B95. Hypo and Hyperfunction of the hypthalamic hypophysial system Flashcards
What are the major hormones lost in panhypopituitarism and what is lost first?
how much of the gland is lost before symptoms occur.
panhypopituitarism, occurs with 75% loss of adenohypophysis parenchyme
Hormones lost, in order:
- GH
- LH
- FSH
- ACTH
- TSH
What are the causes of panhypopituitarism
- Tumors
- pituitary adenoma
- craniopharyngioma - Rathke pouch embryonic rmenant tumor, seen in children.
- other CNS tumors
- Granulomatous diseases
- Irradiation
- Trauma -
- skull fractures
- birth trauma
- Surgery
- Sheehan syndrome
- Autoimmune hypophysitis
- Tumors or disorders of the hypothalamus
- Congenital agenesis, exceptionally rare.
What is the presentation of Sheehan syndrome? Why is the posterior pituitary spared?
Presentation:
- poor lactation is usually the first sign, as the woman should be lactating
- loss of pubic hair,
- fatigue - signs of hypthyroidism.
The anterior pituitary is supplied by blood from the portal veinous system of the Superior Hypophyseal artery
While the posterior neurohypophysis is supplied directly by arterial branches of the Inferior hypophyseal artery.
Quick bullet point results for deficiencies of each pituitary hormone
GH: Dwarfism
LH/FSH: amenorrhea, decreased libido, impotence, infertility loss of pubic and axillary hair
TSH: hypothyroidism
ACTH: hypoadrenalism (Addison’s syndrome)
Prolactin: no postpartum lactation
Results of GH loss
in children,
- dwarfism, nanosomia
in adults,
- muscle loss
- central obesity
- impaired attention and memory
-
Insulin resistance
- hypercholesterinemia
- hyperlipidemia, LDL and HDL
- central obesity
- loss of bone mass, fractures.
Effects of low LH/FSH
menstrual abnormalities or amenorrhea
Infertility
loss of muscle mass
loss of pubic, axillary, and facial hair
decreased libido
impotense
delayed or absent puberty
imcropenis, impaired sexual development of both sexes.
Effects of low ACTH
- Results in adrenal insufficiency, without pigmentation
- hypoglycemia
- fatigue, vomitting
- anemia
- hyponatremia
Addisonian crisis:
- sudden lower body pain
- confusion, psychosis,
- severe lethargy
- hypoglycemia
- hyponatermia
- hyperkalemia
- hypotension
- severe vomitting and diarrhea, unclear cause probably CNS
- coma, death
hypercalcemia in 10% for unclear reasons.
Effect of low TSH
- hypothyroidism
- fatigue and confusion
- mental slowing
- low BMR
- low cold tolerance
- low heart rate
- low blood pressure
- weight gain and hair loss
Effect of low prolactin
just low impaired lactation
may also cause low libido but not really tho
What causes hyperpituitarism?
Adenomas of specific cell types in the anterior lobe are by far the most frequent cause.
Less commonly there is hyperplasia or carcinomas of the anterior pituitary
Paraneoplastic syndromes
and some hypothalamic disorders.
How are pituitary adenomas classified?
What are the cell types of each called?
Based on the hormones they produce, detected by immunohistostaining
- Corticotrophs - ACTH
- Somatotrophs - GH
- Lactotrophs - Prolactin
- Mammosomatotorphs - secrete both Prolactin and GH
- Thyrotrophs - TSH
- Gonadotrophs - FSH.
- Silent - cells stain for a hormone, but it is not secreted and does not have clinical manifestations.
- Hormone negative
- Rare cases are plurihormonal
What is the size classifications of pituitary adenomas
microadenomas smaller than 1 cm
macroadenomas above 1 cm.
What is the presentation of pituitary adenomas, what causes them?
95% are sporadic
5% are familial
Secretory adenomas are discovered based on their clinical symptoms of their overexpressed hormone
Hormone-negative adenomas are usually discovered as macroadenomas, and are often discovered due to their compression effects causing hypopituitarism and bilateral temporal hemanopia.
What are the mutations associated with pituitary adenomas?
GNAS1 mutations to the GsAlpha protein, ablating its GTPase activity, and causing persistent activity of the Gs signaling. This is found in about 40% of GH adenomas and in a minority of ACTH adenomas.
TP53 mutations are not common, but if they are present, they are associated with aggressive invasion and recurrence of the adenomas.
Familial pititary adenoma syndromes have mutation in one of these four genes:
- MEN1
- CDKN1B
- PRKAR1A
- AIP
What is the gross morphology and histology of a pituitary adenoma?
Well cricumscribed, soft tumor, the color of gray matter.
microadenomas remain confined to sella turcica
Macroadenomas can extend in all directions, downward and
- erode the sella turcica bones, and invade locally into the cavernous and sphenoid sinuses.
- Can grow upwards and compress the optic chiasm bilateral temproal hemanopia
Histology:
- solid cords or sheets of uniform, polygonal cells. There is sparse connective tissue.
- nuclei may be uniform or pleomorphic with low/absent mitosis.
- the cytoplasm can be acidophilic basophilic or chromophobic based on the secretory type of cell, but its function is not predictable from its H&E stain.
- The singular cell type within the tumor and the very little stroma distinguishes it from the normal anterior pituitary tissue (which has a heterogenous mix of cells).
- p53 mutations cause adenomas with high mitotic figures, called atypical adenomas, which are more locally invasive and recurrent.
