Acromegaly

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Growth hormone is secreted in pulses and stimulates hepatic and peripheral IGF-1. When exposure begins after growth plates have fused, stature does not increase; instead, hands, feet, facial bones, tongue, skin and viscera change slowly. The delay to diagnosis allows cardiovascular, respiratory, metabolic, neoplastic and musculoskeletal morbidity to accumulate before the pituitary lesion is discovered.

Diagnosis is biochemical, not visual. An elevated age-adjusted IGF-1 compatible with the clinical setting is the central screening signal, while failure of growth hormone to suppress during a locally validated glucose test can support confirmation. Random growth hormone is unreliable because secretion is pulsatile. Discordance merits repeat expert interpretation rather than forcing the result to fit the photograph or MRI.

Treatment aims are broader than removing a sellar mass. The pituitary multidisciplinary team seeks safe tumour control, biochemical normalisation, preservation or replacement of other axes and reduction of excess mortality. Residual hypertension, diabetes, obstructive sleep apnoea, joint damage and fracture risk need their own continuing treatment even after IGF-1 is controlled.

Key points

Acromegaly is usually caused by a growth-hormone-secreting pituitary adenoma; excess insulin-like growth factor 1 drives gradual soft-tissue, skeletal and metabolic change after epiphyseal closure.
Compare old photographs, ring and shoe size, facial contour, dentition, voice, sweating and hand symptoms because the patient and clinician may normalise a phenotype that evolved over years.
Measure age-adjusted IGF-1 first when suspicion is credible; repeat a discordant result and consider nutrition, hepatic or renal disease, poorly controlled diabetes, pregnancy, oral oestrogen and assay factors.
An oral glucose tolerance test assessing growth-hormone suppression can resolve uncertainty, but interpretation must use the laboratory's validated assay and endocrine protocol rather than a universal cut-off.
Dedicated pituitary MRI follows biochemical confirmation, with formal visual fields for optic pathway contact and a complete assessment of the remaining pituitary axes.
Transsphenoidal surgery is usual first-line treatment for a resectable adenoma; postoperative biochemistry determines whether surveillance, repeat surgery, medicine or radiotherapy is appropriate.
Long-acting somatostatin receptor ligands, cabergoline and the growth-hormone receptor antagonist pegvisomant have distinct biochemical, tumour and safety monitoring profiles and require specialist selection.
Control of hormone excess does not erase established risk: actively assess blood pressure, glucose, sleep apnoea, cardiovascular disease, arthropathy, vertebral fracture, thyroid disease and colorectal risk.
Sudden severe headache, visual deterioration, ophthalmoplegia or haemodynamic illness suggests pituitary apoplexy or acute cortisol deficiency and overrides the routine acromegaly pathway.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Somatotroph pituitary adenoma

Autonomous growth-hormone secretion from a pituitary adenoma raises integrated IGF-1 exposure, producing the characteristic progressive soft-tissue, skeletal and metabolic changes.

Mixed pituitary secretion

Some pituitary tumours secrete growth hormone alongside another pituitary hormone, so co-secretion and compression-related deficiency must be assessed rather than assuming an isolated axis disorder.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Growth hormone becomes autonomous
Adenomatous pituitary cells release growth hormone without normal physiological control, while pulsatile secretion makes a single random concentration an unreliable representation of total exposure.
2
IGF-1 mediates tissue growth
Growth hormone stimulates hepatic and peripheral IGF-1, which drives gradual enlargement of acral tissues, facial bones, tongue, skin and internal organs after epiphyseal closure.
3
Metabolic and structural injury accumulates
Persistent hormone exposure promotes insulin resistance, cardiovascular remodelling, sleep-disordered breathing, arthropathy and skeletal fragility, with some damage continuing despite later biochemical control.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Acral enlargement

Tight rings, larger gloves or shoes, broad spade-like hands, heel-pad thickening and progressive soft-tissue bulk are classic longitudinal clues.

Facial and oral change

Coarsened features, frontal prominence, enlarged nose or lips, macroglossia, prognathism, interdental spacing and a deeper voice often become obvious when photographs are compared.

Skin and nerve effects

Excess sweating, oily thickened skin, skin tags, paraesthesia and bilateral carpal-tunnel symptoms reflect soft-tissue and neural compression effects.

Cardiometabolic phenotype

Hypertension, insulin resistance or diabetes, left-ventricular hypertrophy, cardiomyopathy and arrhythmia may dominate risk even when appearance seems mildly changed.

Respiratory sleep burden

Snoring, witnessed apnoea, daytime somnolence and difficult airway anatomy should prompt formal assessment for obstructive sleep apnoea.

Pituitary mass presentation

Headache, bitemporal field loss, diplopia, menstrual disturbance, sexual dysfunction or secondary adrenal and thyroid deficits can arise from the adenoma rather than hormone excess itself.

Musculoskeletal morbidity

Back pain, kyphosis, vertebral fracture, degenerative large-joint pain and limited function can persist after biochemical control and should not be dismissed as normal ageing.

Red flags requiring action

Thunderclap or rapidly severe headache with visual loss, ophthalmoplegia, vomiting or reduced consciousness may be pituitary apoplexy and needs emergency hydrocortisone assessment, MRI and pituitary-neurosurgical contact.
Hypotension, hyponatraemia, hypoglycaemia, profound weakness or recurrent vomiting in a patient with a large pituitary tumour can indicate ACTH deficiency and requires immediate glucocorticoid protection.
Rapidly worsening acuity or field loss indicates threatened vision from tumour or haemorrhage and warrants same-day specialist assessment rather than routine endocrine follow-up.
Chest pain, syncope, decompensated heart failure or a significant arrhythmia needs acute cardiovascular management alongside endocrine review because acromegalic cardiomyopathy can be clinically important.
Severe daytime sleepiness with safety-critical driving or perioperative airway concern requires prompt sleep and anaesthetic planning, not reassurance based on eventual tumour treatment.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Age-adjusted serum IGF-1First step
Why
Screen for integrated growth-hormone action and provide the main biochemical treatment target.
Interpretation and limitations
Confirm elevation against the laboratory's age and assay range; repeat unexpected results after reviewing nutritional state, liver or renal disease, diabetes, pregnancy and oral oestrogen.
02
Oral glucose growth-hormone suppression test
Why
Test whether physiological glucose-mediated suppression is lost when diagnosis remains uncertain.
Interpretation and limitations
Use the endocrine unit's glucose load, sampling schedule and assay-specific threshold; adequate suppression argues against active acromegaly, while diabetes can complicate interpretation.
03
Dedicated contrast pituitary MRI
Why
Localise the adenoma and define size, chiasmal contact, cavernous sinus involvement and resectability after biochemical confirmation.
Interpretation and limitations
A small incidental lesion does not replace valid biochemistry; an invasive macroadenoma changes surgical expectation and long-term imaging needs.
04
Formal visual-field assessment
Why
Quantify optic pathway function when MRI shows contact or the history suggests visual loss.
Interpretation and limitations
Bitemporal loss supports chiasmal compression; worsening fields accelerate intervention even if central acuity remains apparently preserved.
05
Complete pituitary hormone profile
Why
Detect co-secretion and deficiencies before surgery or medical treatment.
Interpretation and limitations
Assess morning cortisol urgently, free T4 with TSH, prolactin, gonadotrophins and sex hormones; do not infer central sufficiency from a normal-looking trophic hormone alone.
06
Cardiometabolic and sleep assessment
Why
Establish modifiable complications that influence perioperative and long-term risk.
Interpretation and limitations
Record blood pressure, HbA1c or glucose, ECG and clinically indicated echocardiography; use a validated sleep pathway rather than symptom history alone when apnoea is likely.
07
Bone thyroid and colorectal risk review
Why
Identify recognised associated morbidity requiring surveillance outside the pituitary axis.
Interpretation and limitations
Consider vertebral imaging or bone assessment, thyroid examination or ultrasound when indicated, and colonoscopic timing through current local and specialty guidance rather than an automatic identical schedule for everyone.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Normal constitutional features

Stable large hands or coarse facial features without documented progression are less suggestive; serial photographs, ring size and shoe size help demonstrate genuine longitudinal change.

Pseudoacromegaly

Severe insulin resistance or other non-growth-hormone states can resemble the phenotype, but repeatedly normal, well-interpreted age-adjusted IGF-1 argues against active acromegaly.

Incidental pituitary lesion

A small sellar lesion may be unrelated; compatible repeated biochemistry must support hormone excess before the MRI finding is treated as causal.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01CONFIRMSuspected acromegalyFirst stepProgressive acral or facial change, characteristic complications or an incidental pituitary lesion creates credible suspicion.

1Document longitudinal physical change, associated morbidity, medicines, pregnancy or oestrogen exposure and the symptoms of pituitary compression or deficiency.
2Measure age-adjusted IGF-1 and repeat a borderline or discordant result after addressing reversible physiological, systemic and assay influences.
3Use the local oral glucose growth-hormone suppression protocol when confirmation is required; do not substitute one random growth-hormone sample.
4After biochemical confirmation, arrange dedicated MRI, vision assessment when indicated, complete pituitary profiling and referral to a pituitary multidisciplinary team.

02OPERATEResectable pituitary adenomaA growth-hormone-secreting lesion is technically suitable for surgery and the patient accepts operative management.

1Optimise diabetes, blood pressure, sleep apnoea, airway and cardiovascular risk with endocrine, anaesthetic and surgical teams; consider preoperative medicine only for a defined benefit.
2Undertake transsphenoidal resection in an experienced pituitary centre, preserving normal gland where feasible and documenting tissue for expert pathology.
3Monitor early cortisol, sodium, fluid balance, vision and neurological state, treating adrenal insufficiency or AVP disturbance promptly.
4Reassess IGF-1 and growth hormone at the correct postoperative interval, then classify remission, residual disease or discordance before additional treatment.

03PERSISTPersistent or unresectable diseaseBiochemical activity remains after surgery or safe complete resection is not possible.

1Reconfirm biochemical activity, review postoperative MRI and pathology and define whether mass control or hormonal control is the dominant problem.
2Select a long-acting somatostatin receptor ligand, cabergoline, pegvisomant, further surgery or a combination according to tumour receptors, disease severity, glucose status and patient preference.
3Apply current NHS commissioning criteria to high-cost therapy and monitor the treatment-specific risks rather than using IGF-1 as the only safety check.
4Consider stereotactic or fractionated radiotherapy for selected residual disease, explaining delayed efficacy, hypopituitarism and the need for lifelong imaging and hormonal surveillance.

04COMPLICATIONSWhole-person risk reductionAcromegaly is diagnosed or biochemical control has been achieved after treatment.

1Screen and actively treat hypertension, dysglycaemia, sleep apnoea and cardiovascular disease using the relevant national and local pathways.
2Assess joint disability, carpal tunnel, vertebral fracture and bone health, offering analgesic, surgical, rehabilitation or osteoporosis care where indicated.
3Plan thyroid and colorectal assessment from current specialist guidance, age, symptoms, previous findings and local screening arrangements.
4Review quality of life, body-image change, work, driving, fertility and mental health because biochemical remission alone may not restore function.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

Suppress adenoma growth-hormone secretion and sometimes reduce tumour volume in persistent, unresectable or selected preoperative disease.

Long-acting somatostatin receptor ligand

Use the current product-specific intramuscular or deep-subcutaneous specialist regimen and titrate at labelled intervals from IGF-1, symptoms and tolerability.

Monitor gallbladder effects, gastrointestinal symptoms, bradycardia, glucose, thyroid and injection complications; pasireotide has a particularly important hyperglycaemia burden and selection is specialist.

Block peripheral growth-hormone receptors when other treatment has not achieved adequate biochemical control.

Pegvisomant

Initiate and titrate subcutaneous treatment only through the current specialist commissioning policy, using age-adjusted IGF-1 rather than growth hormone to guide effect.

Check liver tests and injection sites and continue MRI surveillance because growth hormone concentrations are not interpretable for response and tumour secretion is not directly suppressed.

Provide an oral dopamine-agonist option that can lower IGF-1 in selected milder disease or contribute to combination treatment.

Cabergoline

Use a low oral specialist dose with gradual titration under the current BNF and SmPC, most often for modest residual activity or mixed prolactin secretion.

Review nausea, postural hypotension, somnolence, impulse-control change and cardiac or fibrotic surveillance requirements; biochemical non-response should not prolong ineffective treatment.

Prevent adrenal crisis and restore endocrine function lost through tumour, surgery or radiotherapy.

Pituitary hormone replacement

Replace each confirmed deficient axis with the endocrine regimen, establishing cortisol cover before levothyroxine and matching gonadal or AVP treatment to individual need.

Recovery and new late deficits are both possible; TSH cannot titrate central hypothyroidism and desmopressin without water-balance education risks severe hyponatraemia.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Cardiometabolic disease

Hypertension, diabetes, ventricular hypertrophy, cardiomyopathy and arrhythmia arise through sustained growth-hormone and IGF-1 effects and materially influence long-term risk.

Obstructive sleep apnoea

Macroglossia and upper-airway soft-tissue enlargement narrow the airway, causing snoring, nocturnal obstruction, daytime somnolence and additional cardiovascular burden.

Persistent musculoskeletal morbidity

Joint degeneration, carpal-tunnel compression and vertebral damage may remain after hormone control because established bony and soft-tissue changes are not fully reversible.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Follow age-adjusted IGF-1 with the same validated assay where possible, timed to the chosen therapy; investigate persistent clinical-biochemical discordance rather than escalating reflexively.
Use growth hormone only in the context of the relevant postoperative or treatment protocol, recognising that pegvisomant makes the concentration unsuitable for assessing biochemical control.
Repeat pituitary MRI according to residual tumour, therapy and prior growth; obtain earlier imaging for new headache, vision change, cranial neuropathy or unexpected biochemical deterioration.
Reassess cortisol, thyroid, gonadal and water balance after surgery and periodically after radiotherapy because hormone loss may evolve years later.
Track blood pressure, glucose or HbA1c, weight, sleep-apnoea treatment and cardiovascular symptoms even after remission, escalating to cardiology or respiratory care when indicated.
Review product-specific medicine safety including liver tests with pegvisomant, glucose and gallbladder effects with somatostatin analogues, and dopamine-agonist behavioural or fibrotic harms.
Monitor pain, mobility, carpal-tunnel symptoms, vertebral health, thyroid findings, colorectal follow-up and patient-reported quality of life as separate outcomes from hormone values.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Photographs are longitudinal data

A decade-old portrait may demonstrate jaw, nose and brow change more convincingly than a single physical examination in an unfamiliar patient.

Normal random growth hormone proves little

Pulsatile secretion creates low troughs even in disease, so screening rests on IGF-1 and confirmation on a validated dynamic context.

A normal IGF-1 needs context

Severe liver disease, malnutrition, uncontrolled diabetes or oral oestrogen can lower IGF-1 and conceal otherwise credible growth-hormone excess.

Control is not cure of morbidity

Bony enlargement, osteoarthritis, vertebral damage and some cardiometabolic risk can persist despite excellent postoperative biochemistry.

Pegvisomant changes the marker

Receptor blockade can raise circulating growth hormone while normalising IGF-1, so the former should not drive dose escalation.

Radiotherapy is a delayed trade-off

Hormonal benefit may take years, while pituitary deficits can emerge long afterwards; both bridge therapy and lifelong surveillance require ownership.

11Common pitfallsFrequent interpretation and management errors.

01
Do not diagnose acromegaly from appearance or an incidental pituitary MRI without compatible, repeated, assay-aware biochemistry.
02
Do not exclude disease with one random growth-hormone concentration or apply a suppression threshold from a different assay uncritically.
03
Do not order MRI as the first screening test and then let a tiny incidental lesion override a normal, well-interpreted IGF-1.
04
Do not consider transsphenoidal surgery complete care without postoperative cortisol, sodium, vision and timed biochemical assessment.
05
Do not monitor pegvisomant using growth hormone or omit liver testing and interval tumour imaging.
06
Do not discharge patients from cardiometabolic, sleep, bone and colorectal risk management simply because IGF-1 normalises.
07
Do not promise reversal of established facial, skeletal or joint change; discuss realistic functional and cosmetic outcomes with sensitivity.