Endocrinology: Pituitary Disease (Complete)

• Basics: What Is Pituitary Disease? | Anatomy and Neighbours | Hormones and Axes | How Pituitary Disease Presents | Pituitary Function Tests | Visual Fields and Imaging
• Pituitary tumours: Pituitary Adenomas: Overview | Non-functioning Adenoma | Prolactinoma | Other Causes of Hyperprolactinaemia | Acromegaly | Cushing's Disease | TSH-secreting Adenoma | Pituitary Incidentaloma
• Other sellar masses: Craniopharyngioma | Rathke's Cleft Cyst | Other Sellar Lesions
• Hypopituitarism: Hypopituitarism: Causes | Hypopituitarism: Clinical Features | Hormone Replacement | Sheehan's Syndrome | Hypophysitis | Empty Sella
• Emergency: Pituitary Apoplexy
• Posterior pituitary: Diabetes Insipidus (AVP Deficiency) | Diagnosing Polyuria | Diabetes Insipidus: Treatment | Nephrogenic DI (AVP Resistance) | SIADH
• Treatment: Transsphenoidal Surgery | Post-operative Care | Radiotherapy
• Special situations: Pregnancy | Genetic Syndromes | Head Injury and Older Adults | Driving
• Revision: Drug Reference Table | Spot the Diagnosis | Exam-style Scenarios | Key Points | Guidelines and Further Reading

🧠 The pituitary is a pea-sized gland under the brain that controls most of the other endocrine glands. Pituitary disease causes problems in three ways: too much of a hormone (e.g. prolactin, growth hormone, ACTH), too little (hypopituitarism), or pressure on nearby structures - above all the optic chiasm.
Your four questions for every patient: Is a hormone in excess? Which hormones are deficient - especially cortisol? Is there pressure on the optic chiasm or other structures? Is this an emergency (apoplexy, adrenal crisis, untreated diabetes insipidus)?

What Is Pituitary Disease?

Most pituitary disease is caused by benign adenomas. These are common - small ones are found in about 1 in 10 people on MRI scans - but only a minority cause problems. Pituitary disease can be grouped as:

• Hormone excess:
  • Prolactinoma - the commonest.
  • Acromegaly (growth hormone).
  • Cushing's disease (ACTH).
  • Rarely, a TSH-secreting adenoma.
• Hormone deficiency (hypopituitarism): From tumours, surgery, radiotherapy, infarction, inflammation or injury.
• Mass effects: Visual loss, headache and cranial nerve palsies.
• Posterior pituitary disorders: Diabetes insipidus (lack of vasopressin) and abnormal vasopressin secretion.

💡 Clinical Pearl: In every patient with a pituitary problem, ask: "Could this person be cortisol-deficient?" Missed ACTH deficiency is the commonest avoidable cause of death in pituitary disease.

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Anatomy and Neighbours

The pituitary sits in a bony cup at the base of the skull - the sella turcica - connected to the hypothalamus above by the pituitary stalk.

• Anterior pituitary (adenohypophysis): True glandular tissue. It is controlled by hypothalamic hormones carried down the stalk in a portal blood system.
• Posterior pituitary (neurohypophysis): An extension of the brain. Hypothalamic neurons make vasopressin (ADH) and oxytocin, which travel down the stalk and are released here.

Important neighbours - these explain the mass effects:

• Optic chiasm (directly above): A tumour growing upwards compresses the crossing fibres from both nasal retinas, causing bitemporal hemianopia.
• Cavernous sinuses (on each side): Contain cranial nerves III, IV, V1, V2 and VI and the internal carotid artery. Lateral spread or apoplexy causes double vision, ptosis and facial numbness. A third nerve palsy is the commonest.
• Hypothalamus (above): Damage causes disordered appetite, temperature, sleep and thirst.
• Sphenoid sinus (below): The surgical route for transsphenoidal surgery.

💡 MRCP Pearl: A pituitary tumour compresses the chiasm from below, so field loss starts in the upper temporal quadrants. A craniopharyngioma compresses from above, so it starts in the lower temporal quadrants.

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Hormones and Axes

💡 Key concept: Prolactin is the only anterior hormone mainly under inhibitory control (dopamine). Anything that compresses the stalk and blocks dopamine - even a non-secreting tumour - raises prolactin (the "stalk effect"), while the other hormones fall.

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How Pituitary Disease Presents

• Hormone excess:
  • Galactorrhoea and amenorrhoea (prolactin).
  • Enlarging hands and feet (growth hormone).
  • Cushingoid features (ACTH).
• Hormone deficiency:
  • Fatigue, low libido, amenorrhoea, erectile dysfunction.
  • Cold intolerance.
  • Hyponatraemia.
  • Hypotension.
  • Adrenal crisis during illness.
• Mass effect:
  • Headache.
  • Bitemporal visual field loss - often unnoticed by the patient (bumping into things, car accidents).
  • Double vision, cranial nerve palsies.
  • Rarely CSF rhinorrhoea or hydrocephalus.
• Acute presentation: Pituitary apoplexy - sudden headache, visual loss and collapse.
• Incidental finding: A pituitary lump seen on a brain scan done for another reason.
• Posterior pituitary: Polyuria and thirst (diabetes insipidus).

Order of hormone loss: As a tumour enlarges, hormones are usually lost in a predictable order:

• 1. Growth hormone.
• 2. LH and FSH.
• 3. TSH.
• 4. ACTH.

Memory aid: "Go Look For The Adenoma". Prolactin is usually raised rather than lost. Diabetes insipidus is rare with pituitary adenomas - if present, think of craniopharyngioma, metastasis, hypophysitis or an infiltrative disease.

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Pituitary Function Tests

Basal tests (ideally at 9 am):

• Cortisol axis: Cortisol and ACTH.
• Thyroid axis: TSH and free T4. In pituitary disease, TSH may be low or "normal" despite a low FT4.
• Gonadal axis: LH, FSH and oestradiol (women) or 9 am testosterone (men). Low sex hormones with low or normal gonadotrophins means pituitary failure. In post-menopausal women, "normal" gonadotrophins are abnormally low.
• Prolactin: If raised, screen for macroprolactin (a large, inactive form).
• Growth hormone axis: IGF-1 - reflects GH activity over time.
• Water balance: Sodium, plasma and urine osmolality.

Dynamic tests:

• Short Synacthen test: Assesses the ACTH–cortisol axis. It may be falsely normal in the first 4–6 weeks after a pituitary insult (surgery, apoplexy), because the adrenals have not yet shrunk.
• Insulin tolerance test (gold standard for ACTH and GH reserve): Insulin-induced hypoglycaemia should provoke cortisol and GH release. It is contraindicated in ischaemic heart disease, epilepsy and in older people. Specialist units only.
• Glucagon stimulation test (and others): A safer alternative for GH and cortisol reserve.
• Oral glucose tolerance test with GH: Diagnoses acromegaly - glucose normally suppresses GH; in acromegaly it does not.
• Water deprivation test or copeptin tests: For diabetes insipidus.

💡 Clinical Pearl: A "normal" TSH does not exclude hypothyroidism in pituitary disease. Always check the free T4.

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Visual Fields and Imaging

• Bedside visual fields: Confrontation with a red pin is a useful screen but insensitive.
• Formal perimetry (e.g. Humphrey fields): Needed for any tumour close to or touching the chiasm, at diagnosis and during follow-up.
• Visual acuity, colour vision (Ishihara plates), eye movements and fundoscopy (optic atrophy in long-standing compression).
• MRI pituitary with gadolinium contrast: The imaging test of choice. It shows tumour size, extension upwards (chiasm), sideways (cavernous sinus) and downwards (sphenoid sinus).
• CT: Used in emergencies, to show calcification (craniopharyngioma) and for surgical planning. It can miss small lesions and apoplexy.
• Ophthalmology: Joint follow-up for chiasmal compression; optical coherence tomography helps predict visual recovery.

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Pituitary Adenomas: Overview

Pituitary adenomas - now also called pituitary neuroendocrine tumours (PitNETs) - are benign tumours of anterior pituitary cells. They are classified by:

• Size:
  • Microadenoma: Under 1 cm. Rarely causes mass effects.
  • Macroadenoma: 1 cm or more. Can compress the chiasm and cause hypopituitarism.
  • Giant adenoma: Over 4 cm.
• Function:
  • Non-functioning (about 30–40%; mostly gonadotroph cells that make little active hormone).
  • Prolactinoma (about 40%).
  • Somatotroph - GH (about 10–15%).
  • Corticotroph - ACTH (about 5–10%).
  • Thyrotroph - TSH (under 1%).
• Behaviour: Most grow slowly. A minority invade the cavernous sinus or bone ("aggressive" adenomas). True pituitary carcinoma with distant spread is very rare.

Assessment of every adenoma:

• Hormone excess screen (prolactin, IGF-1, and tests for Cushing's if clinically suspected).
• Full pituitary function.
• Visual fields if near the chiasm.
• MRI.
• Review by a pituitary multidisciplinary team.

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Non-functioning Adenoma

Mechanism: A tumour that secretes no clinically active hormone. With no hormonal symptoms to draw attention, it grows silently until it causes mass effects. It is the commonest pituitary macroadenoma, typically found in people in their 50s–60s.

Clinical pattern:

• Visual field loss (bitemporal), often noticed late.
• Headache.
• Hypopituitarism: Fatigue, low libido, erectile dysfunction, amenorrhoea, hyponatraemia.
• Often found incidentally on scans.

Investigations:

• Full pituitary function.
• Prolactin is often mildly raised (stalk effect), usually below about 2,000 mU/L. A much higher level suggests a prolactinoma instead - which matters, because prolactinomas are treated with drugs, not surgery.
• MRI and formal visual fields.

Management:

• Transsphenoidal surgery if there is visual compromise, progressive growth or apoplexy. Vision often improves after decompression.
• Observation with serial MRI for small tumours away from the chiasm.
• Radiotherapy for residual tumour that is growing.
• Replace deficient hormones.
• Dopamine agonists are not effective.

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Prolactinoma

Mechanism: The commonest functioning pituitary tumour. High prolactin suppresses GnRH and therefore LH and FSH, causing hypogonadism, and stimulates breast milk production.

Clinical pattern:

• Women: Usually present early with a microprolactinoma:
  • Oligomenorrhoea or amenorrhoea.
  • Galactorrhoea.
  • Infertility.
  • Low libido, vaginal dryness.
  • Reduced bone density.
• Men: Often present late with a macroprolactinoma:
  • Low libido and erectile dysfunction, often ignored for years.
  • Headache, visual field loss, hypopituitarism.
  • Gynaecomastia and galactorrhoea occasionally.

Investigations:

• Serum prolactin - the level correlates with tumour size:
  • Microprolactinomas: often 1,000–5,000 mU/L.
  • Macroprolactinomas: usually over 5,000 mU/L, often very much higher.
• Exclude pregnancy, drugs, hypothyroidism, CKD and macroprolactin.
• MRI pituitary.
• Pituitary function and visual fields for macroadenomas.
• "Hook effect": An extremely high prolactin can saturate the assay and give a falsely modest result. Ask the lab to dilute the sample when a large tumour has an unexpectedly "low" prolactin.

Management - dopamine agonists are first-line, even for large tumours affecting vision:

• Cabergoline (preferred): Usually 250–500 micrograms once or twice weekly, titrated to normalise prolactin. In most patients it normalises prolactin, shrinks the tumour (often within weeks) and restores vision and fertility.
• Bromocriptine: An alternative, sometimes preferred when trying to conceive, because there is long safety experience in pregnancy.
• Side effects:
  • Nausea, dizziness and postural hypotension.
  • Headache.
  • Nasal congestion.
  • Impulse control disorders - gambling, hypersexuality, compulsive shopping. Warn patients and families.
  • Depression.
  • Cardiac valve fibrosis at high doses - echocardiographic surveillance is advised at higher cumulative doses.
  • CSF leak as an invasive macroadenoma shrinks.
• Stopping treatment: Consider cautious withdrawal after about 2 years of normal prolactin and marked tumour shrinkage. Recurrence is common, so monitor.
• Surgery or radiotherapy: For resistance or intolerance to dopamine agonists.
• Microprolactinoma in women not wanting fertility: The combined pill or HRT to protect bone is an option, with monitoring.

💡 Clinical Pearl: Unlike other pituitary tumours, a macroprolactinoma compressing the chiasm is treated first with medicine (cabergoline), not surgery. Vision often improves within days.

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Other Causes of Hyperprolactinaemia

A raised prolactin is common and is often not caused by a prolactinoma. Work through the causes before scanning:

• Physiological:
  • Pregnancy and breastfeeding - always check a pregnancy test.
  • Stress (including a difficult venepuncture), sleep, exercise, nipple stimulation, sexual activity.
• Drugs (block dopamine):
  • Antipsychotics - especially risperidone, amisulpride and haloperidol.
  • Metoclopramide and domperidone.
  • Some antidepressants, opioids, methyldopa, verapamil, oestrogens.
• Stalk compression (loss of dopamine inhibition): Non-functioning adenomas, craniopharyngioma, other sellar masses. Usually only a mild rise.
• Other diseases:
  • Primary hypothyroidism (high TRH stimulates prolactin).
  • Chronic kidney disease (reduced clearance).
  • Polycystic ovary syndrome.
  • Cirrhosis.
  • Chest wall injury or herpes zoster (neural stimulation).
  • Seizures (a transient rise).
• Macroprolactinaemia: Prolactin bound to antibodies forms large, biologically inactive complexes. The lab detects a high level but the patient has no symptoms. The lab screens for it by polyethylene glycol (PEG) precipitation. It needs no treatment.

💡 Clinical Pearl: Before requesting an MRI for a raised prolactin, check a pregnancy test, TFTs, renal function, the drug chart and macroprolactin. Repeat a mildly raised level on a calm, unhurried sample.

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Acromegaly

Mechanism: A pituitary adenoma (almost always) produces excess growth hormone, which drives the liver to make IGF-1. Together they cause overgrowth of bone, cartilage and soft tissue, insulin resistance and organ enlargement.

• Before puberty (open growth plates): Gigantism.
• In adults: Acromegaly. Changes are so gradual that diagnosis is typically delayed by 5–10 years - old photographs are revealing.

Clinical pattern:

• Appearance:
  • Coarse facial features, frontal bossing, large nose.
  • Prognathism (protruding jaw), widened spaces between the teeth, a large tongue.
  • Increasing ring and shoe size, spade-like hands.
  • Thick, oily, sweaty skin; skin tags.
• Symptoms:
  • Headache.
  • Excessive sweating.
  • Joint pain (arthropathy).
  • Carpal tunnel syndrome.
  • Snoring and sleep apnoea.
  • Deep voice.
  • Fatigue.
• Complications:
  • Hypertension.
  • Diabetes and impaired glucose tolerance.
  • Cardiomyopathy and heart failure.
  • Colonic polyps and colorectal cancer.
  • Goitre.
  • Visual field loss and hypopituitarism (macroadenoma).
• Prognosis: Untreated, mortality is significantly increased, mainly from cardiovascular and respiratory disease.

Investigations:

• IGF-1 (the best screening test): Raised for the patient's age.
• Oral glucose tolerance test with GH: Failure of GH to suppress after 75 g glucose confirms the diagnosis. A random GH is unhelpful because GH is secreted in pulses.
• MRI pituitary; visual fields; full pituitary function.
• Screen for complications: colonoscopy, echocardiogram, sleep study, HbA1c, BP.

Management:

• Transsphenoidal surgery: First-line. Curative in most microadenomas and fewer macroadenomas.
• Medical therapy (residual disease, or not fit for surgery):
  • Somatostatin analogues - octreotide LAR or lanreotide, monthly injections. They reduce GH and often shrink the tumour. Side effects: gallstones, GI upset, hyperglycaemia.
  • Pegvisomant - a GH receptor blocker. Normalises IGF-1 in most patients but does not shrink the tumour. Monitor LFTs and the tumour.
  • Pasireotide - causes hyperglycaemia.
  • Cabergoline - for mild disease.
• Radiotherapy: For persistent disease. It takes years to work and causes hypopituitarism.
• Goal: A normal IGF-1 for age, with treatment of complications. Soft-tissue changes improve; bony changes do not.

💡 MRCP Pearl: Screen with IGF-1, confirm with GH on an OGTT. Do a colonoscopy at diagnosis - acromegaly increases colorectal neoplasia.

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Cushing's Disease

Mechanism: A pituitary corticotroph adenoma - usually a tiny microadenoma - secretes ACTH, driving both adrenals to over-produce cortisol. It is the commonest cause of endogenous Cushing's syndrome, typically in women aged 25–45.

Clinical pattern: Gradual onset of Cushingoid features: purple striae, bruising, proximal myopathy, central obesity, hypertension, diabetes, osteoporosis and psychological change.

Diagnosis:

• Confirm cortisol excess: overnight dexamethasone suppression, urinary free cortisol, late-night salivary cortisol.
• ACTH is normal or mildly raised.
• MRI pituitary - the adenoma is often too small to see.
• Inferior petrosal sinus sampling confirms a pituitary source.

Management:

• Transsphenoidal surgery, with remission in about 70–90% of microadenomas.
• After successful surgery, patients need hydrocortisone until the suppressed normal pituitary recovers, which may take months to years.
• For persistent disease: medical therapy (metyrapone, osilodrostat, pasireotide), radiotherapy, or bilateral adrenalectomy (risk of Nelson's syndrome).

See the Adrenal Disease chapter for full investigation and management of Cushing's syndrome.

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TSH-secreting Adenoma

Mechanism: A rare adenoma secreting TSH, which drives the thyroid to overproduce hormone. It is usually a macroadenoma by diagnosis.

Clinical pattern: Thyrotoxicosis with a goitre, sometimes with mass effects. There is no Graves' eye disease.

Investigations:

• Raised FT4 and FT3 with a non-suppressed (normal or high) TSH.
• Raised alpha subunit and SHBG.
• MRI shows a pituitary tumour.
• Exclude assay interference and thyroid hormone resistance first.

Management: Transsphenoidal surgery; somatostatin analogues; radiotherapy. Do not treat the thyroid with radioiodine or surgery, which removes feedback and may make the tumour grow.

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Pituitary Incidentaloma

Definition: A pituitary lesion found on imaging done for another reason. They are found in up to 10–20% of MRI scans - most are microadenomas or small cysts that never cause harm.

Assessment:

• History and examination for hormone excess or deficiency, and visual symptoms.
• Hormone tests:
  • Prolactin and IGF-1 in all.
  • Tests for Cushing's if clinically suspected.
  • Full pituitary function for macroadenomas (and for microadenomas with symptoms).
• Formal visual fields if the lesion is close to or touching the chiasm.
• Dedicated pituitary MRI if the incidental scan was not designed to image the pituitary.

Follow-up:

• Microadenoma (no hormone excess): Repeat MRI at about 1 year; if stable, less frequently or discharge.
• Macroadenoma: MRI at about 6–12 months, then periodically; repeat pituitary function and fields.
• Surgery: For visual compromise, growth, apoplexy or hormone excess.

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Craniopharyngioma

Mechanism: A benign but locally aggressive tumour arising from remnants of Rathke's pouch - the embryological origin of the anterior pituitary. It usually lies above the sella (suprasellar). It is often cystic and calcified, and contains thick fluid described as "machinery oil". Peak incidence is in children (5–14 years) and in adults aged 50–75.

Clinical pattern:

• Visual loss - starting in the lower temporal quadrants, because it compresses the chiasm from above.
• Headache and raised intracranial pressure (hydrocephalus).
• Hypopituitarism; growth failure and delayed puberty in children.
• Diabetes insipidus - common, unlike pituitary adenomas.
• Hypothalamic damage: Severe obesity, disrupted sleep, temperature dysregulation, behavioural change.

Investigations: MRI, and CT to show calcification, which is characteristic. Full pituitary function, including water balance, and visual fields.

Management:

• Surgery (transsphenoidal or transcranial) with or without radiotherapy. Approaches that limit hypothalamic damage are preferred.
• Lifelong hormone replacement, often including desmopressin.
• Management of hypothalamic obesity.
• Recurrence is common.

💡 MRCP Pearl: A child with headache, short stature, polyuria and a calcified suprasellar mass = craniopharyngioma.

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Rathke's Cleft Cyst

Mechanism: A benign, fluid-filled cyst - also a Rathke's pouch remnant - lying between the anterior and posterior pituitary.

Clinical pattern: Usually small and found incidentally. Larger cysts can cause headache, visual loss, hypopituitarism, mild hyperprolactinaemia or, occasionally, inflammation.

Management: Observation with MRI for small asymptomatic cysts; surgical drainage for symptomatic or enlarging cysts.

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Other Sellar Lesions

• Meningioma: Arises from the tuberculum sellae, causing visual loss with relatively preserved pituitary function.
• Metastases (breast and lung commonest): Often present with diabetes insipidus, because they spread via the blood supply to the posterior pituitary. Also cause cranial nerve palsies and rapid symptoms.
• Germ cell tumours (germinoma): Children and young adults, with DI, hypopituitarism and visual loss. Tumour markers (hCG, AFP) may be raised in blood or CSF.
• Infiltrative and inflammatory disease:
  • Sarcoidosis.
  • Langerhans cell histiocytosis (DI with lytic bone lesions).
  • TB.
  • Granulomatosis with polyangiitis.
  • IgG4-related disease.
  • Haemochromatosis (selective gonadotrophin loss).
• Carotid aneurysm: Can mimic a pituitary mass - it must be excluded on imaging before surgery.

💡 Clinical Pearl: A sellar mass with diabetes insipidus is unlikely to be a simple adenoma. Think of craniopharyngioma, metastasis, hypophysitis, germinoma, sarcoid or Langerhans cell histiocytosis.

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Hypopituitarism: Causes

Definition: Deficiency of one or more pituitary hormones. When all are lost, it is called panhypopituitarism.

Causes - remember the "9 Is":

• Invasive: Pituitary adenoma (the commonest), craniopharyngioma, metastases, other sellar tumours.
• Iatrogenic: Pituitary surgery; cranial radiotherapy (hypopituitarism develops gradually over years, so annual testing is needed).
• Infarction: Sheehan's syndrome; pituitary apoplexy.
• Injury: Traumatic brain injury; subarachnoid haemorrhage.
• Inflammation: Hypophysitis - lymphocytic, IgG4-related, or immune checkpoint inhibitors.
• Infiltration: Sarcoidosis, haemochromatosis, Langerhans cell histiocytosis.
• Infection: TB, meningitis, abscess (rare).
• Isolated: Single-hormone deficiencies, e.g. Kallmann syndrome (GnRH deficiency with loss of smell).
• Idiopathic and genetic: Congenital causes in children.

Drugs that suppress the axes:

• Glucocorticoids suppress ACTH.
• Opioids suppress the gonadal and ACTH axes.
• Anabolic steroids suppress gonadotrophins.

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Hypopituitarism: Clinical Features

Features depend on which hormones are lost and how fast. Onset after a tumour is gradual; after apoplexy or surgery it is sudden.

• ACTH deficiency:
  • Fatigue, weight loss, nausea.
  • Postural hypotension.
  • Hyponatraemia; hypoglycaemia.
  • Adrenal crisis during illness.
  • Pale skin (no pigmentation, unlike Addison's).
  • No hyperkalaemia (aldosterone is preserved).
• TSH deficiency: Hypothyroid features, with a low FT4 and a low or normal TSH.
• LH and FSH deficiency:
  • Women: Amenorrhoea, infertility, loss of libido, vaginal dryness, osteoporosis.
  • Men: Low libido, erectile dysfunction, reduced shaving, small soft testes, loss of muscle, osteoporosis.
  • Both: Fine wrinkling around the eyes and mouth; loss of body hair.
• GH deficiency:
  • Children: Short stature and slow growth.
  • Adults: Fatigue, low mood, poor quality of life, central obesity, reduced muscle and bone mass, adverse lipids.
• Prolactin deficiency: Failure to lactate after delivery - a clue to Sheehan's syndrome.
• Vasopressin deficiency (if the posterior pituitary or hypothalamus is involved): Polyuria and thirst. DI can be masked by untreated cortisol deficiency and appear once hydrocortisone is started, because cortisol is needed to excrete free water.

💡 Clinical Pearl: An older patient with hyponatraemia, fatigue and low libido may have a non-functioning macroadenoma with hypopituitarism, not SIADH. Check 9 am cortisol, FT4, gonadotrophins and testosterone.

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Hormone Replacement

The order matters: Replace cortisol first. Thyroxine increases cortisol breakdown and can precipitate an adrenal crisis in someone with untreated ACTH deficiency.

• ACTH deficiency:
  • Hydrocortisone 15–25 mg daily in 2–3 divided doses, the largest on waking.
  • Sick-day rules, an emergency injection kit and a Steroid Emergency Card.
  • Fludrocortisone is not needed, because aldosterone is preserved.
• TSH deficiency:
  • Levothyroxine, adjusted to keep the free T4 in the mid-to-upper normal range.
  • TSH cannot be used for monitoring.
• Gonadotrophin deficiency:
  • Men: Testosterone (daily gel or long-acting IM injection). Monitor haematocrit, PSA and testosterone levels.
  • Pre-menopausal women: Oestrogen (with progestogen if the uterus is present) until around the age of natural menopause, to protect bone and cardiovascular health.
  • Fertility: Gonadotrophin injections (or pulsatile GnRH in hypothalamic disease) in specialist fertility care.
• GH deficiency:
  • Children: Somatropin to achieve normal growth.
  • Adults (NICE TA64): Somatropin for severe GH deficiency with significantly impaired quality of life, once other deficiencies are replaced. Dose is titrated to IGF-1; continue only if quality of life improves.
• Vasopressin deficiency: Desmopressin (see Diabetes Insipidus: Treatment).
• Lifelong follow-up: Endocrinology review, education about illness and travel, bone density monitoring, and adjusting doses during pregnancy and with interacting drugs.

⚠️ Safety Pearl: Starting levothyroxine before hydrocortisone in undiagnosed hypopituitarism can precipitate adrenal crisis. Always check and replace cortisol first.

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Sheehan's Syndrome

Mechanism: The pituitary enlarges by up to about twice its size in pregnancy, but its blood supply does not increase. A major postpartum haemorrhage with hypotension can cause the gland to infarct.

Clinical pattern:

• Failure to lactate (prolactin deficiency) - often the first clue.
• Failure of periods to return after delivery.
• Fatigue and loss of pubic and axillary hair.
• Hypothyroid features.
• Hyponatraemia and hypoglycaemia.
• Adrenal crisis.

It can present acutely within days of delivery, or insidiously years later.

Investigations: Full pituitary function; MRI, which later shows an empty or small sella.

Management: Lifelong hormone replacement - cortisol first.

💡 MRCP Pearl: Postpartum haemorrhage → inability to breastfeed → no return of periods = Sheehan's syndrome.

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Hypophysitis

Mechanism: Inflammation of the pituitary. It enlarges the gland and stalk and then destroys hormone-producing cells.

Types:

• Lymphocytic hypophysitis: Autoimmune, classically in women in late pregnancy or after delivery. Causes headache, early ACTH deficiency, and often DI. It can mimic an adenoma on MRI, but the gland is symmetrically enlarged with a thickened stalk.
• Immune checkpoint inhibitor hypophysitis: Especially with ipilimumab (anti-CTLA-4), usually within the first 2–3 months of treatment. Causes headache and fatigue, with ACTH, TSH and gonadotrophin deficiency. The ACTH deficiency is usually permanent.
• IgG4-related, granulomatous and secondary forms: Sarcoid, TB, granulomatosis with polyangiitis.

Management:

• Replace hormones, especially hydrocortisone.
• Glucocorticoids at higher doses for significant mass effect or visual compromise.
• Surgery only if compression does not respond.
• Immunotherapy can usually continue once replacement is established.

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Empty Sella

Mechanism: CSF fills the sella turcica, flattening the pituitary against its floor.

• Primary empty sella: A defect in the membrane above the sella, often in obese, hypertensive women and in idiopathic intracranial hypertension. Usually an incidental finding with normal pituitary function.
• Secondary empty sella: Follows pituitary surgery, radiotherapy, apoplexy or Sheehan's syndrome. Hypopituitarism is common.

Management: Check pituitary function once, and treat any deficiency. Assess for raised intracranial pressure if there are headaches or papilloedema.

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Pituitary Apoplexy

Mechanism: Sudden haemorrhage or infarction within a pituitary tumour - often a previously unknown macroadenoma. The gland swells rapidly inside the rigid sella and compresses the chiasm, cavernous sinuses and remaining normal pituitary. Acute ACTH deficiency causes the life-threatening part.

Triggers:

• Anticoagulation.
• Major surgery (especially cardiac bypass).
• Pregnancy.
• Dopamine agonists.
• Dynamic pituitary tests.
• Head injury.
• Hypertension.

Often there is no trigger.

Clinical pattern:

• Sudden, severe "thunderclap" headache, often behind the eyes.
• Vomiting.
• Visual loss or field defects.
• Ophthalmoplegia and double vision (third nerve palsy commonest; ptosis).
• Reduced consciousness.
• Meningism.
• Hypotension and hyponatraemia from adrenal insufficiency.

It easily mimics subarachnoid haemorrhage or meningitis.

Investigations:

• MRI - the investigation of choice. CT may miss it.
• Urgent bloods: cortisol, electrolytes, TFTs, prolactin, IGF-1, gonadotrophins, glucose.
• Formal visual assessment.

Management (UK pituitary apoplexy guidelines):

• Hydrocortisone immediately in any unstable patient, without waiting for results. Give 100–200 mg IV, then 2–4 mg/hour by infusion, or 50–100 mg IM 6-hourly.
• Fluids and electrolyte correction.
• Urgent joint neurosurgical and endocrine review.
• Surgical decompression for severely reduced acuity, severe or worsening field defects, or deteriorating consciousness.
• Conservative management (steroids and monitoring) for stable patients without major visual loss. Ocular palsies alone often recover without surgery.
• Long term: Reassess pituitary function at 4–8 weeks; many patients need lifelong replacement. MRI follow-up.

⚠️ Safety Pearl: Thunderclap headache with visual loss or ophthalmoplegia - think pituitary apoplexy. Give hydrocortisone and arrange an urgent MRI. A normal CT does not exclude it.

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Diabetes Insipidus (AVP Deficiency)

Mechanism: Too little vasopressin (AVP, ADH) is produced, so the kidneys cannot concentrate urine. Patients pass large volumes of dilute urine and must drink to keep up. The condition was renamed arginine vasopressin deficiency in 2022 to avoid confusion with diabetes mellitus. The kidney form is now called AVP resistance.

Clinical pattern:

• Polyuria (over about 3 litres a day in adults) and nocturia.
• Intense thirst, often for ice-cold water.
• Very dilute urine.
• Sodium is usually high-normal while the patient can drink, but becomes dangerously high if water access is lost - for example if unconscious, after surgery, nil by mouth, or with an impaired thirst sense.

Causes of AVP deficiency (cranial DI):

• Idiopathic (often autoimmune).
• Pituitary or hypothalamic surgery.
• Head injury.
• Tumours: Craniopharyngioma, germinoma, metastases (not usually adenomas).
• Infiltration: Sarcoidosis, Langerhans cell histiocytosis.
• Hypophysitis.
• Genetic: Familial forms; Wolfram syndrome (DIDMOAD - diabetes insipidus, diabetes mellitus, optic atrophy, deafness).

⚠️ Safety Pearl: Omitting or delaying desmopressin in hospital can cause fatal hypernatraemia (an NHS patient safety alert). If a patient with DI is nil by mouth or vomiting, give desmopressin by another route and monitor sodium closely.