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Related Subjects: |Adrenal Physiology |Addisons Disease |Phaeochromocytoma |Adrenal Adenomas |Adrenal Cancer |Cushing Syndrome |Cushing Disease |Congenital Adrenal hyperplasia |Primary hyperaldosteronism (Conn's syndrome) |ACTH |McCune Albright syndrome |Male Infertility |Prolactin |Prolactinoma |Sheehan's syndrome

Always check 9 am cortisol and replace if low or inadequate response on short synacthen

About

• Usually benign tumour often asymptomatic arising from the anterior pituitary
• Incidence 77 per 100,000
• See other articles on Pituitary apoplexy and Acromegaly

Aetiology

• Monoclonal benign tumour s
• Various gene mutations have been found

Types

• Lactotrophs release prolactin
• Somatrophs release GH
• Corticotroph releases ACTH
• Thyrotrophs release TSH
• Gonadotrophs release LH and FSH

Tumour Activities

• Prolactinomas 57%
• Nonfunctioning adenonomas 28%
• GH secreting 11%
• ACTH secreting 2%
• TSH secreting < 1%

Tumour types

• Hormone secreting vs Hormone non secreting
• Macroademonas (>10mm) and Microadenomas (<10 mm)
• 5% are inherited e.g MEN syndrome autosomal dominant

Pathophysiology

• The clinical effects of the hormone often predominate over that of the tumour mass
• Pressure effects can cause headaches and pressure on the optic chiasma and hypopituitarism and stalk effects with mildly elevated prolactin as dopamine inhibition blocked
• Tumours may rarely bleed presenting as headache
• Damage to the posterior pituitary and hypothalamus can cause Diabetes insipidus and obesity
• Breaches in the dura and sphenoid bone can lead to CSF rhinorrhoea

Hypopituitarism - in usual order

• LSH/FSH/GH effect with low testosterone and oestrogen. There is a loss of libido and secondary sexual characteristics. The testes are small and soft. Skin is smooth and finely wrinkled around the eyes.
• TSH loss: There is a low T4 and low TSH with pituitary hypothyroidism.
• ACTH loss: ACTH loss will cause reduced adrenal steroid production. Mineralocorticoid function is intact as it is controlled by the RAA system.
• Vasopressin loss: Polyuria and polydipsia of Diabetes insipidus

Clinical

• Effect of Hormone excess e.g. Prolactin, GH, ACTH
• Effect of pressure from a large tumour
• Diabetes insipidus
  • Check visual fields for Bitemporal hemianopia.
  • Morning headache and even ophthalmoplegia
  • Stalk effect - compression of pituitary stalk leads to loss of dopamine inhibition on pituitary and rise in prolactin
• Hypopituitary: low testosterone and sex hormones with infertility, low ACTH with hypoadrenalism, Hypothyroid with low TSH

Investigations

• Assess pituitary function. Initially, a 9 am cortisol and PRL should be checked and testosterone, LH, FSH, TSH. Check IGF-1 if Acromegaly suspected.
• A short Synacthen test may be done to assess cortisol response
• MRI pituitary sellar protocol views - assess size and extrasellar extension.
• A water deprivation test may be performed if posterior pituitary failures is suspected.
• Using vertical height classify as those > 10 mm = macroadenoma. 10 mm = mesoadenoma and under 10 mm are microadenomas
• Goldman perimetry and assessment of visual acuity

Differential of Pituitary mass seen in Sella and suprasellar cistern

• Pituitary adenoma
• Craniopharyngioma
• Meningioma
• Metastasis
• Dermoid, epidermoid, Rathke's pouch
• Aneurysm
• Bacterial or Fungal Abscess
• Sarcoidosis, Histiocytosis X
• Lymphocytic hypophysitis
• Germinoma
• Optic glioma
• Inflammatory disease

Histology of Adenomas

• Cells can be divided by staining. Immunofluorescence and other markers used
• Chromophobes (usually non secretory)
• Chromophils
  • Basophils (ACTH, LPH, TSH,FSH,LH,MSH)
  • Acidophils (PRL, GH)

Pituitary Imaging

• Plain X rays have little role nowadays
• CT: good for bone structure and calcification. Radiation.
• MRI: shows up gland, blood vessels, CSF spaces and imaging of choice.

Pituitary Adenoma Management

• Cushing's disease
  • Trans-sphenoidal surgery
  • Radiotherapy
  • Drugs (Ketoconazole, metyrapone)
  • Bilateral Adrenalectomy
• Prolactinoma
  • Prolactinomas are the only pituitary tumour where medical rather than surgical management is first line. They respond well to low dose dopamine agonists such as bromocriptine and cabergoline. The tumour shrinks in size and over time the treatment can be withdrawn with regular follow up by measuring prolactin and MRI.
  • Females present with infertility and galactorrhoea and hirsutism and men with reduced libido. Pressure effects symptoms and signs may be seen. CSF rhinorrhoea may be seen.
  • Macroprolactinomas are associated with PRL > 3000 mU/L and this may also be elevated in a non-functioning adenoma pressing on the stalk but this rarely yields a PRL > 2000 mU/L.
  • Response to one of the dopamine agonists e.g. Cabergoline is seen in 90% and 75% using Bromocriptine. Cabergoline is preferred as long half-life, more effective and less side effects than bromocriptine. Sometimes shrinkage of an invasive prolactinoma can lead to a CSF leak.
  • Surgery is uncommon for prolactinomas other than pituitary apoplexy with persistent neurological signs. See topic. Surgery performed by endoscopic endonasal transsphenoidal pituitary surgery. Risks are low.
  • Radiotherapy may be recommended for aggressive or malignant prolactinomas or recurrence
• Acromegaly
  • Large tumour causing pressure effects or hormonal effects and unresponsive to other methods can be treated by surgery or radiotherapy. Some may be removed by transsphenoidal surgery. Larger ones can need Trans frontal surgery. Radiotherapy may be used
  • Drugs (Dopamine agonists, somatostatin analogues, GH receptor antagonists)
• Nonfunctioning Adenoma
  • Nonfunctioning adenomas are manifest by their pressure effects and so present as macroadenomas. Headaches are commonest. Altered libido and sexual functioning may help identify affected males. The exam may show bitemporal hemianopia, optic atrophy and reduced acuity. Lateral extension can affect cavernous sinus and cause diplopia and ophthalmoplegia and ptosis.
  • If there are no compressive symptoms then a watch and wait policy is fine and visual fields monitored. If there is compression then surgery as discussed above is advocated. Complications are more with transient bleeding, diabetes insipidus, SIADH and CSF leaks. Radiotherapy may be used for the more aggressive tumour s
• Management of Hypopituitarism
  • Educate about need to double dose if any intercurrent illness. Patients should carry a steroid card and inform healthcare professionals.
  • Steroids: Hydrocortisone 10 mg morning, 5 mg at noon and 5 mg evening is best guess starting dose and increase dose x 2-3 when unwell. Prednisolone is an alternative
  • Thyroid: TSH is of little use. Usually, Thyroxine 100 mcg od caution in elderly and angina when lower doses may be used. Range 75-150 mcg/day.
  • GH: if GH deficiency then 0.3-1 mg SC in evening
  • Oestrogen (Females) Oestrogen +/- Progesterone formulations
  • Testosterone: Testosterone 250 mg im ever 2-3 weeks also patches are available
  • ADH for diabetes inspidus:Desmopressin 10-40 mcg / day intranasal 2-3 times. or 300-600 mcg/day PO in 2-3 doses