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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