cimetidine
• Sulpiride
The most common cause of hyperprolactinemia in practice is drug use.
• Approximately 1:3 of the cases are idiopathic. Approximately 35% of hyperprolactinemias have pituitary adenoma and 35% have primary hypothyroidism (In these patients, increased TRH secretion reduces the dopamine effect in the hypothalamus and leads to an increase in PRL release.
Clinic
• Galactorrhea is seen in 2:3 of hyperprolactinemias. Amenorrhea and infertility occur due to anovulation caused by hyperprolactinemia. Amenorrhea can be seen in 15% of cases without galactorrhea. Galactorrhea + amenorrhea
2/3 of those have hyperprolactinemia. 1/3 of them have prolactinoma.
Effects of hyperprolactinemia on reproductive functions
1. Decrease in granulosa cell count and FSH binding
2. Suppression of pulsatile release of GnRH from the hypothalamus (basis of anovulation)
3. Inhibition of estradiol production from granulosa cell
4. Inadequate luteinization
5. Decrease in progesterone secretion
• Prolactin binds to its receptors on the adrenal gland, causing mild adrenal stimulation and also increases DHEA-S. Increased DHEA-S level leads to hirsutism. Since it blocks the conversion of prolactin T to DHT, its clinical manifestations remain mild despite increased androgen production.
Early-onset hyperprolactinemia can lead to puberty tarda.
• Situations where prolactin should be measured:
► Infertile women and hypogonadotropic infertile men
► Amenorrhea
► Galactorrhea
► Hirsutism with amenorrhea
► Anovulatory bleeding
► Puberty tarda
Diagnosis
• A high serum PRL level in two separate measurements makes the diagnosis and the diagnostic algorithm is as follows:
► Pregnancy and lactation are excluded.
► Medications taken are questioned.
► TSH is measured in all hyperprolactinemia cases to rule out hypothyroidism.
► Pituitary MRI is applied to rule out prolactinoma.
► If no cause is found, idiopathic diagnosis is made.
Treatment
• The treatment to be offered to the patients should be planned according to the clinical complaint. Complaints can be corrected with dopamine agonist agents.
Dopamine agonists (ergot alkaloids)
1. Bromocriptine
2. Cabergoline
3. Methergolin
4. Pergolide
5. Lysuride
• The first treatment option in microadenomas and macroadenomas should always be a medical approach. Other treatment options for macroadenomas are transsphenoidal excision and radiotherapy.
• Adenoma may enlarge during pregnancy. It is meaningless to measure PRL in the follow-up of pregnancy and pituitary adenoma cases (physiologically, PRL increases 10 times during pregnancy). For this reason, pregnant women are followed by visual field measurement, and if there is a change, pituitary MRI is applied. Bromocriptine can be used if needed.
The most suitable agent in pregnancy is bromocriptine. Pituitary adenoma is not a contraindication for pregnancy and lactation.