CHAPTER 20: THE ENDOCRINE SYSTEM

PITUITARY
• Hyperpituitarism and Pituitary Adenomas
o Anterior lobe adenoma is the most common cause of hyperpituitarism
 Pituitary adenomas can be functional or silent
• Both composed of single cell type and produce single predominant tumor
• Exception: adenomas that secrete two hormones (GH and PRL)
 Can be microadenomas (< 1 cm) or macroadenomas (>1 cm in diameter)
 Most occur as isolated lesions, associated w/ multiple endocrine neoplasia type 1
(MEN-1)
o Pathogenesis
 G-proteins – GNAS1 gene
• Mutation in α -subunit may result in constitutive activation  persistent
levels of cAMP and unchecked proliferation
 Two distinctive morphologic features of most adenomas are their cellular
monomorphism and absence of a reticulin network
o Prolactinomas
 Most common type of hyperfunctioning of pituitary adenoma
 Hyperprolactinemia causes amenorrhea, galactorrhea, loss of libido, and infertility
• Other causes of hyperprolactinemia are pregnancy, high-dose estrogen
therapy, renal failure, hypothyroidism, hypothalamic lesions, dopamine-
inhibiting drugs, etc.
 Stalk effect  any mass in suprasellar compartment may disturb normal inhibitory
influence of hypothalamus on PRL secretion, resulting in hyperprolactinemia
 Therefore, mild elevations of serum PRL ( < 200 ug/L) in an individual w/ pituitary
adenoma do not necessarily indicate PRL-secreting neoplasm
o Growth Hormone-Producing Adenomas
 Second most common type
 Persistent hypersecretion of GH stimulates hepatic secretion of IGF-I (somatomedin
C)
 Before epiphyses close  GH adenomas result in gigantism
 After epiphyses close  acromegaly
 GH excess also associated w/ abnormal glucose tolerance and DM, generalized
muscle weakness, htn, arthritis, osteoporosis and CHF
o Corticotroph Cell Adenomas
 These stain positively w/ periodic acid-Schiff (PAS) stains because of glycosylated
ACTH protein
 May be clinically silent or cause hypercortisolism aka Cushing Syndrome
 After surgical removal of adrenals, the inhibitory effect of corticosteroids on
hypothalamus-pituitary axis is lost, resulting in mass effects of pituitary tumor –
Nelson Syndrome
 ACTH prehormone, which includes the melanocyte-stimulating hormone, will
continue to be synthesized, so patients may also present w/ hyperpigmentation
o Other Anterior Pituitary Neoplasms
 LH and FSH adenomas
• Neoplastic cells usually demonstrate immunoreactivity for common
gonadotropin α -subunit and the specific β -FSH and β -LH subunits
• FSH is usually the predominant secreted hormone
 TSH adenomas
  Nonfunctioning pituitary adenomas
 Pituitary carcinomas
• Hypopituitarism
o Can be congenital or acquired
o Hypopituitarism accompanied by evidence of posterior pituitary dysfunction in forms of
diabetes insipidus is almost always of hypothalamic origin
o Anterior pituitary hypofunction usually caused by:
 Nonfunctioning pituitary adenomas
 Ischemic necrosis of anterior pituitary causing insufficiency (in general, AP tolerates
ischemic insults fairly well – loss of ½ of AP parenchyma causes no clinical
consequences; >75% symptoms develop)
• Sheehan syndrome  postpartum necrosis of AP; during pregnancy, AP
enlarges due to hypertrophy of PRL-secreting cells w/o an increase in blood
supply, making it vulnerable to ischemic injury
 Ablation of pituitary by surgery/radiation
 Less common causes  sarcoidosis, TB, trauma, metastatic neoplasms, mutations of
Pit-1
• Posterior Pituitary Syndromes