Q6 Endocrine Flashcards
Canvas Case studies - review
Post pituitary Hypo?
Hyper?
Hypo: DI
Hyper: SIADH
Adrenal cortex hypo?
Hyper?
Hypo = Addison’s
Hyper: Cushings
Posterior pituitary is ________ tissue connected to _______ tract. Produces ________ hormones.
Anterior pituitary is ______ tissue connected to ______. Produces _________ hormones.
PP: neural, *, Oxytocin, ADH
AP: vascular, *, TSH, LH/FSH, GH, ACTH, Prolactin
Hypothalamus secretes ?
TRH, GnRH, GHRH/GHIH, CRH, PIH
More important/common type of regulation?
Negative feedback loop.
T/F: Positive feedback loop is common in men
False. Rare in men. Some in women.
Catecholamines release is an example of ______ regulation.
Neural. Needed emergently fast!
Hypothalamic dysfunction usually shows up as
disruption in ADH and regulatory hormones (usually PLactin first - leaking breast milk.
If a patient has a head trauma and starts leaking breast milk, what would you suspect?
Hypothalamic damage.
Vasopressin is secreted in response to _______ and acts on _______ to _______
High serum osmolality (dehydration, concentration).
Distal tubule and collecting ducts
Increase H2O reabsorption.
causes of Neurogenic or central DI
Pituitary failure - lesion in hypothalamus, or pituitary gland, brain tumor, aneurysm, thrombus, infx, genetics, CHI. No ADH secreted.
Nephrogenic DI is _______
Non-responsiveness to ADH by collecting tubules.
Pseudo/psychogenic DI
Excess Water intake overwhelms any signal to retain - kidneys trying to get rid of it!
DI is kidney unable to _______ urine. They pee _____/day. Polydipsia. Rapid dehydration and _____ natremic. _____ urine osmolarity
Concentrate.
8-12L
Hypernatremia (concentration effect),
LOW
Nephrogenic DI is usually _____ onset
Idiopathic DI is usually ______ onset.
gradual
Abrupt.
DI has a _______ serum Na level and a ______ UOP - usually the opposite.
High serum
High
Chlorpropamide, clofibrate, carbamazepine used in the case of ______
ADH Desmopressin(DDAVP) in the case of ______
ADH insufficiency.
No ADH production at all.
Causes of SIADH
Cancer (bladder, prostate, SCLCA, GU, sarcoma)
CNS
Pulmonary (TB, asthma, CF, respiratory failure)
Meds (hypoglycemics, antidepressants, antipsychotics, narcotics, anesthesia, chemotherapy, NSAIDS)
What does SIADH do to the body?
Excess ADH —> increase CD permeability —> increased H2O reabsorption —> increase in ECF —> dilutional Hyponatremia (<135), low fluid osmolarity (<280), increased urine osmolarity compared to serum.
The ______ SIADH onset, the ______ symptoms.
More rapid
Severe
Hyponatremia s/s by severity:
140-130
120-130
<115
140-130 = thirst, impaired taste, anorexia, fatigue.
130-120 = GI symp, vomiting, abd cramps
<115 = CNS confusion, sz, lethargy, muscle twitching and irreversible neuro changes possibl
What other conditions could mimic SIADH?
Diuretics, HF, renal insufficiency.
Tx for SIADH
Hypertonic saline (SLOW)
Fluid restriction (600-800ml/day)
Usually resolves in 3 days.
Demeclocycline = increased renal tubule resistance to ADH
Conivaptan = hospitalized patients with excess ADH
What is central pontine myelinolysis?
Too rapid of infusion of hypertonic saline.
Genetic pituitary failure is _______onset
Non-genetic pit failure is ______ onset. The 9 I’s?
Pediatric
Adult
Invasion (tumor), Infarct, Infiltrated, Immunology, Iatrogenesis (radiation therapy), Infection, Idiopathy, Isolation.
Anterior pituitary VERY sensitive to _______ and ______
Blood flow and oxygen.
What is Sheehan’s syndrome?
Hypopituiatrism resulting from PP Hemorrhage (+/- DIC) due to circulatory collapse and pituitary artery vasospasm.
Will have S/s of loss of all hormones produced by pituitary (including Addison’s -from adrenal, **)
Cortisol deficiency (life threatening)
Thyroid deficiency (TSH)
Gonadal failure/loss of 2nd sex characteristics
Delayed growth (dwarfism), low lean body mass, low bone density
All these things ^^ indicate?
Panhypopituitarism
What is the most difficult thing to manage in hypopituitarism?
Cortisol levels - circulatory collapse.
GH is secreted in a _______ fashion with the largest amount w/in 1hr of sleep
GH ______ effects of skeletal muscle, liver and fat
GH ______ effects of IGF in liver (most important is IGF1) similar to insulin
Direct
Indirect
What is acromegaly?
GH excess - epiphyseal plates don’t close in children = excess vertical height. Face and hands are extra large
Cardiac hypertrophy - 33-50% with Left HF.
What causes excess IGF-1 production
Ie Excess GH
Pituitary adenoma - tumor.
Pituitary tumors most often result in excess prolactin not excess ______
GH - but it is possible.
What is pseudo acromegaly?
Acromegaly features with insulin resistance, NL GH and IGF1. Results from high dose Minoxidil (Rogaine)
Effects of chronically elevated GH levels?
Renal tubules —> increase Ph reabsorption so hyperphosphatemia.
Impaired carbohydrate tolerance —-> increased metabolic rate, inhibited peripheral glucose uptake, increased hepatic glucose production, insulin resistance and hyperinsulinemia —> T2DM
What lab is the most sensitive to excess growth hormone?
IGF 1
Somatostatin analogs are used to treat ______. Some examples are _______. Another tx is Pegvisomant which reduces tissue sensitivity to _______
GH excess
Octreotide, Ianreotide.
GH
Why is GH serum level not a good thing to measure?
Since it is secreted in Pulsitile fashion, the levels vary too much
Main cause of prolactin excess?
Pituitary adenoma.
Other than lactation and pregnancy, Prolactin is inhibited by _______
Dopamine (Catecholamines)
From: hypothalamic neurons
Pituitary neurons
Nonlactotroph-produced dopamine that flows over to lactotrophs.
Causes of prolactin (PRH) excess other than tumor
Primary Hypothyroidism
Renal failure
Drugs (antipsychotics, metoclopramide, TCAs, methyldopa, estrogens)
Why does high PRH impair fertility?
Suppresses GnRH pulses, impaired. FSH/LH release, blunts ovarian response to gonadotropins.
Everything is confused so they get amenorrhea.
In presence of PRH excess, women may get amenorrhea. Men get:
Hypogonadism, ED, impaired libido,galactorhea, Hirsutism, osteopenia, CNS symptoms.
In the case of PRH excess symptoms - what should you do first?
After that?
Careful eval of medication use!
Serum prolactin (NOT after a breast exam or after sexual intercourse)
What does a Prolactin level of 45 mean?
18? 248?
NL <20
>50 -> r/o non-pituitary cause
>200 = brain MRI
How do you treat PRH excess?
Dopaminergic agonists (Paroldel, cabergoline, pergolide
Glands that do NOT listen to the HPA axis?
Parathyroid glands.
Most common case of HyPOparathyroid?
Thyroidectomy with all 4 glands removed
What is DiGeorge syndrome?
Cardiac arrhythmias that result in sudden death from not regulating calcium
What other electrolyte imbalances can be tied to hypoparathyroid?
Hypomgnesemia (caused by ETOH abuse, malnutrition, malabsorption, Aminoglycoside abx and TPN) OR
Hyperphosphatemia (decreased PTH means decreased serum Ca = increased serum Ph - seesaw)
Hypocalcemia - s/s?
Decreased threshold for nerve/muscle firing:
Muscle spasm, hyper reflexia, sz, laryngeal spasm, asphyxiation.
Chvostek, Trousseau w/ BP cuff.
Others: parkansonian symptoms, bony deformities, hair loss, dry skin, cataracts,
Tx of hypoparathyroidism?
Acute = IV Ca+
Chronic = PO Vit D and Ca.
Fortes (Teripartide) off label for hypoparathyroidism, also used to treat osteoporosis.
Hyperparathyroid usually seen in the situation where one of the 4 gland hijaks, hypertrophied (usually hyperplasia or tumor related) and goes to town secreting hormones while others back away and let the big one handle it.
MEN-1/2-a, HRPT2 and CASR mutations are related to ________ cancer.
Thyroid/parathyroid
Vit D deficiency, CKD, intestinal malabsorption can result in?
Hypocalcemia and then secondary hyperparathyroidism.
What is Albright’s Hereditary Osteodystrophy?
Pseudohyperparathyroidism (PHP)
CKD results in primary/secondary/tertiary ___________parathyroidism?
Tertiary
Hyper
Glands hypertrophy since they’re always working so hard.
Why do you see polyurea/polydipsia in hyperparathyroidism?
Why do you see HTN?
Too much Ca can effect renal tubules to have decreased responsiveness to ADH.
Plasma renin activity increased.
According to the following body systems, what symptoms might you see in hyperparathyroidism (+/- hypercalcemia)?
GU (Stones and thrones)
GI (Groans)
MSK (bones)
CNS (psychic overtones)
Cardiovascular
GU - stones
GI - abd pain, pancreatitis, PUD, constipation, anorexia, N/v
MSK - osteoporosis, kyphosis, fractures, muscle weakness, arthralgia
CNS - memory loss, confusion, stupor, coma
Cardio - HTN
Gold standard tx for hyperparathyroidism?
Surgical removal of gland/tumor.
Anterior lobe adrenal axis secretion of ACTH is responsible for _______ and _______
Stress hormone regulation (cortisol, Adrenalin, NE)
Androgen production
The “GFR” of the adrenal cortex?
Medulla?
Salt (mineralocorticoids from the zona glomerulosa)
Sugar (glucocorticoids from the zona fasciculata)
Sex (androgens from the zona reticularis)
Medulla = Catecholamines.
Glucocorticoids regulate _______ and ________
Immune system and metabolism.
_______ produced by pituitary in response to ________ by the Hypothalamus in response to: DIMES?
ACTH
CRH
Digestion
Immune System
Mood and emotion
Energy storage and expenditure
Sexuality.
How can the adrenal cortex have an immediate effect?
Because it has stored cholesterol and it activates the cholesterol desmolase pathway.
When the immediate storage is dipped into, the gene transcription for replacement of those stores is also put into action.
Chronic exposure to stress:
Adrenal cortical cells hypertrophy and hyperplasia and so it’s producing excess hormones.
How can blindness affect HPA axis?
Their ACTH pulsitile secretion pattern is messed with because it is driven by light/dark patterns/QUES and sleep/wake cycles.
What is a Dexamethasone challenge?
Mimics properties of cortisol - Used to test the negative feedback loop of HPA axis to see where the problem might be with ACTH.
in a healthy axis, giving Dexamethasone should cause ______
With a AP tumor, if you give_______ dose Dexamethasone, then ACTH ________ will occur
With an Adrenal cortical tumor Dexamethasone will _______
Inhibition of ACTH
HIGH
suppression
NOT suppress ACTH - the tumor ignores all ques.
Is Addison’s hypo or hyper function of the _______ gland?
Adrenal
HYPO
If something is LOW then you ADD something to it to bring it back to normal.
What is the main hormone affected by Addison’s?
What other hormones are affected?
Cortisol.
Mineralocorticoids, Glucocorticoids, and androgens.
Addison’s disease:
Middle age
>90% of gland destroyed before s/s appear
Autoimmune is most common (link between T1and T2DM and pancreatitis). Infection, infiltration, hemorrhage and genetics (x-linked so males affected: adrenoleukodystrophy, adrenomyeloneuropathy)
Path report of adrenal gland biopsy in Addison’s?
Small, misshapen, atrophic glands infiltrated with lymphocytic cells.
Clinical manifestation of Addison’s?
PRIMARY: Weakness, fatigue, anorexia, weight loss, N/D hyperpigmentation, mood/memory changes.
Men do not have s/s of androgen loss, however women may lose some secondary sex characteristic (axillary and pubic hair)
Secondary: normal aldosterone and K levels and no hyperpigmentation.
Primary Addisons’ lab values will show _______ ACTH with ______ cortisol, and ______potassium, ______ Na, ______ glucose.
Secondary hypopcortisolism ______ ACTH, _____ potassium
HIGH
LOW
HIGH
Low, Low
Pituitary is secreting more ACTH to try to stimulate cortisol, however gland is not responding.
Low, normal.
Tx for Addison’s?
Replace hormones : glucocorticoids and possible mineralocorticoids.
150mg Na/day
Cushings is _____ function of _______
HYPER
Adrenal - excess cortisol.
If something is high, you want to “CUSH/CRUSH it down”
Difference between Cushing’s disease and Cushing’s syndrome.
DISEASE = excess ACTH from pituitary and loss of NL feedback inhibition.
SYNDROME = high cortisol (NL pituitary)
Corticotropin _______ Cushing’s disease is the most common. Some causes?
Dependent
ACTH-secreting pituitary tumor
ACTH-secreting cancers (SCLC, thymoma, pancreatic tumors, carcinoid tumors, medullary thyroid CA + pheochromocytoma)
CRH-secreting tumors = ACTH excess = excess cortisol.
Corticotropin independent tumors (Cushing’s syndrome ) are _____ common overall but ______ common in children (girls) and caused by ______ tumors.
Less
More
Adrenal (produces own cortisol not caring about the ACTH levels)
Clinical presentation of Cushings (Hypercortisolism) by category
Excess Mineralocorticoids - fluid accumulation w/ excess Na reabsorption.
Excess Glucocorticoids - fat accumulation, cortisol-induced insulin resistance (metabolic syndrome), increased gluconeogenesis, increased glycogen storage in liver), cortisol-related muscle/protein wasting = weakness + atrophy, increased bone resorption, Hypercalcuria and stones, collagen loss with thin skin, hyperpigmentation, immune suppression, hippocampal neurons affected by high cortisol = alterations in mental status, depression ->schizophrenia.
Excess Androgens - hirsutism, acne, oligomenorrhea, deep voice, male pattern baldness, clitoral hypertrophy, infertility
Excess Catecholamines - vasoconstriction and HTN,
Other: Protein wasting, catabolic effects
Testing for Cushings
Dexamethasone suppression test, cortisol and ACTH, Brain/abd MRI.
RET protooncogene and Von Hippel-Lindau are associated with ________
Pheochromocytoma
What are some clinical manefestations of pheochromocytoma
Acute HTN episodes triggered by Exercise, tyrosine, pressure on tumor or anesthesia.
Diaphoresis, tachycardia, palpitations, severe HA. Hypermetabolism, glucose intolerance and inhibition of insulin release. Increased SVR. Heat intolerance, weight loss, constipation despite increased appetite.
What happens if pheochromocytoma tumor ruptures?
Abrupt drop in BP, rigid painful abd (HIGHLY vascular tumors), can be Lethal.
Test for pheochromocytoma?
Drugs to stabilize while waiting for definitive treatment?
Serum and urine Catecholamines.
MRI
Refer! Get that tumor out of there!
AA blockers
BBlockers.
Hyperaldosteronism : _______ potassium levels _______ aldosterone secretion (_______ relationship).
Low
Increase
InDirect
Late distal tubule and collecting ducts are ________ sensitive to cortisol and aldosterone. Since circulating cortisol are ______ than aldosterone, it is usually the ______ that has more effect on these areas of the kidneys. CortisoNE has _____ affinity than cortiSOL.
Equally.
Much higher
Cortisol.
Lower.
Conn Disease is ________
Primary hyperaldosteronism.
Benign single aldosterone-producing adenoma.
OR bilateral adrenal hyperplasia.
Hallmark signs of primary hyperaldosteronism.
Increased Na reabsorption and hypervolemia WITHOUT EDEMA (renal tubule “escape mechanism” where Na shifted to distal tubule where it is exchanged for K —> hypokalemia.
Secondary hyperaldosteronism due to _______ levels.
Chronically elevated renin levels which means increased activation of angiotensin II.
What can cause secondary hyperaldosteronism?
Things that cause chronic increase renin level:
Shock, dehydration, low albumin
CKD - renal artery stenosis, heart failure, cirrhosis
Pregnancy, OCPs
Renin secreting renal tumors,
Diuretics and chewing tobacco
Barter Syndrome
Secondary hyperaldosteronism
Defects in tubular reabsorption of K —> hypokalemia —> increased renal secretion of prostaglandins —> increased renin/aldosterone offset somewhat by the aldosterone SUPPRESSION of hypokalemia.
if you have hypokalemia, renin/aldosterone secretion is _______.
**
Hallmark S/s of hyperaldosteronism
HTN —> increased volume or aldosterone-mediated vasoconstriction.
L Ventricular hypertrophy/dilation
Hypokalemia (severe)
Metabolic alkalosis (severe)
In primary hyperaldosteronism, ______ suppresses renin. If _____ is NOT suppressed, then suspect ________
Increased arterial pressure
Renin is not suppressed (high renin level),
Secondary hyperaldosteronism.
If you suspect hyperaldosteronism, check:
Treat with:
Serum aldosterone, renin and ratio between two
Serum Na and K
Aldosterone suppression test
CT/MRI to r/o adrenal adenoma
surgery, spironolactone or eplerenone for adrenal hyperplasia.
Gynecomastia in males - consider treating with _____ because of it’s ________ effects.
Spironolactone
Anti-androgen
Grave’s and Hashimoto’s are ______ and may be ______
Autoimmune
Familial.
What do thyroid hormones do? (7)
Increase O2 consumption (except in Brian, testes and spleen)
Increase BMR by 60-100%
Absorb and metabolize carbs (glucose, glycogenolysis and gluconeogenesis)
Metabolize fatty acids
Degrades proteins faster than they can be synthesized (catabolism)
Enzyme system activation
Vitamin and mineral metabolism
New onset a-fib in an older (75yo) woman? Consider_____
Hyperthyroid
Iodine is absorbed in the small intestine as _______ and transported to _______. TSH assists in creating Iodine PUMP to pull iodine in against a steep concentration gradient. In the gland, iodide is _________ to _______ and bound to _____. The thyroid gland can also recycle iodine by capturing it as it’s released from ________
IodiDE
Thyroid gland.
Oxidized
Iodine
Tyrosine
Thyroglobulin .
Dietary iodine is obtained from fish and seafood. Those in mountainous regions may have more incidence in thyroid disease due to low dietary iodine. not a problem in USA mostly because of iodized salt.
Thyroglobulin is STORED iodine. The body usually has a _____ supply stored this way.
2-3 month
T4, T3 - which one is the metabolically active form?
T3 - has an empty spot “the key”
RT3 is not active - has a missing spot but reverse chemical structure.
RT3 predominates in illness: fever, burns, malnutrition, anorexia.
Thyroid hormone is _______ bound and ___ free. Mostly bound to ______ and some bound to ______
99%
1%
TBG (thyroid binding globulin) - produced in liver
Albumin/pre-albumin
In kidney disease, you loose _________. In liver disease you loose _______ and therefore ________. However in acute hepatitis, late AIDS, there is an ________ of _______
TT4 (total T4) and TT3
TBG
TT4 and TT3
Increase TBG.
Contrast with iodine could cause a thyroid gland _______ in someone with an unhealthy thyroid which causes an abrupt cessation in the production of T4. A healthy gland is able to escape this blockade, however a sick gland my never recover and stay blocked.
What effect does ORAL estrogens have on the thyroid hormones?
ORAL estrogens go to liver 1st and increase serum TBG by 30-50%. This decreased T4 by 20-35%.
The brain senses this drop in T4, and stimulates production. Eventually it will level out.
How does pregnancy effect thyroid hormones?
Increase TBG (double by 20weeks), increased gland size, and increased circulating iodide.
In pregnancy, TSH and FT4 ______, TT4_____, TT3 ______ .
In hyperthyroid TSH ______, FT4 ______, TT4, T3 _______
In Hypothyroid TSH ______, FT4, TT4 and TT3 ______
Stay the same, increase, increase
Decrease, increase, increase
Increase, decrease, decrease.
TSH immunoglobulins (mom has Hashimoto’s) or anti-thyroid drugs DO cross placenta and may start affecting baby’s thyroid glands.
Single best test for thyroid fxn?
TSH
If high (>.3-.5) more likely to be antibody positive and increased risk for clinical hypthyroiditis.
HIGH TSH = hyPOthyroid thyroid is trying to get it functioning
In hyPOthyroidism, TSH will be ______ and T4 will be ______
TSH elevated
T4 high.
What is it not helpful to look at TT4 levels?
Measures albumin.
Only draw FreeT3 when?
Numbers aren’t making sense
Ex: low TSH with normal T4
Sign of T3 thyrotoxicosis.
Graves is ______thyroid
Hashimoto’s is ________thyroid
Graves = hyperthyroid
Hashimoto’s = hypothyroid (Motomoto is a chunky - he must have a SLOW metabolism :P)
What meds can induce hypothyroid?
Amiodarone, lithium.
How is Grave’s (hyper) AND Hashimoto’s (hypo) both autoimmune?
In Grave’s, the autoantibodies bind to and activate TSH receptors.
In Hashimoto’s, the auto immune cells attack and destroy the gland
Hashimoto’s is low ____, Grave’s is high _______
T4
T3
Graves’ disease can turn into Hashimoto’s
Subacute Thyroiditis - virus attacks thyroid gland and it dumps (emptys out) - PAINFUL. 1st stage is hyperthyroid symptoms, and then a 2nd stage “recovery” period of hypothyroid symptoms while stores are being regenerated. 10% have permanent hypothyroidism. Postpartum is similar to this, but without PAIN.
Prognosis for invasive fibrous thyroiditis?
Chronic iodine insufficiency where goiter turns hard and fibrous. Not concerning unless starts to press on adjacent structures in which case it can be surgically removed.
Exophthalmos is ________ and caused by _______ while Opthalmopathy (thyrotoxicosis) is ______ and caused by _______
Non-reversible; unknown immune mechanism. Severe sequelae. Forward protrusion of eye.
Reversible; SNS over activity contracting levator muscle. NO forward protrusion of eye.
Things that stimulate the release of GHRH and subsequently GH
Grhelin, amino acids, fatty acids, hypoglycemia.
FreeForm Drawings.
What are the ways that the body recycles iodine
