Hyperprolactinemia

Summary

Hyperprolactinemia is defined as a condition of elevated levels of prolactin (PRL) hormone in the blood. The PRL hormone is secreted by the anterior pituitary gland and is responsible for breast development and lactation. Many factors contribute to the development of hyperprolactinemia. The most common cause is PRL-secreting pituitary adenomas Pituitary adenomas Pituitary adenomas are tumors that develop within the anterior lobe of the pituitary gland. Non-functioning or non-secretory adenomas do not secrete hormones but can compress surrounding pituitary tissue, leading to hypopituitarism. Secretory adenomas secrete various hormones depending on the cell type from which they evolved, leading to hyperpituitarism. Pituitary Adenomas (prolactinomas). Diagnosis is achieved through hormonal testing to rule out other endocrine conditions and confirmatory imaging tests. Dopamine agonists are the 1st-line drugs for treatment. Refractory cases require surgery and possibly radiation therapy.

Summary

• Definition: Increased production of prolactin by the anterior pituitary
• Occurs physiologically during pregnancy, lactation, and periods of stress.
• Pathological hyperprolactinemia is most often the result of pituitary adenomas and less commonly due to primary hypothyroidism and/or dopamine antagonists (e.g., metoclopramide, haloperidol).
• Women with pathological hyperprolactinemia present with galactorrhea, loss of libido, infertility, menstrual dysfunction, and/or osteoporosis.
• Men generally present with loss of libido, erectile dysfunction, and/or gynecomastia.
• The diagnosis is confirmed by repeated measurement of early morning prolactin levels. After ruling out hypothyroidism, a cranial MRI should be performed to detect pituitary adenomas.
• Management consists of dopamine agonists (e.g., bromocriptine, cabergoline) and treating the underlying cause.

Causes

• Physiological
  • Stress, pregnancy, lactation, nipple stimulation, crying baby, sexual orgasm, sleep, exercise
• Pathological
  • Prolactinoma: benign, prolactin-producing tumor of the anterior pituitary gland. → The most common pathological cause.
  • Damage to the hypothalamus and/or infundibular stalk
  • Severe primary hypothyroidism: ↓ T3/T4 → ↑ TRH → ↑ prolactin
  • Drugs
    • Dopamine antagonists
      • Antiemetics: metoclopramide, domperidone
      • Antipsychotics (e.g., haloperidol, risperidone)
    • Certain tricyclic antidepressants: e.g., clomipramine
    • Dopamine synthesis inhibitors: α-methyldopa
    • Oral contraceptive pills
    • Verapamil
    • Opiate analgesics
    • Histamine H2-receptor antagonists (cimetidine, ranitidine)
  • Certain types of focal epilepsy: directly after temporal lobe seizures, due to proximity to the hypothalamus à The prolactin blood level typically normalizes after one hour.
  • Chronic renal failure à due to decreased PRL clearance or disordered hypothalamic regulation.

Important – فكرة سؤال
Pituitary adenomas are the most common cause (∼ 50%) of pathological hyperprolactinemia.	تذكر

Clinical features

• Females
  • Galactorrhea إدرار الحليب (especially premenopausal women) à Galactorrhea is seen in ∼ 80% of premenopausal women with hyperprolactinemia. Galactorrhea is uncommon among postmenopausal women
  • Primary and/or secondary amenorrhea, or irregular menses
  • Infertility → Due to disrupted ovulation. About 5–14% of all cases of secondary amenorrhea are caused by hyperprolactinemia.
  • Loss of libido
  • Atrophic endometrium and vaginal atrophy (menopausal symptoms)
  • Osteoporosis (after several years)
• Males
  • Galactorrhea (but is very rare).
  •  Loss of libido فقدان الرغبة الجنسية , erectile dysfunction الضعف الجنسي, infertility  العقم
  • Gynecomastia التثديà بسبب تقصان كمية التستوستيرون وبالتالي فإن هرمون الايستروجين سيحفز نمو الثدي
  • Reduced facial and body hair نقصان كمية الشعر على الوجه والجسم
  • Osteoporosis هشاشة العظام

Important – فكرة سؤال
Patients with hyperprolactinemia due to a pituitary adenoma may also present with bitemporal hemianopsia and headache due large tumor compressing the optic chiasm. إذا كان السبب Pituitary adenoma فمن المحتمل أن يشكو المريض من عمى نصفي وصداع وهذا يدل على أن حجم الورم كبير وسبب ضغط على الــ optic chiasm	تذكر

Diagnosis

• Always exclude states such as pregnancy, lactation, hypothyroidism and medications before starting the work-up of hyperprolactinemia.
  دائما وأبدا استثني الأمراض الأخرى التي تؤدي لزيادة هرمون برولاكتين مثل الحمل، الرضاعة، خمول الغدة الدرقية، بعض الأدوية
• Serum prolactin levels.
• TSH, T4 levels: to exclude primary hypothyroidism
• In premenopausal women: pregnancy test
• MRI: done only after the confirmation of high prolactin levels and to rule out pituitary adenomas (pituitary adenomas usually present with prolactin > 200 ng/mL)

Treatment

• Dopamine agonists (treatment of choice): bromocriptine, cabergoline, quinagolide.
• Treat the underlying cause معالجة السبب
  • Transsphenoidal resection of the pituitary adenoma
  • Discontinue or lower the dose of the offending drug ايقاف الدواء المسبب لزيادة الـ برولاكتين إن كان السبب أحد الأدوية المعروفة
  • Treatment of primary hypothyroidism
  • Renal transplant for patients with CRF

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