Pathology of pituitary gland

By: Shifaa’ Qa’qa’

• Sella turcica

• Adenohypophysis (80%):

- epithelial cells

- acidophil , basophil , chromophobe

- Somatotrophs, Mammosomatotrophs, Corticotrophs, Thyrotrophs, Gonadotrophs

- blood supply from the low-pressure portal venous system.

• Neurohypophysis:

- modified glial cells, axonal processes, axon terminals (from nerve cell bodies in the supraoptic

and paraventricular nuclei of the hypothalamus)

- Oxytocin, antidiuretic hormone (ADH) /vasopressin

- Receives its blood directly from arterial branches

• pituitary disease:

Hyperpituitarism ---- anterior pituitary adenoma

Hypopituitarism ---- ischemic injury, surgery, radiation, inflammatory reactions, nonfunctional pituitary adenomas

• Local mass effects:

radiographic abnormalities of the sella turcica

bitemporal hemianopsia

headache, nausea, and vomiting (+ICP)

Seizures, obstructive hydrocephalus

cranial nerve palsy

• pituitary apoplexy:

rapid enlargement of the lesion

acute hemorrhage into an adenoma

depression of consciousness, sudden headache, neusea , vomitting, vision loss---hypopituitarism

neurosurgical emergency

HYPERPITUITARISM AND PITUITARY ADENOMAS

The most common cause of hyperpituitarism is an adenoma arising in the anterior lobe.

Hyperplasia of the anterior pituitary,

Carcinomas of the anterior pituitary (rare)

extrapituitary tumors,

hypothalamic disorders

• Pituitary adenomas: Functional Nonfunctioning --- +IHC stain hormone negative---- -IHC stain / null cell Sporadic ---- G protein mutation Inherited (5%)---- MEN1, CDKN1B, PRKAR1A, and AIP Microadenomas ----- less than 1 cm Macroadenomas ----- exceed 1 cm ----- Nonfunctioning ----- hypopituitarism

• Gsα

• G-protein mutations

• Mutation in the α-subunit/ GNAS mutations

• Interferes with GTPase activity

• TP53 mutaion

• pituitary adenoma:

well-circumscribed

cellular monomorphism

absence of a significant reticulin network

Atypical adenomas: brisk mitotic activity, P53 mutation, aggressive behavior (invasion and recurrence)

• Prolactinomas

- M.c hyperfunctioning pituitary adenoma

- Microadenomas / macroadenomas

- Hyperprolactinemia (amenorrhea, galactorrhea, loss of libido, and infertility). subtle in men and older women

Hyperprolactinemia: • prolactin-secreting pituitary adenomas • pregnancy, • high-dose estrogen therapy • renal failure • hypothyroidism, • hypothalamic lesions • dopamine-inhibiting drugs (e.g., reserpine) • any mass in the suprasellar compartment may disturb

the normal inhibitory influence of hypothalamus on prolactin secretion

• Growth Hormone–Producing (Somatotroph Cell) Adenomas:

- 2nd m.c

- insulin-like growth factor I (somatomedin C)------- liver

- Gigantism---- increase in body size,long arms and legs---- before the epiphyses close

- Acromegaly ---- soft tissues, skin, and viscera bones ----- after closure of the epiphyses

• abnormal glucose tolerance and diabetes mellitus,

• generalized muscle weakness,

• hypertension,

• arthritis,

• osteoporosis,

• and congestive heart failure.

• Adrenocorticotropic Hormone–Producing (Corticotroph Cell) Adenomas:

Hypercortisolism Cushing disease

Cushing syndrome

Hyperpigmentation /MSH

Nelson syndrome ---- hypercortisolism does not develop ---- No adrenals

• Gonadotroph (luteinizing hormone [LH]–producing and follicle-stimulating hormone [FSH]–producing) adenomas:

Mass effect

Thyrotroph (thyroid-stimulating hormone [TSH]–producing) adenomas:

1%

rare cause of hyperthyroidism

HYPOPITUITARISM

• Loss or absence of 75% or more of the anterior pituitary parenchyma.

Causes: • Nonfunctioning pituitary adenomas • Ischemic necrosis(Sheehan syndrome, DIC, sickle

cell anemia, elevated intracranial pressure, traumatic injury, and shock of any origin)

• surgery or irradiation • sarcoidosis • Tuberculosis • Trauma • metastatic neoplasms

• Hypopituitarism accompanied by evidence of posterior pituitary dysfunction in the form of diabetes insipidus is almost always of hypothalamic origin

Manifestations:

• Children--- growth failure (pituitary dwarfism) ---- growth hormone deficiency

• Gonadotropin deficiency (amenorrhea and infertility in women and to decreased libido, impotence, and loss of pubic and axillary hair in men)

• TSH---- Hypothyroidism

• ACTH----- hypoadrenalism

• Prolactin deficiency---- failure of postpartum lactation.

• MSH deficiency -------------- pallor

POSTERIOR PITUITARY SYNDROMES

• Oxytocin:

stimulates the contraction of smooth muscle in the pregnant uterus and of muscle surrounding the lactiferous ducts of the mammary glands.

Impairment of oxytocin synthesis and release has not been associated with significant clinical abnormalities.

• ADH: Released in response to: - increased plasma oncotic pressure, - left atrial distention - Exercise - certain emotional states,

----- collecting tubules of the kidney to promote the resorption of free water

• ADH deficiency causes diabetes insipidus, a condition characterized by excessive urination (polyuria)

Causes:

- head trauma,

- neoplasms,

- inflammatory disorders of the hypothalamus and pituitary,

- surgical procedures involving the hypothalamus or pituitary

- spontaneously (idiopathic)

• Central diabetes insipidus (ADH deficiency)

• Nephrogenic diabetes insipidus

• Large volumes of dilute urine with an inappropriately low specific gravity.

• Serum sodium and osmolality are increased as a result of excessive renal loss of free water,

• Resulting in thirst and polydipsia.

Dehydration

• syndrome of inappropriate ADH (SIADH) secretion:

ADH excess

resorption of excessive amounts of free water, hyponatremia

• The most common causes of SIADH

- secretion of ectopic ADH by malignant neoplasms (particularly small cell carcinomas of the lung)

- non-neoplastic diseases of the lung

- local injury to the hypothalamus or neurohypophysis.

- hyponatremia,

- cerebral edema, and resultant neurologic dysfunction.

- Although total body water is increased, blood volume remains normal, and peripheral edema does not develop.