Friday 30 October 2015

Pituitary tumours

1. Different types of Pit Tumours + its clinical features

  • Pit adenomas
    • most common
    • peak incidence 35-60yo
    • 3 types
      • Functioning: hormone excess and cause clinical manifestation 
      • Non functioning aka silent: demo of hormone production at tissue level only, without clinical manifestations of hormone excess- may cause hypopituitarism as it encroach and destroy adjacent anterior it parenchyma
      • (Both functioning and non functioning pit adenomas are composed a single cell type and produce a single predominant hormone but there are exceptions eg mammosomatotroph- excess GH and prolactin produced)
      • Hormone negative: absence of IHC reactivity/ ultrastructural evidence of hormone production 
      • (Non functioning and hormone neg adenomas are likely to present at a later stage and hence more likely to be macroadenoma.
    • incidentally diagnosed as microadenomas 
    • Classification 
      • by size (micro, macro and giant adenoma)
      • by patho 
        • ACTH cell
        • GH cell
        • prolactin cell
        • mammosomatotroph
        • TSH cell
        • Gonadotroph cell adenoma)
  • Pit carcinoma
  • Others (mets, epithelial, neural mesenchymal)

Signs and symptoms
  • Excess hormones & Mass effect
  • **Mass effect: the effect of a growing mass that results in secondary pathological effects by pushing on or displacing surrounding tissue.
    • Intracranial mass: headache and vomitting
    • hypopituitarism: compression leading to loss of normal anterior pit hormone production
    • bitemporal hermianopia
    • hyperprolactinemia due to stalk effect

Morphology
  • soft, well circumcised lesion
  • larger lesions extend and often compress the optic chiasm and adjacent structures- invasive adenomas
  • In larger adenomas, foci of haemorrhage and/ or necrosis are common
  • Histology
    • monomorphic
    • uniform round cells
    • delicate stippled chromatin -> salted pepper apperance
    • mitotic activity- scanty
Types of pit tumours
  • Prolactinoma
    • most frequent 
    • cytoplasm weakly acidophillic or chromophobe
    • sparsely/ densely granulated
    • Rupture of cells and intracellular Ca2+ leaks out and Ca2+ accumulates, resulting in dystrophic calcification -> pituitary stone
    • this tumour is characterised by 
      • efficiency (eventhough tumour is small, it will secrete hormones)
      • proportionality (size of tumour affects the amount of hormone prod)
    • Clinical signs and symptoms
      • amenorrhea
      • galactorrhea
      • loss of libido
      • infertility
      • ** Pregnancy, high dose estrogen therapy, renal failure, hypothyroidism, hypothalamic lesions and dopamine inhibiting drugs or mass in the suprasellar compartment can disturb the normal inhibitory influence of hypothalamus on prolactin secretion -> results in hyperprolactetinemia (stalk effect)
  • Growth hormone-producing adenoma
    • 2nd most common type of functional pituitary adenoma 
    • quite large when clinically symptomatic because the clinical manifestation of excessive GH is subtle
    • acidophillic
    • sparesely/ densely granulated cells
    • IHC postive for GH and cytokeratin
    • Diagnosed by increased GH and IGF-1; with glucose loading, there is no suppression of GH
  • Corticotroph cell adenoma 
    • microadenomas when diagnosed
    • stain positively with PAS stains due to carboydrate content
    • densely granulated and basophilic 
    • IHC postive for ACTH
    • Present as?
      • clinically silent
      • cause hypercortisolism due to stimulatory effect of ACTH on the adrenal cortex -> Cushing syndrome
      • cause hypercortisolism due to excessive production of ACTH by the pit -> Cushing Disease
    • large, clinically agressive corticoptroph cell adenomas may develop after surgical removal of adrenal glands for treatment of Cushing syndrome, can result in Nelson syndrome 
      • No hypercortisolism as adrenal glands are absent 
      • patients present with mass effects of the pit tumour
      • also presents in hyperpigmentation due to increased secretion of MSH
  • Gonadotroph adenomas
    • difficult to recognise 
    • secrete hormones inefficiently and variably, and secreted hormones do not cause a recognisable syndrome 
    • only detected when tumours are so large that they cause neurologic signs and symptoms
  • Thyrotroph adenomas
  • Pit adenomas (very rare!) 
    • local extension beyond the sella turcica
    • distant mets
3. Medical and surgical management of pit tumours
  • Surgery
    • transphenoidal approach esp in patients with progressive mass effect eg visual loss, hyperfunction, failure of medical treatment and pituitary apoplexy
    • must remove all cells. If not, can lead to recurrence
  • Medical
    • Prolactinoma -> dopamine agonist to reduce hyperprolactinemia & tumour size
    • GH producing adenoma -> somatastation analogues but doesn't reduce tumour size
  • Gamma knife
  • Radiation
    • esp for incomplete surgical resection, recurrent tumours, those that are unfit for surgery
    • can lead to hypopituitarism, glioma or sarcoma 
Hypopituitarism
Sheehan syndrome - postpartum necrosis of the ant pit
During pregnancy, ant pit enlarges considerably as there is a physiologic increase in the size and no of prolactin secreting cells. However, this isn't accompanied by an increase in blood supply from the low-pressure portal venous system. The enlarged gland is vulnerable to ischaemic injury esp in women who xperience significant haemorrhage during parturition. 
Post pit, as it receives blood supply directly from arterial branches (superior and inferior hypophyseal arteries),  is less susceptible. 

Pituitary apoplexy
- pit undergoes haemorrhage due to increased BP

DDx to pit tumour are Suprasellar tumours:
- induce hypo/ hyper functionaing of ant pituitary
- diabetes insipidus
- 2 main types are Gliomas from chiasm (malignant) & craniopharyngiomas (benign)


4. Craniopharyngioma (malignant transformation is rare unless exposed to radiation)
  • 2 types
    • adamantinomatous 
      • stratified squamous epitheium
      • losee reticulum
      • calcification
      • chronic inflammation
      • cholestrol rich yellow fluid -> as tumours produce lots of fats
    • papillary
      • solid and papillary sheets of squamous epithelum
      • no keratin, no calcification, no cysts
      • no reticulum

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