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Hyperprolactinaemia

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Description: Hyperprolactinaemia is a condition characterized by abnormally high levels of prolactin in the blood, often leading to symptoms like menstrual irregularities, infertility, and galactorrhea.
Type: Hyperprolactinaemia is typically not inherited and does not follow a clear pattern of genetic transmission. Most cases are associated with prolactin-secreting pituitary adenomas (prolactinomas) or other secondary causes such as medications, hypothyroidism, and kidney disease. However, there are rare genetic conditions, such as multiple endocrine neoplasia type 1 (MEN1), that can include hyperprolactinaemia as part of their spectrum. In such cases, the genetic transmission follows an autosomal dominant pattern.
Signs And Symptoms: In women, high blood levels of prolactin are typically associated with hypoestrogenism, anovulatory infertility, and changes in menstruation. Menstruation disturbances experienced in women commonly manifests as amenorrhea or oligomenorrhea. In the latter case, irregular menstrual flow may result in abnormally heavy and prolonged bleeding (menorrhagia). Women who are not pregnant or nursing may also unexpectedly begin producing breast milk (galactorrhea), a condition that is not always associated with high prolactin levels. For instance, many premenopausal women experiencing hyperprolactinemia do not experience galactorrhea and only some women who experience galactorrhea will be diagnosed with hyperprolactinemia. Thus, galactorrhea may be observed in individuals with normal prolactin levels and does not necessarily indicate hyperprolactinemia. This phenomenon is likely due to galactorrhea requiring adequate levels of progesterone or estrogen to prepare the breast tissue. Additionally, some women may also experience loss of libido and breast pain, particularly when prolactin levels rise initially, as the hormone promotes tissue changes in the breast.In men, the most common symptoms of hyperprolactinemia are decreased libido, sexual dysfunction, erectile dysfunction/impotence, infertility, and gynecomastia. Unlike women, men do not experience reliable indicators of elevated prolactin such as menstruation to prompt immediate medical consultation. As a result, the early signs of hyperprolactinemia are generally more difficult to detect and may go unnoticed until more severe symptoms are present. For instance, symptoms such as loss of libido and sexual dysfunction are subtle, arise gradually, and may falsely indicate a differential cause. Many men with pituitary tumor–associated hyperprolactinemia may forego clinical help until they begin to experience serious endocrine and vision complications, such as major headaches or eye problems.Long-term hyperprolactinaemia can lead to detrimental changes in bone metabolism as a result of hypoestrogenism and hypoandrogenism. Studies have shown that chronically elevated prolactin levels lead to increased bone resorption and suppression of bone formation, leading to reduced bone density, increased risk of fractures, and increased risk of osteoporosis. The chronic presence of hyperprolactinemia can lead to hypogonadism and osteolysis in men.
Prognosis: Hyperprolactinaemia, characterized by elevated levels of prolactin in the blood, has a generally favorable prognosis with appropriate treatment. The outcome depends on the underlying cause:
- **Prolactinomas:** These benign tumors often respond well to medical treatment with dopamine agonists like cabergoline or bromocriptine, which can normalize prolactin levels and reduce tumor size. Surgery may be considered if medication is ineffective or not tolerated.
- **Medication-induced:** Discontinuing or switching the offending drug typically resolves the elevated prolactin levels.
- **Other conditions:** Addressing underlying conditions such as hypothyroidism or renal failure can also normalize prolactin levels.

With accurate diagnosis and proper management, patients usually experience significant symptomatic relief and can lead normal, healthy lives. Regular follow-up is essential to monitor and manage any recurrence or complications.
Onset: Hyperprolactinaemia often has a gradual onset. The condition is characterized by elevated levels of prolactin in the blood, which can result from various causes such as pituitary tumors (prolactinomas), hypothyroidism, or certain medications. Because the symptoms may develop slowly, it can sometimes go unnoticed until more prominent signs such as menstrual irregularities, galactorrhea (unexpected milk production), or decreased libido arise. Early detection and management are crucial to mitigate complications.
Prevalence: The prevalence of hyperprolactinaemia varies depending on the population and the criteria used for diagnosis. In the general population, it is estimated to affect around 0.4% of individuals. It is more commonly diagnosed in women than in men, particularly in those of reproductive age, with prevalence rates in women ranging from 5% to 10%.
Epidemiology: Hyperprolactinaemia is a condition characterized by an abnormally high level of prolactin in the blood. It is relatively common, especially among women of reproductive age. Epidemiologically, it affects approximately 0.4% of the general adult population, with a higher prevalence in women than in men. Among women presenting with reproductive issues such as amenorrhea or galactorrhea, the prevalence of hyperprolactinaemia can be as high as 5-10%.
Intractability: Hyperprolactinaemia, which involves elevated levels of prolactin in the blood, is not typically considered intractable. It can often be managed effectively with medications such as dopamine agonists (e.g., bromocriptine or cabergoline), which help lower prolactin levels. In some cases, if the underlying cause is a prolactin-producing pituitary tumor, surgery or radiation therapy might be required. Treatment success depends on the underlying cause and timely intervention.
Disease Severity: Disease Severity: Hyperprolactinaemia can vary in severity. Mild cases may present with few or subtle symptoms, while more severe cases can cause significant symptoms such as galactorrhea (milk production), menstrual irregularities in women, sexual dysfunction in men, and infertility. Severe cases can also indicate the presence of a prolactin-secreting pituitary adenoma (prolactinoma), which may require medical or surgical treatment.
Healthcare Professionals: Disease Ontology ID - DOID:12700
Pathophysiology: Pathophysiology of Hyperprolactinaemia:
Hyperprolactinaemia is a condition characterized by elevated levels of prolactin in the blood. Prolactin is a hormone produced by the anterior pituitary gland, primarily responsible for lactation and breast development.

1. **Hypothalamic-Pituitary Regulation**: Normally, prolactin secretion is under inhibitory control by dopamine, which is produced in the hypothalamus and transported to the anterior pituitary via the pituitary stalk.

2. **Increased Prolactin Production**: Conditions that disrupt dopamine production or its transport can lead to increased prolactin levels. This includes pituitary adenomas (prolactinomas), hypothalamic disease, or damage to the pituitary stalk.

3. **Pharmacological Causes**: Certain medications, such as antipsychotics, antidepressants, and antihypertensives, can inhibit dopamine action or synthesis, resulting in elevated prolactin levels.

4. **Physiological Causes**: Normal physiological states such as pregnancy, stress, exercise, and sleep can also transiently increase prolactin levels.

5. **Pathological Causes**: Other potential causes include primary hypothyroidism, which increases thyrotropin-releasing hormone (TRH) and subsequently stimulates prolactin release, as well as chronic renal failure, which reduces prolactin clearance.

The elevated prolactin levels can impact reproductive system function, leading to symptoms such as menstrual disturbances in women and hypogonadism in men. Other symptoms may include galactorrhea (milk production) in both sexes, sexual dysfunction, and, in cases of large prolactinomas, symptoms of mass effect like headaches and visual disturbances.
Carrier Status: For hyperprolactinaemia, carrier status is not applicable (N/A) as it is not typically considered a genetic carrier condition. Hyperprolactinaemia is a condition characterized by an abnormally high level of prolactin in the blood, often caused by prolactin-secreting pituitary tumors (prolactinomas), medication side effects, or other underlying health issues.
Mechanism: **Mechanism:**

Hyperprolactinaemia is a condition characterized by elevated levels of prolactin in the blood. Prolactin is a hormone produced by the anterior pituitary gland, and it plays a crucial role in lactation and various reproductive functions. The underlying mechanisms leading to hyperprolactinaemia can be physiological, pathological, or pharmacological. These mechanisms include:

1. **Physiological Causes:**
- Pregnancy: High estrogen levels stimulate prolactin production.
- Lactation: Suckling stimulates prolactin release.

2. **Pathological Causes:**
- Prolactinomas: Benign pituitary tumors that secrete prolactin.
- Hypothyroidism: Reduced thyroid hormone levels lead to increased thyrotropin-releasing hormone (TRH), which stimulates prolactin release.
- Chronic kidney disease: Impaired clearance of prolactin from the bloodstream.

3. **Pharmacological Causes:**
- Medications: Antipsychotics, antidepressants, and certain antiemetics can block dopamine receptors, reducing dopamine's inhibitory effect on prolactin secretion.

**Molecular Mechanisms:**

1. **Dopamine Inhibition:**
- Dopamine acts as a prolactin-inhibiting factor. It binds to D2 receptors on lactotroph cells in the anterior pituitary, inhibiting prolactin synthesis and secretion. Any disruption in the dopaminergic pathway (e.g., due to medications or pituitary stalk compression) can lead to increased prolactin levels.

2. **Thyrotropin-Releasing Hormone (TRH):**
- TRH stimulates prolactin secretion. Hypothyroidism increases TRH, leading to elevated prolactin levels.

3. **Estrogen Stimulation:**
- Estrogen directly stimulates lactotroph proliferation and prolactin gene expression. Elevated estrogen levels, as seen in pregnancy or estrogen-secreting tumors, can increase prolactin production.

4. **Prolactin Receptor Downregulation:**
- Continuous high levels of prolactin can lead to downregulation of prolactin receptors, altering feedback mechanisms that normally control prolactin secretion.

Understanding these mechanisms provides insight into the diverse etiologies of hyperprolactinaemia and helps guide effective diagnosis and treatment strategies.
Treatment: Treatment for hyperprolactinemia is usually dependent upon its cause, ranging from hypothyroidism, drug-induced hyperprolactinemia, hypothalamic disease, idiopathic hyperprolactinemia, macroprolactin, or prolactinoma. Therefore, in order to provide the proper management of hyperprolactinemia, the pathological form and physiological increase in prolactin levels are differentiated, and the correct cause of hyperprolactinemia must be identified before treatment. For functional asymptomatic hyperprolactinemia, the treatment of choice is removing the associated cause, including antipsychotic therapy. However, prolactin levels should be drawn and monitored both prior to any discontinuation or changes to therapy, and afterwards. With symptomatic hyperprolactinemia, stopping antipsychotic drugs for a short trial period are not recommended due to the risk of exacerbation or relapse of symptoms. Options for treatment include decreasing the dose of antipsychotics, adding aripiprazole as an adjunctive therapy, and switching antipsychotics as a last resort. In pharmacologic hyperprolactinemia, the concerning drug can be switched to another treatment or discontinued entirely. Vitex agnus-castus extract may be tried in cases of mild hyperprolactinemia. No treatment is required in asymptomatic macroprolactin and instead, serial prolactin measurements and pituitary imaging is monitored in a regular follow-up appointments.Medical therapy is the preferred treatment in prolactinomas. In most cases, medications that are dopamine agonists, such as cabergoline and bromocriptine (often preferred when pregnancy is possible), are the treatment of choice used to decrease prolactin levels and tumor size upon the presence of microadenomas or macroadenomas. A systematic review and meta-analyses has shown that cabergoline is more effective in treatment of hyperprolactinemia than bromocriptine. Other dopamine agonists that have been used less commonly to suppress prolactin include dihydroergocryptine, ergoloid, lisuride, metergoline, pergolide, quinagolide, and terguride. If the prolactinoma does not initially respond to dopamine agonist therapy, such that prolactin levels are still high or the tumor is not shrinking as expected, the dose of the dopamine agonist can be increased in a stepwise fashion to the maximum tolerated dose. Another option is to consider switching between dopamine agonists. It is possible for the prolactinoma to be resistant to bromocriptine but respond well to cabergoline and vice versa. Surgical therapy can be considered if pharmacologic options have been exhausted.There is evidence to support improvement in outcomes of hyperprolactinemic individuals who have shown to be resistant to or intolerant of the treatment of choice, dopamine agonists, through radiotherapy and surgery.
Compassionate Use Treatment: Compassionate use treatment for hyperprolactinaemia may involve the use of medications not yet officially approved for this condition but available through special regulatory programs for patients with serious or life-threatening conditions.

Off-label or experimental treatments for hyperprolactinaemia typically include medications or approaches not specifically FDA-approved for this condition but could be used based on clinical rationale or preliminary research. Examples include:

1. **Cabergoline and Bromocriptine**: While primarily approved for hyperprolactinaemia, they might be used in different dosing regimens or combined with other medications experimentally.

2. **Somatostatin Analogues**: Drugs like octreotide, used primarily for acromegaly or neuroendocrine tumors, might be investigated for their effects on prolactin-secreting tumors.

3. **Temozolomide**: An alkylating agent typically used for glioblastoma, has been explored in aggressive pituitary tumors resistant to conventional treatment.

4. **Pasireotide**: A newer somatostatin analogue, under investigation for its efficacy in treating resistant prolactinomas.

Always, such treatments should be undertaken under the direct supervision and guidance of a specialized healthcare provider, often in a clinical research setting.
Lifestyle Recommendations: For the management of hyperprolactinaemia, consider the following lifestyle recommendations:

1. **Diet and Nutrition:** A balanced diet rich in fruits, vegetables, whole grains, and lean proteins can help maintain overall health.
2. **Stress Management:** Practices such as yoga, meditation, and deep-breathing exercises can help reduce stress, which may influence prolactin levels.
3. **Adequate Sleep:** Ensure sufficient and consistent sleep, aiming for 7-9 hours per night.
4. **Regular Exercise:** Engage in regular physical activity to help regulate hormones and improve overall health.
5. **Avoid Alcohol and Drugs:** Reduce or eliminate alcohol and recreational drug use, as these can impact hormone levels and overall well-being.
6. **Monitoring Medication:** Discuss with your healthcare provider about any medications you are taking that might affect prolactin levels, and follow their recommendations closely.

Implementing these lifestyle changes can support the management of hyperprolactinaemia in conjunction with medical treatments.
Medication: Prolactin secretion in the pituitary is normally suppressed by the brain chemical dopamine, which binds to dopamine receptors. Drugs that block the effects of dopamine at the pituitary or deplete dopamine stores in the brain may cause the pituitary to secrete prolactin without an inhibitory effect. These drugs include the typical antipsychotics: phenothiazines such as chlorpromazine (Thorazine), and butyrophenones such as haloperidol (Haldol); atypical antipsychotics such as risperidone (Risperdal) and paliperidone (Invega); gastroprokinetic drugs used to treat gastro-esophageal reflux and medication-induced nausea (such as that from chemotherapy): metoclopramide (Reglan) and domperidone; less often, alpha-methyldopa and reserpine, used to control hypertension; and TRH. The use of estrogen-containing oral contraceptives are also known to increase prolactin levels when taken in high doses >35 μg. The sleep drug ramelteon (Rozerem) also increases the risk of hyperprolactinaemia. Particularly, the dopamine antagonists metoclopramide and domperidone are both powerful prolactin stimulators and have been used to stimulate breast milk secretion for decades. However, since prolactin is antagonized by dopamine and the body depends on the two being in balance, the risk of prolactin stimulation is generally present with all drugs that deplete dopamine, either directly or as a rebound effect.
Repurposable Drugs: For hyperprolactinemia, some repurposable drugs include:

1. **Cabergoline**: Originally used to treat Parkinson's disease, this dopamine agonist is effective in lowering prolactin levels.
2. **Bromocriptine**: Another dopamine agonist, initially used for treating type 2 diabetes and Parkinson's disease, which also helps reduce prolactin production.

These drugs can help manage hyperprolactinemia by acting on dopamine receptors to inhibit prolactin secretion.
Metabolites: Hyperprolactinaemia is characterized by an elevated level of prolactin in the blood. This condition is typically assessed by measuring serum prolactin concentration. There are no specific "metabolites" associated with hyperprolactinaemia itself, as prolactin is a hormone rather than a metabolite. Elevated prolactin can influence various metabolic pathways, but these changes are secondary to the primary condition.
Nutraceuticals: There is no established evidence that specific nutraceuticals are effective in treating hyperprolactinaemia. The condition is typically managed with medications like dopamine agonists (e.g., bromocriptine, cabergoline) or addressing the underlying cause, such as a pituitary tumor. Always consult with a healthcare provider for appropriate diagnosis and treatment options.
Peptides: Hyperprolactinaemia is characterized by elevated levels of prolactin in the blood. Prolactin is a peptide hormone produced by the anterior pituitary gland. Elevated prolactin can result from various causes, including pituitary adenomas (prolactinomas), hypothyroidism, stress, and certain medications. Treatment typically focuses on addressing the underlying cause and may include medication such as dopamine agonists which help reduce prolactin levels.