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52 Cards in this Set
- Front
- Back
What are the parts of the pituitary gland?
- where do they originate from and what changes occur in their development? |
Anterior Pit = Adenohypophysis
- from an ectodermal evagination of pharyngeal epithelium (Rothke's Pouch) - loses its connections to oral cavity Posterior Pit = Neurohypophysis - from ventral evagination of floor of diencephalon - maintains connections to hypothalamus through pituitary stalk |
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Pituitary Gland
- where is it located? - size? - what important structures is it near? |
- situated in base of skull, protected by Sella Turcica ("turkish saddle")
- 6x12 mm - Lateral to sella = cavernous sinus: houses internal carotids, CN III, IV, V1, V2, VI - Ant and inf to Sella = sphenoid sinus - Sup = optic chiasm |
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What is the pituitary's vascular supply?
- function? |
= Hypophyseal Portal System
... delivers hypthalamic releasing hormones to anterior pituitary |
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What peptide hormones are secreted by the ant pituitary? What controls each of their releases?
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ACTH (regulated by CRH from hypothalamus)
GH (regulated by GHRH (mostly) and somatostatin (-) from hypothalamus) TSH (regulated by TRH from hypothalamus) LH/FSH (regulated by GnRH from hypothalamus) Prolactin (TONIC INHIBITION via DOPAMINE from hypothalamus) |
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ACTH
- secreted by? - target organ? - effect? - excess/deficiency? |
- secreted by ant pit
- target: adrenal glands - effect: stimulates cortisol synth/secretion (cortisol has negative feedback on ACTH secretion) - excess: Cushing Syndrome - deficiency: adrenal insufficiency |
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TSH
- secreted by? - target organ? - effect? - excess/deficiency? |
- secreted by ant pit
- target: thyroid - effect: stimulate TH (T3 and T4) synth/secretion (TH has negative feedback on TSH secretion) - excess: hyperthryroidism - deficiency: hypothyroidism |
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GH
- secreted by? - target organ? - effect? - excess/deficiency? |
- secreted by ant pit
- target: multiple tissues (bone, cartilage, muscles, etc.) - effect: growth! in many tissues (esp liver), stims synth of IGF-1 (somatomedin C), which causes growth (IGF-1 has negative feedback on GH secretion) - excess: Acrogmegaly (or Gigantism if before epiphyseal plates are closed) - deficiency: growth retardation or adult clinical sx |
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Gonadotropins
- secreted by? - target organ? - effect? - excess? - deficiency? |
= LH and FSh
- secreted by ant pit - target: ovary/testes - effect: cause estradiol secretion and gametogenesis [females]; testosterone secretion and spermatogenesis [males] - excess: precocious puberty - deficiency: hypogonadism |
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Prolactin
- secreted by? - target organ? - effect? - excess? - deficiency? |
- secreted by ant pit
- target: mammary glands - effect: initiation and maintenance of lactation - excess: galactorrhea and amenorrhea - deficiency: inability to lactate after delivery |
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Posterior Pituitary
- what hormones does it secrete? - where are they synthesized? |
- secretes Oxytocin and Vasopressin (ADH)
- both synthesized in hypothalamus (supraoptic nuclei and paraventricular nuclei)... travel to neurohypophysis by pituitart stalk |
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Vasopressin/ADH
- regulation? - target organ? - effect? - excess? - deficiency? |
- regulated by plasma osmolality and "effective" circulating blood volume
- target: collecting tubule of kidney - effect: increase in water permeability - excess: SIADH = syndrome of inappropriate secretion of ADH) - deficiency: central diabetes insipidus |
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Oxytocin
- regulation? - target organ? - effect? |
- regulated by neurotransmitters (cholinergic, alpha-adrenergic)
- target: breast and uterus - effect: milk letdown reflex; contractions of uterus during labor |
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Pituitary Tumors
- frequency? - malignant? - incidental frequency? |
= 10% of intracranial neoplasms
- BENIGN (almost always) - incidental finding in 10-20% people |
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How are pituitary tumors classified?
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classification based on size:
- microadenoma (<1 cm) - macroadenoma (>1 cm) |
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What is the difference between Cushing Syndrome and Cushing Disease???
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Syndrome - all etiologies
Disease - ACTH-secreting tumor IN THE PITUITARY! most common endogenous etiology |
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Cushing's Syndrome
- what is? - cause? (what is most common?) |
= constellation of clinical signs/sx caused by chronic glucocorticoid excess
CAUSES: ** most common = chronic high-dose glucocorticoid (steroid) inkate - pituitary tumor (Cushing's Disease) = most common endogenous etiology |
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What are the different endogenous causes of Cushing's Syndrom?
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ACTH-dependent: increased ACTH
- pituitary tumor (Cushing's Disease) -other ACTH-independent: increased cortisol - adrenal adenoma/carcinoma - other Pseudo-Cushing's Syndrome - alcoholism - major depressive disorder |
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What are some of the main signs/sx of Cushing's Syndrome?
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- central obesity (with thin arms/legs)
- moon facies - increased supraclavicular fat pads (buffalo hump) - hirsutism on face - acne - hyperpigmentation |
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Diagnosis of Cushing's Syndrome
- which is best?? |
1. Urinary Free Cortisol Measure
- BEST TEST! - (+) is value of cortisol is >3x upper limit of normal - requires 24-hr urine sample 2. Overnight Low-Dose Dexamethasone Suppression Test - take 1 pill at 11 p.m. --> should have negative feedback on ACTH secretion and shut down adrenals, thus reducing cortisol to <3ng/dL by 8 a.m. - If (+) is value >3 ng/dL at 8 a.m. **many false-positives (due to obesity, alcoholism, depression) --> must confirm (+) with urine free cortisol test 3. Loss of Diurnal Variation of Cortisol Secretion - Normally, highest cortisol levels are in the morning and cortisol is lowest at 11 p.m. - (+) if cortisol is ALWAYS high |
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What is Dexamethasone?
- use? |
= synthetic cortisol
- used to test for Cushing's Syndrome bc has a much longer t1/2 than natural cortisol |
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How do you differentiate between ACTH-dependent and ACTH-independent Cushing's Syndrome?
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Check plasma ACTH!
< 5 pg/ml = ACTH-independent (Adrenal Cushing's Disease - bc no problem with ACTH from pituitart, just extra cortisol secreted from adrenals) ... do CT of adrenals > 10 pg/ml = ACTH-dependent (Pituitary or Ectopic Cushing's) 5-10 pg/ml = Not difinitive **Ectopic Cushing's has much higher ACTH than Cushing's Disease (pit tumor) |
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What is Ectopic Cushing's Disease?
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ACTH secreted by neuroendocrine tumors...
- Bronchial Carcinoids = most common - other: SCC of lungs, islet cells tumor of pancreas, pheochromocytoma, medullary carcinoma of thyroid |
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How do you differentiate between Pituitary v. Ectopic Cushing?
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1. High Dose Dexamethasone Suppression Test
- most ppl with pituitary tumors will suppress ACTH secretion after high dose dexa... ectopic patients will not 2. Petrosal Sinus Sampling - catheter inserted into petrosal sinus which drains pituitary venous system (measures ACTH coming directly from pit) - if pituitary tumor, will have high ACTH; if ectopic, ACTH will be low/normal - INVASIVE (last resort) |
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What is the next step after a patient tests positive for Cushing's?
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MRI of pituitary!!
Note: do NOT do MRI before dx Cushing's (bc 10-20% ppl will have a pituitary incidentaloma pit tumor, but it might not be causing the Cushing's) |
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What is treatment for Cushing's?
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surgical resection
-- if ectopic, resect tumor -- if adrenal, do unilateral adrenalectomy ...sometimes followed by radiation |
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Acromegaly
- what is? - cause? |
= excessive production of GH
- 99% due to pituitary tumor |
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What is Gigantism?
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due to GH-secreting tumoes arising in childhood -- bc epiphyses are not yet closed
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What are some clinical sx of acromegaly?
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- enlarged facies
- acral enlargement - heel pad thickness >22 mm - prognathism/malocclusion (enlargement/forward protrusion of jaw) - arthralgias - carpal tunnel syndrome (englarged bones press agains median n) - HTN, diabetes (GH increases blood vol and insulin resistance) - sweating!!!! - oily/greasy skin - skin tags - sleep apnea (due to enlargement of oral cavity) |
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What are some of the major long-term consequences of acromegaly?
What is the #1 cause of death? |
CV Disease:
**# cause of death = cardiomyopathy Neuropathy Arthropathy - bones do not shrink after surgery - soft tissue changes return to normal Hypertension ***High risk of Colon Cancer |
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What is the mnemonic for the long-term effects of acromegaly?
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CHANC
c= cardiomyopathy h= hypertnsion a= arthropathy n=neuropathy c= colon cancer |
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Diagnosis of Acromegaly?
- what is the best test? - what is the gold standard? - why are they not the same?? |
1. High levels of IGF-1 (somatomedin C)
- *BEST TEST!! - 10-15% false negatives 2. Failure of GH fall after OGTT (Oral Glucose Tolerance Test) - **Gold standard - but difficult to do, so done second - give oral glu (1 g/kg), then measure GH every 30 min for 2 hours - normally, glu has negative feedback on GH release... if have tumor, GH doesn't fall - GH > 1 ng/ml = ACROMEGALY 3. If test positive, do MRI of pituitary |
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Treatment of Acromegaly?
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1. Transspehnoidal Surgery = 50% curative
2. Adjunctive tx if necessary - somatostatin analogues (e.g., SANDOSTATIN) --> inhibits GH secretion and shrinks what's left of tumor - Radiation - (occasional) dopamine agonists, GH receptor antagonists ***Screen for colon cancer/polyps |
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Prolactinomas
- micro or macroadenomas - sx |
**most common secretory pit tumor!!
= micro OR macroadenomas SX women: amenorrhea, infertility, galactorrhea men: decreased libido, impotence, (sometimes) galactorrhea both: (if macro) mass effects - headache, vision changes, etc (due to compression) |
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What are the most common secretory pituitary tumors??
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PROLACTINOMAS
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Diagnose Prolactinoma?
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- High Prolactin
- Abnormal pituitary MRI - Must exclude other etiologies of high prolactin... (esp bc 10-20% ppl have pit incidentalomas) |
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What are other etiologies of high prolactin besides prolactinoma?
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- primary hypthyroidism
- renal failure - cirrhosis (can't metab estradiol --> stims prolactin secretion) - pregnancy - stress (bc prolactin is a stress hormone) - drugs - dopamin antagonists - non-functioning pit adenomas or infiltration of h-p axis (e.g., sarcoidosis)- compression of pit stalk prevents dopamine from traveling down to pit |
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Treatment for Prolactinoma?
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***Almost always medical!
- Dopamin agonists - e.g., Bromocriptine or Cabergoline --> shrink tumor - surgery and radiation ONLY for pts who don't respond to drugs |
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Thyrotrope Adenoma
- frequency? - clinical presentation? - tx? |
- RARE (<1% all pit tumors)
- 2 clinical presentations: (1) Hyperthyroidism - goiter, other classic sx -- High T3/T4 BUT inappropriately normal/elevated TSH (in normal hyperthyroidism, T3/T4 feedback inhibit TSH, so TSH is LOW) (2) mass effects - headache, abnormal visual fields -Tx: Surgery |
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Gonadotrope Adenoma
- what does it secrete? - nick name? why? - clinical presentation? - tx? |
- secretes FSH, LH, or alpha subunit
- aka: "nonfunctioning adenoma" - no obvious clinical sx related to these hormones - 2 clinical presentations due to macroadenoma (1) mass effects - headache, abnormal visual fields (2) hypopituitarism - deficiency of other pit hormones - Tx: Surgery |
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Diabetes Indipidus (DI)
- types? - sx? - onset? |
- due to insufficient secretion of ADH (CENTRAL/NEUROGENIC)
or - due to resistance of the kidney to ADH action (NEPHROGENIC) - sx: polyuria and polydyspia - pts with central DI have predilection for cold or iced drinks - Central DI - abrupt onset - Neph DI - slow onset |
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Causes of Central DI
- most common? |
1. congenital (autosomal dominant)
2. acquired - iatrogenic (following surg) = most common! - trauma - neoplasms - ischemia (Sheehan's Synd) - granulomas (Sarcoidosis) - infections (TB) - autoimmune - idiopathic ..... really, any destruction of hypothalamic area |
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Causes of Nephrogenic DI
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1. Congenital (x-linked)
2. Acquired - renal disease - e.g, sickle cell, polycystic kidney disease, amyloidosis, obstructive uropathy - **Electrolyte disorders: HYPOKALEMIA, HYPERCALCEMIA - **Drugs: LITHIUM, demeclocycline ...anything that affects kidneys |
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Diagnosis of DI?
- how do you determine which type? |
- polyuria (high)
- urine specific gravity (low) - urine osmolality (low) ... = DILUTE URINE **Differentiate Central DI from Nephrogenic DI... - give ddAVP (synthetic ADH) --> if respond, must be central DI; if don't respond (nephrogenic DI bc kidneys don't use the ADH you just gave them) |
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What is ddAVP?
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= synthetic ADH
- given to differentiate btwn central and nephrogenic DI |
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Treatment of DI?
- central? - nephrogenic? |
Central: give ddAVP
Nephrogenic: NSAIDs and Thiazides |
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Hypopituitarism
- most common cause? - 2 common types? |
= deficiency of one or multiple pituitary hormones
(partial or panhypopituitarism=all) - GH, FSH, LH first to be lost... - TSH, then ACTH, then ADH last - Macroadenoma = most common cause! - 2 types: -- Sheehan's Syndrome - Pituitary Apoplexy |
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Sheehan's Syndrome
- what is? - cause? - clue to dx? |
= ischemic pituitary necrosis following childbirth
- assoc'd with postpartum hemorrhage and hypotension - **clue to dx: failure to lactate |
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Pituitary Apoplexy
- what is/cause? - presentation? |
= hemorrhagic infarction of pituitary adenoma
- presents ACUTELY with headaches, change in mental status, opthalmoplegia, visual loss - variable degrees |
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Diagnosis of Pituitary Apoplexy?
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- MRI of hypothalamus/pituitary - will show bleeding
- endocrine testing - assess for deficiencies |
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Treatment of Pituitary Apoplexy?
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Depends on etiology...
- possibly neurosurgery - hormone replacement (if deficiency) |
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Pituitary Incidentalomas
- what are? - frequency? - most common one? - other causes? |
- Found incidentally by imaging the brain or on autopsy
- 10-20% people not suspected to have pituitary disease - most common = microadenoma - could also be: craniopharyngioma germ cell tumor, glioma, metastases from breast, lung, etc....... |
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Pituitary Incidenalomas
- workup/follow-up? |
- Must exclude hormonal hypersecretion: PRL, IGF-1, TSH, Free T4, overnight dexamethasone suppression test, etc
- Use LH/FSH levels as a marker to see if tumor shrinks after pregnancy If macroadenoma, must rule out hypopituitarism - test visual fields **Follow up with periodic MRI: 6 months, 1, 2, 5 years |