What are the typical clinical presentations of pituitary tumours in adults and which examinations and investigations should be performed?

Pituitary Tumours: Clinical Presentation, Examination, and Investigation

Clinical Presentations

Pituitary tumours present through three primary mechanisms: hormonal hypersecretion syndromes, mass effect symptoms, and hypopituitarism—with the triad of headache, visual impairment, and hypogonadism representing the most common constellation in surgical series. 1

Hormonal Hypersecretion Syndromes

Prolactinomas (most common functional adenoma):

• Females: menstrual irregularities, primary or secondary amenorrhea, galactorrhea, infertility, and decreased libido 2, 3
• Males: decreased libido, erectile dysfunction, gynaecomastia, and infertility 2, 3
• Children/adolescents: delayed or arrested puberty, growth failure, and primary amenorrhea in girls 4, 2

Acromegaly/Gigantism (growth hormone excess):

• Progressive coarsening of facial features, enlargement of hands and feet, and metabolic complications 3

Cushing Disease (ACTH excess):

• Weight gain, central obesity, purple striae, hypertension, and glucose intolerance 3

TSH-secreting adenomas (rare, ~1% of cases):

• Hyperthyroidism symptoms including palpitations, weight loss, and heat intolerance 2, 5

Mass Effect Symptoms

Visual disturbances are critical warning signs:

• Visual field defects (classically bitemporal hemianopsia) from optic chiasm compression 1, 2
• Visual acuity impairment requiring urgent formal assessment 1
• Complete visual loss can occur and represents a surgical emergency 2

Neurological symptoms:

• Headache, particularly with macroadenomas ≥10mm 1, 2
• Cranial nerve palsies (III, IV, VI) causing diplopia and ocular motility problems 1, 2
• Raised intracranial pressure in severe cases 1

Pituitary apoplexy (acute hemorrhage/infarction):

• Sudden severe headache, acute visual loss, and altered consciousness—this is a neurosurgical emergency 1

Hypopituitarism

Occurs in 34-89% of macroadenomas 1:

• Gonadotropin deficiency: delayed/arrested puberty, hypogonadism, infertility 2
• TSH deficiency: fatigue, cold intolerance, weight gain 2
• ACTH deficiency: fatigue, weakness, hypotension 2
• Growth hormone deficiency: growth failure and short stature in children 2
• Central diabetes insipidus: extremely rare at initial presentation unless apoplexy has occurred 1

Gender and Age Differences

Important clinical pitfall: Males typically present later with larger, more invasive tumours due to less obvious hormonal symptoms 6:

• Males have tumours averaging larger size with higher rates of suprasellar extension and cavernous sinus invasion 6
• Females present 3-4.5 times more commonly but with earlier-stage disease due to menstrual disturbances prompting evaluation 4, 2
• Children more commonly harbor macroprolactinomas with aggressive behavior compared to adults 2

Examination Approach

Essential Clinical Assessments

Visual assessment (mandatory for all macroadenomas):

• Formal visual field testing (perimetry) for any tumour approaching or compressing the optic chiasm 1
• Visual acuity testing 1
• Fundoscopy to assess for papilledema or optic atrophy 1
• Critical caveat: Visual deterioration is an urgent indication for surgical decompression 2

Neurological examination:

• Cranial nerve function, particularly III, IV, and VI for extraocular movements 1, 2
• Assessment for signs of raised intracranial pressure 1

Endocrine examination:

• Signs of hormone excess (acromegalic features, Cushingoid appearance, thyrotoxicosis) 3
• Signs of hypopituitarism (pale, dry skin, loss of secondary sexual characteristics, delayed puberty in adolescents) 2
• Galactorrhea assessment in suspected prolactinomas 4, 2

Investigation Protocol

Biochemical Evaluation

Comprehensive pituitary hormone assessment (required for all patients):

Prolactin measurement:

• Single blood sample at any time of day for suspected hyperprolactinaemia 4
• Critical pitfall: Check for macroprolactin in mildly elevated cases, as macroprolactinaemia occurs in 10-40% of adults with hyperprolactinaemia and has low biological activity 2
• High-dose hook effect: Perform serial dilutions in patients with large pituitary lesions but paradoxically normal or mildly elevated prolactin, as very high prolactin can saturate immunoassays 2

Complete pituitary function testing:

• Gonadotropins (LH, FSH) and sex hormones (testosterone in males, estradiol in females) 3
• Thyroid function (TSH, free T4) 3
• Morning cortisol and ACTH 3
• IGF-1 for growth hormone assessment 3
• Specific stimulation/suppression tests in selected situations 3

Imaging

MRI with high-resolution pituitary protocols is the gold standard 1:

• Contrast enhancement increases conspicuity of adenomas, which typically appear as hypoenhancing lesions 1
• Determines tumour size, extent, and relationship to critical structures (optic chiasm, cavernous sinus) 1
• Macroadenomas defined as ≥10mm diameter 1, 7

Histopathological Assessment

When tissue is obtained (typically post-surgery):

• Basic immunostaining panel including pituitary hormones, cytokeratin, and Ki-67 5
• Ki-67 proliferation index ≥3% combined with local invasion predicts 25% recurrence rate 5
• Molecular markers guide prognosis and treatment decisions 5

Genetic Testing

Consider genetic assessment in specific populations:

• All children and adolescents with pituitary adenomas due to higher prevalence of genetic abnormalities 2, 5
• Young adults with prolactinomas or growth hormone excess 5
• Syndromes to screen for: familial isolated pituitary adenoma, MEN1, MEN1-like syndrome, AIP mutations 4, 5

Follow-up Surveillance

Regular monitoring is essential:

• MRI surveillance to monitor for tumour growth or recurrence 1
• Periodic hormonal evaluation to assess pituitary function 1
• Repeat visual field testing if concerns about tumour growth affecting vision 1