Non-functioning pituitary adenoma

Overview

•NFPAs account for ~15% of all pituitary adenomas - most common pituitary macroadenoma presenting to neurosurgery

•Produce no clinically active hormone - grow silently until large enough to compress surrounding structures

•Typical presentation age 30-60; usually macroadenomas at diagnosis

Presentation

•Mass effect symptoms:

•Headache - dull, persistent, often worse at night (dural stretching)

•Bitemporal hemianopia - optic chiasm compression; nasal fibres of optic nerves compressed, eliminating temporal fields bilaterally

•Cranial nerve palsies (III, IV, VI) - if cavernous sinus invaded: diplopia, ptosis, ophthalmoplegia

•Hypopituitarism symptoms (axes fail in order: GH → LH/FSH → TSH → ACTH → prolactin):

•Fatigue, weight gain, cold intolerance - secondary hypothyroidism (low TSH + low T4)

•Erectile dysfunction, low libido / oligomenorrhoea, amenorrhoea - secondary hypogonadism (low LH/FSH)

•Reduced muscle mass, increased fat mass - GH deficiency

•Postural hypotension, hyponatraemia, reduced stress response - secondary adrenal insufficiency (low ACTH → low cortisol); potentially life-threatening

🎯

Secondary hypothyroidism exam trap: pituitary failure → low TSH + low T4. Primary hypothyroidism → high TSH + low T4. Low TSH with low T4 = look for a pituitary cause, not a thyroid one.

⚠️

Stalk effect: any large sellar mass compressing the pituitary stalk impairs dopamine delivery → mild hyperprolactinaemia (typically <2000 mU/L). A prolactinoma large enough to cause mass effect produces prolactin well above this. Do not treat an NFPA with cabergoline assuming it is a prolactinoma without this distinction.

Investigations

🥇 First-line

•Pituitary hormone profile - TSH, free T4, LH, FSH, ACTH (9 am), cortisol (9 am), GH, IGF-1, prolactin, testosterone/oestradiol

•Formal visual field assessment (Humphrey perimetry) - documents optic chiasm compression

🏆 Gold standard

•MRI pituitary with gadolinium contrast - defines tumour size, suprasellar extension, optic chiasm involvement, cavernous sinus invasion

🥈 Second-line

•Dynamic endocrine testing (e.g. short Synacthen test for secondary adrenal insufficiency, insulin tolerance test for GH deficiency) - when baseline results equivocal

Differential diagnosis

Key differentials for a sellar mass with hypopituitarism

Diagnosis	Key distinguishing feature
Prolactinoma	Prolactin markedly elevated (typically >2000 mU/L for macroadenoma); first-line: cabergoline, not surgery
Primary hypothyroidism	TSH elevated (not low); other axes unaffected
Cushing's disease	ACTH and cortisol elevated; cushingoid features (central obesity, striae, hypertension)
Pituitary apoplexy	Thunderclap headache, sudden visual loss, acute hypopituitarism - neurosurgical emergency
Craniopharyngioma	Calcification on imaging; Rathke's pouch origin; more common in children/young adults

Management

•All cases discussed at specialist pituitary MDT

•Surgical: Transsphenoidal decompression - first-line for macroadenomas with mass effect (especially visual compromise)

•Hormone replacement post-operatively: hydrocortisone must be started before levothyroxine - giving thyroxine first in unrecognised adrenal insufficiency precipitates an Addisonian crisis

•Radiotherapy: Adjuvant stereotactic radiotherapy considered for residual or recurrent tumour

🚨

Always replace secondary adrenal insufficiency with hydrocortisone before starting levothyroxine. Thyroxine increases metabolic demand and can precipitate a fatal Addisonian crisis if adrenal insufficiency is unrecognised.

Complications

•Permanent hypopituitarism - may pre-date surgery or result from surgical trauma; requires lifelong hormone replacement

•Pituitary apoplexy - haemorrhage/infarction into tumour; sudden severe headache, visual loss, collapse; neurosurgical emergency

•Diabetes insipidus - post-operative posterior pituitary/stalk damage; polyuria and polydipsia; managed with desmopressin

•Secondary adrenal crisis - life-threatening if adrenal insufficiency unrecognised during illness, surgery, or stress

•Tumour recurrence - ~10-20% within 10 years; higher with residual tumour at surgery; long-term MRI surveillance required