Write a short note on prolactinoma and acromegaly.

General Principles

Pituitary adenomas are classified by size — microadenoma (< 10 mm) and macroadenoma (≥ 10 mm) — and by function. They produce disease in three ways: hormone excess, mass effect (headache, bitemporal hemianopia from optic chiasm compression, cranial nerve III, IV and VI palsies from cavernous sinus involvement), and hypopituitarism from compression of normal gland.

Prolactinoma

The commonest functioning pituitary tumour. Prolactin is unique among pituitary hormones in being under tonic inhibition by dopamine from the hypothalamus — a fact that explains both the causes and the treatment.

Clinical features:

• Women (usually microadenomas, presenting early): oligomenorrhoea or amenorrhoea, galactorrhoea, infertility, reduced libido, and long-term osteoporosis from oestrogen deficiency.
• Men (usually macroadenomas, presenting late): erectile dysfunction, reduced libido, infertility, gynaecomastia, and features of mass effect — headache and visual field loss. Galactorrhoea is uncommon in men.

Causes of hyperprolactinaemia — must be excluded before diagnosing a prolactinoma:

• Physiological: pregnancy, lactation, nipple stimulation, stress, sleep, exercise
• Drugs (a very common cause): antipsychotics (risperidone, haloperidol), metoclopramide, domperidone, methyldopa, verapamil, oestrogens, opioids, SSRIs
• Pituitary stalk compression by any sellar mass — the "stalk effect", interrupting dopamine delivery and causing modest hyperprolactinaemia
• Primary hypothyroidism — raised TRH stimulates prolactin
• Chronic kidney disease, cirrhosis, chest wall lesions, PCOS

Investigations:

• serum prolactin (repeated; markedly raised levels correlate with tumour size — very high levels indicate a macroprolactinoma, modest elevation suggests drug effect or stalk compression)
• MRI pituitary with contrast
• visual field testing (formal perimetry)
• assessment of the other pituitary axes
• thyroid and renal function
• pregnancy test. Check for macroprolactin (a biologically inactive complex) where the level is raised without symptoms, and be aware of the "hook effect" — very high prolactin can produce a falsely low assay result, corrected by diluting the sample.

Management:

• Dopamine agonists are first-line — cabergoline (preferred, better tolerated and more effective) or bromocriptine. They shrink the tumour and normalise prolactin in the majority, including large macroadenomas, so medical therapy precedes surgery even for large tumours with visual compromise — a key point distinguishing prolactinoma from other pituitary tumours.
• Adverse effects: nausea, postural hypotension, and, at high doses, impulse control disorders and (with older ergot agents) cardiac valvulopathy.
• Trans-sphenoidal surgery for dopamine agonist intolerance or resistance, or apoplexy; radiotherapy rarely.
• Pregnancy: dopamine agonists are usually stopped once pregnancy is confirmed in microadenomas, with monitoring for symptoms of tumour expansion.

Acromegaly

Definition: the clinical syndrome caused by excess growth hormone in adults, almost always from a pituitary somatotroph adenoma (rarely ectopic GHRH). In children, before epiphyseal fusion, the same excess causes gigantism. Most effects are mediated by IGF-1 produced in the liver.

Clinical features — insidious, developing over years, so old photographs are diagnostically valuable:

• Acral enlargement: increasing hand and foot size (changing ring and shoe size — a classic history), spade-like hands.
• Facial coarsening: prognathism with dental malocclusion and increased interdental spacing, frontal bossing, enlarged nose and lips, macroglossia.
• Skin and soft tissue: thickened oily skin, excessive sweating, skin tags, carpal tunnel syndrome (from soft tissue swelling), deep voice from laryngeal thickening.
• Systemic: hypertension, cardiomyopathy with heart failure, impaired glucose tolerance and diabetes, obstructive sleep apnoea, arthropathy and back pain, goitre, hypercalciuria and renal stones.
• Increased risk of colonic polyps and colorectal carcinoma — colonoscopic surveillance is recommended.
• Mass effect and hypopituitarism from the adenoma; hyperprolactinaemia from co-secretion or stalk effect.

Investigations:

• Serum IGF-1 — the best screening test, since it reflects integrated GH secretion and is not subject to pulsatility.
• Oral glucose tolerance test with GH measurement — the confirmatory test: failure of GH to suppress after a glucose load. (Random GH is useless because secretion is pulsatile.)
• MRI pituitary; formal visual field testing; assessment of all pituitary axes.
• Assess complications: blood pressure, fasting glucose and HbA1c, ECG and echocardiography, sleep study, colonoscopy, and dental and rheumatological assessment.

Management:

• Trans-sphenoidal surgery — first-line and potentially curative, particularly for microadenomas.
• Medical therapy for persistent disease after surgery, or where surgery is unsuitable: somatostatin analogues (octreotide, lanreotide) — first-line medical treatment, also causing tumour shrinkage; pegvisomant (GH receptor antagonist) for resistant disease; cabergoline as an adjunct, especially with co-secreted prolactin.
• Radiotherapy for residual disease not controlled by surgery and drugs; effect is slow and hypopituitarism is common in the long term.
• Treat comorbidities — diabetes, hypertension, sleep apnoea, arthropathy — and continue lifelong biochemical surveillance, since recurrence occurs years later. Mortality is increased, largely cardiovascular, and normalises with biochemical control.