Pituitary Tumours

Introduction

Pituitary adenomas are benign tumours arising from the anterior pituitary gland. They are common - present on incidental MRI or at autopsy in up to 10-20% of the population - and the great majority are small, asymptomatic and never diagnosed.¹ Clinically significant pituitary tumours are much less common, with a prevalence of around 1 in 1,000.

Pituitary adenomas are classified in two independent ways, and both matter for how a patient presents and is managed.

Prolactinoma is the commonest functioning pituitary adenoma, followed by GH-secreting and then ACTH-secreting adenomas. Non-functioning adenomas are the commonest type overall and, because they cause no hormonal syndrome, tend to grow large before being detected through mass effect - see the dedicated Hyperprolactinaemia, Acromegaly and Cushing Syndrome articles for the disease-specific detail on each functioning subtype.

Clinical features

A pituitary tumour can present in four distinct ways, and it is worth thinking through all four for any patient in whom one is suspected.

1. Mass effect

As an adenoma enlarges beyond the confines of the pituitary fossa (sella turcica), it compresses surrounding structures.

• Bitemporal hemianopia - the classic finding, from compression of the optic chiasm, which sits directly above the pituitary gland. Because the chiasm carries the crossing nasal (nasal retina, temporal field) fibres from each eye, superior compression characteristically affects the upper temporal quadrants first, progressing to a full bitemporal hemianopia.
• Headache - from stretching of the dura over the sella, often frontal or retro-orbital
• Cranial nerve palsies - lateral extension into the cavernous sinus can compress cranial nerves III, IV, VI and the ophthalmic/maxillary divisions of V, causing diplopia, ptosis or facial sensory loss
• Hydrocephalus - rare, from obstruction of the third ventricle by a very large suprasellar extension

2. Hormone excess

The syndrome produced depends on the cell type of origin. Each has its own dedicated article covering presentation, diagnosis and management in full.

3. Hypopituitarism from compression

A large adenoma, whether functioning or not, can compress the surrounding normal pituitary tissue and stalk, causing loss of one or more anterior pituitary hormones (hypopituitarism) and, if the stalk is compressed, a mild rise in prolactin from loss of tonic dopamine inhibition (stalk effect - see the Hyperprolactinaemia article). Gonadotrophins and GH are typically lost first, with ACTH and TSH deficiency occurring later - though the order is not absolute and all axes should be checked.

4. Incidental finding

Small, non-functioning adenomas (incidentalomas) are increasingly identified on MRI or CT performed for unrelated reasons. Once found, they still require basic hormonal screening and, if large or close to the chiasm, visual field assessment - but most simply need periodic surveillance imaging.

Pituitary apoplexy

Pituitary apoplexy is sudden haemorrhage or infarction into a pituitary adenoma (most often one not previously known about) and is an endocrine and neurosurgical emergency.² It classically presents with:

• Thunderclap headache - sudden, severe, retro-orbital or frontal
• Sudden visual loss or visual field defect
• Ophthalmoplegia - from cavernous sinus involvement, causing diplopia and ptosis
• Nausea, vomiting and meningism - from blood irritating the meninges, which can mimic subarachnoid haemorrhage
• Acute hypopituitarism, most dangerously secondary adrenal insufficiency, which can precipitate cardiovascular collapse if unrecognised

Investigations

Work-up of a suspected or confirmed pituitary tumour has three components, run in parallel.

Imaging

MRI of the pituitary with fine cuts through the sella is the investigation of choice, defining size, extent of suprasellar or cavernous sinus extension, and relationship to the optic chiasm.¹ CT is a reasonable alternative where MRI is contraindicated or unavailable acutely.

Hormonal assessment

A full anterior pituitary hormone profile is required for every newly identified adenoma, both to detect a functioning tumour and to assess for hypopituitarism from compression:

• Prolactin - markedly raised (often over 5,000 mU/L) suggests a prolactinoma; a mild-to-moderate rise may instead reflect stalk compression by a non-functioning tumour
• IGF-1 (± OGTT with GH suppression if raised) - screens for acromegaly
• 9 am cortisol (± short Synacthen test) and overnight dexamethasone suppression test/24-hour urinary free cortisol if Cushing's disease is suspected
• TSH and free T4 - a low free T4 with an inappropriately normal or low TSH indicates secondary hypothyroidism
• LH, FSH, testosterone or oestradiol - assess the gonadotrophic axis

Visual assessment

Formal visual field testing (perimetry) is required whenever a macroadenoma abuts or compresses the optic chiasm, to document any bitemporal field loss objectively and to monitor for improvement after treatment.

Management

Management depends on whether the tumour is functioning, its size, and whether it is causing mass effect. The disease-specific articles cover treatment of each functioning subtype in detail; the principles common to all pituitary tumours are summarised here.

• Prolactinoma - almost always treated medically first, with a dopamine agonist (cabergoline or bromocriptine), even when large - see the Hyperprolactinaemia article
• Acromegaly (GH-secreting) - trans-sphenoidal surgery first line, with somatostatin analogues, pegvisomant or radiotherapy for residual disease - see the Acromegaly article
• Cushing's disease (ACTH-secreting) - trans-sphenoidal surgery first line - see the Cushing Syndrome article
• Non-functioning adenoma - surveillance MRI for small, asymptomatic incidentalomas; trans-sphenoidal surgery if there is visual field loss, significant mass effect, or growth on serial imaging
• Radiotherapy - reserved for residual or recurrent tumour not controlled by surgery or medical therapy in any subtype, given the slow onset of effect and long-term risk of hypopituitarism

Surgical approach

Trans-sphenoidal surgery (through the nose and sphenoid sinus) is the standard approach for almost all pituitary adenomas, avoiding a craniotomy in the great majority of cases. A craniotomy is occasionally needed for very large tumours with extensive suprasellar or lateral extension.

Managing hypopituitarism

Whether caused by the tumour itself or by its treatment, deficient axes need lifelong hormone replacement - hydrocortisone for ACTH deficiency, levothyroxine for TSH deficiency, sex hormone replacement for gonadotrophin deficiency, and GH replacement in selected patients. Cortisol replacement is corrected before thyroxine if both are deficient, because starting levothyroxine first can precipitate an adrenal crisis by accelerating cortisol metabolism. Patients on hydrocortisone need a steroid emergency card and sick day rule counselling.

Red flags

Prognosis

Most pituitary adenomas are benign and slow-growing, and outcomes are generally good with appropriate treatment. Microprolactinomas and most microadenomas in general have an excellent prognosis with medical therapy or surgical cure. Larger tumours, particularly those invading the cavernous sinus, are less likely to be cured surgically and more often require combination therapy or radiotherapy, with a higher risk of permanent hypopituitarism and, for functioning tumours, higher long-term cardiovascular and metabolic risk if hormone excess is not fully controlled.

Pituitary apoplexy carries a good prognosis for survival with prompt steroid replacement, though visual and hormonal recovery vary and many patients are left with some degree of permanent hypopituitarism requiring lifelong replacement and monitoring.