Growth hormone deficiency

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

Growth hormone contributes to body composition, lipid handling, bone remodelling, muscle performance and psychological wellbeing beyond linear growth. Adult deficiency can therefore have meaningful morbidity, yet its manifestations overlap with depression, sleep disorders, obesity, menopause, chronic inflammatory disease, anaemia and the effects of other pituitary deficits. Testing should begin with a credible anatomical or endocrine pre-test probability.

Secretion is pulsatile and falls with age and higher body mass, so neither a random growth-hormone value nor an isolated low-normal IGF-1 establishes the diagnosis. Dynamic testing challenges the hypothalamic-pituitary reserve. Insulin-induced hypoglycaemia is a traditional reference test, but glucagon stimulation or a licensed oral secretagogue test may be safer alternatives in selected patients. Every response threshold belongs to a specific protocol, assay and clinical context.

Replacement is not an empirical energy tonic. A specialist confirms eligibility, optimises other axes, excludes active neoplasia, records baseline quality of life and cardiometabolic status, teaches an injection device and titrates cautiously. NICE continuation depends on meaningful benefit, while long-term care balances IGF-1, symptoms, bone and metabolic outcomes against fluid retention, glucose intolerance and tumour surveillance.

Key points

Adult growth-hormone deficiency is most credible after pituitary or hypothalamic disease, surgery, radiotherapy, trauma, genetic disease or multiple other pituitary deficits; fatigue and central adiposity alone are not diagnostic.
Recognised effects include impaired quality of life, reduced exercise capacity and lean mass, increased visceral fat, adverse lipids and reduced bone density, but each is nonspecific and alternative causes remain important.
A random growth-hormone concentration cannot diagnose deficiency because normal secretion is pulsatile; IGF-1 supports the assessment but a value inside the reference range does not reliably exclude disease.
Most adults require a supervised dynamic stimulation test chosen for comorbidity, local expertise and assay; insulin tolerance testing is hazardous in seizure or significant cardiovascular or cerebrovascular disease.
Establish and safely replace cortisol deficiency before adjusting thyroid hormone or performing a provocative test that could precipitate hypoglycaemia or physiological stress.
NICE TA64 restricts somatropin for adult-onset deficiency to severe biochemical disease, significant QoL-AGHDA impairment and appropriate treatment of other pituitary deficits, with a defined nine-month benefit review.
Somatropin is titrated individually to clinical response and age-adjusted IGF-1 rather than body weight alone; oedema, arthralgia, carpal-tunnel symptoms and dysglycaemia commonly signal excessive exposure.
Active tumour must be excluded and prior intracranial disease remains under surveillance; new severe headache or visual symptoms require reassessment rather than assuming a benign replacement adverse effect.
Young people treated for childhood-onset deficiency need a named transition plan and usually reassessment after linear growth, while permanent structural or genetic contexts may alter how confirmation is approached.

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

Pituitary or hypothalamic lesion

Tumours and structural hypothalamic-pituitary disease can reduce growth-hormone secretion, often alongside deficits in cortisol, thyroid or gonadal axes.

Pituitary treatment or injury

Surgery, cranial radiotherapy or trauma may damage somatotroph cells or their hypothalamic control and can produce evolving deficiency over time.

Persistent childhood-onset deficiency

Congenital or childhood pituitary disease may continue into adulthood, but adult retesting is needed when permanent structural deficiency is not already established.

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

1
Pulsatile growth hormone falls
Reduced hypothalamic stimulation or pituitary reserve lowers episodic growth-hormone secretion, which cannot be assessed reliably with one random concentration.
2
IGF-1 signalling decreases
Lower growth-hormone action reduces hepatic and peripheral IGF-1 effects on muscle, fat, bone remodelling and lipid handling.
3
Adult functional effects accumulate
Body composition, exercise performance, bone strength and psychological wellbeing may deteriorate gradually, overlapping with many common non-endocrine conditions.

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

Relevant pituitary history

A sellar tumour, cranial irradiation, pituitary surgery, apoplexy, infiltrative disease, traumatic brain injury or congenital hypothalamic-pituitary disorder substantially raises pre-test probability.

Multiple-axis deficiency

Coexisting ACTH, TSH and gonadotrophin deficits make organic growth-hormone deficiency more plausible, while also providing competing explanations for fatigue and body-composition change.

Body-composition change

Reduced lean mass, increased central adiposity and impaired exercise capacity can occur, but require comparison with ageing, physical inactivity, medicines and nutritional state.

Metabolic and skeletal effects

Adverse lipids, reduced bone mineral density and fracture vulnerability may accompany longstanding deficiency and should be treated by their own risk pathways as well as endocrine care.

Quality-of-life burden

Low energy, reduced concentration, social withdrawal and diminished wellbeing are relevant only after depression, sleep disturbance and inadequately replaced cortisol, thyroid or gonadal axes are addressed.

Childhood-onset transition

A young adult previously receiving growth hormone may still need replacement for bone and body composition, but childhood idiopathic deficiency can resolve and often warrants formal retesting.

Possible treatment excess

New oedema, joint stiffness, paraesthesia, carpal-tunnel symptoms, headache or worsening glucose after starting somatropin suggests that dose or safety needs review.

Red flags requiring action

Hypotension, vomiting, hypoglycaemia, hyponatraemia or reduced consciousness in pituitary disease suggests cortisol deficiency; give emergency glucocorticoid treatment before pursuing growth-hormone testing.
Severe hypoglycaemia, seizure, loss of consciousness or ischaemic symptoms during a dynamic test requires immediate protocol resuscitation and termination of the study.
New visual-field loss, ophthalmoplegia or abrupt severe headache may indicate pituitary tumour growth or apoplexy and needs urgent imaging and specialist assessment.
Evidence of active malignancy or progressive intracranial tumour precludes routine somatropin initiation and requires oncology-endocrinology review under the current product information.
Papilloedema symptoms, severe recurrent headache, visual disturbance, nausea or vomiting after replacement can indicate intracranial hypertension and warrant urgent examination and treatment interruption advice.
Somatropin in an acute critical illness following major surgery, polytrauma or respiratory failure raises a specific safety concern; the responsible endocrine and critical-care teams must review continuation.

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
Clinical pre-test probability assessmentFirst step
Why
Establish whether hypothalamic-pituitary disease is sufficiently likely to justify specialist dynamic testing.
Interpretation and limitations
Structural lesions, cranial treatment and multiple pituitary deficits strengthen the case; nonspecific fatigue without such context should redirect evaluation toward more common causes.
02
Age-adjusted serum IGF-1
Why
Provide a stable supportive marker of growth-hormone action and a later replacement target.
Interpretation and limitations
A low result supports deficiency but may reflect malnutrition, hepatic disease, uncontrolled diabetes or oral oestrogen; a normal result does not exclude organic adult deficiency.
03
Insulin tolerance test
Why
Assess growth-hormone and often ACTH reserve through supervised insulin-induced hypoglycaemia when safe.
Interpretation and limitations
The test is valid only if the protocol achieves adequate hypoglycaemia; interpret peak hormone using local assay criteria and avoid it with seizure disorder or important cardiac or cerebrovascular disease.
04
Alternative dynamic stimulation test
Why
Evaluate reserve when insulin tolerance testing is contraindicated, impractical or unsuitable.
Interpretation and limitations
Glucagon or a locally available licensed secretagogue test has its own timing, contraindications and body-mass or assay considerations; thresholds are not interchangeable between methods.
05
Complete pituitary-axis profile
Why
Identify deficiencies that require prior treatment and confirm the wider organic context.
Interpretation and limitations
Assess morning cortisol or reserve, free T4 with TSH, prolactin, gonadotrophins and sex hormones; correct cortisol first and interpret central axes rather than relying on trophic hormones alone.
06
Pituitary MRI review
Why
Define the underlying lesion and establish tumour stability before replacement when structural disease is known or suspected.
Interpretation and limitations
Compare with prior imaging, treatment and pathology; an empty sella or small incidental lesion alone does not prove severe growth-hormone deficiency.
07
QoL-AGHDA questionnaire
Why
Document disease-specific quality-of-life impairment and meet the NICE adult treatment framework where applicable.
Interpretation and limitations
For adult-onset treatment under TA64, use the stated baseline eligibility threshold and repeat at nine months; a sub-threshold improvement triggers discontinuation under the guidance.
08
Baseline metabolic and bone assessment
Why
Measure treatable comorbidity and provide safety comparators before somatropin.
Interpretation and limitations
Record weight, waist or body composition where used, blood pressure, glucose or HbA1c, lipids and clinically indicated DXA or fracture evaluation rather than attributing every abnormality to one axis.

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

Obesity

Higher body mass physiologically reduces growth-hormone responses and can reproduce fatigue and altered body composition without true pituitary deficiency.

Depression or sleep disorder

Low mood, poor concentration, fatigue and reduced activity commonly mimic the syndrome; a credible pituitary context and valid dynamic testing discriminate it.

Other pituitary hormone deficits

Untreated cortisol, thyroid or gonadal deficiency can cause similar symptoms and must be identified and optimised before attributing morbidity to growth hormone.

Chronic systemic disease

Anaemia, inflammatory disease and menopause can alter energy, muscle and bone outcomes without impaired pituitary growth-hormone reserve.

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

01ASSESSPossible adult deficiencyFirst stepSymptoms occur in a person with pituitary disease, cranial treatment or another credible hypothalamic-pituitary risk.

1Confirm the anatomical and treatment history, review every pituitary axis, medicines, sleep, mood, nutrition and systemic disease, and document objective morbidity.
2Measure IGF-1 in an assay-aware context, recognising influences that can lower it and that a normal result may not exclude organic disease.
3Stabilise cortisol and other clinically important deficits before choosing a dynamic test; never provoke hypoglycaemia in an unsafe setting.
4Have an endocrinologist select and interpret the validated stimulation protocol, integrating the result with pre-test probability rather than labelling symptoms alone.

02INITIATESpecialist somatropin trialSevere deficiency and the applicable NICE eligibility requirements have been documented.

1Exclude active tumour, review prior malignancy and intracranial imaging, optimise other hormone replacement, record QoL-AGHDA, glucose, lipids, weight and bone risk.
2Agree realistic goals, product choice, injection training, storage, missed-dose advice and prescribing ownership through the specialist or shared-care pathway.
3Start the age- and comorbidity-appropriate product dose and titrate gradually from IGF-1, clinical benefit and oedema, joint, nerve and metabolic adverse effects.
4Complete the NICE nine-month quality-of-life reassessment after the initial titration and stop adult-onset treatment when the required improvement is not achieved.

03TRANSITIONChildhood-onset transferLinear growth is complete or a young person approaches transfer from paediatric growth-hormone care.

1Create a named handover containing original diagnosis, stimulation tests, MRI, genetics, treatment response, other axes, cancer history and current device.
2Pause and retest using the transition service protocol when persistence is uncertain; do not assume an idiopathic childhood label remains valid forever.
3For persistent severe deficiency arising before age 25, apply NICE advice on treatment through attainment of adult peak bone mass, then reassess adult continuation criteria.
4Protect uninterrupted cortisol, thyroid or AVP replacement during retesting and support self-management, fertility, education, work and prescription continuity.

04ADVERSESymptoms during replacementOedema, arthralgia, paraesthesia, headache, visual symptoms or worsening glycaemia occurs after starting or increasing somatropin.

1Assess timing, dose, injection technique, IGF-1, glucose, blood pressure and other causes; reduce or pause treatment under specialist advice when exposure is excessive.
2Examine urgently for papilloedema or tumour symptoms when headache is severe, recurrent or accompanied by nausea or visual change.
3Revisit thyroid and cortisol replacement because growth hormone can alter peripheral thyroid handling and reveal latent central insufficiency.
4Resume only with an explicit lower-dose and surveillance plan when serious pathology is excluded and expected benefit continues to justify risk.

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

Replace deficient growth-hormone action to improve eligible adults' quality of life, body composition, metabolic profile and bone-related outcomes.

Somatropin

Use the selected licensed subcutaneous preparation at a low individual starting dose, then titrate gradually to age-adjusted IGF-1, response and adverse effects under specialist care.

Do not use with active tumour and review acute critical illness; monitor oedema, arthralgia, carpal tunnel, glucose, headache or papilloedema, thyroid and cortisol needs and recurrence of prior intracranial disease.

Prevent adrenal crisis while other pituitary deficits are investigated and treated.

Hydrocortisone replacement

Establish the current physiological endocrine regimen and stress-dose education before provocative testing or somatropin when ACTH deficiency is present.

Never delay emergency parenteral hydrocortisone for testing in an acutely unwell patient; both under-replacement and chronic excess can mimic poor wellbeing attributed to growth-hormone deficiency.

Correct a common coexisting pituitary deficit so symptoms and somatropin benefit can be interpreted fairly.

Levothyroxine for central hypothyroidism

After cortisol safety is secured, titrate the individual oral regimen using free T4 and clinical assessment rather than TSH alone.

Growth-hormone replacement may lower free T4 or reveal central hypothyroidism; reassess after initiation or dose change and avoid using a suppressed or normal TSH as the dose target.

Treat persistent hypogonadism and support bone, sexual and general health before attributing residual quality-of-life symptoms to growth hormone.

Gonadal hormone replacement

Use an individual oestrogen- or testosterone-based specialist regimen after fertility goals, contraindications and sex-specific monitoring have been reviewed.

Oral oestrogen can alter IGF-1 response and somatropin requirement; contraception, thrombosis, cancer, haematocrit, prostate and uterine safeguards depend on the chosen medicine.

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

Adverse body composition

Reduced anabolic signalling can lower lean mass and increase central fat, contributing to impaired physical function and metabolic risk.

Low bone strength

Reduced bone remodelling and coexistence of other pituitary deficits can decrease bone density and increase fracture vulnerability.

Cardiometabolic burden

Unfavourable lipid handling and body composition may add cardiovascular risk, although comorbidity and other hormone deficits also influence outcomes.

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

Review monthly during early titration where the local protocol requires, checking IGF-1, symptoms, injection technique, adherence and fluid-retention or nerve-compression effects before each increase.
Keep IGF-1 within the specialist age-adjusted target and avoid chasing the upper range when clinical benefit is already present or adverse effects emerge.
Repeat QoL-AGHDA at nine months for NICE adult-onset eligibility and document whether the required improvement supports continuation rather than allowing an open-ended unassessed trial.
Monitor glucose or HbA1c, weight, waist or body composition, blood pressure and lipids, particularly in older adults or those with obesity, diabetes or steroid replacement.
Recheck free T4 and review cortisol safety after initiation and dose changes because somatropin can expose inadequate central thyroid or adrenal replacement.
Maintain MRI or oncology surveillance appropriate to the original pituitary lesion, cranial irradiation or previous malignancy; investigate new headache or visual change promptly.
Review bone density, vertebral fracture risk and vitamin D or osteoporosis treatment at a clinically appropriate interval; bone benefit develops slowly and does not replace standard fracture prevention.
Confirm product, device, supply route, injection-site health and shared-care responsibilities at every transfer, as brands and devices are not casually interchangeable.

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

Probability precedes provocation

Dynamic tests perform best when a structural or multi-axis context makes deficiency plausible; indiscriminate testing of fatigue creates false labels.

Normal IGF-1 is not an exclusion test

Adults with organic pituitary disease can have a value inside the age range, particularly when pre-test probability is high enough to justify stimulation testing.

The test chooses the threshold

Insulin, glucagon and secretagogue protocols generate different responses, while assay and body mass also matter; one numerical cut-off cannot migrate safely between them.

Quality of life is a formal outcome

Under NICE TA64, baseline and nine-month QoL-AGHDA scores are treatment criteria, not decorative questionnaires added after prescribing.

Oral oestrogen changes dose biology

First-pass hepatic exposure can blunt IGF-1 generation, so starting, stopping or changing route needs specialist reinterpretation rather than automatic escalation.

Childhood labels may not persist

Some isolated childhood-onset cases recover at transition, whereas structural, genetic or multiple-axis disease has a much stronger likelihood of continuing into adulthood.

More hormone is not more vitality

Fluid retention, arthralgia and dysglycaemia increase with excessive exposure; replacement seeks physiological benefit, not supraphysiological performance enhancement.

11Common pitfallsFrequent interpretation and management errors.

01
Do not diagnose adult growth-hormone deficiency from tiredness, obesity, one low IGF-1 or a random growth-hormone sample.
02
Do not perform an insulin tolerance test without experienced supervision, rescue facilities, adequate cortisol assessment and explicit screening for seizure and vascular contraindications.
03
Do not use a stimulation-test threshold borrowed from another assay, protocol or body-mass context.
04
Do not start somatropin before active tumour is excluded, other pituitary deficits are appropriately treated and baseline benefit measures are recorded.
05
Do not titrate to symptoms alone or exceed an age-adjusted IGF-1 target in pursuit of nonspecific energy improvement.
06
Do not ignore oedema, carpal-tunnel symptoms, hyperglycaemia or severe headache as unavoidable features of effective replacement.
07
Do not continue an adult-onset trial indefinitely without the NICE nine-month QoL-AGHDA benefit assessment.
08
Do not allow growth-hormone retesting at transition to interrupt life-preserving cortisol, thyroid or AVP treatment.