GC067 I Keep On Bumping Into People On My Side
Homonymous hemianopia is the loss of vision in the same half of the visual field in both eyes, typically caused by a lesion in the contralateral optic tract, lateral geniculate nucleus, optic radiation, or occipital cortex, leading patients to collide with objects or people on their blind side.
I Keep on Bumping Into People on My Side: Pituitary Tumours & Hypopituitarism
Lecture Map
The title "I keep on bumping into people on my side" is a clinical vignette describing bitemporal hemianopia — the classic visual field defect caused by a pituitary tumour compressing the optic chiasm from below. Because nasal retinal fibres (which carry temporal visual fields) decussate at the chiasm, a midline compressive lesion knocks out both temporal fields. The patient literally cannot see people approaching from the side [1][2].
This lecture, delivered by Prof. Karen S.L. Lam (Medicine) and Prof. Gilberto Leung (Surgery), covers three interlinked domains [1]:
- Pituitary tumours — types, presentations, diagnosis, and treatment (surgery, radiation, medical)
- Hypopituitarism — causes, clinical features, investigation, and replacement therapy
- Diabetes insipidus — now renamed AVP-Deficiency (AVP-D) or AVP-Resistance (AVP-R)
This topic is bread-and-butter endocrinology for the Fourth Summative. Past papers have tested diabetes insipidus diagnosis and differentiation (2016 SAQ Q4), visual field defects from pituitary lesions, and hormonal axis interpretation. Expect MCQs on prolactinoma management, SAQs on investigation of hypopituitarism, and minicases integrating visual field loss with endocrine workup.
Core Anatomy and Physiology (First Principles)
The pituitary gland sits in the sella turcica, directly below the optic chiasm. When a pituitary tumour grows upward (suprasellar extension), it compresses the chiasm. The fibres that cross at the chiasm are from the nasal halves of each retina — these carry the temporal visual fields. Hence compression → bitemporal hemianopia [1][2].
Key concept: The nasal fibres decussate; temporal fibres do not. A chiasmal lesion therefore produces a bitemporal (heteronymous) field defect, not a homonymous one. [1]
The anterior pituitary has five cell types producing six hormones, regulated by hypothalamic releasing/inhibiting hormones delivered via the hypophyseal portal system:
| Cell Type | Hormone | Hypothalamic Regulator | Target |
|---|---|---|---|
| Lactotroph | Prolactin (PRL) | Dopamine (inhibitory) | Breast |
| Somatotroph | Growth Hormone (GH) | GHRH (+) / Somatostatin (−) | Liver (IGF-1), bone, muscle |
| Corticotroph | ACTH | CRH (+) | Adrenal cortex (cortisol) |
| Thyrotroph | TSH | TRH (+) | Thyroid (T3/T4) |
| Gonadotroph | LH, FSH | GnRH (+) | Gonads |
The posterior pituitary stores and releases AVP (ADH) and oxytocin, synthesized in the hypothalamus and transported down the pituitary stalk.
Why Prolactin Is Special
Prolactin is the ONLY anterior pituitary hormone under predominantly inhibitory control (by dopamine). This means anything that disrupts the pituitary stalk — tumour compression, surgery, trauma — removes dopamine inhibition and raises prolactin. This is called the "stalk effect" and is critical for differentiating a true prolactinoma from stalk-compression hyperprolactinaemia [1][2].
Presentations of Pituitary Tumours
Three main presentations [1]:
- Local symptoms — visual loss, headache
- Signs and symptoms of pituitary hormone hyper-secretion and hypo-secretion
- Incidental finding on skull X-ray, CT scan, or MRI
- Visual loss: Bitemporal hemianopia (classic); can progress to complete blindness if untreated. May start as a subtle upper temporal quadrantanopia (chiasm compressed from below, affecting inferior nasal fibres first).
- Headache: Non-specific, dull, aching. Not related to acutely raised ICP because pituitary tumours grow slowly [2]. The mechanism is thought to be dural stretching or cavernous sinus invasion.
- Cranial nerve palsies: Large tumours with lateral extension into the cavernous sinus can compress CN III, IV, V₁, V₂, VI → diplopia, facial numbness.
- CSF rhinorrhoea: If tumour erodes through the floor of the sella into the sphenoid sinus.
These depend on whether the tumour secretes a hormone (functioning adenoma) or destroys normal pituitary tissue (causing hypopituitarism).
Found in ~10% of brain MRIs. Most are non-functioning microadenomas. Management depends on size and hormonal activity.
Types of Pituitary Tumours
Three main types [1]:
- Pituitary adenomas — more common in adults
- Craniopharyngiomas — more common in children
- Pituitary carcinomas — very rare; primary or secondary
6–18% of all brain tumours. Unselected autopsy series: prevalence 12–22%; most common being prolactinomas. [1]
Size classification:
- Microadenoma: < 10 mm
- Macroadenoma: ≥ 10 mm
Practical consideration: Usually no hypopituitarism if microadenoma (< 1 cm). [1]
This makes sense — a small tumour hasn't yet compressed enough normal pituitary tissue to cause hormonal deficiency.
Functioning adenomas (70–80%) vs. Non-functioning adenomas (20–30%) [1]
| Type | Proportion of Functioning | Presentation |
|---|---|---|
| Prolactinomas | Most common | Galactorrhoea, amenorrhoea (women); impotence, ↓ libido (men) |
| GH-producing | Second most common | Acromegaly (adults) / Gigantism (children) |
| ACTH-producing | ~10% | Cushing's disease |
| Glycoprotein-secreting (TSH, FSH, LH, α/β subunits) | Rare | TSH-oma → hyperthyroidism; FSH/LH → usually hypopituitarism / mass effect |
| Non-functioning | 20–30% of all | Hypopituitarism / pituitary mass effect / visual loss |
Exam Trap: Non-Functioning Macroadenoma vs. Prolactinoma
A non-functioning macroadenoma compressing the stalk can cause mild hyperprolactinaemia (usually < 3× normal, i.e., < 1500 mU/L). A true prolactinoma typically causes PRL > 10× normal (> 5000 mU/L). If PRL is only mildly elevated with a large tumour, think stalk compression, NOT prolactinoma. The case vignette on the lecture slide illustrates this perfectly: PRL 1923 mU/L (< 4× normal) with a 2.1 cm tumour = stalk compression by non-functioning adenoma [1].
Transcription factors that regulate pituitary cytogenesis [1]:
- TPIT (TBX19) — corticotroph differentiation
- Pit1 (POU1F1) — lactotroph, mammosomatotroph, somatotroph, thyrotroph differentiation
- SF1 (NR5A1) — gonadotroph differentiation
Why this matters:
- Improves diagnostic accuracy: Immunohistochemical staining for transcription factors gives strong nuclear staining (vs. patchy cytoplasmic staining with hormonal stains alone) [1]
- Prognostic implications: e.g., SF1-lineage tumours (gonadotroph) run a relatively benign course; after complete resection, recurrence is rare [1]
The term "Pituitary Neuroendocrine Tumour (PitNET)" has been proposed by pathologists as a new name, but is not widely supported by endocrinologists. [1]
Key features [1]:
- 50% have calcification present (this is a classic radiological finding — look for suprasellar calcification on CT)
- 50% present with symptoms in childhood
- 25% present between ages 20–40
- Hypopituitarism (e.g., growth retardation in children)
- Stalk compression → diabetes insipidus (because AVP travels down the stalk)
- Chiasmal compression — common
- Obstruction to 3rd ventricle → hydrocephalus
Craniopharyngiomas arise from Rathke's pouch remnants. They are histologically benign but locally aggressive. The bimodal age distribution (childhood peak, adult peak at 50–70) is classic exam fodder.
Diagnosis of Functioning Pituitary Adenomas
Diagnosis [1]:
- Prolactin usually > 10× normal (i.e., > 5000 mU/L)
- Tumour shrinkage by > 50% in 90% of patients treated with dopamine agonists
The second point is both diagnostic and therapeutic — if a tumour shrinks dramatically on dopamine agonist therapy, it confirms it is a true prolactinoma.
Diagnosis [1]:
- Screening: Serum IGF-1 — above normal for age and gender
- Confirmation: Non-suppressible serum GH during OGTT
- Nadir > 0.4 ng/mL (AACE 2011)
- Nadir > 1 ng/mL (AES 2014)
Why IGF-1 and not random GH? GH is pulsatile and fluctuates throughout the day (exercise, stress, sleep all affect it). IGF-1 is produced by the liver in response to GH but has a long half-life and stable levels → better screening test.
Why OGTT? In normal physiology, glucose loading suppresses GH release. In acromegaly, the autonomous GH secretion from the tumour is NOT suppressed → GH remains elevated (nadir remains above threshold).
Not detailed on these slides but covered in the Cushing's/adrenal lecture. Key principle: demonstrate hypercortisolism first (24-hour urinary free cortisol, overnight dexamethasone suppression test, late-night salivary cortisol), then localize (ACTH levels, high-dose dexamethasone suppression, inferior petrosal sinus sampling).
MRI (magnetic resonance imaging): imaging modality of choice. [1]
MRI with gadolinium contrast is superior to CT for soft tissue resolution of the sella. The normal pituitary enhances brightly; microadenomas enhance less (hypoenhancing on early post-contrast images). CT is useful for craniopharyngiomas (detects calcification).
Non-stressed prolactin usually < 3× normal in non-prolactinoma causes [1]
| Category | Examples | Mechanism |
|---|---|---|
| Physiological | Pregnancy, lactation | Oestrogen stimulation of lactotrophs |
| Pathological — Stalk/hypothalamic lesions | Tumours compressing stalk | Loss of dopamine inhibition |
| Drugs | Antipsychotics, antiemetics (metoclopramide, domperidone), methyldopa, H₂ antagonists | Block central dopaminergic pathways |
| Hypothyroidism | ↑ TRH → stimulates lactotrophs | TRH is a weak prolactin-releasing factor |
| Renal failure | Impaired dopamine action; ↓ prolactin clearance | Both central and peripheral mechanisms |
| Oestrogen medications | OCP, HRT | Direct lactotroph stimulation |
| Chest wall injury | Herpes zoster, thoracotomy | Afferent neural stimulation (mimics suckling reflex) |
| Idiopathic | — | Diagnosis of exclusion |
High-Yield Drug Causes of Hyperprolactinaemia
Antipsychotics (especially typical > atypical) are the most common drug cause. They block D₂ receptors → remove dopamine inhibition of prolactin. Always check medication history before diagnosing a prolactinoma!
Treatment of Pituitary Tumours
Indications [1]:
- All tumours causing pituitary hyperfunction
- All macroadenomas
- For prolactinomas, medical treatment may be preferred
Transsphenoidal: route of choice
- Approach: transnasal endoscopic or sub-labial Transfrontal: very large suprasellar extension, severe chiasmal compression [1]
Why transsphenoidal? It avoids brain retraction — the surgeon goes through the nose/sphenoid sinus directly into the sella. It has lower morbidity than craniotomy.
Advantages: Rapid decrease in secretion and tumour size [1] Disadvantages: Residual/recurrence especially if macroadenomas; hypopituitarism; diabetes insipidus [1] Acute complications: Post-operative bleeding; CSF rhinorrhoea [1]
Conventional external irradiation [1] Radiosurgery: "Gamma knife"; "X-knife" — not used if suprasellar extension to within 5 mm of optic chiasm [1]
| Advantage | Disadvantages | |
|---|---|---|
| Radiation | Restrains tumour growth | Delayed effect on hormone secretion; Higher incidence of hypopituitarism |
Useful adjunct to surgery. May be primary therapy for macroprolactinomas. [1]
Why delayed effect? Radiation causes DNA damage that takes months to years to fully manifest as cell death and reduced hormone production. Patients need ongoing hormonal monitoring for years post-radiation.
3. Medical Treatment
Effects usually reversible on drug withdrawal. [1] Adjunct to surgery/RT except for prolactinomas, for which this may be the sole treatment. [1]
Prolactinomas: > 90% patients achieve normal PRL and reduction in size on dopamine agonists [1] Acromegaly: IGF-1 normalised in only 10% (meta-analysis); no size reduction [1] FSH-producing tumours: reduce FSH but not tumour size [1]
Side effects: Nausea, vomiting, orthostatic hypotension, headache, dizziness. Usually much less with cabergoline. [1]
Cabergoline vs. bromocriptine: Less frequent dosing; more convenient; more effective; much higher cost. Screen for clinical valvular disease if high total dose such as ≥ 300 mg. [1]
Why screen for valvular disease? High-dose cabergoline (as used in Parkinson's disease, not typical prolactinoma doses) activates serotonin 5-HT₂B receptors on cardiac valves → fibrotic valvulopathy. At prolactinoma doses this risk is very low, but screening is recommended at cumulative doses ≥ 300 mg.
Long-acting analogues IMI every 4–6 weeks [1]:
- Octreotide LAR, Lanreotide: predominantly act on sstr2; decrease secretion of GH & TSH-producing tumours; decrease size in 50% of patients
- For acromegaly: 60% achieve normal GH/IGF-1
- Pasireotide LAR: high affinity for sstr5; effective for ACTH-producing tumours & more effective for some GH-producing tumours
- Oral Octreotide capsules twice daily: FDA approved June 2020
- Oral non-peptide selective sstr2 agonist: in clinical trials
Side effects: Gallstone formation; may affect glucose tolerance (hyperglycaemia is common with Pasireotide) [1]
Why gallstones? Somatostatin inhibits cholecystokinin (CCK) release → reduced gallbladder motility → bile stasis → gallstone formation.
Why hyperglycaemia with Pasireotide? Pasireotide binds sstr5, which is expressed on pancreatic beta cells → inhibits insulin secretion more than octreotide does.
Pegvisomant — blocks GH receptor [1]
- Daily injections — normal IGF-1: 90% in 12-month study; 76% in long-term study (compliance problem)
- No decrease in tumour size (monitor for increase)
- Side effect: elevated liver transaminases (5% of patients)
- High cost; available only in some countries
Why doesn't it shrink the tumour? Pegvisomant blocks GH action peripherally at the receptor level — it doesn't affect the tumour itself. Without the negative feedback from IGF-1, the tumour could theoretically grow, hence the need for MRI monitoring.
| Drug Class | Drug Examples | Main Indication | Mechanism | Key Side Effects |
|---|---|---|---|---|
| Dopamine agonist | Cabergoline, Bromocriptine | Prolactinoma (1st line, may be sole Rx) | Activates D₂ receptors on lactotrophs → ↓ PRL, ↓ tumour size | Nausea, orthostatic hypotension, valvulopathy (high dose) |
| Somatostatin analogue | Octreotide LAR, Lanreotide, Pasireotide | Acromegaly, TSH-oma, Cushing's (Pasireotide) | sstr agonist → ↓ GH/TSH/ACTH secretion | Gallstones, hyperglycaemia (Pasireotide) |
| GH receptor antagonist | Pegvisomant | Acromegaly (refractory) | Blocks GH receptor → ↓ IGF-1 | ↑ liver transaminases; no tumour shrinkage |
Hypopituitarism
I. Structural damage of hypothalamus, pituitary, or pituitary stalk [1]:
The mnemonic is "T-I-I-I-I-I" (Tumours, Trauma, Infarction, Infiltration, Infections, Immunologic):
| Cause | Examples | Key Details |
|---|---|---|
| Tumours | Large pituitary/hypothalamic tumours | Most common cause overall |
| Trauma | Surgery, radiation therapy, head injury | Complication of RT for NPC is especially relevant in HK [1] |
| Infarction | Sheehan's syndrome (postpartum pituitary necrosis); pituitary apoplexy | Sheehan's: haemorrhage during delivery → pituitary ischaemia. Apoplexy: acute haemorrhage/infarction into a pre-existing adenoma |
| Infiltration | Haemosiderosis/haemochromatosis, histiocytosis, sarcoidosis | Iron deposition or granulomatous disease |
| Infections | TB, syphilis, mycosis, toxoplasmosis (AIDS) | Consider in immunocompromised |
| Immunologic | Lymphocytic hypophysitis — may be a side effect of immune checkpoint inhibitors (CTLA-4, PD-1 inhibitors); isolated ACTH deficiency | Increasingly important with cancer immunotherapy |
II. Functional disorders: isolated or multiple [1]:
| Type | Examples |
|---|---|
| Genetic | Panhypopituitarism; isolated GH deficiency; Kallmann syndrome (isolated LH/FSH deficiency ± anosmia) |
| Reversible | Emotional deprivation (↓ GH); anorexia nervosa (↓ LH/FSH ± TSH) |
Kallmann Syndrome
This is isolated hypogonadotrophic hypogonadism (low LH/FSH → low sex steroids) associated with anosmia (absent smell). The embryological reason: GnRH neurons and olfactory neurons both originate from the olfactory placode. Failure of migration of these neurons → both deficiencies.
Usually no hypopituitarism if microadenoma (< 1 cm) [1] Complication of radiotherapy for head and neck tumours such as nasopharyngeal carcinoma (NPC) [1] — this is especially high-yield for HKU given the high prevalence of NPC in Southern China May be hypothalamic in origin — elevated prolactin and diabetes insipidus often present [1] ACTH deficiency — often asymptomatic and unmasked by stress [1]
ACTH Deficiency: The Silent Killer
A patient with partial ACTH deficiency may have adequate basal cortisol for normal daily activities but cannot mount a cortisol stress response. During illness, surgery, or trauma, they develop adrenal crisis (hypotension, shock, hyponatraemia). This is why stress-dose steroids are life-saving and must be prescribed perioperatively for these patients.
Hypopituitarism: Low oestrogen/testosterone; FSH/LH normal or ↓ [1] Gonadal failure: Low oestrogen/testosterone; FSH/LH ↑ [1] Examples of gonadal failure: Turner syndrome (45,X); Klinefelter syndrome (47,XXY) [1]
| Feature | Onset Before Puberty | Onset After Puberty |
|---|---|---|
| Female | Primary amenorrhoea, impaired breast development | Secondary amenorrhoea |
| Male | Small testes/penis/scrotum; ↓ facial/pubic/axillary/body hair; high-pitched voice; ↓ muscle mass & strength | ↓ libido; impotence; ↓ morning erections; infertility; ↓ shaving frequency; failure of scalp hair to recede |
| Eunuchoidism | If no growth impairment: arm span > height; lower segment > upper segment; delayed epiphyseal closure | Not applicable (epiphyses already closed) |
| Testes | Small | Soft, size normal or mildly decreased; normal external genitalia |
Why eunuchoidism? Sex steroids (especially oestrogen, even in males via aromatisation) are responsible for epiphyseal closure. Without them, long bones keep growing → disproportionately long limbs (arm span exceeds height).
Gold standard for GH & ACTH deficiency: Insulin Tolerance Test (ITT) [1]
- Measures GH and cortisol responses to hypoglycaemia
- Contraindicated if epilepsy or coronary artery disease
How it works: IV insulin → hypoglycaemia (glucose must fall below 2.2 mmol/L) → physiological stress → hypothalamus should release CRH and GHRH → ACTH and GH should rise. If they don't, the axis is deficient. The beauty of the ITT is that it tests both axes simultaneously.
Alternative tests for adult GH deficiency [1]:
- Glucagon test
- Macimorelin test (oral non-peptide agonist of GH secretagogue receptor [ghrelin receptor])
ACTH deficiency [1]:
- Cortisol response to 1 μg Short Synacthen Test (SST) + normal or ↓ basal ACTH
- Impaired adrenal response because of prolonged deprivation of tonic ACTH stimulation
Why does the SST work for secondary (pituitary) ACTH deficiency? If ACTH has been deficient for weeks/months, the adrenal cortex atrophies. It can no longer respond briskly even to exogenous ACTH (synacthen). This is why an inadequate cortisol response to SST supports ACTH deficiency — the adrenals have "forgotten" how to respond.
| Axis | Test | Expected Abnormal Result |
|---|---|---|
| GH | IGF-1 (screen); ITT or glucagon or macimorelin (confirm) | ↓ IGF-1; inadequate GH rise |
| ACTH | Basal cortisol + ACTH; 1 μg SST; ITT | ↓ cortisol, normal/↓ ACTH; inadequate cortisol rise |
| TSH | Serum fT4, TSH | ↓ T4 with normal or ↓ TSH ("inappropriately normal" TSH) |
| LH/FSH | Serum sex hormones, LH, FSH | ↓ sex hormones with normal/↓ LH/FSH |
| Prolactin | Basal, non-stressed PRL | ↑ if stalk compression or prolactinoma |
TRH test: rarely indicated in daily clinical practice [1] LHRH test: if diagnosis uncertain or fertility induction being considered [1]
The 'Inappropriately Normal' Concept
In secondary (pituitary) deficiency, the tropic hormone (TSH, ACTH, LH/FSH) is not elevated despite a low target hormone. In primary gland failure, you'd expect the tropic hormone to be sky-high (feedback loop trying to compensate). The word "inappropriately normal" is the key exam discriminator between primary and secondary endocrine failure.
Replacement therapy [1]:
| Deficiency | Replacement |
|---|---|
| GH deficiency | GH: children & adults; daily subcutaneous injection. Weekly sustained-release GH approved by FDA. |
| Gonadotrophin deficiency | Testosterone (males), oestrogen ± progestagen (females). For fertility: HMG/HCG or recombinant FSH/LH |
| TSH deficiency | Thyroxine (levothyroxine) |
| ACTH deficiency | Hydrocortisone (cortisol) |
Critical order of replacement: Always replace cortisol before thyroxine. Why? Thyroxine increases cortisol metabolism. If you start thyroxine in a patient with unrecognised ACTH deficiency, you can precipitate an adrenal crisis.
Monitoring difference: In primary hypothyroidism you monitor TSH. In secondary (pituitary) hypothyroidism, TSH is useless — you monitor free T4 levels instead.
Diabetes Insipidus (DI) — Now AVP-D or AVP-R
Definition: Deficiency of, or resistance to, arginine vasopressin (AVP / ADH), leading to impaired ability to produce concentrated urine in response to ↑ serum osmolality or volume depletion [1]
Presentation: Polyuria, polydipsia ± hypernatraemia. Copious quantity of dilute urine. [1]
Diagnosis: Inadequate rise in urine osmolality despite high serum osmolality — basally or during water deprivation test [1]
AVP-Deficiency (AVP-D) — formerly Cranial DI: [1]
- Lesions of hypothalamus, pituitary stalk, or posterior pituitary
- Urine osmolality increases with DDAVP treatment
AVP-Resistance (AVP-R) — formerly Nephrogenic DI: [1]
- No response to AVP or DDAVP
- Genetic or acquired (e.g., lithium, hypercalcaemia, hypokalemia, chronic kidney disease)
Reason for name change: to eliminate confusion with diabetes mellitus and endorse a name that more accurately reflects the disease's aetiology [1]
- Withhold fluids → monitor body weight, serum osmolality, urine osmolality at intervals
- Normal response: urine osmolality rises > 600 mOsm/kg (concentrating urine)
- DI: urine remains dilute (< 300 mOsm/kg) despite rising serum osmolality (> 295 mOsm/kg)
- Give DDAVP (desmopressin):
- AVP-D (cranial): urine osmolality rises > 50% → kidneys respond to exogenous AVP
- AVP-R (nephrogenic): urine osmolality does NOT rise → kidneys are resistant
| Feature | AVP-D (Cranial) | AVP-R (Nephrogenic) |
|---|---|---|
| AVP production | ↓ or absent | Normal or ↑ |
| Response to DDAVP | ✓ (urine concentrates) | ✗ (no response) |
| Common causes | Post-neurosurgery, head trauma, craniopharyngioma, idiopathic | Lithium, hypercalcaemia, chronic kidney disease, genetic |
| Treatment | DDAVP (intranasal/oral) | Treat underlying cause; thiazide diuretics (paradoxical effect); low-salt diet |
Case: F/40, oligomenorrhoea for 1 year (interval 28→70–90 days) [1]
- PRL 1923 mU/L (N < 500) — ~4× normal, NOT > 10× normal
- Low oestrogen; LH/FSH not elevated
- Normal fT4, TSH, 1 μg SST
- Visual fields normal; no acromegalic/Cushingoid features
- MRI: tumour 2.1 cm, left suprasellar extension encroaching on optic chiasm
- Bromocriptine started → PRL ↓ to 145; menstruation returned BUT no tumour shrinkage on 4-month MRI
- Diagnosis: Hyperprolactinaemia due to stalk compression by non-functioning pituitary macroadenoma
- Transsphenoidal surgery: tumour stained negative for all pituitary hormones
- Post-op: Diabetes insipidus + ITT showed subnormal peak cortisol and GH → oral DDAVP and hydrocortisone 10 mg OM required
Learning Points from This Case
- PRL < 10× normal + large tumour = stalk compression, not prolactinoma
- Bromocriptine lowered PRL (by directly suppressing remaining normal lactotrophs) and restored menstruation, but did not shrink the non-functioning tumour → further evidence it wasn't a prolactinoma
- Surgery was required because it was a macroadenoma with chiasmal encroachment
- Post-operative complications: DI (posterior pituitary/stalk damage) and hypopituitarism (ACTH + GH deficiency) → need long-term replacement
- Immunohistochemistry confirmed non-functioning (stained negative for all hormones)
Exam Intelligence
-
Visual field defect interpretation: "A patient bumps into things on their sides. What visual field defect? Where is the lesion?" → Bitemporal hemianopia; optic chiasm compression.
-
Prolactinoma vs. stalk compression: Given PRL level and tumour size, differentiate. The PRL threshold (> 10× vs. < 3×) is the key discriminator.
-
Diagnosis of acromegaly: Why is IGF-1 used for screening? Why OGTT for confirmation? What are the cut-offs?
-
DI investigation: Past paper 2016 SAQ Q4 directly asked about this — biochemical confirmation (serum osmolality ↑, urine osmolality ↓, urine specific gravity ↓), water deprivation test, DDAVP differentiation [3].
-
Causes of hypopituitarism: The "T-I-I-I-I-I" mnemonic with specific examples. Sheehan's syndrome is a classic stem. Lymphocytic hypophysitis from checkpoint inhibitors is increasingly tested.
-
Hypogonadism: Differentiate central (low LH/FSH) from peripheral (high LH/FSH). Features of pre-pubertal vs. post-pubertal onset.
-
Craniopharyngioma: Calcified suprasellar tumour in a child with growth retardation and DI → classic stem.
-
Post-operative complications of transsphenoidal surgery: DI, hypopituitarism, CSF rhinorrhoea, bleeding.
| Trap | Correct Answer |
|---|---|
| PRL 2000 mU/L with 3 cm tumour → prolactinoma? | No — stalk compression by non-functioning adenoma |
| Random GH elevated → acromegaly? | No — GH is pulsatile; need IGF-1 screening + OGTT confirmation |
| Low cortisol + normal ACTH → primary adrenal insufficiency? | No — "inappropriately normal" ACTH = secondary (pituitary) ACTH deficiency |
| Start thyroxine first in panhypopituitarism? | No — always replace cortisol first to avoid adrenal crisis |
| DI = always cranial? | No — differentiate AVP-D (cranial) from AVP-R (nephrogenic) with DDAVP response |
Q1: A 35-year-old woman presents with amenorrhoea and galactorrhoea. MRI shows a 6 mm pituitary microadenoma. Serum PRL is 8500 mU/L (N < 500). What is the diagnosis and first-line treatment?
- Markscheme: Prolactinoma (microprolactinoma). First-line: dopamine agonist (cabergoline preferred over bromocriptine). > 90% achieve normal PRL with tumour shrinkage. Surgery reserved for drug-intolerant/resistant cases.
Q2: A 45-year-old man presents with coarsened facial features, enlarged hands and feet, and excessive sweating. What investigations would you perform to confirm the diagnosis?
- Markscheme: Screening: serum IGF-1 (elevated for age/gender). Confirmation: OGTT with GH measurement — GH nadir > 1 ng/mL (AES 2014) confirms acromegaly. MRI pituitary to locate tumour.
Q3: List four causes of hyperprolactinaemia other than prolactinoma.
- Markscheme: (1) Drug-induced (antipsychotics, antiemetics, methyldopa); (2) Stalk compression by non-functioning pituitary macroadenoma; (3) Primary hypothyroidism (↑ TRH); (4) Pregnancy/lactation; (5) Renal failure; (6) Chest wall injury. (Any four)
Q4: A child presents with growth retardation and a calcified suprasellar mass on CT. What is the most likely diagnosis? Name three complications of this tumour.
- Markscheme: Craniopharyngioma. Complications: (1) Hypopituitarism/growth retardation; (2) Diabetes insipidus (stalk compression); (3) Bitemporal hemianopia (chiasmal compression); (4) Hydrocephalus (3rd ventricle obstruction). (Any three)
Q5 (based on 2016 SAQ Q4): A patient with polyuria has serum osmolality 305 mOsm/kg and urine osmolality 120 mOsm/kg. (a) What do these results suggest? (b) What test differentiates AVP-D from AVP-R? (c) What result would you expect in each?
- Markscheme: (a) Diabetes insipidus — high serum osmolality with inappropriately dilute urine. (b) Administer DDAVP (desmopressin) after water deprivation test. (c) AVP-D: urine osmolality rises > 50% (response to exogenous AVP). AVP-R: no significant rise in urine osmolality (kidney resistant to AVP).
High Yield Summary
Pituitary tumours present with (1) local mass effects (bitemporal hemianopia, headache), (2) hormonal hyper- or hypo-secretion, or (3) incidentally. The most common type is the prolactinoma. Key diagnostic principles: PRL > 10× normal = prolactinoma; PRL < 3× normal with large tumour = stalk compression by non-functioning adenoma. MRI is the imaging modality of choice. Treatment: dopamine agonists are first-line for prolactinomas (may be sole treatment); transsphenoidal surgery is route of choice for other adenomas and macroadenomas; radiation is adjunctive. Somatostatin analogues are used for acromegaly (60% normalise IGF-1); pegvisomant blocks GH receptor peripherally.
Hypopituitarism is caused by structural damage (tumours, trauma, infarction [Sheehan's], infiltration, infection, immunologic [checkpoint inhibitor hypophysitis]) or functional disorders (genetic [Kallmann], reversible [anorexia]). The insulin tolerance test is gold standard for GH and ACTH axes. Always replace cortisol before thyroxine.
Diabetes insipidus (now AVP-D or AVP-R): diagnose with serum/urine osmolality; differentiate cranial from nephrogenic with DDAVP response. Craniopharyngiomas are the key pituitary tumour of childhood — look for calcification on CT.
Active Recall - Pituitary Tumours & Hypopituitarism
[1] Lecture slides: GC 067. I keep on bumping into people on my side.pdf (slides 1–25) [2] Senior notes: Block A - I keep on bumping into people on my side_ pituitary tumours; hypopituitarism.pdf (p.1) [3] Past papers: 2016 Fourth Summative SAQ.pdf (Q4, p.2) [4] Senior notes: Block A - Two cases of polyuria and polydipsia.pdf (p.3) [5] Senior notes: Ryan Ho Opthalmology.pdf (p.74 — neuro-ophthalmology and visual pathway disorders)
GC066 I Have Fluctuating BP
Fluctuating blood pressure refers to significant variability in blood pressure readings over short periods, which may result from autonomic dysfunction, medication effects, arterial stiffness, or emotional and physiological stressors, and can increase the risk of cardiovascular events.
GC068 Indigestion And ‘heartburn’
Indigestion (dyspepsia) and heartburn are upper gastrointestinal symptoms characterized by epigastric discomfort, bloating, and a retrosternal burning sensation typically caused by gastric acid reflux or impaired digestion.