Pituitary Disease — Clinical Case

DCE Long Case

Patient brief (provided to trainee)

Patient: Mr David Thompson, 54 years old, truck driver. [1]

Presenting complaint: Two-year history of progressive enlargement of his hands and feet. His wife has noticed his face is changing — his jaw is more prominent and his features are coarsening. Over the past year he has been diagnosed with type 2 diabetes and hypertension. His wife reports very loud snoring with witnessed apnoeas and he falls asleep at the wheel, nearly causing an accident. He has bilateral hand paraesthesia and numbness, worse at night. [1]

Past history:

• Type 2 diabetes diagnosed 8 months ago (HbA1c 64 mmol/mol on metformin 1 g twice daily)
• Hypertension diagnosed 6 months ago (on perindopril 5 mg daily, amlodipine 10 mg daily)
• Bilateral carpal tunnel syndrome (right wrist decompressed 18 months ago)
• Gallstones (incidental finding on ultrasound) [1]

Family history: Father had type 2 diabetes and died of myocardial infarction at age 68. Mother alive, hypothyroid. [1]

Social history: Truck driver for 30 years. Smokes 15 cigarettes per day. Drinks 20 standard drinks per week. The sleepiness while driving is a significant occupational safety concern. [1]

Examination findings (trainee elicits):

• Alert, oriented, cooperative. Coarse facial features — frontal bossing, prognathism with interdental spaces, large nose, oily sweaty skin
• BP 158/96, HR 82 regular, RR 16, SpO2 97% on room air, temp 37.0, BMI 31
• Large spade-like hands, thickened fingers, oily skin, multiple skin tags over neck and axillae
• Bilateral carpal tunnel scars; Tinel sign positive at the left wrist; reduced sensation in median nerve distribution bilaterally
• Cardiac apex displaced 1 cm laterally, normal heart sounds, no murmur
• Chest clear
• Visual fields full to confrontation (no bitemporal hemianopia)
• Cranial nerves intact
• Proximal muscle strength slightly reduced (4+ in shoulder abduction bilaterally)
• Shoe size has increased from 10 to 12 over the past 2 years [1]

Investigations:

• IGF-1: 3.2 times the upper limit of normal for age and sex
• OGTT GH nadir: 8.2 microgram per litre (failure to suppress below 1.0 confirms acromegaly)
• Prolactin: 260 mU/L (reference range below 500) — mild elevation consistent with stalk effect
• 9 AM cortisol: 320 nmol/L (normal)
• TSH 1.4 mU/L, free T4 12 pmol/L (normal)
• LH 3 U/L, FSH 5 U/L, testosterone 8 nmol/L (low-normal, consistent with mild hypogonadism)
• HbA1c 64 mmol/mol, fasting glucose 9.2 mmol/L
• Lipids: total cholesterol 5.8, LDL 3.8, HDL 0.9, triglycerides 2.4
• MRI pituitary: 16 mm macroadenoma with suprasellar extension abutting but not elevating the optic chiasm; mild left cavernous sinus invasion (Knosp grade 2)
• Visual fields (Humphrey): full
• Colonoscopy: two tubular adenomas removed (6 mm and 4 mm)
• Echocardiogram: concentric left ventricular hypertrophy with normal systolic function (EF 60%), diastolic dysfunction grade 1, no significant valvular disease
• Sleep study: severe obstructive sleep apnoea (AHI 38 events per hour) [1]

Candidate's structured presentation (model)

Opening statement: [1]

"Mr David Thompson is a 54-year-old truck driver who presents with a 2-year history of progressive acral enlargement, prognathism, and coarsening facial features, with recently diagnosed type 2 diabetes, hypertension, and severe obstructive sleep apnoea with near-miss driving incidents. His IGF-1 is 3.2 times the upper limit of normal and his oral glucose tolerance test confirms failure of growth hormone suppression, confirming acromegaly. His MRI shows a 16 millimetre somatotroph macroadenoma with suprasellar extension abutting the chiasm and mild left cavernous sinus invasion. His echocardiogram shows acromegalic cardiomyopathy with concentric left ventricular hypertrophy, and his sleep study confirms severe obstructive sleep apnoea with an apnoea-hypopnoea index of 38. [1]

His main problems are:

1. Acromegaly from a somatotroph macroadenoma — biochemically active with local invasion
2. Acromegalic cardiomyopathy — concentric LVH with grade 1 diastolic dysfunction
3. Severe obstructive sleep apnoea (AHI 38) with occupational safety risk
4. Type 2 diabetes with poor control (HbA1c 64) — exacerbated by GH excess
5. Hypertension (sub-optimally controlled at 158 over 96)
6. Bilateral carpal tunnel syndrome (right decompressed, left ongoing)
7. Colonic adenomas (two removed) — increased colon cancer risk
8. Dyslipidaemia and cardiovascular risk — smoker, diabetic, hypertensive
9. Mild hypogonadism (testosterone 8) — may be from mass effect or GH-IGF1 axis
10. Occupational and driving safety — sleep apnoea causing near-miss accidents [1]

This is a multisystem disease with significant mortality risk from cardiovascular causes. My management plan addresses the primary disease (surgery first) and each comorbidity systematically." [1]

Investigation summary: [1]

"The diagnosis of acromegaly is biochemically confirmed. The IGF-1 of 3.2 times the upper limit of normal is the integrative marker of chronic growth hormone excess. The failure of GH to suppress below 1.0 microgram per litre on the oral glucose tolerance test — it remained at 8.2 — confirms autonomous somatotroph secretion that escapes the normal negative feedback of hyperglycaemia. The prolactin of 260 is only mildly elevated and represents the stalk effect — it is disproportionate to the tumour size and confirms this is not a prolactinoma. The MRI localises the tumour: a 16 millimetre macroadenoma with suprasellar extension abutting the chiasm and Knosp grade 2 cavernous sinus invasion, which predicts a lower likelihood of surgical cure. The colonoscopy finding of two tubular adenomas confirms the increased colonic neoplasia risk in acromegaly. The echocardiogram confirms acromegalic cardiomyopathy — concentric left ventricular hypertrophy is the cardiac signature of chronic GH and IGF-1 excess and is a leading contributor to the excess cardiovascular mortality." [1]

Management plan: [1]

1. Transsphenoidal surgery first-line. Refer to an experienced pituitary neurosurgeon. The Knosp grade 2 cavernous sinus invasion means complete resection may not be possible, and he is likely to need post-operative medical therapy. Cure is defined as normal IGF-1 and GH below 1.0 microgram per litre with an OGTT nadir below 0.4. [1]

2. Pre-operative CPAP for obstructive sleep apnoea. This is urgent given the near-miss driving incident. Refer to a sleep physician for CPAP titration. He must be advised not to drive until the sleep apnoea is treated. This is both a clinical and a medico-legal obligation. [1]

3. Medical therapy if not cured after surgery. Start a first-generation somatostatin analogue (octreotide LAR 20 to 30 mg IM every 4 weeks, or lanreotide autogel 90 to 120 mg SC every 4 weeks). If IGF-1 is not controlled, escalate to pegvisomant (GH receptor antagonist) or pasireotide (with close glucose monitoring given his diabetes). [1]

4. Optimise diabetes control. Continue metformin. Consider an SGLT2 inhibitor or GLP-1 receptor agonist for cardiovascular and renal protection. Glucose control will improve as the GH excess is treated. Avoid pioglitazone given the risk of fluid retention with his cardiomyopathy. [1]

5. Aggressive cardiovascular risk management. Smoking cessation is the highest priority. Intensify blood pressure control (target below 130 over 80) — add a thiazide or consider ACE inhibitor dose escalation. Start a statin (atorvastatin 40 mg) — his LDL is above target for a high-risk diabetic. Aspirin is not routinely indicated for primary prevention. [1]

6. Address cardiomyopathy. The concentric LVH and diastolic dysfunction will improve with biochemical control of acromegaly. Monitor with echocardiogram every 1 to 2 years. Start an ACE inhibitor or ARB for its anti-remodelling effect. Avoid excessive fluid loading. [1]

7. Left carpal tunnel syndrome. May improve with biochemical control. If persistent, refer for surgical decompression. [1]

8. Colonoscopy surveillance. Repeat at 3 years, or sooner if symptoms. The finding of adenomas confirms increased risk. [1]

9. Smoking cessation and alcohol reduction. Brief intervention, nicotine replacement therapy or varenicline, referral to Quitline. [1]

10. Assess and replace any post-surgical hypopituitarism. Full pituitary panel post-operatively. If ACTH deficiency develops, start hydrocortisone FIRST, then levothyroxine (monitored by free T4, not TSH). Testosterone replacement if confirmed deficient. [1]

Examiner discussion questions

Q: "You mentioned Knosp grade. What is that and why does it matter?" [1]

"The Knosp classification grades cavernous sinus invasion on MRI based on the relationship of the tumour to the intercarotid line. Grade 0 is no invasion. Grade 1 is tumour medial to the intercarotid line. Grade 2 is tumour up to the intercarotid line. Grade 3 is tumour beyond the intercarotid line, displacing the carotid. Grade 4 is total encasement of the carotid artery. Mr Thompson is Knosp grade 2, which means the tumour abuts but does not invade beyond the intercarotid line. This predicts a moderate probability of surgical cure — grades 0 and 1 have a high cure rate, while grades 3 and 4 have a very low cure rate because the tumour in the cavernous sinus cannot be safely resected. For Mr Thompson, I would expect partial resection with likely need for post-operative medical therapy." [1]

Q: "His testosterone is 8. How does acromegaly cause hypogonadism?" [1]

"There are several mechanisms. First, the tumour itself may compress the normal gonadotrophs or the stalk, disrupting GnRH delivery to the gonadotrophs. Second, the co-secretion of prolactin — some somatotroph adenomas co-secrete prolactin as a mammosomatotroph tumour — inhibits gonadotropin secretion. Third, the elevated GH and IGF-1 may directly suppress the hypothalamic-pituitary-gonadal axis. Fourth, his obesity and type 2 diabetes contribute to functional hypogonadism from peripheral conversion of androgens to oestrogens in adipose tissue. For Mr Thompson, the testosterone of 8 is borderline low and the LH and FSH are in the normal range, suggesting a combination of central and peripheral mechanisms. I would re-check a morning testosterone after the acromegaly is biochemically controlled — it may normalise. If it remains low and he is symptomatic, I would offer testosterone replacement, but only after ensuring there is no active prostate cancer." [1]

Q: "Why does his echocardiogram show LVH when he is not severely hypertensive?" [1]

"The concentric left ventricular hypertrophy in acromegaly is not solely from hypertension. Growth hormone and IGF-1 directly stimulate cardiac myocyte hypertrophy and collagen deposition. The result is a specific cardiomyopathy characterised by concentric LVH with biventricular enlargement, initially with diastolic dysfunction (impaired relaxation) and preserved systolic function, progressing to systolic dysfunction and heart failure if untreated. Mr Thompson has the early stage — concentric LVH with grade 1 diastolic dysfunction and normal EF. The hypertension (158 over 96) is a contributing factor but not the sole cause. This cardiomyopathy is the leading cause of the excess cardiovascular mortality in acromegaly and is the reason biochemical control is so important — early disease is reversible, but advanced cardiomyopathy may not be." [1]

Q: "He nearly had a car accident. What are your medico-legal obligations?" [1]

"This is a critical safety issue. Mr Thompson has severe obstructive sleep apnoea (AHI 38) with documented near-miss driving events. In Australia, the Austroads guidelines require that a patient with a medical condition that impairs driving must be advised of their legal obligation not to drive. For a commercial vehicle driver like Mr Thompson, the standards are stricter. I would: first, counsel him clearly and document the advice that he must not drive until the sleep apnoea is treated. Second, refer him urgently for CPAP therapy and a sleep physician review. Third, if he continues to drive against advice, I have a duty to notify the licensing authority — the specific legal requirement varies by state, but the principle is that public safety overrides patient confidentiality when there is an imminent risk to others. Fourth, I would involve his GP and occupational health service to support the process. This is one of the most challenging but important conversations I will have with this patient." [1]

Q: "After surgery he develops diabetes insipidus. How do you manage that?" [1]

"Post-operative diabetes insipidus is common after transsphenoidal surgery — it occurs in 10 to 30% of patients, usually transiently. It presents with polyuria (typically above 3 litres per 24 hours), dilute urine (osmolality below 300 mOsm per kg), and rising serum sodium. I monitor serum sodium and urine output closely for the first 2 weeks post-surgery. [1]

For Mr Thompson, if he develops DI, I would: first, ensure he has free access to water — the thirst mechanism is intact in central DI, so if he can drink, he will self-regulate. Second, if the polyuria is severe or he is unable to maintain adequate oral intake, I start desmopressin — typically 1 to 2 microgram subcutaneously or intravenously, or 100 to 200 microgram orally. I titrate to allow a period of diuresis each day to avoid water intoxication and hyponatraemia. Third, I monitor for the triphasic response — after initial DI from stalk oedema (days 1 to 5), there may be a phase of SIADH from uncontrolled vasopressin release from the degenerating posterior pituitary (days 5 to 14), followed by permanent DI if the hypothalamic neurons are destroyed. This means I must check sodium daily for at least 2 weeks and adjust desmopressin accordingly. If DI persists beyond 3 to 6 months, it is likely permanent and requires lifelong desmopressin." [1]

DCE Short Case — Examination of the Acromegalic Patient

Instruction

"Examine this patient's face and hands. You have 7 minutes for examination and 8 minutes for discussion." [1]

Key signs the patient demonstrates (model — a patient with treated or partially treated acromegaly)

• General appearance: Coarse facial features, elongated face, frontal bossing, prominent supraorbital ridges, large fleshy nose, macrognathia with underbite, interdental spaces, prognathism
• Skin: Oily, sweaty (hyperhidrosis), thickened, multiple skin tags (acrochordons) over neck and axillae, acanthosis nigricans in skin folds (if insulin resistance)
• Hands: Enlarged, spade-like, thickened fingers ("paw-like"), doughy texture to palms, positive Tinel sign (carpal tunnel), reduced grip strength, Heberden nodes if coexistent osteoarthritis
• Feet: Enlarged, increased shoe size, pad over the heel
• Chest: Barrel chest, gynaecomastia (if hypogonadism), cardiorespiratory signs if cardiomyopathy or sleep apnoea
• Other: Goitre (thyroid enlargement common in acromegaly), missing teeth (from prognathism and malocclusion), carpal tunnel release scars [1]

Presentation template

"I examined this patient's face and hands. On general inspection, the patient has coarse facial features with frontal bossing, prominent supraorbital ridges, a large fleshy nose, macrognathia with prognathism and widened interdental spaces, and oily sweaty skin with multiple skin tags over the neck and axillae. [1]

Examining the hands, both hands are enlarged and spade-like with thickened fingers. The palms are doughy. There is a surgical scar over the right wrist consistent with a previous carpal tunnel release, and Tinel sign is positive at the left wrist with reduced sensation in the median nerve distribution. There is reduced grip strength bilaterally. The skin is oily and sweaty. There is no active synovitis but there is reduced range of movement at the metacarpophalangeal joints consistent with acromegalic arthropathy. [1]

In summary, these findings are consistent with acromegaly — growth hormone excess causing acral enlargement, prognathism, hyperhidrosis, skin tags, and carpal tunnel syndrome. The bilateral hand involvement and the carpal tunnel release scar suggest long-standing disease. I would like to take a full history including changes in ring, shoe, and glove size, snoring, headaches, visual symptoms, and sweating. I would confirm the diagnosis with serum IGF-1 and an oral glucose tolerance test, image the pituitary with MRI, and screen for the complications of acromegaly — cardiomyopathy with echocardiogram, obstructive sleep apnoea with a sleep study, and colonic polyps with colonoscopy." [1]

Discussion

1. Summarise your findings and conclusion: "These findings — acral enlargement, prognathism, hyperhidrosis, skin tags, and bilateral carpal tunnel syndrome — are consistent with acromegaly. The diagnosis is delayed by an average of 7 to 10 years because the changes are insidious. By the time of presentation, most patients have complications." [1]

2. Why does acromegaly cause carpal tunnel syndrome? "Growth hormone and IGF-1 excess stimulate proliferation of connective tissue and synovium in the flexor compartment of the wrist, narrowing the carpal tunnel and compressing the median nerve. It is typically bilateral and may precede the diagnosis by years." [1]

3. What is the significance of the skin tags? "Skin tags are common in acromegaly and reflect the trophic effects of GH on skin. They are also associated with insulin resistance and colonic polyps — their presence should prompt colonoscopy, as acromegaly increases colon cancer risk." [1]

4. What are the cardiovascular complications of acromegaly? "Acromegalic cardiomyopathy — concentric left ventricular hypertrophy with diastolic then systolic dysfunction — is the leading cause of death. Hypertension, arrhythmia, valvular regurgitation, and premature coronary disease are also common. Biochemical control of GH and IGF-1 restores mortality to population norms." [1]

5. How would you screen for the complications? "Echocardiogram for cardiomyopathy and valvular disease, sleep study for obstructive sleep apnoea (affects up to 70%), colonoscopy for colonic polyps and cancer, full anterior pituitary panel for hypopituitarism, and visual fields for chiasm compression. These are not optional — they are essential components of the initial assessment." [1]