Hypopituitarism
Partial or complete deficiency of anterior pituitary hormones (± posterior). Causes include pituitary adenoma, surgery, radiotherapy, Sheehan syndrome, and infiltrative disease. Presents with features of target organ hormone deficiency. Cortisol deficiency is most acutely dangerous. Requires lifelong hormone replacement.
Key Facts
Definition: deficiency of one or more anterior pituitary hormones; panhypopituitarism = all anterior pituitary hormones deficient Commonest cause: pituitary adenoma (non-functioning or treated); also surgery, radiotherapy, Sheehan syndrome (postpartum pituitary necrosis), apoplexy, infiltrative (sarcoidosis, haemochromatosis, histiocytosis), TBI, empty sella Hormone loss order (typically): GH → LH/FSH (gonadotrophins) → TSH → ACTH → (prolactin — rare); GH is most sensitive to damage, ACTH most resistant Most dangerous deficiency: ACTH (cortisol) — can cause fatal adrenal crisis; must be replaced BEFORE thyroxine (thyroxine increases cortisol metabolism → may precipitate adrenal crisis) Diagnosis: basal pituitary hormones + target organ hormones; insulin tolerance test (ITT) — gold standard for GH and ACTH deficiency (induces hypoglycaemia → assesses cortisol and GH response) Sheehan syndrome: postpartum pituitary necrosis (massive obstetric haemorrhage → pituitary infarction); failure to lactate, failure to resume menses, fatigue, hypothyroidism
Overview
Key Facts
Hypopituitarism requires systematic assessment of all pituitary axes. Cortisol replacement must precede thyroxine. GH deficiency is common after pituitary surgery/radiotherapy and contributes significantly to quality of life impairment.
Epidemiology
Prevalence ~40-50 per 100,000. More common with age (pituitary adenomas). Sheehan syndrome: rare in developed countries but still common worldwide.
Aetiology
Pituitary adenoma (most common overall), pituitary surgery, cranial radiotherapy, Sheehan syndrome, pituitary apoplexy, infiltrative (sarcoidosis, haemochromatosis, Langerhans cell histiocytosis), autoimmune (lymphocytic) hypophysitis, traumatic brain injury, empty sella, congenital (Kallmann syndrome, septo-optic dysplasia).
Pathophysiology
Destruction or compression of anterior pituitary → progressive loss of hormone secretion. Hormones lost in order of sensitivity to damage: GH most vulnerable, then gonadotrophins, then TSH, then ACTH.
Clinical Presentation
GH Deficiency
- Adults: fatigue, reduced muscle mass, increased body fat (central), impaired QoL, reduced exercise capacity, osteoporosis
- Children: growth failure, short stature
Gonadotrophin Deficiency (LH/FSH)
- Women: amenorrhoea, infertility, reduced libido, vaginal dryness, osteoporosis
- Men: reduced libido, erectile dysfunction, reduced muscle mass, infertility, gynaecomastia, osteoporosis
- Both: reduced body hair, fine facial wrinkles
TSH Deficiency (Secondary Hypothyroidism)
- As per hypothyroidism BUT TSH is LOW/normal (cannot use TSH to monitor — use free T4)
ACTH Deficiency (Secondary Adrenal Insufficiency)
- Fatigue, weight loss, postural hypotension, nausea, hypoglycaemia
- NO hyperpigmentation (ACTH is low), NO hyperkalaemia (aldosterone preserved — RAAS intact)
- Risk of adrenal crisis with illness/stress
Posterior Pituitary (if involved)
- Diabetes insipidus: polyuria, polydipsia (craniopharyngioma, surgery, infiltrative)
Red Flags
- Acute pituitary apoplexy: sudden headache, visual loss, ophthalmoplegia, hypopituitarism → emergency
- ACTH deficiency presenting as collapse → adrenal crisis
- Postpartum failure to lactate + failure to resume menses → Sheehan syndrome
Differential Diagnosis
| Diagnosis | Key Features | Investigation |
|---|---|---|
| Primary hypothyroidism | High TSH (vs low in hypopituitarism) | TFTs |
| Primary adrenal insufficiency | High ACTH, hyperpigmentation, hyperkalaemia | ACTH, SST |
| Primary hypogonadism | High LH/FSH (vs low in hypopituitarism) | LH, FSH |
| Chronic fatigue syndrome | Normal hormones | Exclusion diagnosis |
| Anorexia nervosa | Low weight, body image distortion, functional hypogonadism | History, BMI |
Diagnosis / Investigation
Basal Hormones
- 9am cortisol: <100 nmol/L = likely deficient; >450 nmol/L = sufficient
- Free T4 (NOT TSH — TSH unreliable in secondary hypothyroidism)
- LH, FSH, oestradiol (women), testosterone (men)
- IGF-1: screening for GH deficiency
- Prolactin: low (panhypopituitarism) or high (stalk effect/prolactinoma)
Dynamic Tests
- Insulin tolerance test (ITT): gold standard for GH and ACTH deficiency; IV insulin → hypoglycaemia (glucose <2.2 mmol/L) → adequate cortisol rise >450 nmol/L, adequate GH rise >5 μg/L (adults) excludes deficiency
- Contraindications to ITT: epilepsy, ischaemic heart disease, elderly → use glucagon stimulation test instead
- Short Synacthen test: for secondary adrenal insufficiency (may be normal in early/partial ACTH deficiency as adrenals not yet atrophied)
Imaging
- Pituitary MRI (gadolinium): adenoma, empty sella, infiltrative disease, apoplexy
Visual Fields
- Formal perimetry if macroadenoma/chiasmal compression
Management
Hormone Replacement (Order Matters)
- Hydrocortisone (FIRST — before thyroxine): 15-25 mg/day in divided doses; sick-day rules; steroid card + MedicAlert
- Levothyroxine: 50-150 μg/day; monitor by free T4 (NOT TSH); start AFTER cortisol replacement confirmed
- Sex steroids: women — HRT or OCP (if premenopausal); men — testosterone replacement (gel, injection)
- GH replacement: recombinant human GH (somatropin); dose titrated by IGF-1; improves QoL, body composition, bone density; NICE TA64
- Desmopressin: if DI present (see separate topic)
- Fertility: gonadotrophin injections (LH/FSH analogues) when fertility desired (sex steroids alone do not restore fertility)
Monitoring
- Cortisol: clinical assessment (no reliable biochemical marker — monitor symptoms, avoid Cushingoid features)
- Free T4: target upper half of reference range
- Testosterone/oestradiol: target normal range
- IGF-1: target within normal age-adjusted range
Referral Criteria
- Endocrinology: all hypopituitarism
- Neurosurgery: pituitary adenoma/apoplexy
- Fertility: when pregnancy desired
Prognosis
With adequate hormone replacement, life expectancy approaches normal (though some excess cardiovascular mortality persists, possibly related to GH deficiency or suboptimal cortisol replacement). Quality of life may remain impaired despite biochemical replacement. GH replacement improves QoL, body composition, and cardiovascular risk profile. ACTH deficiency carries ongoing risk of adrenal crisis (~5-10 episodes per 100 patient-years).
Other Relevant Information
Anterior Pituitary Hormones — Order of Loss
| Hormone | Sensitivity | Target |
|---|---|---|
| GH | Most sensitive (lost first) | IGF-1, tissues |
| LH/FSH | Second | Gonads |
| TSH | Third | Thyroid |
| ACTH | Most resistant (lost last) | Adrenals |
Primary vs Secondary Hormone Deficiency
| Feature | Primary | Secondary (Pituitary) |
|---|---|---|
| Stimulating hormone | HIGH | LOW |
| Target hormone | LOW | LOW |
| Example | Primary hypothyroidism: high TSH | Secondary hypothyroidism: low TSH |
| Key difference | Monitor stimulating hormone | Monitor target hormone |