Pituitary adenoma (mechanism of disease)

This is a mechanism of disease map for pituitary adenoma, in which we define the pituitary adenoma and discuss its etiologies and various manifestations.

ADDITIONAL TAGS:
Headache
Pituitary adenoma
Etiology
Core concepts
Neoplasia / mutation
Inflammation / cell damage
Genetic / hereditary
Microbial pathogenesis
Cardiovascular pathology
Biochemistry
Hormone dysregulation
Pharmacology / toxicity
Immune system dysfunction
Flow gradients physiology
Nervous system pathology
Respiratory gas regulation
Signs / symptoms
Labs / tests / imaging results
Activating mutation in the GNAS gene
Manifestations
Pituitary adenomas:
Well-circumscribed, benign tumors of the endocrine gland located in the sella turcica in the middle cranial fossa.
Histology: monomorphic, polygonal cells arranged in sheets or cords; no  connective tissue or reticulin.
Normally, the anterior pituitary secretes ACTH, TSH, LH, FSH, GH, MSH, and prolactin. The posterior pituitary secretes ADH and oxytocin.
genetic / familial (5%)
sporadic (90%)
Activation of signal transduction pathway via Gs protein
Increased levels of cAMP
Increased the mitotic activity of the pituitary cell
Multiple endocrine neoplasia type 1
Mutation of the MEN1 gene (chromosome 11)
Altered expression of menin protein
Familial isolated pituitary adenoma syndrome
Mutations in the AIP gene
Carney complex
Loss of function mutation in the PRKAR1A gene (encodes regulatory subunit (R1α) of protein kinase A)
Nonsecretory pituitary adenomas (does not secrete hormones)
Secretory pituitary adenomas:  hormone secretion → Hyperpituitarism
Mass effect (compression and/or displacement of adjacent structures)
Compression of the optic chiasm
Bitemporal hemianopsia
Hypopituitarism
GH deficiency: short stature (during childhood); weight gain, weakness, depression
Prolactin def: lactation failure (women)
FSH/LH def: amenorrhea, irregular periods, infertility, delayed puberty, low libido, testicular atrophy, loss of axillary/facial/pubic hair, gynecomastia
TSH def: hypothyroidism: weight gain, cold intolerance, lethargy, constipation, dry skin
ACTH def: adrenal insuff: weight loss, weakness, hypotension, chronic hyponatremia, hypoglycemia
ADH def: central diabetes insipidus: polyuria, polydipsia
Prolactinoma (aka lactotroph adenoma) (~40%) → hyperprolactinemia → reduced bone density due to suppression of estrogen, galactorrhea, amenorrhea; reduced libido and infertility
Somatroph adenoma (10-15%) → ↑ Growth hormone → acromegaly or gigantism
Corticotroph adenoma (Cushing disease) (~5%) → ↑ ACTH → secondary hypercortisolism → skin (bruises, stretches, hirsutism, delayed wound healing); anxiety; depression/anxiety; low libido, amenorrhea; bone fractures; osteopenia; insulin resistance; 2ndary htn
Thyrotroph adenoma (~1%) → ↑ TSH → secondary hyperthyroidism → heat intolerance, frequent bowel movements, sweating, weight loss, pretibial myxedema, lid lag, tachycardia, palpitations, hypertension, tremor, anxiety, hyperreflexia
Gonadotroph adenoma (1%) → ↑ LH and FSH → minimal signs and symptoms