Krafts – Pituitary Path – 2.5.10
Anterior Pituitary
•GH, ACTH, TSH, LH, FSH, and prolactin.
•Controlled by hypothalamus horms.
Most stim release of ant pit horm except
dopamine which inhibits prolactin
secretion.
•Most problems happen here.
Acidophils GH PL
“B FLAT”
Basophils FSH LH ACTH TSH
Hypopituitary S/Sx:
↓ GH
Kid: pituitary dwarfism
Adult: muscle weakness
↓ FSH/LH
loss of libido
menstrual abnorm
loss of body hair
↓ PL
inability to lactate
↓ TSH
2nd Hypothyroidism
↓ ACTH
adrenal insufficiency
Posterior Pituitary
-extension of hypothalamus
stores oxytocin & ADH.
•Oxytocin: labor, milk let-down,
cuddling (after orgasm), monogamy
(vole studies), trust (investment
experiment). Changes don’t cause Sx
unless preg or nursing
-ADH (vasopressin)
•Hypothalamus makes them
Posterior pituitary stores them
1
Hyperpituitarism:
Too much anterior pituitary
hormone(s)
Causes
•pituitary adenoma (table pg 2)
•destruction of end organs
•hypothalamic disorders
•hyperplasia of anterior lobe
•carcinoma of anterior lobe
Posterior pituitary syndromes -- ADH
Diabetes Insipidus
Syndrome of Inappropriate ADH Secretion
Hypopituitarism
Too little anterior pituitary
hormone(s)
Causes
•Pituitary destruction
•Ischemic necrosis
•Empty sella syndrome
•Pituitary apoplexy
•Hypothalamic lesions
Clinical:
not always clear Sx
•Insidious, chronic
•One or two hormones
•Panhypopituitarism rare
•GH, then FSH/LH, TSH, ACTH
Cause
•Central (ADH deficency) or nephrogenic (kidney prob)
• ADH
•Pee dilute urine – kidney cant conc urine
•Serum Na & osmolality increases  brain effects
•cause: Head trauma, tumors, alcohol consumption
•Increase water intake
Urine tastes bland (unlike diabetes mellitus)
Tx: inc water intake, give ADH
• ADH
•Retain water -- very conc urine
•Blood becomes hypotonic
•Usually mild, sometimes bad
•Ectopic ADH production (small-cell lung CA)
•Tx: Decrease water intake
2
Krafts – Pituitary Path – 2.5.10
Cause
pituitary
adenomas
GENERAL
Clinical
•None, for a while!
•Endocrine abnormalities
(sometimes)
•Mass effects
•visual deficits1
•increased
intracranial
pressure
•HYPOpit –if big enough &
non secreting it can compress
the normal pit  dec
Epidemiology
•Common
•Adults
•MEN I (multiple
endocrine neoplasia
syndromes – hereditary)
-TSH –secreting is
least common
-Autopsy (30%)
Molecular:
•Mutated GNAS1 gene
(mutant G protein)
•Mutated MEN-1 gene
•Mutated RAS, c-MYC genes
(activating mutation)
Path
•Within sella or beyond
•1 cm
•“Invasive” – bengin tumor don’t
invade, but if they get big enough
they can press into the
surrounding tissue
•Can bleed suddenly (emergency)
Micropath
•Sheets/cords
•Uniform cells of one type (acidophil etc)
•May have pleomorphic nuclei
•May have mitoses
•Can’t tell type w/o immunohistochemical
stain
-great variation!
(image of it will not be on exam)
Prolactinoma
•Commonest type of pituitary adenoma
•Efficient secretion
•Amenorrhea, galactorrhea
•Other things can increase prolactin! Stalk effect = disruption of hypothalamic input to pit  inc prolactin
•Can treat with dopamine receptor agonists (bromocriptine) Other adenoma’s Tx by surgery
Growth Hormone
Adenoma
Gigantism
•Pre-pubertal adenoma
•Very tall
•Very very long arms, legs
ACTH Adenoma4
FSH/LH adenoma
Other manifestations of GH adenoma:
•Diabetes mellitus
•Hypertension
•Arthritis
•Gastrointestinal carcinoma
Dx Labs:
• GH (spurts throughout day)
• IGF-I (better)
•GH unresponsive to glucose (should dec)
Tx: surgery & radiation to get GH back to normal
Acromegaly
•Post-pubertal adenoma
•Very tall
•Enlarged bones of face (frontal bossing, big jaw, coarse facial
features) hands
•Makes ACTH (from POMC) POMC  ACTH, MSH, endorphin
•Cushing syndrome (too much cortisol for many dif causes. Sx = glucose intolerant, buffalo hump, moon facies)
•Cushing disease (special cushing syn w/ACTH adenoma)
•Nelson syndrome – if you remove the adrenal gland, you will lose inhibit effects on cortisol  uncontrolled pit adenoma growth
•Inefficient
•Gets big
3
Krafts – Pituitary Path – 2.5.10
1. bilateral hemianopsia – missing sight in lateral fields on both sides from
the pit tumor pressing on the optic nerve.
3.
2. know this chart! There is too big grps of molecules that  cancer. Some
molecules (red) make the cells grow. If you have a genetic abnormality that turns
one of these on all the time  neoplasia (cancer)  uncontrolled growth. Things
that inhibit growth (blue) things that stop cell cycle at certain pts to check DNA. If
you screw up those genes then it is like taking the breaks off. Some of these are
affected in pituitary ademona – RAS (looks like it is always on)!
(which gene?) mutation makes it always on – when it binds to recp the
GDP falls off & GTP falls on  stim adenyl cyclase. w/adenoma it can
get turned off, it can lose the extra phosphate.
4. exogenous ingestion is the most common. Paraenoplastic – tumor in lung
makes something that looks like ACTH & the adrenal response to it w/cortisol.
4
Krafts – Pituitary Path – 2.5.10
Types
Pituitary
Destruction
Cause
•Big pituitary adenoma
•Surgery or radiation
Ischemic
Necrosis
(Sheehan’s
syndrome)
•Pituitary gets BIG, blood flow stays
same (pregnancy is the most common
cause)
•Hemorrhage (delivery) causes
hypotension
•Pituitary (already hypoxic) becomes
necrotic
Empty Sella
Syndrome
•Arachnoid, CSF herniation  takes up
space  Pituitary compression
•Usually NO hypopituitarism!
Pituitary
Apoplexy
•Sudden infarction of adenoma
•Meningeal symptoms
•Can be deadly
Hypothalamic
Lesions
•Tumors, infections
•Rare!
Path
Questions:
1. What happens to pituitary hormone output if you cut off hypothalamic input?
2. What’s apoplexy?
3. Sponge Bob,why is panhypopituitarism so rare?
Answer:
1.  prolactin  all other hormones
2. apoplexy (greek apoplexia, to strike down, disable by a stroke): sudden paralysis with loss of consciousness and sensation, caused by the damaging of blood vessels in the brain.
3. Why, Clucky, it’s because the pituitary has such a big reserve!