Pituitary Pathology: Gupta Flashcards
What is the most common cause of hypopituitarism?
75% of parenchyma must be lost or absent for hypopituitarism to manifest itself.
Most common causes:
-Nonfunctioning adenoma
-Sheehan syndrome (postpartum necrosis of ant. pit. due to rapid enlargement of pit. during preg. then hemorrhage at childbirth causing infarcted anterior pituitary) Post. pit. usually not affected because it has a better blood supply. Ant. pit. blood supply is venous blood (already low O2 content). classic clinical scenario: mom can’t lactate after birth.
- Empty sella syndrome- for one reason or another (surgery, herniation of CSF into sella turcica), the pit. gland is effectively absent in the sella turcica.
What are the most common cause of hyperpituitarism?
Adenoma arising in the anterior lobe.
Less commonly: pituitary carcinomas and hypothalamic disorders.
What are the histologic and molecular findings associated with anterior pituitary adenomas?
Histology:
Typically composed of uniform, polygonal cells arrayed in sheets or cords. Supporting connective tissue, or reticulin, is sparse, accounting for the soft, gelatinous consistency. Mitotic activity is usually sparse. Cytoplasm is either eosinophilic, basophilic, or chromophibic, depending on the type and amount of secretory product within, but is generally uniform. *This cellular monomorphism and the absence of reticulin network distinguish pit. adenomas from nonneoplastic anterior pit. parenchyma.
Molecular findings:
G-protein mutations are one of the most common alterations in pituitary adenomas.
~40% of somatotroph cell adenomas bear GNAS mutations that abrogate the GTPase activity of Gsalpha, leading to constitutive activation of Gsalpha, persistent generation of cAMP, and unchecked cellular proliferation. *GNAS mutations are absent in the other trophic cell because their hypothalamic release hormones do not act via cAMP-dependent pathways.
What is the most common type of hyperfunctioning adenoma?
Lactotroph adenoma- most common, account for 30% of cases. Increased serum levels of prolactin cause amenorrhea, galactorrhea, loss of libido, and infertility. Mass effect. Tx- bromocriptine.
What are the clinical manifestations of the different adenoma cell types?
::Lactotroph- most common, account for 30% of cases. Increased serum levels of prolactin cause amenorrhea, galactorrhea, loss of libido, and infertility. Mass effect. Tx- bromocriptine.
::Somatotroph- Second most common. Gigantism in children, acromegaly in adults. Gonadal dysfunction, diabetes mellitus, gen. muscle weakness, HTN, arthritis, CHF, ^ risk of GI cancer.
::Corticotrophs- Excess ACTH leads to Cushing’s syndrome (hypercortisolism) and Nelson syndrome (rapid enlargement of a pre-existing ACTH-secreting pituitary adenoma that occurs after the removal of both adrenal glands because of the lack of the negative feedback of cortisol on the production of ACTH).
Less frequently:
::Gonadotrophs- secrete hormones insufficiently and variably. Hypogonadism. Secretory products usually do not cause a recognizable clinical syndrome. Usually mass effect is why they are recognized. Impaired secretion of LH –> v energy and libido in men and amenorrhea in premenopausal women.
::Thyrotroph- 1% of all pit. adenomas. Rare cause of hyperthyroidism.
Nonfunctioning pit. adenomas consist of 25-30% of all pit. adenomas. Cause mass effects (loss of lateral visual fields “bitemporal hemianopsia” due to compression of optic chiasm). Hypopituitarism by compressing viable structures.
What are the genetic associations of the different pituitary adeonomas?
The overwhelming majority of pituitary adenomas are sporadic in nature, but ~5% of cases arise from the defects in the following genes:
::Gain of function:
GNAS- GH adenomas- constitutively turned on
Protein kinase A, regulatory subunit 1- GH & prolactin
Cyclin D1- Aggressive adenomas
HRAS- Pituitary carcinomas
::Loss of function: - familial
MEN1- GH, prolactin, and ACTH adenomas
CDKN1B- ACTH adenomas
Aryl hydrocarbon receptor interacting protein (AIP)- GH adenomas (esp in pts
What are the clinical manifestations of hypopituitarism?
Can’t grow (GH)
Can’t lactate (PRL)
Can’t make babies (FSH/LH)
Adrenal insufficiency (ACTH) hypoglycemia, dehydration, weight loss, and disorientation. Additional signs and symptoms include weakness, tiredness, dizziness, low blood pressure that falls further when standing (orthostatic hypotension), cardiovascular collapse, muscle aches, nausea, vomiting, and diarrhea.
Thyroid insufficiency (TSH) mentally and physically slow
What are the posterior pituitary syndromes?
Diabetes insipidus- polydypsia/polyuria b/c no ADH
SIADH- Retain too much water b/c too much ADH. Hyponatremia
What do acromegaly pts die of?
dilated cardiomyopathy
Describe the epidemiology, histology, and pathophysiology of craniopharyngiomas.
Found most often in children but also in adults 50-60yo.
Thought to arise from vistigial remnants of Rathke’s pouch.
Slow growing tumors, accounting for 1-5% of intracranial tumors.
Pts. usually present with headaches and visual disturbances although children can also present with growth retardation due to compression of anterior pituitary.
Genetics- abn. of the WNT signalling pathway found in kids.
Histology: compact lamellar wet keratin pearls (kind of similar to squamous cell carcinoma) and baseloid (dark staining) cells
