Pituitary tumours: non-functioning adenoma and

• A pituitary tumour that does not secrete a hormone a clinician can measure in blood is called a non-functioning pituitary adenoma (NFPA). It behaves as a space-occupying lesion: it squashes the normal gland, stretches pain fibres, and compresses the optic chiasm above.
• Craniopharyngioma is a different, cystic, partly calcified tumour that arises along the craniopharyngeal duct, usually above the sella, and is classically a disease of childhood and of late middle age.
• The signature problem of both is local mass effect: bitemporal visual field loss, cranial nerve palsies, headache, and hypopituitarism. Hormone excess is not the presenting problem.
• The second tumour to remember in the same space is a Rathke cleft cyst, which is usually a small, incidental, cystic lesion; a parasellar meningioma is the other important mimic.
• Transsphenoidal surgery is first-line whenever there is a visual threat; many small lesions can be watched. Lifelong imaging and endocrine follow-up are required because regrowth is common.

By the end of this page you should be able to:

1. Explain why a non-secreting pituitary adenoma causes hypopituitarism and visual field loss, rather than a hormonal syndrome. ^[2]
2. Plan the initial work-up of a non-functioning pituitary adenoma: imaging, hormone panel, and ophthalmic assessment. ^{[2] [1]}
3. State the surgical indications, the likely visual and endocrine outcomes, and the surveillance plan after surgery. ^[2]
4. Distinguish craniopharyngioma, Rathke cleft cyst and a sellar meningioma from a non-functioning adenoma on clinical and imaging grounds. ^{[3] [4] [5]}
5. Outline the management of craniopharyngioma, including the balance between complete resection and hypothalamus-sparing surgery plus radiotherapy. ^[4]
6. Adapt care in pregnancy, in children and older adults, and in low-resource settings.

Sellar and parasellar tumours are common incidental findings on modern brain imaging, and the non-functioning pituitary adenoma is the commonest of the symptomatic ones. A tumour in this region usually presents in one of three ways: as a mass that compresses the optic chiasm above it, as mass effect within the cavernous sinuses on either side, or as a slow erosion of the hormone-producing cells of the normal gland. Endocrine deficiency is therefore part of the mass-effect story, not a separate disease. Craniopharyngioma compresses the same structures but from a usually more suprasellar position, and Rathke cleft cyst and meningioma are the two lesions most likely to be mistaken for it.

The newest guidance used for this topic were the Pituitary Society 2025 international consensus statement on pituitary incidentalomas ^[1], the Endocrine Society 2016 guideline on hormonal replacement in hypopituitarism in adults ^[7], and the European Society of Endocrinology 2025 revision of its guideline on aggressive pituitary tumours and carcinomas ^[6]. For the NFPA, the claims were cross-checked against published NFPA surgical series ^[2], and for craniopharyngioma against a 2019 primer ^[4]. For the mass-effect section the text drew on a standard neuro-ophthalmology review ^[3].

Clinically non-functioning pituitary adenomas are, after prolactinomas, the commonest symptomatic pituitary adenoma subgroup in most surgical series. ^[2] They are benign but, like cardiac myxoma, behaviourally troublesome because of where they sit. The older terms "non-secreting" and "null cell" survive in textbooks; the 2017 WHO classification of endocrine tumours recognises eight immunohistochemical subtypes (silent gonadotroph, corticotroph, somatotroph, thyrotroph, lactotroph, plurihormonal Pit-1, null cell, and double or triple), but the clinical management does not change with subtype. ^[2]

Size matters more than name. By convention a pituitary adenoma is a microadenoma when it measures under 1 cm in diameter, a macroadenoma from 1 cm upwards, and a giant adenoma at 4 cm or more. ^[2] Only macroadenomas are big enough to threaten vision. ^{[3] [1]}

Craniopharyngioma is classified differently. It is a WHO grade 1 epithelial tumour of the sellar or parasellar region that arises from remnants of the craniopharyngeal duct. Two subtypes matter at the bedside:

• Adamantinomatous craniopharyngioma shows a bimodal age distribution, with peaks at 5 to 15 years and 45 to 60 years. It is mainly cystic, often calcified, and driven in most cases by somatic mutations in CTNNB1, the gene encoding beta-catenin. ^[4]
• Papillary craniopharyngioma is essentially an adult tumour, arising mainly in the fifth and sixth decades. It is usually a solid tumour and frequently carries a BRAF V600E mutation. ^[4]

Rathke cleft cyst is not a neoplasm at all but a benign cyst arising from remnants of Rathke's pouch. ^[5] Sellar and parasellar meningiomas are dural-based, extra-axial tumours arising from arachnoid cap cells. ^[3]

Non-functioning pituitary adenomas are estimated to have a prevalence of 7 to 41 per 100,000 and an annual incidence of 0.65 to 2.34 per 100,000, and the incidence has risen over time as more lesions are found incidentally on brain imaging. ^[2] Their overall burden is comparable to that of other pituitary adenomas, but they are diagnosed later because they do not produce a hormonal syndrome. ^[2]

Craniopharyngioma is rare. It is one of the commonest brain tumours of childhood, but it occurs at any age and is also seen in middle-aged adults. ^[4] The incidence figures in the literature vary between registries and studies, and authors quote them differently; what is consistent is the bimodal age distribution described above. ^[4]

Pituitary incidentalomas of all kinds are common at post-mortem (a pooled mean of about 10.7% of autopsies find one), but are found on MRI in only about 2.7 per 1,000 scans. ^[1] About 43% of imaging-detected incidental adenomas are macroadenomas. ^[1] Microadenomas grow slowly, with pooled estimates of about 3.3 events per 100 person-years, and macroadenomas about 12.5 per 100 person-years. ^[1]

Rathke cleft cysts are common findings in the pituitary gland and surrounding tissues at post-mortem, and they are among the most common sellar lesions; clinically apparent ones are much less common. ^[5]

There is no known modifiable risk factor for a sporadic non-functioning pituitary adenoma. The classical view is clonal expansion of a pituitary cell after one or more somatic mutations, but the only clear associations are with a few familial syndromes (multiple endocrine neoplasia type 1, familial isolated pituitary adenoma, Carney complex), which are rare and are usually flagged by young age or multiple tumours. ^[2] A useful negative clue: immune infiltration, granulomatous disease or metastatic disease can produce an indistinguishable sellar mass, so a rapidly progressive lesion in an older patient with known cancer should be biopsied. ^[2]

For craniopharyngioma the aetiology is embryological rather than neoplastic in the usual sense. Adamantinomatous tumours carry CTNNB1 (beta-catenin) mutations in most cases; papillary tumours carry BRAF V600E mutations in the majority. ^[4] Neither type has a known environmental cause. A sellar meningioma carries the usual risks of a meningioma: female sex, increasing age, previous cranial irradiation. ^[3]

If the tumour arises in someone who has had radiotherapy for a previous pituitary or brain tumour, the differential changes: radiation-induced meningioma and hypopituitarism from the original treatment should be expected. ^[2]

Step by step, the problem is geometry.

A pituitary adenoma grows in the shallow bony saddle of the sella turcica. It has nowhere to go but up, so it pushes the diaphragma sellae and the optic chiasm upward and forward. ^{[2] [3]} Lateral extension enters the cavernous sinus, where cranial nerves three, four and six run; that is the mechanism of a partial or complete third-nerve palsy with diplopia and ptosis. Downward extension erodes and expands the floor of the sella, which on plain films looks like a "double floor" or "hooked clinoid". ^[3] The stalk is displaced and kinked, which is why prolactin, rather than being low, is often slightly raised from loss of dopamine delivery (disconnection hyperprolactinaemia). ^[2] Age and shrinkage of CSF spaces also matter in older adults, where a small tumour can deform an optic pathway that has become less compliant.

Compression of the normal gland itself produces hypopituitarism. Growth hormone is usually the first axis to fall, then the gonadotrophins, then thyroid-stimulating hormone and finally adrenocorticotrophic hormone, but with a macroadenoma the collapse can be more abrupt and unpredictable. ^[2] The patient therefore arrives not with one missing hormone but with a packaged set of them, plus whichever mass-effect signs have accumulated.

Hypopituitarism itself is dangerous for two reasons. First, secondary adrenal insufficiency removes cortisol, and an intercurrent illness can convert a compensated patient into an adrenal crisis. Second, central hypothyroidism and gonadal failure accumulate long before the diagnosis is made, because the symptoms (fatigue, loss of libido, weight gain, cold intolerance) are vague and mimic common, non-endocrine problems. ^[7] By the time visual symptoms appear the axis may already be substantially lost.

Craniopharyngioma adds a hypothalamic dimension. Its typical suprasellar and retrochiasmal position means that it compresses or infiltrates the hypothalamus and the optic tract from above, producing not only field defects and hypopituitarism but also hypothalamic obesity, sleep disturbance, cognitive change and (in children) growth failure and delayed puberty. ^[4] The tumour is also partly cystic, so its size can change suddenly as cyst fluid accumulates under pressure. ^[4]

Meningioma in the sellar region is a slow, fibrous, dural-based mass arising above and around the sella. It compresses the chiasm from above or from the side, rather than rising through the sella from below, and it is often very vascular. ^[3]

NFPA tissue is soft, tan-coloured and moderately vascular, usually without necrosis unless it has outgrown its blood supply (in which case pituitary apoplexy follows). Microscopically the cells form sheets or cords, with chromophobe, basophil or acidophil cytoplasm, and immunohistochemistry for pituitary transcription factors (SF-1, T-PIT, Pit-1) classifies the subtype. ^[2] The cells may be immunonegative (null cell) or may stain for luteinising hormone, follicle-stimulating hormone, or the glycoprotein alpha subunit. ^[2] Mitotic counts and the Ki-67 index are recorded because higher values mark a more aggressive clinical course. ^[2]

Craniopharyngioma has two distinct microscopic appearances. Adamantinomatous tumours show epithelial nodules, loose "stellate reticulum" and wet keratin, with dystrophic calcification; this is the subtype that forms cholesterol-rich fluid. Papillary tumours are more bland and uniformly epithelial. ^[4] Calcification is common enough that a CT before surgery is useful even when MRI has already been done. ^[4]

Rathke cleft cysts are lined by ciliated cuboidal or columnar epithelium, with goblet cells and occasional squamous metaplasia. They contain mucoid, cholesterol-rich fluid. ^[5] A craniopharyngioma and a Rathke cyst can look alike on imaging; histology separates them, with beta-catenin (CTNNB1) mutations in most adamantinomatous craniopharyngiomas but not in Rathke cysts, and cytokeratins 8 and 2 expressed in Rathke cysts but not in craniopharyngiomas. ^[5]

Sellar meningiomas are firm, gritty, dural-based masses with the whorled architecture of a meningioma and psammoma bodies. ^[3]

The history is often told as a collection of unrelated complaints. A typical NFPA patient is a 50 to 65 year old who presents with slowly worsening vision, headaches, or symptoms of hypogonadism. ^[2] Patients may describe loss of peripheral vision (bumping into things on one side, difficulty with stairs or driving) rather than a black curtain. Headache is common (reported in 16 to 70% of patients with pituitary adenomas) and is often a dull, constant frontal or occipital ache; it may be positional or exacerbated by Valsalva. ^[2] Diplopia suggests cavernous sinus involvement and should raise the possibility of another cause before it is attributed to the adenoma, because it is rare in simple pituitary adenoma. ^[2]

Hypopituitarism produces its own language: loss of libido and erectile dysfunction in men, amenorrhoea or subfertility in women, cold intolerance and weight gain from low thyroid hormone, fatigue, nausea and (in women in particular) the vague ill-health that precedes an eventual crisis. ^[7] The premenopausal woman who has stopped menstruating and who is mildly hypothyroid but whose TSH is normal or low is the person to send for pituitary imaging. Growth hormone deficiency presents as loss of vigour, soft-tissue and muscle loss, and central adiposity.

Pituitary apoplexy, haemorrhage or infarction into the tumour, presents suddenly with a thunderclap headache, vomiting, visual loss and a drop in consciousness, and is covered in the pituitary apoplexy topic. ^[3]

Craniopharyngioma in a child presents with growth failure, visual symptoms and headache from raised intracranial pressure; in an adult, visual loss and hypopituitarism dominate, with memory and personality change if the hypothalamus is involved. Rathke cysts are often found incidentally and are small; when symptomatic they produce headache, visual disturbance and hypopituitarism like a small adenoma. ^[5]

Neuro-ophthalmic examination is the safety-critical step. Check visual acuity, visual fields by confrontation, pupillary responses, colour vision, and ocular motility. ^[3] A bitemporal defect may be subtle when it is an upper quadrantanopia only. Formal perimetry is mandatory for any macroadenoma, or for a lesion within 5 mm of the optic chiasm. ^{[1] [3]} Optic disc pallor is an adverse prognostic sign for visual recovery; nerves without pallor on detection of a bitemporal hemianopia carry the more urgent surgical tempo. ^[3]

General examination looks for the signs of hypopituitarism: pallor, fine wrinkled skin, loss of axillary and pubic hair, small soft testes, a postural drop in blood pressure. Note any signs of hormone excess that would reclassify the adenoma as functioning: coarse hands, enlarged jaw and brow (acromegaly), or Cushingoid features such as facial rounding, supraclavicular fat pads, thin skin, and easy bruising. ^[2] Cranial nerve signs (third, fourth or sixth cranial nerve) reflect parasellar extension. ^[2]

The table covers the lesions a beginner will see in the differential of "sellar or parasellar mass". Craniopharyngioma is the important tumour differential; Rathke cleft cyst is the cyst to recognise; meningioma is the other solid, dural-based lesion.

The clinical mimics of the symptoms matter as much as the imaging mimics. Headache with visual loss can be migraine, glaucoma, ischaemic optic neuropathy, or a demyelinating plaque. Hypopituitarism has to be distinguished from primary adrenal or thyroid failure, in which the pituitary signal is high rather than low, and from functional failure in malnutrition, chronic disease or opioid use. ^[7]

Magnetic resonance imaging of the pituitary with gadolinium is the anatomical investigation. NFPAs are usually hypointense or isointense on T1-weighted images before contrast and show delayed enhancement after it, appearing less bright than the surrounding normal pituitary. ^[2] The study must include the optic chiasm and cavernous sinuses so that the urgency of surgery can be decided. The Knosp grade (0 to 4) describes parasellar extension and carotid artery encasement, and predicts surgical outcome. ^[2] When the appearance is atypical (for example a cystic, calcified or very vascular mass), consider hypophysitis, meningioma, granulomatous disease, or metastasis. ^[2] CT is useful for calcification, and magnetic resonance angiography or CT angiography is needed whenever an aneurysm is in the differential. ^[3]

Craniopharyngioma is best shown by MRI, with calcification best shown by CT. ^[4] Rathke cysts are small intrasellar or suprasellar cysts with variable signal, often T1-bright mucoid content. ^[5] Sellar meningiomas are homogeneously enhancing and dural-based, with a dural tail. ^[3]

The rule is to test everyone, because the size of the tumour does not predict which axes have failed. ^{[1] [2]} The panel is: morning cortisol with ACTH, free thyroxine with TSH, luteinising hormone, follicle-stimulating hormone and oestradiol or testosterone, IGF-1 with provocative growth-hormone testing as needed, and prolactin in every patient. ^{[1] [2]} When morning cortisol suggests hypocortisolism, dynamic testing of the adrenal axis follows.

Hypopituitarism at diagnosis ranges from 37 to 85% in published NFPA series, and panhypopituitarism from 6 to 29%. ^[2] Growth hormone and gonadotrophin failure are the most common single deficits, followed by central hypothyroidism and secondary adrenal insufficiency. ^[2] Hyperprolactinaemia from stalk compression is present in 25 to 65% of patients at diagnosis; a prolactin level under about 100 ng per mL (about 2000 IU per L) fits an NFPA with stalk effect, while a level over 250 ng per mL (about 5000 IU per L) is essentially a prolactinoma. ^[2] The area between the two is a genuine grey zone and requires clinical judgment. ^[2] Central diabetes insipidus at diagnosis is unusual for an NFPA and should make you think of other diagnoses. ^[2]

These thresholds are assay- and population-dependent, and local guidelines should overrule them. The Endocrine Society 2016 guideline on hypopituitarism in adults sets out the detailed replacement approach, including hydrocortisone before thyroxine and the sick-day regimens. ^[7]

Ophthalmic assessment is needed in case of visual complaints and whenever a macroadenoma abuts the chiasm. ^[2] For microadenomas or macroadenomas remote from the chiasm and cavernous sinus no formal visual field assessment is needed. ^[2] For a lesion that touches the chiasm, the 2025 consensus recommends Humphrey automated static perimetry or Goldmann kinetic perimetry whenever the lesion abuts or is within 5 mm of the chiasm, or when visual symptoms exist. ^{[1] [3]} The baseline examination also includes visual acuity, colour vision, pupillary reactions, and ocular motility. ^[3]

Visual field deficits are present in 28 to 100% of NFPA patients at diagnosis in reported series, because the definition and the method of testing vary (small asymptomatic quadrantic defects are missed on confrontation testing). ^[2] Non-secretory macroadenomas are the commonest source of bitemporal hemianopia in adults. ^[3]

For an asymptomatic, non-functioning lesion being watched rather than operated, the 2025 consensus gives these intervals ^[1]:

• MRI at 2 to 3 years for a microadenoma. ^[1]
• MRI at 1 year for a macroadenoma 5 mm or more from the chiasm, then every 2 to 3 years if stable. ^[1]
• MRI at 6 to 12 months for a macroadenoma under 5 mm from the chiasm, then every 1 to 2 years if slowly enlarging and stable. ^[1]
• Hormone testing at 1 to 2 years for all macro- and microadenomas, earlier if symptoms or growth appear.
• Visual fields at 6 months if there is suprasellar extension without surgery, at 1 to 2 years for all macroadenomas, or every 6 to 12 months when the scan interval has been extended to annually. ^[1]

There is no biochemical test that diagnoses an NFPA; the diagnosis is radiological and hormonal by exclusion. A "silent" hormone excess tumour (for example a silent corticotroph adenoma, which represents about 15% of NFPAs, or a sparsely granulated somatotroph, about 2%) behaves as an NFPA clinically but has a more aggressive course. ^[2] Radiologists describe size, consistency (solid versus cystic), T2 signal, stalk deviation, cavernous sinus invasion (Knosp), and distance to the chiasm. The practical severity score is therefore the combination of visual status and endocrine status, not a number.

Craniopharyngioma is also a clinicoradiological diagnosis. MRI shows a suprasellar cystic or mixed mass; CT shows calcification in many (calcification is more common in the adamantinomatous than the papillary subtype). ^[4] Subtyping may need histology after resection. Two molecular tests have become diagnostically useful: nuclear beta-catenin accumulation in adamantinomatous tumours, and BRAF V600E in papillary tumours. ^{[4] [5]}

For Rathke cleft cyst the diagnostic triad is a small, midline, cystic sellar lesion with no calcification, no dural tail, and (when aspirated) mucoid fluid with ciliated epithelium. ^[5] Sellar meningiomas are dural-based, vividly and uniformly enhancing, with a dural tail, and the normal sella may still be visible beneath them. ^[3]

The morbidity of these patients comes less from the tumour than from missed hormone deficiency around the time of surgery, so the endocrine preparation is the first task. ^{[2] [7]} Secondary adrenal insufficiency must be treated with glucocorticoid replacement before operation and covered with stress doses perioperatively. Central hypothyroidism, if severe, must be corrected before an elective procedure because untreated myxoedema increases surgical risk. ^[2] Hypogonadism and growth hormone deficiency are not corrected before surgery unless there is a specific reason. ^[2] The patient and family need an education visit covering sick-day rules and an emergency hydrocortisone kit, exactly as for any patient with hypopituitarism. ^{[7] [1]}

Transsphenoidal surgery is first-line when the adenoma abuts or compresses the optic chiasm and is producing visual field deficits, when there is a cranial nerve palsy or other neurological deficit, or in pituitary apoplexy with visual disturbance. ^{[2] [3]} In the absence of visual impairment, the optimal choice is still debated, particularly for patients with hypopituitarism or unremitting headache, and in those cases the decision must be individualised with the patient. ^[2] Hypopituitarism on its own is not a strong indication, because surgery may improve pituitary function in up to 30% of cases but carries a 2 to 15% risk of additional hormone deficiency. ^[2] Unremitting headache that does not respond to medical treatment can itself be an indication, although relief is not guaranteed. ^[2]

For asymptomatic microadenomas surgical resection is not indicated: growth is rare (3 to 13%) and fewer than 5% grow beyond 1 cm during long-term follow-up. ^[2] For asymptomatic macroadenomas, conservative management is reasonable when the tumour does not reach the chiasm, particularly in older patients with comorbidities. ^[2] Younger patients, tumours near the chiasm, cavernous sinus invasion, and women planning pregnancy push toward earlier surgery. ^{[1] [2]}

The standard approach is transsphenoidal, microscopic or endoscopic; transcranial surgery is now reserved for tumours with a large suprasellar component and little intrasellar tissue. ^[2] Gross total resection is achieved in 60 to 73% of patients. ^[2] Transsphenoidal surgery for NFPA carries a mortality of about 1% in pooled series and postoperative complications (CSF leak, meningitis, vascular injury, persistent diabetes insipidus, new visual field defect) occur in 5% or fewer. ^[2] Complications are less common in higher-volume centres. ^[2]

Visual outcome is good and is the main justification for surgery. In patients with decreased preoperative visual acuity, overall improvement is seen in about 68%, with worsening in about 5%. In patients with visual field deficit, improvement is seen in about 81%, complete recovery in 40%, and deterioration in only 2%. ^[2] Improvement continues through the first postoperative year. ^[2] Longer duration and greater severity of preoperative visual loss predict worse recovery, which is why observation of a compressing tumour has a time cost. ^[2]

Endocrine outcome is less predictable than visual outcome. Preoperative testing shows gonadotrophin deficiency in about half of men and about one quarter of women; after surgery normal total testosterone is restored in roughly 71% of men, while improvement is seen in about 15% of women with preoperative hypogonadism. ^[2] The adrenal axis is re-evaluated at 6 to 12 weeks, thyroid at that time too, and growth hormone status at 6 to 12 months once other axes are replaced. ^[2]

In the early postoperative period, careful observation covers sellar haematoma, CSF leak, meningitis, and the endocrine complications of acute secondary adrenal insufficiency and water-electrolyte disturbance. ^[2] Low-dose transient syndrome of inappropriate antidiuretic hormone secretion occurs in 4 to 20% of patients in the first week, and diabetes insipidus in a further 18 to 31%; triphasic diabetes insipidus, with an initial diuretic phase, an antidiuretic phase and then permanent deficiency, occurs in 3 to 4% of patients. ^[2] A urine output of 3 L or more per day with low urine osmolality is the practical trigger for desmopressin, with regular sodium monitoring to avoid hyponatraemia. ^[2]

Postoperative MRI is usually performed 3 to 6 months after surgery, when debris and packing have resolved; early imaging has improved with modern sequences and can be helpful, but should not be read in the first few weeks. ^[2] Endocrine reassessment follows standard practice: cortisol re-evaluation at 6 to 12 weeks, thyroid after the adrenal axis has been re-established, gonadal function clinically, and growth hormone only after other axes are re-established. ^[2]

Long-term radiological follow-up is essential. NFPA regrowth after surgery alone is seen in 15 to 66% of patients, and after surgery plus radiotherapy in 2 to 28%. ^[2] Recurrence peaks between 1 and 5 years and declines after 10, so at least 10 years of imaging is needed, and longer where a remnant is visible. ^[2] Conventional radiotherapy or stereotactic radiosurgery reduces regrowth (and is reserved for residual or recurrent tumour, or for histology showing high proliferative activity), at the cost of long-term hypopituitarism, radiation optic neuropathy and a small excess of second tumours. ^[2] Medical therapy with dopamine agonists has been tried for residual tumour but the evidence is weak; temozolomide is reserved for truly aggressive adenomas. ^[6]

NFPAs are not a uniformly benign group. Patients have excess comorbidity and modestly increased mortality, mostly cardiovascular, respiratory and infectious, and some adenomas behave aggressively. ^[6] The European Society of Endocrinology 2025 revision sets out how to recognise and manage the aggressive subset (multiple recurrences despite combined treatment, possibly metastatic), and recommends standardised reporting of imaging and histopathology. ^[6] Metastatic pituitary carcinoma is rare and is defined by spread outside the nervous system or by drop metastases. ^[6]

Craniopharyngioma is the other great suprasellar tumour of medical-school teaching. It is rare, partly solid, often cystic, and frequently calcified. It sits above and in front of the chiasm, and behaves like a small, awkwardly placed local bully.

Clinically it presents with the mass triad: raised intracranial pressure (headache, nausea, papilloedema), visual impairment from chiasmal compression, and hypopituitarism. In children the diagnosis may be delayed until growth failure or visual problems become obvious; the visual defect is more likely to start as an inferotemporal quadrantanopia from the tumour's central approach from above. ^{[3] [4]} Hypothalamic involvement produces the distinctive sequelae of this disease: hyperphagia and hypothalamic obesity, sleep disturbance, impaired thirst, temperature dysregulation, emotional lability and cognitive impairment. ^[4] Endocrine deficiency is almost universal by the time the tumour is large: any of ACTH, TSH, gonadotrophin, growth hormone and antidiuretic hormone axes can be lost, and vasopressin deficiency is common, particularly after surgery. ^[4] Imaging shows a cystic and solid suprasellar mass, usually partly calcified, displacing the optic chiasm upward and stretching the hypothalamus. ^[4] Adamantinomatous tumours are usually multi-cystic with "machine-oil" fluid; papillary tumours are solid. ^[4]

Surgery is the mainstay. The modern principle is to be honest about the hypothalamus: if the tumour is favourably localised (no significant hypothalamic involvement), complete resection is the aim; if it invades the hypothalamus, a hypothalamus-sparing, subtotal resection followed by radiotherapy gives equivalent survival with far better quality of life. ^[4] Transsphenoidal or endoscopic routes are preferred for intrasellar components; transcranial surgery is used for predominantly suprasellar masses. ^[4] Stereotactic cyst aspiration or intracystic therapy can control a monocystic adamantinomatous tumour, and proton-beam or conventional radiotherapy is used for residual disease. ^[4] Symptoms subside and vision usually improves, but the price of treatment and of the disease itself is long-term hormone replacement and, in many, lifelong hypothalamic rehabilitation. ^[4]

A special recent development: papillary craniopharyngiomas harbour BRAF V600E in the large majority. Targeted therapy with BRAF and MEK inhibitors has produced dramatic responses in small series and is an emerging option in recurrent or unresectable papillary disease. ^[4] Adamantinomatous tumours, by contrast, are driven by CTNNB1 mutations and are not BRAF-driven, so the same drugs do not apply. ^{[4] [5]}

Rathke cleft cysts are remnants of Rathke's pouch, found incidentally at post-mortem in a large proportion of adults and clinically a common, usually benign, pituitary lesion. ^[5] They are most often discovered on MRI performed for another reason, sit in the sella or suprasellar region, and are distinguished from craniopharyngioma by the absence of calcification, a thin, well-defined cyst wall, and ciliated respiratory epithelium. ^[5] They may be simple to manage or (uncommonly) may behave badly.

The usual story is a middle-aged woman with an incidental cyst. ^[5] Symptomatic patients present as for any cyst: headache (the commonest complaint), visual disturbance, hypopituitarism, hyperprolactinaemia from stalk compression, central diabetes insipidus, or, rarely, cyst infection or rupture. ^[5] In one retrospective series of 105 radiologically diagnosed cysts, 64.8% were managed conservatively and 35.2% came to surgery. ^[5] Headache, visual field defects and endocrine disturbances were much more common in the surgical group. ^[5]

Management follows symptoms. A small, asymptomatic cyst with a stable appearance needs observation with serial MRI and hormonal testing. ^[5] Surgery is indicated when the cyst causes visual dysfunction, significant headache, progressive endocrine deficit, or (rarely) infection. ^[5] Transsphenoidal fenestration and drainage is the standard operation; keeping the sella floor open ("marsupialisation") lowers recurrence rates but is only possible when no CSF leak is present. ^[5] When a CSF leak occurs and the floor must be reconstructed, recurrence is higher. ^[5] Recurrence risk factors also include suprasellar extension, inflammation, reactive squamous metaplasia, superinfection and the use of a fat graft in the cavity. ^[5] For symptomatic recurrence, stereotactic radiosurgery is an effective and low-risk option. ^[5] Surgery helps vision and may help headache in selected patients, but it has not been shown to improve quality of life within the first postoperative year, and it adds a real risk of new hormone deficiency. ^[5] Because the cyst may itself transform or be difficult to distinguish from craniopharyngioma, nuclear beta-catenin staining and BRAF V600E immunohistochemistry (and cyst fluid cytology where possible) should be requested on the resected material. ^[5]

Meningiomas account for roughly 25% of all intracranial tumours, peak in the fifth and sixth decades, and are commoner in women. ^[3] They account for only about 1% of masses in the region of the sella turcica, but by virtue of their position they are the solid lesion most often mistaken for an NFPA on imaging. ^[3] The most common presenting symptom is visual disturbance, followed by headache; hyperprolactinaemia or other endocrine dysfunction is uncommon. ^[3] On MRI they are extra-axial, dural-based, isointense on T1, and enhance intensely and homogeneously; a dural tail and calcification are helpful. ^[3] Cranial nerve signs occur when the cavernous sinus is involved. ^[3]

Surgical resection is often subtotal because the mass is vascular and entwined with visual and vascular structures, so adjunctive radiotherapy, stereotactic radiosurgery or fractionated stereotactic radiotherapy is commonly used for residual or recurrent tumour. ^[3] Hypopituitarism after sellar meningioma is treated exactly as for any other cause.

The complications are shared by all large sellar lesions:

• Visual loss, from bitemporal hemianopia through monocular loss, quadrantanopia, optic disc pallor and atrophy. In craniopharyngioma a superior bitemporal or junctional scotoma may occur. ^[3]
• Hypopituitarism, single or multiple, including ACTH and TSH deficiency; vasopressin deficiency is especially common after surgery for craniopharyngioma or Rathke cyst. ^{[7] [5]}
• Cranial nerve palsies (third, fourth, sixth) from cavernous sinus involvement, and, rarely, carotid compression.
• Headache from dural stretch or raised intracranial pressure; infiltrating hypothalamic tumour can also cause nausea.
• Hyponatraemia postoperatively, from SIADH or ACTH deficiency.
• Cerebrospinal fluid leak, meningitis, haemorrhage and epistaxis after surgery, each in 5% or fewer in NFPA series. ^[2]
• Tumour recurrence or regrowth, in 15 to 66% of NFPA patients treated with surgery alone and in 2 to 28% with surgery plus radiotherapy; craniopharyngioma recurrence is common after subtotal resection. ^{[2] [4]}
• Hypothalamic obesity, sleep disorder and cognitive impairment in craniopharyngioma, which are often the dominant long-term problem. ^[4]

The outlook for an NFPA is good when it is treated in a centre of excellence with modern transsphenoidal surgery, radiotherapy available for recurrence, and endocrine care. Overall survival approaches that of the general population when hypopituitarism is treated well; the excess mortality seen in registry studies comes mainly from cardiovascular, cerebrovascular and respiratory disease, and is greater in women and in patients diagnosed young. ^[2] Visual outcome is the area where early surgery rewards: complete recovery of a visual field defect occurs in about 40% and improvement in about 81%; deterioration after surgery occurs in only 2%. ^[2] Recovery of pituitary function after surgery is unpredictable; 6 to 15% of patients have additional hormone deficiencies. ^[2]

Craniopharyngioma has high long-term survival in most series, but quality of life and neurocognitive function are often impaired. ^[4] The trade-off between complete resection and hypothalamus-sparing surgery is the single most important decision in that disease. ^[4] Rathke cleft cyst patients do well after observation or fenestration, but recurrence occurs and reoperation may be needed. ^[5] Sellar meningioma is slow-growing and its prognosis depends on the feasibility of resection; subtotal resection with adjunct radiotherapy is common. ^[3]

There is no primary prevention. Screening is not generally recommended in the asymptomatic population, although the 2025 consensus supports surveillance of known lesions.

Follow-up is therefore the real "treatment" for the remainder of the patient's life:

• Endocrine review every 6 to 12 months at first, with re-evaluation of axes annually thereafter. ^{[1] [2]}
• Pituitary MRI at the size- and position-based intervals above, for at least 10 years after surgery. ^{[1] [2]}
• Formal visual fields per the schedule given earlier (6 months with suprasellar extension, 1 to 2 years for macroadenomas, 6 to 12 months when the scan interval has been relaxed). ^[1]
• A steroid emergency card, sick-day rules, and (where possible) an emergency hydrocortisone kit for everyone with ACTH deficiency, including postoperative patients. ^[7]

Screening for hypopituitarism should be repeated whenever the clinical picture changes, and after surgery, in the first year after radiotherapy, and at transition from paediatric care. ^[7]

Children. Craniopharyngioma is a disease of children and carries the heaviest long-term cost; therefore hypothalamus-sparing surgery plus radiotherapy is the preferred strategy where appropriate, and growth, puberty and cognitive function need active management. ^[4] A "non-functioning" adenoma in childhood is rare and should prompt consideration of an inherited syndrome. ^[2] Rathke cysts in children are usually clinically irrelevant.

Adolescents and transition. Pituitary tumours cross the divide between paediatric and adult services; transition is the highest-risk period for lost follow-up, for incorrect growth-hormone dosing, and for delayed recognition of recurrent craniopharyngioma. Plan the handover explicitly.

Pregnancy. A macro-adenoma abutting the chiasm can enlarge in pregnancy (physiological pituitary enlargement) and threaten vision; dedicated neuro-ophthalmic and endocrine review is needed, and surgery or medical therapy may be required to protect sight. Pregnancy outcomes and replacement details for hypopituitarism are covered in the hypopituitarism topic and in the Endocrine Society guideline. ^[7] The 2025 consensus lists desire for pregnancy or pregnancy itself as an indication for endocrinologist and neurosurgeon review. ^[1]

Older adults. Non-functioning adenomas are mostly diagnosed in the sixth and seventh decades. Frailty, comorbidity and anticoagulation increase surgical risk; in a very elderly patient with intact vision, observation of a stable macroadenoma 5 mm or more from the chiasm is sensible. ^{[1] [2]} Replacement doses in older adults and at transition are lower; avoid over-replacement, which carries excess cardiovascular risk. ^[7]

Women and men. Women with a non-functioning adenoma are diagnosed later and have worse comorbidity profiles in registry series; offer fertility-preserving counselling before any gonadotrophin-suppressing treatment. ^[2]

The same principles apply with the tools available.

• Imaging. Contrast-enhanced MRI is the investigation that changes management. If it is unavailable, CT of the sella still finds macroadenomas and calcification, but it cannot reliably separate a small cyst from a microadenoma or characterise cavernous sinus invasion. Where MRI is unavailable or unaffordable, prioritise it for visual threat and for any neurological deterioration. ^[3]
• Visual assessment. Formal perimetry is luxurious; confrontation visual fields, repeated daily in an inpatient or weekly in clinic, will detect almost all clinically important deterioration. Look for the bitemporal pattern and for optic disc pallor. ^[3]
• Endocrine testing. Morning cortisol is the safest single adrenal test and its interpretation should follow local laboratory guidance (see hypopituitarism). Repeat free thyroxine and TSH only when affordable. Dynamic testing and growth hormone assessment can be deferred: growth hormone replacement is expensive and testing is pointless where replacement cannot be funded. ^[7]
• Drugs and replacement. Hydrocortisone and levothyroxine are the two that cannot be substituted. Where hydrocortisone is unavailable, short-acting oral glucocorticoids such as prednisone can be substituted using local formulary equivalence and reviewed by an endocrinologist. Desmopressin for central diabetes insipidus is expensive; where it cannot be obtained, planned fluid and salt management with patient education is lifesaving. ^[7]
• Surgery. Transsphenoidal surgery needs an experienced neurosurgeon; where none is available locally, early referral to a regional centre is safer than a delayed or inexperienced operation. ^[2]
• Pathology. The resected tumour should go to histology whenever possible; beta-catenin and BRAF staining (where available) clarify the craniopharyngioma subtype and guide follow-up and targeted therapy. ^{[4] [5]}
• Causes specific to setting. Sheehan syndrome (postpartum pituitary infarction) is a common cause of hypopituitarism wherever obstetric care is limited; traumatic brain injury is another. Both behave as mass lesions do not need surgery but do need replacement. ^[7]

Related MedGrasp pages (plain text): hypopituitarism; pituitary apoplexy and pituitary incidentaloma; acromegaly; Cushing syndrome; hyperprolactinaemia; headache; visual loss; central diabetes insipidus; hyponatraemia; growth hormone deficiency; meningioma. (Prerequisites and related entries in front matter are left empty for this curriculum-gap topic, as for the other pituitary topics.)