Pituitary and Hypothalamus I Flashcards
Where is the pituitary
in the sells turcica of the sphenoid bone
made up of anterior (adenohypophysis) , intermediate, and posterior (neurohypophysis) lobes
What hormones do the pituitary lobes release
anterior: FSH, LH, ACTH, TSH, PRL, GH
posterior: Oxytocin, ADH (vasopressin)
Intermediate: Endorphins, MSH (melanocyte stimulating hormone)
What is the function of the hormones released from the hypothalamus
TRH: stim TSH and PRL GnRH: stim FSH and LH CRH: stim ACTH, MSH, and endorphins GHRH: stim GH Dopamine: inhibit PRL SS: inhibit GH and TSH
What are the different ways you can evaluate hormone levels
blood (capillary/finger prick; venipuncture*, arterial)
urine (sample, or 24 hour collection)- clean catch (ex. catecholamines 2/2 pheo)
tissue bx (ex. thyroid tissue bx)
What are the types of urine specimens
UA- dipstick, pH, specific gravity, protein, glucose, ketone
Micro- sediment, crystals, casts, WBC, RBC
How do you get a 24 hour urine collection
discard first morning void
collect for next 24 hrs
record last void time
keep urine cool
What are different hormone testing levels and how can they be used
- Direct random test: long half life hormone/ not protein bound (TSH)
- Free/total fraction: protein bound hormone (total T3/T4)
- Abs against hormone: AI dz (thyroid)
- Precursor hormone: hyperadrenergic states (ovarian hyperplasia), androstenedione, estrogen, testoterone
- Hormone ration: FSH:LH (infertility)
How can time make a difference in certain hormone tests
some hormones are pulsatile, or have shorter half lives
- Cortisol: 6-8 AM
- GH: at night
Everything in endocrine is basically
a feedback loop!
Primary: target hormone
Secondary: Pituitary
Tertiary: Hypothalamus
When would you use a suppression test
When you suspect HYPERfunctioning of a gland
ex: excess cortisol- Dexamethasone suppression test (normally dexamethasone will suppress adrenals and lower cortisol)
When would you use a stimulation test
When you suspect HYPOfunctioning
ex: low cortisol- ACTH stimulation test (when you give ACTH, adrenals should respond positively to it)
What are the disorders of the hypothalamus (tertiary d/o)
tumors (craniopharyngioma)
inflammation
infiltration (sarcoidosis)
mets tumor
Tertiary disorders are often associated with
loss of posterior pit fxn= central diabetes insipidus
What is the responsibility of the different vasopressin receptors
V1a- mediate pressor activity
V1b/V3- modulate ACTH secretion
V2- renal water excretion and Coag factor VIII ation
Give examples of when vasopressin is high and low
Alcohol inhibits ADH= you pee all the time
Hypotension/shock= high ADH bc you want to keep water
How do V2 agonists (Desmopressin) work
decrease water excretion in central diabetes insipidus and nocturnal enuresis (reduce urine flow)
-improve platelet responsiveness (hemophilia A, VWB dz, uremic coagulopathy)
What happens in diabetes insipidus
You have low ADH= massive urine excretion
this is a WATER problem, not a salt problem
What causes central diabetes insipidus
*Idiopathic (AI/inflammatory)
Trauma, CNS/pit surgery, anoxic encephalopathy (veterans, NFL players)
Primary tumors
Mets tumors (leukemia, lymphoma)
Granulomatous diseases
Autosomal Dominant
Pregnancy (placenta makes an enzyme that degrades ADH)
How does central Diabetes Insipidus usually present
acutely, unremitting thirst, polyuria, cave cold beverages, through day and night
What is the test for diabetes insipidus
Water deprivation test: Fluid deprive, and urine osm should be low. give desmopressin, and Uosm should spike
What is nephrogenic diabetes insipidus
ADH is produced, but the receptors dont work
No response to desmopressin; plasma ADH will be high before and after dehydration
MCC is chronic lithium use, or, hypercalcemia
What is primary polydipsia
Psych d/o in which pt drinks a shit ton of water; Na does not rise
Sna and Sosm are mid-low at start
Thirst does not improve!!
How do you treat neurogenic diabetes insipidus (same as central)
Decrease UOP by increasing ADH activity
Replace lost fluids! (avoid hypernatremia)
What is DDAVP
Desmopressin! synthetic ADH (makes you keep fluid)
Good Tx to reduce nocturia, provide adequate sleep, control diuresis during day
-Liquid nasal (potent), or tablet (less potent)
If desmopressin is not effective in treating diabetes insipidus, what can you give
Chlorpropamide: anti-diuretic, promote renal response to ADH- but, high risk HYPOglycemia
Carbamazepine: enhance response to ADH
Clofibrate: increase ADH release
-Carb and clo decrease UOP up to 50%
How do you treat nephrogenic DI
correct underlying disorder, dc offending drug (stop lithium or normalize calcium)
Thiazide + low salt diet: induce mild volume depletion (hypovolemia)= proximal tubule Na and H2O reabsorption= reduced UOP
What is SIADH
Inappropriately high ADH= water retention; high urinary sodium loss (with little water loss)- this is a salt problem, not a water problem
Hyponatremia (<135) w/o edema
What are the different levels of hyponatremia in SIADH
mild: 130-135
mod: 125-129
severe: <125
- Acute= <24 hrs
- chronic= >24 hr
What are causes of SIADH
Ectopic production (malignancy) Baroreceptor dysregulation (CNS infection, mass, hemorrhage, or MS) (PNA, TB) (Pain, Nausea) Multifactorial (antidepressants, narcotics, antipsychotics, cancer, chemo)
What are symptoms of hyponatremia (in SIADH)
nausea W/O vomiting, confusion, HA
severe: vomiting, somnolence, seizure, GCS <8
How do you treat SIADH
Restrict fluid intake (bc they are already holding so much fluid)
gently give hypertonic fluids to reverse Sx (sz)
(not common) Demeclocline and lithium (impair renal response to ADH)
(not common) Vasopressin antagonist (block ADH receptor so you pee more)
What is a craniopharyngioma
MC sellar tumor of childhood- usually suprasellar
arise from rathke’s pouch and extend into diencephalon
can be cystic or full of lipid rick viscous fluid
How do craniopharyngiomas present in kids
growth retardation
pubertal delay
visual field loss
projectile vomiting (sign of very bad brain tumor)
Depending on the size, what anatomic damage can pituitary tumors have
visual field loss CN injury (VI paralysis= bitemporal hemianopsia) hypopituitarism CSF leak DI (not common)
What is hypothalamus/pituitary regulation
CNS send signal to hypothalamus
hypothalamus to pituitary
pituitary to target gland
-target gland send negative feedback to pituitary and hypothalamus
Explain the different hypothalamic-pituitary tumors and their Sx (overview)
Cushing’s: high cortisol, central obesity, striae, hyperglycemia, osteoporosis, hirsutism
TSH Adenoma: thyroid goiter, thyrotoxemia
Acromegaly: acral enlargement, soft tissue swelling, cardiac hypertrophy, HTN, hypergycemia, sleep apnea
Prolactinoma: galactorrhea, amenorrhea, infertility, hypogonadism
Non-fxn adenoma: central effects, hypogonadism, clinically silent
What is the MC pituitary adenoma
Prolactinoma (40-45%)- secretes prolactin
Sx: galactorrhea, amenorrhea, infertility, hypogonadism
What can cause diffuse pituitary hyperplasia
pregnancy
prolonged primary hypothyroid/hypogonadism
GhRH secreting tumor
Somatomamatotrophic hyperplasia in Carney complex
What is a discrete pituitary tumor
monoclonal origin
20-30% are aggressive, invading adjacent structures (bone, sinuses, etc.); but size and extension not signs of aggressive behavioe
true malignancy <1%
What is a pituitary incidentaloma
found incidentally on MRI or autopsy
no hormonal activity
Track with PRL measurement
-If PRL wnl, <5mm no additional study; 6-9mm repeat MRI in 2 years (per UTD)
How do intrasellar pituitary tumors present
HA pituitary hypofunction (low GH>LH/FSH>TSH>ACTH)
How do suprasellar pituitary tumors manifest
impinge optic chiasm (bilateral hemianopsia)
obstruct 3rd ventricle, hydrocephalus, altered sensorium
How do lateral extension pituitary tumors present
impinge CN III, IV, or VI
LR6, SO4, AO3
How do inferior erosion pituitary tumors present
spinal fluid leak, meningitis
What is the physiologic function of PRL
Milk production fat and carb metabolism vitamin D metabolism fetal development **Mammary gland development (puberty) **Initiate lactation postpartum
How is PRL regulated
secreted from lactotrophs of anterior pituitary in pulsatile manner
Inhibited by dopamine
Stimulated by TRH
Increased by chest wall motion and nipple stimulation (sleep, exercise, sex, stress, pregnancy, lactation)
What does PRL do
Suppress GnRH (low LH and FSH= altered menses and fertility) Stimulate adrenal androgen production= weight gain and hirsutism
What are female S/Sx of hyperprolactinemia
irregular menses, galactorrhea
infertility, HA, depression, menopause Sx, low libido, weight gain
What are male S/Sx of hyperprolactinemia
Loss of libido
galactorrhea, infertility, impotence, depression, gynecomastia
What is the difference in size oh prolactinomas based on gender
Women: Micro because they come in sooner
Men: Macro bc they wait to be seen
What are some causes of increased PRL
increased lactotroph # (pituitary tumor, pregnancy, hypothyroid/high TRH, chest wall injury)
Decreased PRL disposal (renal failure, Macroprolactinemia)
“Increased PRL” is noted on labs as
Diluted 50, stalk effect not prolactinoma (dopamine effects decreased by stalk injury) 50-10, med cause If >100, likely a tumor (100-150) 40-200**, drugs or stalk compression 300-500, macroadenomas
What is the “hook effect” in hyperprolactinemia
Extremely high levels of PRL may read falsely low on undiluted samples- so if you have a large tumor with a very low PRL level, get a diluted sample
Who needs a fasting serum PRL level
all patients with galactorrhea, gynecomastia, and/or hypogonadism
(then get MRI w/ and w/o)
What are pharm causes of hyperprolactinomas
Dopamine antagonist (reglan, 1 gen anti-psych) Dopamine depleting (methyldopa, reserpine) TCA, Verapamil, estrogens, antiandrogens, opiate, H2 blocker
If a woman comes in with galactorrhea and amenorrhea, first thing you get is
PREGNANCY TEST!
then get a PRL level
Main Tx for prolactinomas
Dopamine agonist (Bromocriptine BID w/ food; Cabergoline) \+/- surgical resection if extremely resistant (transsphenoidal resection, radiation) (Micro do NOT progress to Macro)
What is the difference in bromocriptine and cabergoline
Bromo: high success, drug of choice in infertility, but many ADE
Caber: more tolerable, less ADE, biweekly dosing
-High dose cabergoline can cause valvular heart diseae
