Acromegaly

Meet the patient

A 42-year-old man is referred by his dentist, who has watched the gaps between his front teeth widen over three years and finally asked why he needs new shoes every winter. His rings no longer fit, he snores himself awake, and his GP diagnosed type 2 diabetes six months ago. His wife, looking at a wedding photograph from a decade ago, says simply that his whole face has changed. Examination finds a prognathous jaw, frontal bossing, a macroglossic tongue and a bitemporal hemianopia on confrontation.[1][2]

The single question that must be answered before anyone prescribes, scans or operates is the question that runs this whole disease: has a serum IGF-1 been sent, age- and sex-matched? Everything below exists to convert that one number into a diagnosis, a tumour and a cure.[1]

What acromegaly actually is — akron, megas, and the gigantism fork

Acromegaly is chronic, autonomous growth-hormone excess in a skeleton whose growth plates have fused, and in over 99 percent of cases the source is a monoclonal pituitary somatotroph adenoma. The same hormone excess acting before epiphyseal fusion produces pituitary gigantism (excess linear growth, tall stature); after fusion it produces acromegaly (acral and soft-tissue enlargement). The tumour biology, workup and treatment are identical — the only difference is the developmental state of the growth plate at onset.[1][6]

The rare non-pituitary source is ectopic GHRH from a bronchial carcinoid, pancreatic neuroendocrine tumour, small-cell lung cancer or phaeochromocytoma, which drives somatotroph hyperplasia (not a discrete adenoma) and a markedly raised plasma GHRH. True ectopic GH from a pancreatic or lung tumour is vanishingly rare. The clue to either is acromegaly with a small or normal-looking pituitary on MRI — the tumour is elsewhere.[1]

Etymology for viva gold: akron is Greek for extremity, megas for large — the disease is named for exactly what you see, the hands and feet outgrowing their rings and shoes. Pair that with the gigantism fork and you have the definitional answer examiners want.[1]

[1]

Four axes carry management meaning. A microadenoma (under 10 mm) is usually cured by one operation; a macroadenoma (10 mm or more) is more often invasive, compresses the chiasm, invades the cavernous sinus and leaves residual disease. Densely granulated tumours express abundant somatostatin receptor subtype 2 (SSTR2) and answer to octreotide and lanreotide; sparsely granulated tumours carry fibrous bodies, express little SSTR2, respond poorly to somatostatin receptor ligands and often need the GH-receptor antagonist pegvisomant. Most cases are sporadic, but early onset or a family history should raise MEN1 (MEN1), Carney complex (PRKAR1A), McCune-Albright (mosaic GNAS), familial isolated somatotroph adenoma (germline AIP, classically gigantism in a young man) and the very rare X-linked acrogigantism (Xq26.3 duplication, GPR101).[1][7]

How common, how missed — the eight-year delay

Acromegaly is rare, and it is almost always diagnosed late — that delay is the disease's signature and its main harm. The incidence is about 3 to 4 per million per year and the prevalence 40 to 60 per million in classic series, though active-screening programmes that measure IGF-1 in suspicious cohorts push the figure toward 130 per million, implying a large burden of unrecognised disease. Men and women are affected equally, the mean age at diagnosis is 40 to 45, and a typical patient has had symptoms for 8 to 10 years before the diagnosis is made.[1][2]

Patients rarely reach an endocrinologist first. They arrive through a dentist (widening tooth spaces), a podiatrist (increasing shoe size), a jeweller (ring resizing), a cardiologist (new heart failure) or a diabetologist (new diabetes) — which is why the disease is so often missed until a complication is entrenched. The clinical risk, more than any single cause, is delay: the longer the GH excess smoulders, the more cardiac, articular and metabolic damage accumulates, much of it only partially reversible after cure.[1]

The case for a low-threshold IGF-1: because the phenotype is insidious and the delay is measured in years, a single IGF-1 in any patient with two or more acromegaly-associated features (new diabetes with acral change, refractory sleep apnoea, resistant hypertension, bilateral carpal tunnel, enlarging hands or feet, or an incidental pituitary lesion) is the single highest-yield intervention to shorten that delay. It is cheap, stable and highly discriminating, and the screening studies that used it doubled the apparent prevalence.[1]

[1]

GH to IGF-1 — the one effector axis, and the gsp oncogene that lights it

Acromegaly is autonomous GH hypersecretion from a monoclonal somatotroph adenoma that has stopped listening to feedback — and the molecular driver of roughly a third of those tumours is a single point mutation. In health the hypothalamus balances stimulatory GHRH against inhibitory somatostatin to set the pulsatile rhythm of GH release, which peaks in slow-wave sleep. GH acts mainly through the hepatic GH receptor, switching on the JAK2-STAT5 cascade to drive transcription of IGF-1; both GH and IGF-1 feed back negatively on the somatotroph (short loop) and the hypothalamus (long loop).[6]

The acromegalic adenoma ignores all of that — and crucially, the glucose load that would normally switch GH off fails to do so, which is exactly the principle the 75 g OGTT exploits. Because IGF-1 has a long plasma half-life and reflects integrated GH secretion over days, it is the ideal screening marker; pulsatile GH never is.[1]

The gsp oncogene — the one molecular fact to carry. Somatotrophs are physiologically driven by GHRH through a G-protein-coupled receptor that raises cyclic AMP, activates protein kinase A, phosphorylates CREB, and stimulates both GH secretion and somatotroph proliferation. In about 30 to 40 percent of sporadic somatotroph adenomas a somatic activating mutation in the GNAS gene (encoding the Gs-alpha stimulatory subunit) locks the G-protein in its GTP-bound, permanently on state — the so-called gsp oncogene — producing constitutive, receptor-independent cAMP signalling. The cAMP / PKA / CREB axis is the final common pathway for almost every somatotroph adenoma, which is why it is the target the exam wants.[6]

[6]

Mass effect completes the picture. A macroadenoma compresses the optic chiasm (a bitemporal hemianopia, classically beginning in the superior temporal quadrants), the surrounding normal pituitary (hypopituitarism in the order gonadotrophs, then thyrotrophs, then corticotrophs), and the cavernous sinus (cranial nerves III, IV, V1, V2 and VI).[1]

The slow overgrowth — how the patient actually looks

The clinical face of acromegaly is slow tissue overgrowth layered with metabolic, cardiovascular and mechanical complications that have usually been present for years by the time the diagnosis is made — so describe it system by system, the way the examiner wants.[1][2]

Acral and facial change is the signature. Hands and feet enlarge (rings no longer fit; shoe size climbs), the skin thickens and turns oily, frontal bossing and mandibular prognathism remodel the skull, the interdental spaces widen into a diastema and malocclusion, and the tongue enlarges (macroglossia). A dentist may flag the tooth separation years before anyone measures an IGF-1.[1]

Neurological. Headache (dural stretch, or a true raised-pressure headache), bitemporal hemianopia (the chiasmal sign that demands urgent imaging), and bilateral carpal tunnel syndrome from soft-tissue swelling around the median nerve; a proximal myopathy contributes to the fatigue.[1]

Cardiovascular — the lethal system. Hypertension affects roughly a third to half of patients, driven by sodium retention and a high cardiac output. The heart then develops a specific biventricular hypertrophic acromegalic cardiomyopathy in three recognisable stages: an early hyperdynamic phase (high-output, preserved systolic function), an intermediate phase of biventricular hypertrophy with diastolic dysfunction (exertional dyspnoea, impaired relaxation), and a late phase of systolic heart failure with dilatation, arrhythmia (atrial fibrillation, ventricular ectopy) and valvular regurgitation. Early biochemical control reverses much of this; advanced disease does not.[1][5]

Respiratory. Obstructive sleep apnoea affects over half of patients (macroglossia, a thickened pharynx, a hypertrophied epiglottis, a large neck), the upper airway is hypertrophied, and a goitre may coexist — together these make anaesthesia genuinely hazardous.[5]

Metabolic. Hyperhidrosis and heat intolerance (a GH-driven rise in basal metabolic rate), insulin resistance with impaired glucose tolerance or type 2 diabetes, dyslipidaemia, and hypercalciuria with nephrolithiasis.[1]

Musculoskeletal. The acromegalic arthropathy (knee, hip, spine — from cartilage and bone overgrowth) is one of the least reversible complications, progressing to premature osteoarthritis, deformity and chronic pain; spinal stenosis and carpal tunnel complete the picture.[5]

Other. Visceromegaly (cardiomegaly, hepatosplenomegaly), goitre, colonic polyps and an increased risk of colorectal cancer, skin tags (acrochordons), fatigue, menstrual disturbance or erectile dysfunction, and occasionally galactorrhoea when the tumour co-secretes prolactin.[5]

Split the coarse face — the differential face-off

The decisive discriminator is always the biochemistry, not the face. In true acromegaly the IGF-1 is high and GH fails to suppress on the OGTT; in every mimic the IGF-1 is normal with appropriate suppression.[1]

[1] [2]

The one-line discriminator beneath: a coarse face with a high IGF-1 and a non-suppressible GH is acromegaly; the same face with a normal IGF-1 is pseudoacromegaly, hypothyroidism, pachydermoperiostosis or Cushing — and the OGTT settles it.[1]

The bedside round — old photographs, the visual fields, and the comorbidities

Bedside assessment rarely makes the diagnosis, but it finds the phenotype, the chiasmal sign and the comorbidities that will determine perioperative risk — and it runs in three moves.[1]

• Compare with old photographs. Because the change is insidious, patients and families are poor historians. A driving-licence or wedding photo from 5 to 10 years earlier often reveals the slow coarsening no one has noticed.
• Examine the phenotype and the visual fields. Hands (size, skin thickening, ring tightness, thenar wasting, joint swelling), feet and shoe size, face (frontal bossing, prognathism, dental spacing, macroglossia), skin (oily, skin tags, acanthosis nigricans), then visual fields by confrontation followed by formal Humphrey perimetry for any macroadenoma or visual symptom — the classic deficit is a bitemporal hemianopia, often superior first.
• Hunt the comorbidities. Cranial nerves III, IV, V1, V2 and VI for cavernous sinus involvement, the cardiovascular system (blood pressure, heart sounds, signs of failure), the neck for goitre, the abdomen for organomegaly — and book glucose and HbA1c, lipids, echocardiogram, polysomnography and colonoscopy.[1][2]

Biochemistry before pictures — the three-step diagnostic ladder

Never scan, never operate, until the biochemistry is done. The Endocrine Society algorithm runs in a fixed order: screen with IGF-1, confirm with a 75 g OGTT, localise with MRI — then assess the other pituitary axes and the comorbidities. Examiners expect the exact thresholds.[3]

Step 1 — screen. A single serum IGF-1, age- and sex-matched, is the best screening test, because IGF-1 reflects integrated GH secretion over the preceding days and is far more stable than pulsatile GH. A normal age- and sex-matched IGF-1 effectively excludes acromegaly; an elevated value in the right clinical context mandates confirmation.[3]

Step 2 — confirm. After an overnight fast, give 75 g oral glucose and measure GH at 0, 30, 60, 90 and 120 minutes. In health glucose suppresses GH to a nadir under 1 ng/mL; acromegaly is confirmed when GH fails to suppress under 1 ng/mL. With modern high-sensitivity chemiluminescence assays the consensus cut-off is stricter — under 0.4 ng/mL — because residual secretion in an older normal range can still mean disease.[3][4]

Step 3 — localise. A pituitary MRI with gadolinium finds the adenoma, sizes it (micro versus macro), defines its relationship to the optic chiasm and cavernous sinus, and grades invasion (Knosp grade). If the MRI shows no adenoma, suspect ectopic GHRH: measure a plasma GHRH (markedly elevated) and image chest, abdomen and pelvis with CT for a bronchial carcinoid, pancreatic neuroendocrine tumour or other source.[1][3]

[3]

Step 4 — the other axes. Assess the remaining pituitary hormones for hypopituitarism: 9 am cortisol (or short synacthen test), free T4 and TSH, testosterone or oestradiol with FSH and LH, and prolactin (a macroadenoma may stalk-effect raise it modestly; a co-secreting mammosomatotroph adenoma raises it markedly).[2]

Step 5 — comorbidity bundle. Humphrey perimetry for any macroadenoma or visual symptom, then HbA1c and fasting glucose, lipid profile, echocardiogram (LV mass, systolic and diastolic function), polysomnography, and colonoscopy at diagnosis — because the colorectal polyp and cancer risk demands it.[3][5]

Remission is a paired target, not a single number. Once treated, biochemical control (remission) means a normal age- and sex-matched IGF-1 plus a random GH under 1 ng/mL (or an OGTT GH under 0.4 ng/mL with sensitive assays). These consensus criteria, refined across successive Acromegaly Consensus conferences, are the targets that return mortality toward the general population.[4]

The classic trap — declaring control on GH alone. A high IGF-1 with a normal OGTT nadir can occur in pregnancy, with oestrogen therapy, or in adolescence; a normal IGF-1 with a non-suppressible GH may reflect assay interference or pegvisomant therapy (which lowers IGF-1 without lowering GH). A random GH alone is never diagnostic — GH is pulsatile, peaking after meals, exercise and stress — which is why IGF-1 screens, the OGTT confirms, and both are always read against age- and sex-matched ranges.[4]

Pituitary apoplexy — the one emergency

Acromegaly is overwhelmingly a chronic, elective disease — the one true emergency is pituitary apoplexy, haemorrhagic infarction of the adenoma, and the first drug is hydrocortisone. It presents with sudden severe headache, vomiting, rapidly progressive visual loss, ophthalmoplegia (a cranial nerve III palsy), and in severe cases altered consciousness or meningism.[3][1]

The resuscitation sequence, in order:[3]

• Intravenous hydrocortisone 100 to 200 mg stat, then 50 to 100 mg every 6 to 8 hours — because acute cortisol deficiency from corticotroph destruction is the immediate threat to life. Do not wait for a cortisol result.
• Intravenous fluids and haemodynamic support.
• Urgent pituitary MRI to confirm apoplexy.
• Urgent transsphenoidal surgical decompression if vision is deteriorating or consciousness is depressed; conservative management with close monitoring is acceptable in a stable patient without visual deficit.[1][3]

[1] [3]

A patient who presents in decompensated acromegalic cardiomyopathy (acute heart failure) needs standard heart-failure therapy — oxygen, diuretics, afterload reduction — but the disease-modifying step is biochemical control of the GH and IGF-1.[5]

Surgery first, then suppress — the four-rung ladder

[1]

The treatment is a multimodal, lifelong programme built around four rungs — surgery, somatostatin receptor ligands, the GH-receptor antagonist pegvisomant, and radiotherapy — with cabergoline as an adjunct and comorbidity management running in parallel. The aim is biochemical control (normal IGF-1 plus GH under 1 ng/mL), tumour mass control (relieve chiasmal pressure, prevent regrowth) and protection of remaining pituitary function.[1][3]

Rung 1 — transsphenoidal surgery, first-line. Endoscopic endonasal transsphenoidal resection by an experienced pituitary neurosurgeon is first-line for nearly every patient with a discrete adenoma, and is curative when the tumour is completely removed. Remission runs 75 to 95 percent for microadenomas but only 40 to 60 percent for macroadenomas — lower still for invasive, Knosp grade 3 to 4 tumours. Surgery promptly relieves chiasmal compression and removes the GH source at a stroke; complications in expert hands are hypopituitarism, diabetes insipidus, CSF leak, meningitis and cranial nerve injury, and the definitive reassessment is at 12 weeks with IGF-1 and a random or OGTT GH.[1]

The predictors of surgical remission are a small tumour, no cavernous sinus invasion (Knosp grade 0 to 2), a clearly demarcated adenoma, lower preoperative IGF-1 and GH, and densely granulated histology; the decisive negative predictor is cavernous sinus invasion, where complete resection is usually impossible and residual disease is the rule. A short course of a somatostatin receptor ligand before surgery can shrink the tumour and soften the upper airway for intubation, but it is not routine — it has not consistently improved cure rates — and is reserved for delayed surgery or severe pharyngeal overgrowth.[7]

Rung 2 — somatostatin receptor ligands, the medical backbone. SRLs bind somatostatin receptor subtype 2 (and, for pasireotide, SSTR5) on the somatotroph, suppress GH secretion and shrink the tumour in many patients. They are first-line medical therapy for residual disease after surgery, for patients unfit for or refusing surgery, and increasingly as primary therapy for large invasive macroadenomas without chiasmal compression.[7]

• Octreotide LAR: 20 to 30 mg intramuscularly every 4 weeks (titrate within the 10 to 40 mg range). Densely granulated, SSTR2-rich tumours respond best.
• Lanreotide autogel: 60 to 120 mg deep subcutaneously every 4 weeks (stable patients may extend to every 6 to 8 weeks). Equivalent to octreotide LAR.
• Pasireotide LAR: 40 to 60 mg intramuscularly every 4 weeks — a multireceptor ligand (SSTR5 over 2 over 3) with higher biochemical control rates than octreotide or lanreotide, at the cost of a significant risk of hyperglycaemia and diabetes (monitor blood glucose).
• Common SRL adverse effects: gallstones or sludge, steatorrhoea, abdominal cramps, bradycardia and injection-site reactions.[7]

Rung 3 — pegvisomant, the GH-receptor antagonist. Pegvisomant is a genetically modified GH analogue that blocks the hepatic GH receptor, preventing IGF-1 generation. It normalises IGF-1 in the great majority of patients and is the most biochemically effective monotherapy — but it does not shrink the tumour, because it acts peripherally, so a tumour with mass effect must be co-treated with an SRL or watched with MRI. It is given subcutaneously, starting at 10 mg daily and titrating to 30 mg daily by IGF-1 response; monitor liver enzymes for transaminase elevation and rare hepatotoxicity.[1][7]

Rung 4 — cabergoline and radiotherapy. Cabergoline, a dopamine D2 agonist, has a modest GH-lowering effect and is most useful when the tumour co-secretes prolactin or as an add-on in mild residual disease; doses are higher than for prolactinoma — 1 to 3.5 mg per week (typically 1 to 2 mg weekly). It is oral, cheap and well tolerated, with the caveat of cardiac valve fibrosis at high cumulative doses (monitor echocardiogram). Stereotactic radiotherapy is reserved for refractory or residual disease after surgery and medical therapy, or for patients who cannot adhere to lifelong injections: stereotactic radiosurgery (gamma knife) for a focused fraction, fractionated radiotherapy for larger tumours near the optic nerves. Its drawbacks are a slow onset (12 to 60 months), hypopituitarism (the commonest late effect), and small long-term risks of cerebrovascular disease and secondary tumours.[1][3]

[1] [7] [7]

How acromegaly patients come to harm — the preventable list

Three errors account for most of the preventable harm in acromegaly, and all of them are failures of recognition or of the IGF-1 anchor.[1]

• Missing the diagnosis for years, because the slow phenotype is written off as ageing — the eight-year delay is the disease's signature harm and the reason the cardiac and articular damage is often irreversible by the time the IGF-1 is finally sent.
• Declaring control on GH alone without confirming the age- and sex-matched IGF-1 is normal — GH is pulsatile and a single random value misleads; control is a paired target.
• Missing pituitary apoplexy in a known macroadenoma presenting with sudden headache and visual loss, and delaying IV hydrocortisone while waiting for a cortisol result.
• Forgetting the comorbidities after cure — the arthropathy, cardiomyopathy, sleep apnoea and colonic polyp risk persist or progress even after biochemical control, and the patient still needs an echocardiogram, a sleep study and a colonoscopy for life.
• Drug pitfalls unrecognised — pasireotide hyperglycaemia, pegvisomant hepatotoxicity, SRL gallstones, and cabergoline valve fibrosis at high cumulative dose.[1][5]

The comorbidities that outlive the cure

The complications of acromegaly are why it shortens life, and they persist even after biochemical cure if they were established late — so they are the centre of long-term management. They arise from three converging mechanisms — tissue overgrowth (heart, upper airway, joints, colon), GH-driven metabolic derangement (insulin resistance, lipolysis), and tumour mass effect.[5]

[5]

Cardiovascular disease is the leading cause of death — the acromegalic cardiomyopathy (biventricular hypertrophy with diastolic then systolic dysfunction, arrhythmia, hypertension and valvular regurgitation) tracks biochemical control, but established disease may be only partially reversible.[1]

Obstructive sleep apnoea affects over half of patients and is among the commonest and most under-recognised complications: macroglossia, a thickened pharynx and larynx, a hypertrophied epiglottis and a large neck raise both cardiovascular mortality and anaesthetic risk. A formal polysomnogram is part of the baseline workup and CPAP is first-line; the same upper-airway compromise makes the acromegalic airway a classic difficult intubation.[5]

The acromegalic arthropathy is among the most disabling and least reversible complications — it begins as cartilage overgrowth and joint-space widening (knees, hips, spine) and progresses to premature osteoarthritis, and unlike the soft-tissue changes the joint damage does not reverse with biochemical cure, which is why early diagnosis and treatment are the only way to limit it. Vertebral fractures, spinal stenosis, carpal tunnel and a proximal myopathy complete the picture.[5]

Neoplastic. Acromegaly carries an increased risk of colonic polyps and colorectal cancer, which scales with IGF-1 — the rationale for a colonoscopy at diagnosis and surveillance every 3 to 5 years. Thyroid nodules and differentiated thyroid cancer, and possibly breast and prostate nodules, are over-represented, though the magnitude is debated.[5]

Prognosis and the lifelong sentence

Untreated or poorly controlled acromegaly carries a 2- to 3-fold excess mortality, driven by cardiovascular and respiratory disease (and, to a lesser extent, cancer), shortening median survival by roughly 10 years.[1]

With biochemical control — a normal age- and sex-matched IGF-1 plus a random GH under 1 ng/mL — mortality approaches that of the general population, though established cardiomyopathy, arthropathy and sleep apnoea may persist. Earlier diagnosis and aggressive multimodal treatment improve both survival and quality of life.[1][4]

Disposition is lifelong and lives in a multidisciplinary pituitary tumour centre of excellence (PTCOE): endocrinology, neurosurgery, radiation oncology, ophthalmology, cardiology, sleep medicine, gastroenterology and anaesthetics, with IGF-1 and GH every 3 to 6 months, annual MRI for residual disease, repeat visual fields for macroadenomas, and structured comorbidity surveillance (echo, sleep study, HbA1c and lipids, colonoscopy).[4][5]

[1]

Escalation triggers. If IGF-1 rises despite first-generation SRL monotherapy, the moves in turn are up-titration of the SRL within its dose range, addition of pegvisomant (combination therapy), switch to pasireotide, or addition of cabergoline; if the tumour is growing despite medical therapy or there is refractory mass effect, consider stereotactic radiotherapy, and reoperation for a surgically accessible residual. A rising IGF-1 with a stable or shrinking tumour on an SRL points to biochemical escape, not regrowth, and is usually managed medically rather than with radiation.[7]

Special populations — the difficult airway, pregnancy, and gigantism

The acromegalic airway is the classic difficult intubation and a frequent exam stem. The problems stack: macroglossia, a thickened pharynx and larynx, a hypertrophied epiglottis, a large mandible, a short neck and a large thyroid make laryngoscopy and bag-mask ventilation difficult; the sleep apnoea raises the risk of rapid desaturation and postoperative respiratory depression; and the cardiomyopathy limits cardiovascular reserve. The safe approach is anticipate, seniorise and prepare — senior anaesthetic and ENT support on standby, a documented plan for awake fibre-optic intubation or videolaryngoscopy, a difficult-airway trolley at the bedside, and optimisation of cardiac status first.[1][5]

Pregnancy. Fertility is often impaired through hypogonadotrophic hypogonadism (mass effect) or hyperprolactinaemia, and ovulation may return after surgery or a dopamine agonist. Somatostatin analogues are usually stopped in pregnancy (they cross the placenta), though data are limited; pegvisomant has been continued in selected cases where control cannot be maintained otherwise. Because IGF-1 rises physiologically in pregnancy and cannot be used alone for monitoring, rely on GH and clinical signs, and monitor visual fields monthly (the tumour may enlarge under oestrogen). If vision is threatened, transsphenoidal surgery in the second trimester is the option.[3]

Gigantism in children and adolescents shares the workup and surgery-first pathway; AIP-mutation screening is advised, and a GnRH analogue can delay epiphyseal fusion to protect final height while definitive treatment is delivered. The elderly may present with heart failure or new diabetes alone, the acral change dismissed as ageing; with higher surgical risk, primary medical therapy (an SRL plus or minus pegvisomant) is often preferred when the tumour has no chiasmal compression. In MEN1, screen family members — a somatotroph adenoma may be the index tumour, and parathyroid and pancreatic neuroendocrine tumours need surveillance.[1][2]

Evidence, guidelines, and regional deltas

The Endocrine Society / European Society of Endocrinology 2014 clinical practice guideline (Katznelson et al) remains the practice-defining document — it established surgery as first-line, defined the biochemical diagnostic and remission criteria, and laid out the medical-therapy algorithm including pregnancy management.[3] Successive Acromegaly Consensus conferences (Giustina et al, 2020 and 2026) have refined the multidisciplinary management and the complications framework, the 2026 update consolidating the comorbidity agenda.[4][5] The Colao 2019 Nature Reviews Primer is the comprehensive single reference; the Castinetti and Ioachimescu 2026 treatment-landscape review captures the modern pharmacological algorithm, and the Ben-Shlomo and Melmed 2026 pathogenesis review frames the cAMP-driven molecular story behind the gsp oncogene.[1][6][7]

Where the evidence is weak: the exact GH cut-off for remission (under 1 versus under 0.4 ng/mL) is assay- and consensus-dependent; the role of routine preoperative medical therapy, the place of oral octreotide and paltusotine in the long-term algorithm, and the timing and type of radiotherapy (stereotactic radiosurgery versus fractionated) remain debated.[4][7]

The mantra, and the mnemonics

[1]

The mantra: Screen with IGF-1, confirm with glucose, localise with MRI — surgery first, and cardiovascular death is what kills them.[1][3]

Ward-round test — three stems, thirty seconds each

Stem 1 — the new diabetes and the changing face (answer)

A 42-year-old man has enlarging hands, new type 2 diabetes, snoring, and a bitemporal hemianopia. His dentist sent him because the gaps between his teeth keep widening. What is the single best screening test, and what confirms it? Model: The phenotype is acromegaly, and the single best screening test is a serum IGF-1, age- and sex-matched — a normal value effectively excludes it. If IGF-1 is elevated, confirm with a 75 g oral glucose tolerance test: in acromegaly GH fails to suppress under 1 ng/mL (under 0.4 ng/mL with sensitive assays). Then localise with a pituitary MRI with gadolinium and grade cavernous sinus invasion (Knosp grade). The mantra in one breath: screen with IGF-1, confirm with glucose, localise with MRI.[3]

Stem 2 — the residual tumour after surgery (answer)

Three months after transsphenoidal surgery for a macroadenoma, the IGF-1 is still high. The registrar asks whether to start octreotide or pegvisomant. What is the one mechanistic distinction that decides the answer? Model: The distinction the exam wants is this: somatostatin receptor ligands suppress GH secretion and may shrink the tumour (octreotide LAR 20 to 30 mg IM q4wk, lanreotide 60 to 120 mg SC q4wk, pasireotide 40 to 60 mg IM q4wk), whereas pegvisomant blocks the GH receptor and normalises IGF-1 but does NOT shrink the tumour. So for a residual macroadenoma with mass effect, start an SRL; reserve pegvisomant for tumours without mass effect, or combine it. Pasireotide achieves higher control but raises glucose. Either way the lifelong target is a normal IGF-1 plus GH under 1 ng/mL.[7]

Stem 3 — sudden headache and visual loss (answer)

A known acromegalic with a macroadenoma phones in with sudden severe headache, vomiting and double vision, and on arrival has a dilated pupil and a cranial nerve III palsy. What is the diagnosis, and what is the first drug? Model: This is pituitary apoplexy — haemorrhagic infarction of the adenoma — and the first drug is IV hydrocortisone 100 to 200 mg stat, then 50 to 100 mg every 6 to 8 hours, because acute cortisol deficiency from corticotroph destruction is the immediate threat to life. Do not wait for a cortisol result. Give IV fluids, obtain an urgent pituitary MRI, and arrange urgent transsphenoidal surgical decompression if vision is deteriorating or consciousness is depressed. Conservative management is acceptable only in a stable patient without visual deficit.[3]

References

1. [1]Colao A, Grasso LFS, Giustina A, Melmed S, Chanson P, Pereira AM, Pivonello R. Acromegaly Nat Rev Dis Primers, 2019.PMID 30899019
2. [2]Ershadinia N, Tritos NA. Diagnosis and Treatment of Acromegaly: An Update Mayo Clin Proc, 2022.PMID 35120696
3. [3]Katznelson L, Laws ER Jr, Melmed S, et al. Acromegaly: an endocrine society clinical practice guideline J Clin Endocrinol Metab, 2014.PMID 25356808
4. [4]Giustina A, Barkhoudarian G, Beckers A, Ben-Shlomo A, Biermasz N, Biller B, et al. Multidisciplinary management of acromegaly: A consensus Rev Endocr Metab Disord, 2020.PMID 32914330
5. [5]Giustina A, di Filippo L, Fleseriu M, Pivonello R, Petersenn S, Wass J, et al. Consensus on acromegaly complications: an update Pituitary, 2026.PMID 42050227
6. [6]Ben-Shlomo A, Melmed S, et al. Pathogenesis of nonfamilial somatotroph adenomas J Clin Endocrinol Metab, 2026.PMID 41824769
7. [7]Castinetti F, Ioachimescu AG. Current treatment landscape of acromegaly J Clin Endocrinol Metab, 2026.PMID 41965092