Pituitary disease

Central hypothyroidism, ACTH-dependent Cushing’s, secondary adrenal insufficiency, hyperprolactinaemia, acromegaly and AVP deficiency are covered elsewhere

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The pituitary profile

• Includes
  • • TSH, T4, T3
    • Cortisol and ACTH
    • LH, FSH, oestradiol in women and testosterone in men
    • IGF-1
    • Prolactin
    • Electrolytes, CBG
• The posterior pituitary produces ADH and oxytocin (but don’t check these)

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Hypopituitarism

• Causes include
  • • Iatrogenic (surgery, radiotherapy)
    • Head trauma
    • Space occupying lesion
    • Infiltration (granulomatous disease, haemochromatosis, sarcoid)
    • Infections (encephalitis, syphilis)
    • Empty sella syndrome, lymphocytic hypophysitis, Sheehan’s syndrome, pituitary apoplexy
    • Drugs (including opiates)
• The sequence of hormones lost = GH, LH/FSH, ACTH, TSH
• Can present with fatigue, a lack of wellbeing, reduced exercise performance, symptoms of AVP deficiency
• Investigations
  • • Check hormone levels including prolactin
    • Visual fields
    • MRI pituitary
    • Consider dynamic tests such as an insulin tolerance test for GH deficiency
• Treatments to consider
  • • Hormone Replacement Therapy,
    • Steroids (before thyroxine)
    • Testosterone for men (check PSA first)
    • Replace GH if symptomatic
    • Can give DDAVP for AVP deficiency

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Pituitary apoplexy

• Infarction or haemorrhage of pituitary (sometimes due to an adenoma)
• Urgent (but usually not worth waking up neurosurgeons at night)
• Predisposing factors
  • • 25% associated with hypertension
    • Coagulopathies, anticoagulation and thrombocytopenia
    • Pregnancy or oestrogen therapy
    • Diabetes
    • Following head trauma, pituitary surgery, CABG, dynamic pituitary tests, bromocriptine treatment
• 80% have no history of pituitary disease
• 80% have an undiagnosed pituitary adenoma
• Clinical features (variable, mimics other conditions)
  • • Severe frontal (retroorbital) headache
    • Visual disturbance in 60%
    • Ocular palsy (3^rd nerve) in 40%
    • Also 4^th and 6^th CN palsies
    • Vomiting
    • Visual field defects (bitemporal hemianopia)
    • Confusion
    • Signs of hypopituitarism, including a low sodium / adrenal crisis
    • Subarachnoid irritation with a reduced GCS, photophobia, meningism
    • Can have a fever
• Investigation
  • • Take baseline bloods for later analysis
      • • Random cortisol, ACTH, TSH, free T₄ (but half-life of thyroxine is a day, can take a while to fall), prolactin (can be low, normal or high), IGF1, LH, FSH, testosterone (men), oestradiol (women)
        • Clotting
        • Typically normal K+, low Na+
    • Lying and standing BP
    • Often CT first as its quicker – picks it up in around 25% of cases, but more likely to pick up a pituitary mass. Can exclude other diagnoses.
    • Pituitary MRI can diagnose in 90%
    • Consider angiography
    • A lumbar puncture might be contraindicated, but if not, sometimes done to rule out a subarachnoid haemorrhage or meningitis
• Management
  • • IV fluids
    • Then give 100mg IV or IM hydrocortisone TDS (do not wait for the cortisol level). Can taper to a TDS regime (10mg, 5mg, 5mg hydrocortisone)
    • Neuro observations
    • Monitor Na/fluid balance
    • Formal neuro-ophthalmology assessment
    • Consider surgery if low GCS or severe visual disturbance (reduced acuity or visual field defect). Only once stabilised. Operate to protect vision (ideally within 7 days)
    • Urgent advice from neurosurgeons, ophthalmology and endocrinology, skull base MDT
    • Hypothyroidism, hypogonadism and GH deficiency are common and may progress over years – monitor. Endocrine follow up in 4-6 weeks, and ongoing.
    • Do not treat hypothyroidism initially

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Non-functioning pituitary adenoma / incidentaloma

• Incidentalomas are very common (can be found in up to 10% of people)
• Almost always benign, mostly non-functioning
• Management depends on
  • • Size
    • Hormonal status
    • Visual defects – refer for formal testing
• But consider discussion or review by endocrinology in all
• Types
  • • Microadenoma (<10mm) – can be functional, but less likely to cause hypopituitarism
    • Macroadenoma (>10mm)
      • • Evaluate pituitary function in all
        • Can cause hyperprolactinaemia, headache and visual disturbance (bitemporal hemianopia), hypopituitarism.
        • Can cause pituitary apoplexy if headache and neuro-ophthalmic defects
    • Subtypes
      • • Non-functioning adenoma (most common)
        • Prolactinoma
        • Hypersecretion of other pituitary hormones
        • Rathke’s cyst
• Ask about
  • • Visual symptoms
    • Erectile dysfunction
    • Periods
    • Thyroid symptoms
    • Hypoadrenal symptoms
    • Cushing’s symptoms
    • Acromegaly symptoms
• Tests
  • • MRI pituitary
    • 9am cortisol, TSH, T4, prolactin, testosterone in men, LH, FSH, oestradiol, GH, IGF1
    • Need to stop the oral combined contraceptive pill and recheck hormones after 3 months
    • Consider an oral glucose tolerance test (OGTT) for acromegaly
    • Consider a 24-hour urinary free cortisol and overnight dexamethasone suppression test if cushingoid
    • If mass < 1cm – repeat MRI at 1, 2 and 5 years, then discharge if stable appearance
    • If mass > 1cm – repeat MRI at 6 months, 1, 2, 5 years. Do more regular hormone tests. If abutting chiasm – refer surgeons.
    • Do formal visual fields
• Management
  • • Urgent surgery if visual field loss
    • Treat functioning adenomas appropriately
      • • Cabergoline or bromocriptine for prolactinomas
        • Surgery for the rest
    • Radiological monitoring of non-functioning microadenomas, and non-functioning macroadenomas with no visual symptoms
    • Replace hormones if hypopituitarism (especially cortisol, and give before levothyroxine if required)
    • Monitor hormone levels (T4 better than TSH in central hypothyroidism)

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Sheehan’s syndrome

• Severe hypotension secondary to postpartum haemorrhage which causes haemorrhagic infarction of pituitary gland
• Rare, more common in the developing world
• Leads to hypopituitarism
• Mostly affects anterior pituitary: hypothyroid, low prolactin (can’t lactate, no periods), hypoadrenalism, low FSH/LH (amenorrhoea)

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Hypophysitis

• Often due to immunotherapy (especially ipilimumab, nivolumab, pembrolizumab) – more here
• Can be severely hypoadrenal. Check cortisol. Consider high dose prednisolone
• Other causes include autoimmune lymphocytic, granuloma, infections (such as TB), IGG4 disease, Takayasu’s