Lopez: Endocrine Review Flashcards
What correlates with plasma half-life and metabolic clearance of hormones?
- the degree of protein binding
- the thyroid hormones do this a lot
What kind of mechanism does ACTH, LH, FSH, TSH, and glucagon use?
the adenylyl cyclase mechanism -Gs ptn -ATP to cAMP -activation of PKA ...
What mechanism does GnRH, TRH, GHRH, and oxytocin use?
PLC mechanism
- Gq ptn
- activates PLC
- makes DAG and IP3
- DAG gets PKC
- IP3 releases Ca2+ from ER
What mechanism do Thyroid hormones, glucocorticoids, aldosterone, estrogen, and testerone use?
the steroid hormone MOA
- binds cytoplasmic receptor
- dimerizes
- goes to nucleus
- gets the SRE… gene transcription
What is the connection between the hypothalamus and the posterior pit?
-just neural
connection b/w hypothalamus and ant pit
- neural and endocrine
- via the hypothalamic-hypophysial portal vessels
What is a primary endocrine disorder
-low or high levels of hormone due to defect in the peripheral endocrine gland
What is a secondary endocrine disorder?
-low or high levels of hormone due to defect in the pituitary gland
What is a tertiary endocrine disorder
low or high levels of hormone due to defect in the hypothalamus
Ant pit hormones
- TSH
- FSH
- LH
- ACTH
- GH
- Prolactin
What will PRL excess give us clinically?
- galactorrhea and hypogonadism
- it inhibits LH and FSH as well
Where does somatostatin and PIF (dopamine) come from?
the hypothalamus
difference between a functioning and non functioning pituitary adenoma?
- functional: releases active hormone…. lots of it
- non functional: doesn’t
Prolactinoma
-hypogonadism and galactorhea
excess GH symptoms
Acromegaly in adults and gigantism in children
Cushing’s disease
-pituitary tumor w/ an overproduction of cortisol
What syndrome do pituitary adenomas show up in?
MEN1 patients (25% of the time)
What does PRL excess do to LH ad FSH?
lowers them both
What are the two hormones released from the post pit?
ADH and oxytocin
Which hypothalamic nucleus releases ADH?
-Supraoptic nuclei
Which nucleus releases oxytocin?
paraventricular nuclei
What kind of hormones are ADH and oxytocin
neuropeptides
What is secretion of ADH most sensitive to?
plasma osmolarity changes
-gets V1 and V2 receptors
What are the triggers of ADH release?
- high plasma osm
- low BP
- low BV
- high ANGII
- sympathetic stimulation
- dehydration
What is Diabetes insipidus?
- lack of an effect of ADH on the renal collecting duct
- fequent urination
- large volume of urine is dilutes
Central DI
- lack of ADH… so low ADH
- results from damage to pituitary or destruction of hypothalamus
Tx of Central DI?
- desmopressin
- drug that prevents water excretion
NEphrogenic DI
-kidneys are unable to respond to ADH… so high plasma ADH
Causes of Nephrogenic DI?
- drugs like lithium
- Chronic disorders (PCKD, SSA)
- desmopression tx does not work
What is the water deprivation test for DI?
- cut off fluids
- weigh pt every 1-2 hrs for 8 hrs
- measure plasma osmolarity and urine
- if looks like DI, allow pt to drink, administer desmopressin
- then measure plasma and urine osmolality again
SIADH
- excessive secretion of ADH
- excessive water retention
- hypoosmolarity fails to inhibit ADH release
- wathc for sodium below 120…. hyponatremic encephalopathy
What does the adrenal cortex secrete?
- Aldosterone
- Cortisol
- Androgens
What does the adrenal medulla secrete?
E and NE
From outside to inside, name the layers of the adrenal gland and the hormones they secrete
- GFRM
- Glomerulosa: Mineralocorticoid (aldosterone)
- Fasciculata: Glucocorticoids(cortisol), androgens
- Reticularis: Glucocorticoids and androgens again
- Medulla: E and NE (catecholamines)
What is the first step in synthesis of steroid hormones?
- Cholesterol to pregnenolone
- mediated by cholesterol desmolase
- then we split three ways to make Aldosterone, cortisol, or androstenedione
how is Aldosterone made?
- Pregenolone, progesteron, Deoxycorticosterone (DOC), Corticosterone, Aldosterone!
- 3B, 21, 11, aldosterone synthase
How is cortisol made?
- Pregnenolone, 17-OH Pregnenolone, “ “ progesterone, 11-deoxycortisol, cortisol!
- 17, 3B, 21, 11
How are androgens made?
- pregnenolone, 17-OH pregnenolone, DHEA, Androstenedione (androgens!)
- 17, 17+20, 3B
How can you tell a 21 vs and 11 deficiency?
- in 11 deficiency, there will be increased BP due to the mineralocorticoid effect of DOC that builds up
- that doesn’t happen with 21 deficiency because we never get to the DOC point
What does Aldosterone do?
- increases sodium concentration in the blood
- raises BP
What will we have a lot of if there is a 17 alpha deficiency?
- mineralocorticoids
- they will be totally fine because we don’t need 17 for aldosterone synthesis
- that is 3B, 21, 11, aldosterone synthase
What will we have a lot of if there is a 21B deficiency?
- Sex hormones!
- they don’t need 21
- they are just 17, 17+20, 3B
What will we have a lot of in 11B deficiency?
- Sex hormones again!
- again, they don’t need 11
- remember though, there will be high BP b/c of DOC creation
- 21 still works well :)
Which one is the most common deficiency?
- 21B
- high Renin activity for some reason
- also high 17-hydroxyprogesterone
What is Cushing’s syndrome
- high cortisol due to an ADRENAL tumor
- there is just high cortisol… lower down the chain
What is Cushing’s disease?
- high ACTH which leads to high cortisol
- caused by a PITUTARY tumor
What is Addison’s disease?
- caused by autoimmune disease of the adrenal gland
- so… low cortisol, high ADH and high CRH… the adrenal gland is where the problem is at
What is Secondary adrenal insufficiency?
- caused by glucocorticoid drugs suppressing H and P
- everything is low
If we have high ACTH, what else will we have besides high plasma cortisol?
-hyperpigmentation
If we have a primary excess, where is the problem?
the adrenals… so high cortisol, low everything else
If we have a secondary excess, where is the problem?
the pituitary, so high ACTH, pigmentation, and cortisol elevated
-these same things go for deficiency
What is ANGII’s effect on the adrenal cortex?
-makes it secrete aldosterone
Which zone makes aldosterone?
Glomerulosa
What do pancreatic B cells secrete?
insulin
-located more toward the center of the islets of Langerhans
What do alpha cells make?
glucagon
What do the delta cells secrete?
-somatostatin
What is glucagon’s effect on insulin secretion?
increases it
-weird because insulin from B cells will decrease the glucagon from delta cells
What can be use as a long-term marker of endogenous insulin secretion?
C peptide
-it’s secreted in equimolar amounts with insulin
What do the sulfonylurea do the the ATP-dependent K+ channels?
closes them… K+ is stuck in the cell now
- makes the cell depolarize
- Ca2+ channels open
- Ca2+ comes in
- Exocytosis of insulin… yay
- hypokalemia
What kind of receptor does insulin bind?
RTK
- autophosphorylates itself
- insulin down-regulates its own receptor
What are the effects of insulin?
- we start storing stuff
- increased glycogen/lipid/protein synthesis
- decreased lipolysis
- cell growth and differentiation
- decreased gluconeogenesis
When in doubt, what does insulin do to things in the blood?
lowers them!
- increased glucose uptake… low glucose
- increased Ptn synth…. low aa’s
- Increased fat deposition…. low FA;s
- decreased lipolysis…. low ketoacids
- increased K uptake into cells… low K+
What is Type 1 DM?
-inadequate insulin secretion
-destruction of B cells, often as the result of autoimmune disease
-no symptoms until 80% of symptoms are gone
-kids
-ketosis
-
What is Type 2 DM?
- Insulin resistance
- more common type
- progressive exhaustion of active B cells
- pts can make insulin, but no enough to overcome insulin resistance
- adults
- family Hx
- fat ppl
If we are given the mmol/L of glc, how do we get the concentration of glucose in mg/dL?
multiply by 18
What does Glucagon do?
-increases lipolysis and inhibits GA synthesis , which shunts substrates towards gluconeogenesis
What are produced from FA?
Ketoacids!
Where is the vast majority of calcium stored in our body?
-bones and teeth
What does PTH and Vit D do to bone resorption?
increases it
- gives us more Ca2+ in blood
- PTH also helps us reabsorb the Ca2+ from the kidneys
What must the kidneys do to maintain Ca2+?
excrete the same amount of Ca2+ that is absorbed by the GI tract
How is extracellular Pi related to Ca2+ levels?
- inversely related!
- extracellular concentration of Pi is regulated by the same hormones that regulate Ca2+ concentration
What wil PTH do to Pi?
- decrease its reabsorption from the kidney
- so we get phophaturia
- we will also have very high cAMP urine levels for some reason
So, if we have a high serum Ca2+ level, what will that do to our PTH?
inhibit it
What does Vit D do genetically?
- goes in and stops PTH gene and upregulates CaSR gene
- the CaSR will respond to the high calcium levels and also inhibit PTH
What is the active form of Vit D
1,25 cholecalciferol
-24,25 is the inactive form
Where does Vit D get converted into its active form?
the renal prosimal tubule
-by 1 alpha hydroxylase… makes sense
Where does Vit D (cholecalciferol) get the 25 hydroxyl group slapped onto it?
the liver
- that happens first
- so that is the main circulating form of Vit D
Where are the PTH receptors located?
- on the OsteoBLASTS… not clasts
- so, short term, it will increase bone formation via direct action on osteoblast
- basis for use of intermittent synthetic PTH administration in osteoporosis tx
What is the long term actions of PTH?
- high bone resorption
- indirect action on osteoclasts mediated by cytokines released from osteoblast
- Vit D acts synergistically with PTH to stimulate osteoclast activity and bone resorption
At what part of the renal tubule is Ca2+ reabsorbed because of PTH?
- Thick ascending limb
- PTH also gets the 1 alpha hydroxylase… activates Vit D
Vit D effects on Small intestine?
-increase Ca2+ and Pi absorption by increasing calbindin expression
Vit D effects on bone
- sensitizes osteoblasts to PTH
- regulates osteoid production and calcification
Vit d effects on kidney
- promotes Pi reabsorption by proximal nephrons (PTH does opposite)
- minimal actions on Ca2+
Vit D effects on parathyroid gland?
- Directly inhibits PTH gene expression
- Directly stimulates CaSR gene expresion
Primary hyperparathyroidism?
-lots of Pi, cAMP, Ca2+ excretion
-Stone, bones, and groans
-hypercalciuria… stones
-high bone resorption…
-constipation… groans
tx usually requires parathyroidectomy
-HYPERCALCEMIA/HYPOPHOSPHATEMIA
Lab values for hyperparathyroidism?
- PTH: high
- Ca2+: high
- Pi: low
- Vit D: high
Secondary hyperthyroidism?
- increase in PTH levels secondary to low Ca2+ in blood
- causes: renal failure, Vit D deficiency
lab values for Secondary hyperparathyroidism due to renal failure?
- PTH: high
- Ca2+: low
- Pi: high
- Vit D: low
lab values for secondary hyperparathyroidism due to Vitamin D deficiency?
-PTH: high
-Ca2+: low
Pi: low
-Vit D: low
Hypoparathyroidism?
- PTH isn’t made anymore!
- no Vit D
- No Ca2+
- no Pi excretion
- Hypocalcemia/Hyperphosphatemia
lab values for hypoparathyroidism?
- PTH: low
- Ca2+: low
- Pi: high (PTH normally promotes Pi excretion)
- Vit D: low
What is Albright hereditary osteodystrophy?
- inherited autosomal dominant disorder, Gs for PTH in bone and kidney is defective
- Hypocalcemia and hyperphosphatemia develop
- high PTH levels….. so it’s a psuedohypoparathyroidism
- administration of exogenous PTH won’t do shit
lab values for Pseudohypoparathyroidism?
- PTH: high
- Ca2+: low
- Pi: high
- Vit D: low
what is the phenotype for albright hereditary osteodystorphy?
-short stature, short neck, obesity, subcutaneous calcification, shortened metatarsal and metacarpals
What is PTHrP
-secreted by tumor cells…. acts like PTH
lab values for humoral hypercalcemia of malignancy
- PTH: low
- Ca2+: high
- Pi: low
- VitD: low (apparently doesn’t activate that one enzyme…)
Familial hypocalciuric hypercalcemia (FHH)
- auto dominant
- Mutations inactivate CaSR in PT glands
- decreased urinary Ca2+ excretion and increased serum Ca2+
Rickets type 1 and 2
- congenital disorders
- Vit-D deficiency (kinda)
- type 1: no 1 alpha hydroxylase
- type 2: no vitamin D receptor
- lots of Pi and cAMP in the urine
how long does the body have enough Thyroglobulin for if everything were to shut down?
-2 to 3 months
What enzyme is involved with the peripheral conversion of T4 to T3?
-deiodinase
When the availability of iodide is restricted, what is favored more? T3 of T4?
T3
-makes sense because that takes less iodine >
What drugs will inhibit the sodium idodide symporter?
- perchlorate
- thiocynate
- PTU is an effective treatment for hyperthyroidism
What will oddly inhibit organification and synthesis of thyroid hormones?
high levels of Iodide
- this is called the Wolff-Chaikoff effect
- it’s wierd because either too much or too little Iodine will inhibit Thyroid hormone
How are thyroid hormones transported?
in the bloodstream either bound to plasma proteins or free
-mostly bound to ptns (TBG)
What is TSH regulated by?
- TRH
- Free T3
What is something that makes TSH secretion different from GH secretion?
-TSH secretion occurs at a steady rate
Most common cause of thyrotoxicosis?
Graves disease
- Thyroid stimulating Ig’s (TSI) stimulate TSH receptor without TSH hormone
- TSH levels are low because of high circulating levels of thyroid hormones inhibits TSH secretion!
- exophthalmos
