1. Definition / সংজ্ঞা

Hyperprolactinaemia হলো রক্তে serum prolactin level lab-specific normal range-এর উপরে থাকা। Endocrine Society guideline অনুযায়ী, venipuncture stress ছাড়া নেওয়া একটি serum prolactin measurement normal upper limit-এর বেশি হলে diagnosis করা যায়; সাধারণত non-pregnant adult female-এ prolactin <25 ng/mL এবং male-এ আরও কম থাকে, তবে lab reference range follow করতে হবে।

Clinical meaning: বেশি prolactin → hypothalamic GnRH কমে যায় → LH/FSH কমে → hypogonadism, infertility, menstrual disturbance, erectile dysfunction, low libido, galactorrhoea হয়।

2. Causes / কারণ — Point-wise Details

A. Physiological causes — স্বাভাবিক কারণে prolactin বাড়া

1. Pregnancy — estrogen-mediated lactotroph stimulation হয়, তাই prolactin physiologically বাড়ে।
2. Lactation / breast-feeding — nipple suckling prolactin release বাড়ায়।
3. Sleep, stress, exercise, coitus — mild transient elevation হতে পারে। Endocrine Society etiology table-এ pregnancy, lactation, sleep, stress, exercise physiological causes হিসেবে উল্লেখ আছে।

B. Pituitary causes

1. Prolactinoma
   • Pituitary lactotroph adenoma থেকে prolactin excess secretion হয়।
   • Microprolactinoma: <10 mm.
   • Macroprolactinoma: ≥10 mm; headache, visual field defect, hypopituitarism বেশি হতে পারে।
   • Prolactin >250 ng/mL সাধারণত prolactinoma suggest করে, আর >500 ng/mL macroprolactinoma-এর জন্য strongly diagnostic; তবে metoclopramide/risperidone-এর মতো drug-ও >200 ng/mL করতে পারে।
2. Non-functioning pituitary macroadenoma / stalk effect
   • Tumour pituitary stalk compress করলে dopamine inhibition কমে যায় → prolactin moderate rise হয়।
   • Large mass কিন্তু prolactin মাত্র mild হলে hook effect exclude করতে diluted prolactin assay দরকার।
3. Mixed pituitary adenoma
   • GH-secreting adenoma/acromegaly-এর সাথে prolactin co-secretion থাকতে পারে; তাই suspicious case-এ IGF-1 দরকার।

C. Endocrine/systemic causes

1. Primary hypothyroidism
   • TRH বাড়ে → prolactin secretion বাড়ে। Long-standing hypothyroidism pituitary hyperplasia করে tumour mimic করতে পারে; L-thyroxine দিলে reverse হতে পারে।
2. Chronic kidney disease
   • Prolactin clearance কমে যায় এবং central regulation alter হয়; CKD patient-এ moderate hyperprolactinaemia হতে পারে।
3. Cirrhosis / chronic liver disease
   • Hormonal metabolism altered হয়ে prolactin বাড়তে পারে।
4. Chest wall lesion
   • Herpes zoster, thoracic surgery, chest trauma nipple–neural reflex pathway stimulate করতে পারে।
5. PCOS
   • Mild elevation থাকতে পারে, কিন্তু PCOS ধরে নেওয়ার আগে pregnancy, thyroid, drug এবং pituitary cause exclude করা উচিত।

D. Drug-induced causes — খুব common

Endocrine Society guideline অনুযায়ী non-tumoral hyperprolactinaemia-এর সবচেয়ে common cause হলো medication, বিশেষ করে antipsychotic drugs। Typical antipsychotic-এ 40–90% এবং risperidone-এ 50–100% পর্যন্ত hyperprolactinaemia দেখা যেতে পারে।

Common drugs:

1. Antipsychotics: risperidone, paliperidone, haloperidol, chlorpromazine, amisulpride.
2. Antiemetics/prokinetics: metoclopramide, domperidone.
3. Antidepressants: SSRI/TCA rarely.
4. Antihypertensive: verapamil, methyldopa.
5. Opioids: morphine, tramadol-like opioid exposure.
6. Estrogen/OCP: usually mild elevation.

Cause gulo Bangla te Explaines:-

Hyperprolactinaemia-এর Cause গুলো — Point-wise Details

Core mechanism

Prolactin normally dopamine দ্বারা inhibit থাকে। তাই যেসব কারণে dopamine effect কমে যায়, pituitary lactotroph cell stimulate হয়, বা prolactin clearance কমে যায়—সেগুলোতে prolactin বেড়ে যায়।

---

1. Physiological causes — স্বাভাবিক কারণ

1) Pregnancy

Pregnancy-তে estrogen বেশি থাকে, ফলে pituitary lactotroph cell enlarge ও stimulate হয়। তাই pregnancy-তে prolactin অনেক বেড়ে যায়—এটা normal physiological change।

2) Lactation / Breastfeeding

Baby suckling করলে nipple stimulation থেকে neuroendocrine reflex হয়, dopamine inhibition কমে যায় এবং prolactin release বাড়ে। এতে milk production maintain হয়।

3) Sleep, stress, exercise, coitus

ঘুম, mental/physical stress, heavy exercise, sexual activity—এসব কারণে prolactin সাময়িকভাবে mild increase হতে পারে। তাই borderline prolactin elevation হলে repeat test করা ভালো।

---

2. Drug-induced causes — ওষুধজনিত কারণ

Medication হলো hyperprolactinaemia-এর সবচেয়ে common non-tumour cause। বিশেষ করে dopamine-blocking drug prolactin বাড়ায়, কারণ dopamine normally prolactin secretion বন্ধ রাখে।

1) Antipsychotic drugs

Risperidone, paliperidone, haloperidol, chlorpromazine, amisulpride prolactin বাড়াতে পারে। এগুলো dopamine D2 receptor block করে, ফলে prolactin inhibition কমে যায়।
Clinical example: schizophrenia patient risperidone খাওয়ার পর amenorrhoea/galactorrhoea বা male patient-এ low libido/ED হতে পারে।

2) Antiemetic / Prokinetic drugs

Metoclopramide, domperidone dopamine antagonist; nausea, vomiting, gastroparesis বা dyspepsia-তে বেশি ব্যবহার হলে prolactin বাড়তে পারে।

3) Antidepressants

কিছু SSRI ও TCA serotonergic pathway দিয়ে prolactin mild increase করতে পারে। সাধারণত marked elevation কম হয়, কিন্তু symptomatic হলে drug history জরুরি।

4) Antihypertensive drugs

Verapamil, methyldopa prolactin বাড়াতে পারে। Methyldopa central dopamine synthesis কমাতে পারে, আর verapamil dopaminergic regulation alter করতে পারে।

5) Opioids

Opioids hypothalamic dopamine tone কমিয়ে prolactin বাড়াতে পারে। Long-term opioid use-এ hypogonadism ও sexual dysfunction overlap করতে পারে।

6) Estrogen / OCP

Estrogen lactotroph stimulation করতে পারে। OCP সাধারণত mild prolactin rise করে; marked elevation হলে অন্য cause খুঁজতে হবে।

---

3. Pituitary causes — Pituitary gland-related কারণ

1) Prolactinoma

এটা prolactin-secreting pituitary adenoma। Pituitary Society consensus অনুযায়ী pathological hyperprolactinaemia-এর সবচেয়ে common cause হলো prolactinoma।

Microprolactinoma: size <10 mm
Macroprolactinoma: size ≥10 mm

Macroprolactinoma হলে prolactin অনেক বেশি হতে পারে এবং headache, visual field defect, hypopituitarism হতে পারে।

2) Pituitary stalk compression / stalk effect

Pituitary stalk দিয়ে hypothalamus থেকে dopamine pituitary-তে আসে। কোনো tumour stalk compress করলে dopamine পৌঁছাতে পারে না, ফলে prolactin বাড়ে।

Common stalk-effect lesions:

• Non-functioning pituitary macroadenoma
• Craniopharyngioma
• Meningioma
• Rathke cleft cyst
• Metastatic lesion
• Inflammatory/infiltrative lesion

3) Mixed pituitary adenoma

কিছু pituitary adenoma growth hormone ও prolactin একসাথে secrete করতে পারে। তাই acromegaly feature থাকলে IGF-1 check করা দরকার।

---

4. Endocrine causes — Hormonal কারণ

1) Primary hypothyroidism

Primary hypothyroidism-এ TRH বেড়ে যায়। TRH শুধু TSH নয়, prolactin secretion-ও stimulate করে। তাই untreated hypothyroidism-এ prolactin বাড়তে পারে।

Clinical clue: weight gain, cold intolerance, constipation, dry skin, menstrual irregularity + high TSH.

2) PCOS

PCOS-এ mild prolactin elevation দেখা যেতে পারে, কিন্তু PCOS diagnosis দেওয়ার আগে pregnancy, hypothyroidism, drug-induced cause এবং pituitary cause exclude করা উচিত।

3) Adrenal insufficiency

Adrenal insufficiency কিছু ক্ষেত্রে prolactin increase করতে পারে, তবে এটা common cause নয়। Suspicion থাকলে weakness, hypotension, hyperpigmentation, hyponatraemia দেখে evaluate করতে হয়।

---

5. Systemic disease causes — শরীরের অন্য রোগের কারণে

1) Chronic kidney disease / renal failure

Kidney prolactin clearance-এ ভূমিকা রাখে। CKD-তে prolactin clearance কমে এবং hypothalamic regulation alter হয়, তাই prolactin বেড়ে যায়।

2) Liver cirrhosis

Chronic liver disease/cirrhosis-এ hormone metabolism abnormal হয়, ফলে prolactin rise হতে পারে।

3) Seizure

Generalized seizure-এর পর transient prolactin elevation হতে পারে। তাই seizure-এর পরপর prolactin করলে falsely high পাওয়া যেতে পারে।

---

6. Neurogenic / Chest wall causes

1) Chest wall trauma or surgery

Chest wall injury, thoracic surgery বা burn nipple–neural reflex pathway stimulate করে prolactin বাড়াতে পারে।

2) Herpes zoster

Thoracic herpes zoster chest wall nerve irritation করে prolactin increase করতে পারে।

3) Nipple stimulation

Repeated nipple stimulation prolactin release বাড়াতে পারে, lactation reflex-এর মতো mechanism-এ।

---

7. Infiltrative / inflammatory causes

Pituitary বা hypothalamic region-এ inflammatory/infiltrative disease হলে stalk effect বা pituitary dysfunction হতে পারে।

Examples:

• Sarcoidosis
• Tuberculosis
• Langerhans cell histiocytosis
• Autoimmune hypophysitis
• Metastatic tumour

এসব ক্ষেত্রে headache, diabetes insipidus, visual symptoms বা multiple pituitary hormone deficiency থাকতে পারে।

---

8. Laboratory-related apparent causes

1) Macroprolactinaemia

Macroprolactin হলো বড় molecular form of prolactin, biologically less active। এতে lab report-এ prolactin high আসতে পারে কিন্তু patient asymptomatic থাকে। তাই symptoms না থাকলে macroprolactin test করা জরুরি।

2) Hook effect

Large pituitary tumour থাকলেও prolactin falsely low/mild high দেখাতে পারে। Macroadenoma + unexpectedly mild prolactin হলে diluted prolactin assay করতে হয়।

---

সহজ Clinical Shortcut

Hyperprolactinaemia cause মনে রাখার জন্য:

PIT-DRESS

• P = Pregnancy / physiological
• I = Infiltrative/inflammatory pituitary disease
• T = Tumour: prolactinoma, stalk effect
• D = Drugs: antipsychotic, metoclopramide, domperidone
• R = Renal failure
• E = Endocrine: hypothyroidism, PCOS
• S = Stress, sleep, seizure
• S = Stimulation of chest wall/nipple

---

Overview / Summary

Hyperprolactinaemia-এর প্রধান cause হলো pregnancy/lactation, drug-induced hyperprolactinaemia, prolactinoma, pituitary stalk compression, primary hypothyroidism, CKD, liver cirrhosis, PCOS, chest wall lesion এবং macroprolactinaemia। Clinically সবচেয়ে আগে exclude করতে হবে: pregnancy, drugs, hypothyroidism, renal failure—এরপর pituitary MRI consideration।

Actionable Plan / Steps

1. Female reproductive age হলে আগে β-hCG।
2. সব patient-এ drug history: antipsychotic, metoclopramide, domperidone, verapamil, opioid।
3. TSH/FT4, creatinine/eGFR, LFT করুন।
4. Mild elevation + no symptoms হলে macroprolactin test করুন।
5. Persistent unexplained high prolactin, headache/visual symptom বা hypogonadism থাকলে pituitary MRI with contrast করুন।

3. Symptoms / Clinical Features — Point-wise Details

Female symptoms

1. Menstrual disturbance
   • Oligomenorrhoea, amenorrhoea, irregular period.
   • Mechanism: prolactin ↑ → GnRH ↓ → LH/FSH ↓ → anovulation.
2. Infertility / subfertility
   • Ovulation না হওয়ায় pregnancy difficulty হয়।
3. Galactorrhoea
   • Pregnancy/lactation ছাড়া breast milk-like discharge। Endotext অনুযায়ী premenopausal women with prolactinoma-তে amenorrhoea ও galactorrhoea খুব common presentation।
4. Low libido, vaginal dryness, dyspareunia
   • Hypoestrogenism-এর কারণে।
5. Acne/hirsutism-like presentation
   • PCOS overlap থাকতে পারে; true cause evaluate করতে হবে।

Male symptoms

1. Low libido
2. Erectile dysfunction
3. Infertility / low sperm quality
4. Gynecomastia ± galactorrhoea — female-এর তুলনায় কম।
5. Reduced shaving frequency, fatigue, low muscle mass — hypogonadism sign.

Mass effect symptoms — especially macroadenoma

1. Headache
2. Bitemporal hemianopia / visual field defect — optic chiasm compression।
3. Diplopia / cranial nerve palsy — cavernous sinus involvement হলে।
4. Hypopituitarism — ACTH, TSH, gonadotropin deficiency হতে পারে।
5. Pituitary apoplexy — sudden severe headache, vomiting, visual loss; emergency.

Children/adolescents

1. Delayed puberty
2. Growth failure
3. Primary amenorrhoea in girls
4. Hypogonadism in boys
   Endotext notes paediatric patients may present with delayed/arrested puberty, growth failure and weight gain.

Symptoms Explaine in Bangla:-

Hyperprolactinaemia-এর Symptoms / Clinical Features — Bangla Point-wise Details

মূল কথা

Prolactin বেশি হলে GnRH কমে যায়, ফলে LH/FSH কমে এবং estrogen/testosterone কমে যায়। তাই প্রধান symptom হয় menstrual problem, infertility, sexual dysfunction, galactorrhoea। Pituitary tumour বড় হলে headache ও visual field defect হতে পারে।

---

A. Female Patient-এর Symptoms

1. Menstrual disturbance / মাসিকের সমস্যা

• Oligomenorrhoea: মাসিক দেরিতে হওয়া বা cycle লম্বা হওয়া।
• Amenorrhoea: মাসিক বন্ধ হয়ে যাওয়া।
• কারণ: prolactin বেশি হলে GnRH suppress হয় → ovulation কমে/বন্ধ হয়।
• Premenopausal women-এ prolactinoma থাকলে oligo/amenorrhoea খুব common presentation।

2. Infertility / বাচ্চা নিতে সমস্যা

• Ovulation না হলে pregnancy difficult হয়।
• Patient সাধারণত complain করে: “period irregular, conceive হচ্ছে না।”
• Hyperprolactinaemia young women-এর irregular menses ও infertility-এর important cause।

3. Galactorrhoea / বুক দিয়ে দুধ বা দুধের মতো fluid আসা

• Pregnancy বা breastfeeding ছাড়া nipple থেকে milk-like discharge বের হওয়া।
• এক পাশে বা দুই পাশে হতে পারে।
• সব patient-এর galactorrhoea থাকে না; আবার galactorrhoea থাকলেই সবসময় prolactin বেশি হবে এমনও নয়।
• Premenopausal prolactinoma patient-এ galactorrhoea common।

4. Low libido / যৌন ইচ্ছা কমে যাওয়া

• Estrogen কমে যাওয়ার কারণে sexual desire কমে যায়।
• অনেক patient সরাসরি না বললেও history নিলে পাওয়া যায়।

5. Vaginal dryness ও dyspareunia

• Estrogen deficiency হলে vagina dry হয়।
• ফলে intercourse painful হতে পারে।

6. Hypoestrogenism-এর symptoms

• Hot flush
• Mood change
• Sleep disturbance
• Bone pain বা long-term bone loss risk
• Long-standing estrogen deficiency হলে osteopenia/osteoporosis হতে পারে।

---

B. Male Patient-এর Symptoms

1. Low libido

• Male patient-এর সবচেয়ে common complaint হতে পারে sexual desire কমে যাওয়া।
• Prolactin বেশি হলে testosterone কমে যায়।

2. Erectile dysfunction

• Erection maintain করতে সমস্যা হয়।
• অনেক male patient ED নিয়ে আসে, পরে investigation-এ prolactin high ধরা পড়ে।

3. Infertility

• Testosterone ও gonadotropin কমে গেলে sperm production affected হতে পারে।
• Semen quality কমে যেতে পারে।

4. Gynecomastia

• Breast enlargement হতে পারে, যদিও সব male patient-এ হয় না।

5. Galactorrhoea

• Male-এ rare, কিন্তু হতে পারে।
• Male patient-এ nipple discharge থাকলে careful evaluation দরকার।

6. Hypogonadism-এর features

• Fatigue
• Muscle mass কমে যাওয়া
• Reduced shaving frequency
• Low mood
• Reduced morning erection
• Decreased body hair
  Hyperprolactinaemia testosterone deficiency করতে পারে, তাই male patient-এ sexual symptoms গুরুত্ব দিয়ে নিতে হয়।

---

C. Pituitary Tumour / Macroprolactinoma-এর Mass Effect Symptoms

যদি prolactinoma বড় হয় বা pituitary mass থাকে, তখন শুধু hormonal symptom না, pressure effect দেখা যায়।

1. Headache

• Persistent headache হতে পারে।
• Sudden severe headache হলে pituitary apoplexy suspect করতে হবে।

2. Visual field defect

• সবচেয়ে classic হলো bitemporal hemianopia।
• Patient বলতে পারে: “side vision কমে গেছে”, “চলতে গিয়ে পাশে ধাক্কা লাগে।”
• কারণ: pituitary mass optic chiasm compress করে। Hyperprolactinaemia/prolactinoma evaluation-এ headache ও visual field defect গুরুত্বপূর্ণ mass effect symptom।

3. Blurred vision / double vision

• Cavernous sinus involvement হলে cranial nerve palsy হতে পারে।
• Diplopia, ptosis, eye movement problem হতে পারে।

4. Hypopituitarism

Large tumour normal pituitary gland compress করলে অন্য hormone কমে যেতে পারে। যেমন:

• ACTH deficiency → weakness, hypotension
• TSH deficiency → hypothyroid-like symptoms
• LH/FSH deficiency → hypogonadism
• GH deficiency → fatigue, poor quality of life

5. Pituitary apoplexy — emergency symptom

Sudden tumour bleeding/infarction হলে:

• Sudden severe headache
• Vomiting
• Visual loss
• Ophthalmoplegia
• Altered consciousness
  এটা emergency; urgent endocrine/neurosurgical assessment দরকার।

---

D. Children / Adolescent-এর Symptoms

1. Delayed puberty

• Puberty expected age-এর পরও শুরু না হওয়া।
• Boys-এ testicular enlargement না হওয়া, girls-এ breast development না হওয়া।

2. Primary amenorrhoea

• Girl adolescent-এর বয়স হওয়ার পরও period শুরু না হওয়া।

3. Growth problem

• Pituitary lesion থাকলে growth disturbance হতে পারে।

4. Headache/visual symptoms

• Macroadenoma থাকলে child/adolescent-এ headache ও visual complaint হতে পারে।

---

E. Asymptomatic Hyperprolactinaemia

সব patient-এর symptom থাকবে না।
বিশেষ করে macroprolactinaemia থাকলে prolactin report high আসতে পারে কিন্তু patient asymptomatic থাকতে পারে। তাই symptom না থাকলে macroprolactin test দরকার হতে পারে।

---

F. Red Flag Symptoms — জরুরি Referral দরকার

নিচের symptom থাকলে দ্রুত endocrinologist/neurosurgeon referral দরকার:

1. Sudden severe headache
2. Visual field defect
3. Double vision / ptosis
4. Vomiting with headache
5. Altered consciousness
6. Macroadenoma suspected
7. Male patient with very high prolactin + ED/infertility
8. Amenorrhoea + galactorrhoea + headache

---

Clinical Shortcut

Hyperprolactinaemia symptoms মনে রাখার সহজ উপায়:

“MIG-VH”

• M = Menstrual problem
• I = Infertility
• G = Galactorrhoea
• V = Visual problem
• H = Headache / Hypogonadism

---

Overview / Summary

Hyperprolactinaemia-এর প্রধান symptoms হলো female-এ irregular period, amenorrhoea, infertility, galactorrhoea, low libido, vaginal dryness; male-এ low libido, erectile dysfunction, infertility, gynecomastia, hypogonadism। Macroprolactinoma হলে headache, bitemporal hemianopia, blurred vision, diplopia, hypopituitarism হতে পারে।

Actionable Plan / Steps

1. Female patient হলে menstrual history, pregnancy status ও galactorrhoea জিজ্ঞেস করুন।
2. Male patient হলে libido, ED, infertility ও testosterone deficiency symptoms assess করুন।
3. Headache/visual symptom থাকলে urgent pituitary MRI + visual field test consider করুন।
4. Asymptomatic mild elevation হলে macroprolactin check করুন।
5. Symptom + high prolactin থাকলে cause-based evaluation করুন: pregnancy, drugs, TSH, renal function, pituitary MRI।

4. Clinical Diagnosis & Specific Investigations

A. History — must ask

1. Pregnancy/lactation status
2. Menstrual history / fertility history
3. Galactorrhoea, headache, visual symptoms
4. Sexual dysfunction, libido, ED
5. Current drugs: antipsychotic, metoclopramide, domperidone, antidepressant, verapamil, OCP, opioids
6. Hypothyroid symptoms: weight gain, cold intolerance, constipation
7. CKD/liver disease history

B. Clinical examination

1. Vitals, BMI
2. Thyroid exam
3. Breast exam only if clinically needed
4. Visual field confrontation test
5. Signs of hypogonadism
6. Signs of acromegaly/Cushing if suspected

C. Laboratory investigations — specific

1. Serum prolactin
   • Avoid excessive stress during sampling.
   • Borderline/mild elevation হলে repeat sample করা যায়।
   • Dynamic prolactin testing routinely দরকার নেই।
2. Urine/serum β-hCG
   • Female reproductive age হলে pregnancy exclude করা mandatory.
3. TSH + Free T4
   • Primary hypothyroidism exclude/confirm.
4. Serum creatinine/eGFR, LFT
   • CKD/cirrhosis-related cause দেখতে।
5. Macroprolactin test / PEG precipitation
   • Symptoms না থাকলেও prolactin high হলে macroprolactin check করা উচিত; macroprolactin less bioactive এবং unnecessary MRI/treatment এড়াতে সাহায্য করে।
6. Pituitary MRI with contrast
   Indications:
   • Persistent unexplained hyperprolactinaemia
   • Prolactin markedly high
   • Headache/visual symptom
   • Hypopituitarism
   • Drug-induced সন্দেহ হলেও drug stop করা না গেলে বা timing mismatch হলে MRI করা উচিত। Endocrine Society recommends MRI to differentiate medication-induced hyperprolactinaemia from pituitary/hypothalamic mass when drug cannot be stopped and onset does not match medication start.
7. Visual field testing
   • Macroadenoma optic chiasm-এর কাছে হলে formal perimetry.
8. Pituitary hormone profile
   • 8 AM cortisol ± ACTH
   • TSH/FT4
   • LH/FSH + estradiol/testosterone
   • IGF-1 if acromegaly suspected.
9. Bone mineral density / DEXA
   • Long-standing amenorrhoea/hypogonadism, fragility fracture risk, prolonged disease.

---

5. Differential Diagnosis

1. Pregnancy/lactation
2. Primary hypothyroidism
3. Drug-induced hyperprolactinaemia
4. Prolactinoma
5. Non-functioning pituitary adenoma with stalk effect
6. CKD/cirrhosis
7. PCOS with mild prolactin elevation
8. Macroprolactinaemia
9. Acromegaly with mixed GH–PRL adenoma
10. Chest wall trauma/herpes zoster

---

6. Complications — Bangla Explanation

1. Infertility
   Prolactin বেশি হলে GnRH suppress হয়, ফলে ovulation/spermatogenesis কমে যায়।
2. Hypogonadism
   Female-এ estrogen কমে, male-এ testosterone কমে; sexual dysfunction, fatigue, mood change হয়।
3. Osteopenia/osteoporosis
   Long-standing low estrogen/testosterone bone loss করে। Endocrine Society notes hyperprolactinaemia-mediated sex steroid attenuation-এর কারণে bone loss হয়।
4. Visual impairment
   Macroadenoma optic chiasm compress করলে bitemporal hemianopia হতে পারে।
5. Hypopituitarism
   Large adenoma normal pituitary tissue compress করে cortisol/thyroid/gonadal axis কমাতে পারে।
6. Pregnancy-related tumour growth
   Macroprolactinoma pregnancy-তে enlarge হতে পারে; Endotext notes symptomatic growth during pregnancy may occur in about 20–25% of macroprolactinomas.
7. Pituitary apoplexy
   Sudden haemorrhage/infarction → severe headache + visual loss; emergency neurosurgical/endocrine care দরকার।

---

7. Management / Treatment — Guideline-based

A. General principles

1. Asymptomatic mild elevation
   • Repeat prolactin, macroprolactin, cause review।
   • সব asymptomatic microprolactinoma-তে dopamine agonist দরকার নেই; Endocrine Society suggests not treating asymptomatic microprolactinoma routinely.
2. Treat when
   • Amenorrhoea/infertility/galactorrhoea distressing
   • Male hypogonadism/ED/infertility
   • Macroadenoma
   • Visual field defect/headache due to tumour
   • Progressive tumour
   • Low bone density due to hypogonadism
3. Treatment goals
   • Prolactin normalize
   • Gonadal function/fertility restore
   • Galactorrhoea stop
   • Tumour shrink
   • Vision protect

Dopamine agonists are first-line for most prolactinomas; cabergoline is generally more effective and better tolerated than bromocriptine.

---

B. Cause-specific treatment

1. Physiological hyperprolactinaemia

• Pregnancy/lactation হলে usually no treatment.
• Unnecessary dopamine agonist avoid.

2. Drug-induced hyperprolactinaemia

• Symptomatic হলে suspected drug 3 days stop/substitute করে prolactin recheck করা যায়, কিন্তু antipsychotic কখনো psychiatrist/primary physician ছাড়া বন্ধ করা যাবে না।
• Options: dose reduction, switch to prolactin-sparing antipsychotic, or add low-dose aripiprazole. Meta-analysis showed adjunctive aripiprazole had 79.11% prolactin normalization and 5 mg/day may be appropriate.

3. Hypothyroidism-induced hyperprolactinaemia

• Levothyroxine দিয়ে hypothyroidism correct করলে prolactin normalize হতে পারে।

4. Prolactinoma

• First-line: Cabergoline
• Alternative: Bromocriptine, especially pregnancy planning/long safety experience বা cabergoline intolerance.
• Surgery: dopamine agonist resistance/intolerance, visual acuity threatened by rapid progression/apoplexy, CSF leak, cystic/complex lesion.
• Radiotherapy: rare aggressive/resistant cases.

---

8. Pharmacological Drugs — Generic, Class, Dose, Side effect, Interaction, Bangladesh Brand

1) Generic name: Cabergoline.

Therapeutic category: Hyperprolactinaemia / prolactinoma treatment
Pharmacological class: Dopamine D2 receptor agonist; ergot derivative
Why used: Pituitary lactotroph D2 receptor stimulate করে prolactin secretion কমায়, tumour shrink করে, menses/fertility restore করে। MedEx notes cabergoline reduces prolactin released from pituitary and is used for hyperprolactinaemia.

Adult dose:

• Start: 0.25 mg twice weekly
• Titrate: every ≥4 weeks, serum prolactin অনুযায়ী increase
• Usual: 0.5–1 mg/week divided once/twice weekly
• Resistant case: specialist supervisionে higher dose; long-term high dose হলে echocardiography consider
• MedEx dosing: 0.25 mg twice weekly initially; dose increase every 4 weeks; hyperprolactinaemia dose may be increased up to response/max.

Duration:

• Usually long-term, at least 2 years after prolactin normalization and tumour shrinkage; then specialist may taper/withdraw. Endocrine Society notes withdrawal may be considered after 2 years if normoprolactinaemia and significant tumour reduction achieved, with close follow-up.

Common side effects:

• Nausea, vomiting
• Dizziness, postural hypotension
• Headache
• Fatigue
• Constipation
• Rare: impulse control disorder, mood/psychosis worsening, valvular heart disease with high cumulative dose, CSF leak after rapid shrinkage of invasive macroadenoma.

Important interactions:

• Antipsychotics like haloperidol/chlorpromazine may oppose dopamine agonist effect and psychiatric symptoms worsen করতে পারে।
• Metoclopramide/domperidone dopamine antagonist; effect reduce করতে পারে।
• Antihypertensives → hypotension risk বাড়ে।
• Macrolides/azole antifungals caution due to ergot-related toxicity risk. MedEx interaction list includes antihypertensives, antipsychotics and antiemetics such as domperidone/metoclopramide.

Contraindication/caution:

• Uncontrolled hypertension, severe liver disease, history of psychosis, fibrotic valvular disease, ergot hypersensitivity, pregnancy/lactation context specialist decision.

Bangladesh available brand names with strength:
MedEx lists cabergoline brands in Bangladesh with strengths 0.5 mg and 1 mg. Available examples include:

• Argolin 0.5 mg — Opsonin
• Caber 0.5 mg — ACI
• Cabergol 0.5 mg — Popular
• Caberol 0.5 mg — Square
• Cabolac 0.5 mg — Incepta
• Cabolin 0.5 mg / 1 mg — Renata
• Ferticab 0.5 mg — Nuvista

---

2) Generic name: Bromocriptine Mesylate

Therapeutic category: Hyperprolactinaemia / prolactinoma / infertility due to hyperprolactinaemia
Pharmacological class: Dopamine D2 receptor agonist; ergot derivative
Why used: Prolactin secretion inhibit করে; cabergoline unavailable/intolerant হলে useful। Pregnancy planning-এ long safety experience আছে, তবে specialist decision দরকার।

Adult dose:

• Start: 1.25 mg at bedtime with food বা 1.25–2.5 mg once daily
• Titrate: 2.5 mg every 2–7 days as tolerated
• Usual: 2.5–15 mg/day in divided dose
• Take with food to reduce nausea. MedEx states initial hyperprolactinaemia dose 0.5–2.5 mg daily and titration every 2–7 days until response.

Duration:

• Long-term until prolactin normal, symptoms controlled, tumour stable/shrunk; periodic prolactin and MRI follow-up.

Common side effects:

• Nausea/vomiting
• Dizziness, postural hypotension
• Headache
• Nasal congestion
• Constipation
• Sleepiness
• Rare: hallucination/psychosis, impulse control, fibrosis.

Important interactions:

• Antipsychotics/metoclopramide/domperidone reduce effect.
• Antihypertensives increase hypotension risk.
• Macrolides/azole antifungals may increase ergot adverse effects.
• Alcohol worsens dizziness/hypotension.

Bangladesh available brand names with strength:
MedEx lists bromocriptine mesylate 2.5 mg brands in Bangladesh:

• Bromergon 2.5 mg — Sandoz/Novartis
• Bromocriptine 2.5 mg — City Overseas
• Bromodel 2.5 mg — Opsonin
• Bromolac 2.5 mg — Square
• Bromotine 2.5 mg — Nuvista
• Criptine 2.5 mg — Renata

---

3) Generic name: Levothyroxine Sodium

Therapeutic category: Thyroid hormone replacement
Pharmacological class: Synthetic T4 hormone
Why used: Primary hypothyroidism-induced hyperprolactinaemia হলে TRH drive কমিয়ে prolactin normalize করতে সাহায্য করে।

Adult dose:

• Young healthy adult: often 25–50 mcg once daily, then titrate
• Elderly/cardiac disease: 12.5–25 mcg once daily start
• Adjust every 6–8 weeks by TSH/FT4
  MedEx states starting dose 25–50 mcg/day with 12.5–25 mcg increments every 6–8 weeks; severe hypothyroidism starts 12.5–25 mcg/day.

Duration:

• Hypothyroidism chronic হলে usually lifelong; transient thyroiditis হলে reassess.

Side effects: usually overdose-related

• Palpitation, tremor, insomnia
• Weight loss
• Heat intolerance
• AF risk in elderly
• Bone loss if over-replaced

Important interactions:

• Iron/calcium/antacid/PPIs absorption কমায়—separate by 4 hours.
• Warfarin effect increase করতে পারে.
• Carbamazepine/phenytoin metabolism alter করতে পারে.

Bangladesh available brand names with strength:
MedEx lists multiple levothyroxine brands and strengths in Bangladesh, including 25, 50, 75 and 100 mcg preparations.

• Euthycin 50 mcg — Incepta
• Euthyrox 25/50/100 mcg — Janata Traders/Merck
• Synthox 25/50/75/100 mcg — Healthcare
• T4 25/50 mcg — Popular
• Thyrin 25/50/75/100 mcg — Square
• Thyrox 25/50/75/100 mcg — Renata
• Thyronor 12.5/25/50/75/100 mcg — Nuvista
• Thyrotab 50 mcg — Ibn Sina
• Tyroid 50 mcg — ACI

---

4) Generic name: Aripiprazole

Only for antipsychotic-induced hyperprolactinaemia under psychiatrist supervision

Therapeutic category: Antipsychotic; prolactin-sparing adjunct option
Pharmacological class: Atypical antipsychotic; dopamine D2 partial agonist
Why used: Risperidone/haloperidol/paliperidone-induced prolactin elevation কমাতে low-dose aripiprazole add করা যায়; meta-analysis suggests 5 mg/day effective.

Dose:

• Common adjunct dose: 2.5–5 mg once daily, then 5–10 mg/day if needed
• Psychiatric indication dose আলাদা; psychiatrist-directed.

Duration:

• Recheck prolactin after 4–8 weeks; psychiatric stability monitor.

Side effects:

• Akathisia/restlessness
• Insomnia
• Nausea
• Headache
• Somnolence
• Tremor/EPS
• Rare: impulse control disorder, metabolic effects

Interactions:

• Carbamazepine lowers level.
• Fluoxetine/paroxetine/quinidine/ketoconazole increase level.
• Alcohol/CNS depressants increase sedation. MedEx lists these interactions for aripiprazole.

Bangladesh available brand names with strength:
MedEx lists aripiprazole brands in Bangladesh with 2 mg, 5 mg, 10 mg, 15 mg and oral solution 5 mg/5 ml strengths.

• Aripen 10/15 mg — Opsonin
• Aripra 10/15 mg; oral solution 5 mg/5 ml — Incepta
• Ariprazole 5/10 mg — General Pharma
• Ariprex 2/10 mg; oral solution 5 mg/5 ml — Square
• Siznil 10 mg — Orion
• Sizopra 10/15 mg — ACME

---

9. Follow-up Monitoring

1. Prolactin: dopamine agonist শুরু করার 1 month পর, তারপর dose adjustment অনুযায়ী।
2. MRI: macroprolactinoma হলে 3–6 months; microadenoma হলে 1 year বা prolactin/symptom অনুযায়ী। Endocrine Society follow-up includes prolactin measurement starting 1 month after therapy and repeat MRI, especially macroprolactinoma or new symptoms.
3. Visual field: optic chiasm compression থাকলে repeat perimetry।
4. Pituitary hormones: macroadenoma/hypopituitarism suspicion থাকলে।
5. Bone health: long hypogonadism থাকলে calcium/vitamin D status, DEXA, sex hormone restoration।
6. Cabergoline high dose/long duration: cardiac murmur/symptom হলে echocardiography; very high dose prolonged হলে echo consider.

---

10. Prevention / কীভাবে প্রতিরোধ করবেন

1. Unnecessary dopamine-blocking drugs avoid
   • Metoclopramide/domperidone long-term use avoid; antipsychotic হলে prolactin-sparing option consider.
2. Drug history review
   • Amenorrhoea, infertility, galactorrhoea, ED হলে current medicine list review করতে হবে।
3. Hypothyroidism early treat
   • TSH abnormal হলে timely levothyroxine treatment।
4. CKD/liver disease control
   • Underlying systemic disease manage করলে prolactin-related complications কমে।
5. Macroadenoma warning sign educate
   • Severe headache, visual field loss, diplopia হলে urgent referral।
6. Bone protection
   • Long amenorrhoea/hypogonadism হলে vitamin D, calcium intake, weight-bearing exercise, smoking avoidance, DEXA.
7. Pregnancy planning
   • Prolactinoma patient pregnancy চাইলে endocrinologist + gynaecologist follow-up; macroadenoma হলে pre-pregnancy MRI/visual assessment দরকার।

---

Overview / Summary

Hyperprolactinaemia হলো serum prolactin elevation, যার common cause হলো pregnancy/lactation, drug-induced cause, primary hypothyroidism, CKD এবং prolactinoma। Symptoms mainly reproductive: female-এ amenorrhoea, infertility, galactorrhoea; male-এ low libido, ED, infertility; macroadenoma হলে headache/visual field defect। Diagnosis serum prolactin দিয়ে শুরু, এরপর pregnancy test, TSH/FT4, renal/liver function, macroprolactin এবং indicated হলে pituitary MRI। Treatment cause-based; prolactinoma হলে cabergoline first-line, bromocriptine alternative।

Actionable Plan / Steps

1. First test: serum prolactin repeat/confirm + β-hCG + TSH/FT4 + creatinine/eGFR + LFT.
2. Medication review: antipsychotic, metoclopramide, domperidone, verapamil, OCP, opioid.
3. If asymptomatic mild elevation: macroprolactin test.
4. If persistent/unexplained or neuro symptom: pituitary MRI with contrast.
5. If prolactinoma symptomatic: cabergoline 0.25 mg twice weekly start, titrate by prolactin.
6. If hypothyroid: levothyroxine and TSH-guided titration.
7. If antipsychotic-induced: psychiatrist consult; switch/reduce/add aripiprazole.
8. Follow-up: prolactin after 1 month, MRI/visual field according to tumour size.

Reference List

1. Guideline: Melmed S, Casanueva FF, Hoffman AR, et al. Diagnosis and Treatment of Hyperprolactinemia: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2011;96(2):273–288. DOI: 10.1210/jc.2010-1692.
2. Consensus guideline: Petersenn S, Fleseriu M, Casanueva FF, et al. Diagnosis and management of prolactin-secreting pituitary adenomas: a Pituitary Society international Consensus Statement. Nat Rev Endocrinol. 2023;19:722–740. DOI: 10.1038/s41574-023-00886-5.
3. Endotext/NIH: Drummond JB, Molitch ME. Prolactinoma Management. Endotext, NCBI Bookshelf, updated 2025.
4. Journal/meta-analysis: Li X, Tang Y, Wang C. Adjunctive Aripiprazole Versus Placebo for Antipsychotic-Induced Hyperprolactinemia. PLoS ONE. 2013;8(8):e70179. DOI: 10.1371/journal.pone.0070179.
5. Textbook: Harrison’s Principles of Internal Medicine, 21st ed. Section: Endocrinology; Chapter: Pituitary Disorders.
6. Textbook: Davidson’s Principles and Practice of Medicine, 24th ed. Chapter: Endocrine disease.
7. Textbook: Robbins & Cotran Pathologic Basis of Disease, 10th ed. Chapter: Endocrine system—pituitary adenomas.
8. Textbook: Guyton and Hall Textbook of Medical Physiology, 14th ed. Chapter: Pituitary hormones and hypothalamic control.

Md.Rafiqul Islam Lipu Date:-27-05-2026 Wednesday Time:-06-06-29 Pm