Endocrine Flashcards
autocrine
influences own tissue
juxtacrine
influences adjacent tissue
paracrine
influences neighboring tissue
endocrine
influences distant tissues
secreted, go thru blood to distant target
where are hormones broken down? (general)
in target tissue, liver, or kidney
short ghalf life
Hormone products of hypothalamus
6
- Corticotrophin (CRH)
- Gonadotrophin Releasing Hormone (GnRH)
- Growth Hormone Releasing Hormone (GHRH)
- Somatostatin
- Thyrotropin releasing hormone (TRH)
- Prolactin Inhibitory Factor (PIF)
highest level of control in endocrine system
hypothalamus
hypothalamus is controlled by ____
cortical centers in brain
response to emotions and sensory input (can be influenced by stress)
Pituitary
located in sella turcica
behind optic chasm
ant. and post.
Hypothalamus to anterior pituitary pathway
Hormones are made in hypothalamus
transported via pituitary portal circulation
arrive at anterior pituitary
hypothalamus to posterior pituitary pathway
hormones are made in hypothalamus
transported directly by neural network
posterior lobe
What are the targets of hypothalamus’ hormones
stimulation or inhibition of target cells in anterior lobe of pituitary
products of anterior pituitary
6
- adrenocorticotrophic hormone (ACTH) (Corticotrophin)
- Follicle stimulating hormone (FSH)
- Luteinizing hormone (LH)
- Growth hormone (GH)
- thyroid stimulating hormone (TSH)
- Prolactin
products of posterior pituitary
- ADH/vasopressin
2. oxytocin
Hormonal axes general steps
- hypothalamus secretes releasing hormones
- pituitary secretes trophic hormones (growth of gland)
- endocrine glands secrete circulating hormones with metabolic effects
circle back to give feedback to hypothalamus and pituitary
Hypothalamic pituitary adrenal axis
- Hyp. releases corticotrophin releasing hormone (CRH)
- adrenocorticotrophic hormone (ACTH) released by anterior pituitary
- ACTH stimulates adrenal cortex to release glucocorticoid and weakly simulates aldosterone release, trophic to adrenal gland
Gluc.: metabolism regulation, stress response
Aldos: blood pressure and water retention
trophic: growth of gland
hormones involved in hypothalamic pituitary adrenal axis
CRH
ACTH
glucocorticoid + aldosterone
results of the hypothalamic pituitary adrenal axis
metabolism regulation stress respones (Via gluc.)
blood pressure regulation, water regulation (aldos.)
trophic = growth of the adrenal gland
Gonatrotrophin Pituitary Sex axis (not sure proper name ;) )
- Gonadotropin releasing hormone (GnRH) released by hypothalamus
- GnRH stimulates Follicle Stimulating hormone (FSH) and Luteinizing Hormone (LH) release by ant. pituitary
- stimulate estrogen/progesterone/testosterone in sex organs
secondary sex characteristics:
regulate growth of ovaries and testes, output of sex hormones, regulation of menstrual cycle
hormones in the Gonatrotrophin Pituitary Sex axis
GnRH
FSH/LH
progesterone/estrogen, testosterone
results of Gonatrotrophin Pituitary Sex axis
regulation of ovaries/testes growth
control output of sex hormones
regulation of menstrual cycle
Hypothalamic thyroid axis
- Thyrotropin releasing hormone (TRH) released by hypothalamus
- TRH stimulates release of thyroid stimulating hormone/thryotropin in anterior pituitary
- TSH stimulates release of T3 and T4 from thyroid, trophic to thyroid
results:
control of metabolism, growth of thyroid gland
hormones of Hypothalamic thyroid axis
TRH
TSH/thyrotropin
T3 and T4 (thyroxin)
somatostatin
results of Hypothalamic thyroid axis
metabolic control via T3 and T4
growth of thyroid gland
growth axis
- hypothalamus secretes growth hormone releasing hormone (GHRH)
- GHRH stimulates release of growth hormone/somatotropin (GH) in anterior pituitary
- GH stimulates liver to produce somatomedin (insulin like growth factors)
promotes cell growth
inhibits apoptosis
hormones of the growth axis
GHRH
GH/somatotrophin
somatomedin/IGFs
somatostatin
somatostatin
inhibits the growth axis
secreted by hypothalamus
inhibits release of TSH and GH by anterior pituitary
prolactin axis
- prolactin is released by ant. pituitary
2. prolactin stimulates milk production
prolactin is inhibited by
Prolactin Inhibitory Factor (PIF) and Dopamine from hypothalamus
prolactin inhibits
FSH and LH secretion
good bc it prevents you from getting pregnant directly after giving birth
prolactin release is stimulated by
estrogen, thyroid releasing hormone, nipple stimulation
prolactin levels are decreased artificially by
- drugs that mimic dopamine (levodopa, bromocriptine, Requip, Mirapex)
- drugs that block doapime receptors (which leads to increase of dopamine concentrations) [phenothiazines(chlorpromazine) butyrophenones(haloperidol)]
primary endocrine disorders
malfunction of the target organ
thyroid, adrenal gland, gonads
most common
secondary endocrine disorders
malfunction of pituitary
tertiary endocrine disorders
malfunction of hypothalamus
how are secondary and tertiary endocrine disorders diagnosed
checking levels of all the trophic hormones and functions of adrenal cortex (ACTH), thyroid gland (TSH), and gonads (FSH, LH)
bc if it is higher order disease, whole thing will be knocked out
panhypopituitarism
disorder where entire pituitary gland is destroy
caused by
- ischemia/infaction (sheenhan’s syndrome_
- tumor
very rare, presents subtly
functioning pituitary tumor
produces hormones
typically GH and prolactin
micro and macroadenomas
pituitary tumors and optic chiasm
optic nerves cross at the optic chiasm
when there is a pituitary tumor, as it grows, it compresses the optic bias and causes visual field cuts
bitemporal hemianopsia
visual field cuts where central vision is knocked out
caused by pituitary tumor growth and compression of the optic nerves at the optic chiasm
types of pituitary tumors
- pituitary adenoma (macro adenoma or micro adenoma)
- craniopharyngioma
- meningioma
pituitary adenoma
most often microdenomas
benign, functional
craniopharyngioma
benign or malignant
non function
face and oral cavity tumor
meningioma
benign and non function
tumor of the meninges
micro adenomas
less than 1 cm/ 10 mm
usually produce prolactin
prolactinomas symptoms:
galactorrhea (growth of breast tissue, breast milk production)
amenorrhea (bc prolactin surpasses FSH and LH)
treatment mechanisms
micro adenoma
a. dopamine agonists
stimulate the dopamine receptors to suppress prolactin secretion, shrinks growth
b. surgical removal (not easily done bc in hard to reach place)
macroadenomas
commonly secrete growth hormone
greater than 10 mm
different effect on adults and children
macroadenomas in adults
acromegaly
grow after bone epiphyses have closed
coarse facial features, thickening viscera, spade like hands, diabetes
diabetes and acromegaly
growth hormone stimulates the release of insulin like growth factors (looks like insulin) so has high blood sugar levels
micro and macro adenomas and size
microadenomas are found early when they are small, b/c they show symptoms at a small size
macroadenomas don’t show symptoms until larger than 10cm
colloid
found in thyroid, stores the inactive the thyroid hormone
when broken down, releases thyroxin in the blood
which is more active T4 or T3
T3 is more active
T4 is converted to T3
most is bound to albumin in blood (inactive)
thyroid hormone
rate controller for metabolic processes
determines energy levels
excess = hyperthyroid
deficiency=hypothyroid
hyperthyroidism s/s
cardiovascular: neuromuscular: GI: GU: metabolic: dermatologic:
everything is very active, elevated FT4 and low TSH
cardiovascular: tachycardia, increased EF, more prone to heart failure
neuromuscular: tremor, hyperreflexia, irritable, restless, apathetic
GI: diarrhea (move thru GI quickly)
GU: menorrhagia (heavy periods)
metabolic: patients feel hot, weight loss
dermatologic: lush hair, moist, flushed skin
hypothyroidism s/s
cardiovascular: neuromuscular: GI: GU: metabolic: dermatologic:
everything is slowed down
cardiovascular: bradycardia, decreased cardiac output
neuromuscular: sluggish, hyporeflexia, lethargic, placid, depressed
GI: constipation
GU: amenorrhea (spaced out periods)
metabolic: feel cold, weight gain
dermatologic: dry, flaky skin
Goiter
thyroid enlargement
via TH stimulant
may be euthrothyroid, hypothyroid, hyperthyroid
goiter structural classification
diffuse
nodular
substernal
function classification goiters
toxic (producing excess hormones) – hyperthyroid
non-toxic (not producing excess hormones)
once detected status must be determined
how to determine status of goiter
TSH check
disorders causing hyperthyroidism
- toxic nodular goiter
- graves disease
- hashimoto thyroiditis
toxic nodular goiter
nodule begins secreting TSH autonomously (without TRH)
elevated FT4 level, surpassed TSH
must rule out cancer
Hot nodule bc it is functional
grave’s disease
body produces antibodies that mimic TSH
stimulates thyroid– over production of thyroid hormones
elevated FT4 and suppressed TSH
Hashimoto thyroiditis
autoimmune
lymphocytic invasion of thyroid –> destruction of follicular cells (inc. TSH receptors)
causes destruction of colloids and uncontrolled release of T4 in blood
brief periods of hyperthyroidism then hypothyroidism
Treatment for hyperthyroidism
propranolol
methimazole
I131 treatment
surgical
Propranolol
brand name + MOA
hyperthyroidism
Inderal
non specifici beta blocker
blocks adrenergic effects of thyroid toxicity – decreases high cardiac output, tachycardia, restlessness and internal temp.
symptom relief
methimazole
brand name + MOA
hyperthyroidism
blocks synthesis of thyroid hormone
gradual reduction of thyroid hormone (4-8weeks)
nasty side effects, but use in combo with propranolol
I 131 treatment
radioactive iodine given
destroys the thyroid
ideal method but can’t give to pregnant women
hypothyroidism hormone levels and treatment goal
decreased Ft4 and elevated TSH
goal is to replace deficient FT4 hormones and decrease TSH via negative feedback via Levothyroxine
Levothryoxine
brand name + MOA
hypothyroidism
Synthroid
synthetic T4
full dose to younger, quarter dose to older (due to not wanting to cause stressors to the cardiac system)
neonatal hypothyroidism
TH required for nervous system development
levels are maintained via transfer from mother
if not present, develop cretinism (stunted growth and retardation)
essential nonexistent in US
Thyroid emergencies
- myxedema coma
2. thyroid storm
myxedema coma
thyroid emergency
caused by profound hypothyroidism
can’t handle any kind of stress (narcotics, medical illness, surgery)
common in older women
thyroid storm
thyroid emergency
severe hyperthyroidism
may occur without history of disease if rapid destruction
causes high fever, delirium, tachycardia, weight loss
adrenal cortex secretions
glucocorticoids
mineralocorticoids
sex hormones (adrenal androgens)
two layers of adrenal gland
adrenal cortex
adrenal medulla
completely separate organs almost
adrenal medulla secretions
epinephrine and norepinephrine
Glucocorticoid function (5)
Stress hormones
decreases glucose levels in nonessential tissues
increases breakdown of fat, protein
increases gluconeogenesis
inhibits protein synthesis (healthy go tissue)
suppresses inflammatory response
mineralocorticoid funciton
keep fluid balance optimal
major part of blood pressure
major one is aldosterone
adrenal androgens
important in females sexual health, negligible in men
Disorders of adrenal gland
- primary adrenal insufficiency
- adrenal crisis
- cushing’s syndrome
primary adrenal insufficiency
hypo function of adrenal cortex
LOW glucocorticoid and mineralocorticoid
no ability to increase glucocorticoid or mineralocorticoid in response to stress that causes adrenal crisis
etiologies of primary adrenal insufficiency
autoimmune infection (ex. TB) metastatic carcinoma
addisons disease
autoimmune, causes primary adrenal insufficiency
cytotoxic lymphocytes and autoantibodies attach adrenal cortex
kill ability to make glucocorticoid – no response to stress
metastatic carcinoma
primary cancer tumors in lung or breast metastasize in adrenal glands to grow and destroy adrenal tissue
s/s of adrenal insufficiency
- low glucocorticoid (low blood sugar, low blood pressure, poor stress response – hypotension resistant to fluid resuscitation)
- low mineralocorticoid (chronic low sodium, high potassium, hypovolemia
treatment of adrenal insufficiency
hydrocortisone
fludrocortisone
replace what is missing , lifelong
hydrocortisone
brand name + MOA
cortex
glucocorticoid, considered most bioequivalent to cortisone
2/3 in AM, 1/3 in PM bc of cortisone surge before waking
fludrocortisone
brand name + MOA
florin
mineralcorticoid
dosing once daily, prevents passing out or swelling
adrenal crisis
preexisting insufficiency or borderline insufficiency is confronted with stressful event (HA, medical illness, infection, surgery)
causes RAPID loss of blood pressure
cushing syndrome s/s
glucocorticoid excess
characterized by elevated blood glucose
muscle wasting, thin extremities, muscle weakness
osteoporosis, pathological fracture, thin skin easy tearing, stretch marks
redistribution of fat (truncal obesity, moon face)
etiologies of cushing
- iatrogenic cortivosteroids
- ACTH producing pituitary adenomas (cushing disease)
- primary hyperfunctioning of adrenal cortex (tumor or hyperplasia)
- cancers that produce ACTH like proteins
iatrogenic corticosteroids
we have given them steroids for respiratory disease, autoimmune disease, organ transplant or canter treatment but has caused dysfunction
not much we can do
decreased ACTH, decreased natural glucocorticoid
ACTH producing pituitary adenomas
causes hyper function of adrenal cortex
cushing’s disease
increased glucocorticoid, increased ACTH
primary hyper functioning of adrenal cortex caused by
- tumor on adrenal cortex
- adrenal hyperplasia
ignores ACTH, decreased ACTH levels
hyperfunctionadrenal cortex tumor
usually benign
autonomously produces cortisol
primary adrenal cancer is rare
amenable to surgical rustication
** if removed, will have to wait for pituitary to get used to producing again ,will have to supplement and replace or may cause adrenal shock
paraneoplastic syndrome
cancer found somewhere else (lung) that produces a similar protein to ACTH that fools adrenal glands into producing cortisol
Name the cause:
low glucocorticoid (natural)
Low ACTH
Glucocorticoid excess caused by iatrogenic corticosteroids use
Name the cause:
increased glucocorticoid
elevated ACTH
Glucocorticoid excess caused by pituitary adenoma
name the cause:
increased glucocorticoid, decreased ACTH
Glucocorticoid excess caused by adrenal tumor
OR
papaneoplastic syndrome
primary mineral corticoid
aldosterone
primary aldosterone stimulus
kidney
minimally regulated by ACTH
what stimulates renin production?
drop in renal profusion
Renin changes ____ to ____
angiotensinogen to angiotensin-1
ACE enzyme
converts angiotensin-1 to angiotensin-2 in the lungs
angiotensin-2 fxn
causes vasoconstriction
aldosterone secretion from adrenal gland
aldosterone fxn
causes nephron to retain sodium and water
increases blood pressure and renal profusion
steps of RAAS loop
- renin produced in kidney in response to drop in renal perfusion
- Renin activates RAAS, changing plasma angiotensinogen to angiotensin-1
- Angiotensin-1 is converted to Angiotensin 2 but ACE in lungs
- angiotensin-2 causes vasoconstriction and aldosterone secretion
- aldosterone causes nephron to retain sodium (therefore water) ** increases BP and renal perfusion)
- Reapsorbtion of Na means that kidney must give up another positive ion (K or H) `
hyperaldosteronism
mineralocorticoid excess
causes:
edema
elevated blood pressure
hypokalemia and metabolic alkalosis (wasting in urine bc must secrete to hold onto Na)
etiologies of hyperaldosteronism
and treatment
adrenal adenoma (surgical removal of adenoma processing excess aldosterone)
adrenal hyperplasia (spironolactone[aldactone]– aldosterone antagonist, blocks effect at renal tubule)
Hypoaldosteronism
minderalcorticoid deficiency
causes: low blood pressure, hyperkalemia, tendency toward acidosis
most common cause of hypoaldosteroneism
diabetes
hyporeninemic hypoaldosteronism bc kidney damaged so can’t produce renin
parathyroid hormone function (3)
increases Ca absorption from GI tract
mobilizes calcium from bone
decreases calcium loss from urine
*Required for calcium release response to hypocalcemia *
vitamin D function (2)
facilitates calcium absorption in GI tract
deposits Ca in bone
activated by kidney
what other ions have a role in calcium balance
magnesium and phosphorus
active v. inactive calcium
active calcium- ionized
inactive - bound to albumin
why are calcium levels important?
cardiac and skeletal muscle contraction
nerve conduction
coagulation cascade
causes of parathyroid deficiency
iatrogenic (accidental) removal of glands during surgery of thyroid or other structure
autoimmune destruction of calcium receptors in parathyroid – no receptor, to stimulation to secrete
3 types of parathyroid excess
- primary hyperparathyroidism
- secondary hyperparathyroidism
- tertiary hyperparathyroidism
primary hyperparathyroidism 3 causes
only a problem on the gland itself:
- autonomous parathyroid adenoma
- parathyroid hyperplasia
- parathyroid cancer
autonomous parathyroid adenoma
primary hyperparathyroidism
group of cells within a gland pump out PTH without stimulation/regard of Ca++ levels
most common cause, 85%
parathyroid hyperplasia
primary hyperparathyroidism
enlargement of all 4 hyperparathyroid glands therefore increasing production of parathyroid hormone
primary hyperparathyroidism s/s
most common in 50+, women (3x)
mild elevations of serum calcium
relatively asymptomatic
diagnosing primary hyperparathyroidism
elevated serum calcium
elevated intact PTH
primary hyperparathyroidism treatment
asymptomatic hypercalcemia may be treated by vigorous hydration (increasing amounts of calcium released from blood)
otherwise, treated surgically (removal of gland)
secondary hyperparathyroidism causes
patients with chronic kidney disease
failing kidney is unable to excrete PO4 normally, instead excreting Ca
(secondary bc caused by CKD)
secondary hyperparathyroidism pathophysiology
kidneys secrete Ca++ instead of PO4
low serum calcium causes high PTH secretion but can’t maintain Ca balance
failing kidney no longer produces vitamin D so Ca absorption decreases
results in renal osteodystrophy
treatment of secondary hyperparathyroidism
diet management (more Ca++, decrease PO4)
Phos-lo (binds to phosphorus, increased excretion via GI)
Calcitriol/Rocaltrol (synthetic vitamin D, more calcium is absorbed in diet)
tertiary hyperparathyroidism
occurs in pts with CKD following transplant
despite having normalized kidney, parathyroid continues to pump out excessive PTH (used to it)
treatment via surgery
hormones of pancreas:
insulin
glucagon
which hormone is trophic for pancreas?
somatostatin
insulin
produced by beta cells
moves glucose from blood to cell
glycogen formation, suppresses glucose production from liver
glucagon
released in response to cellular hypoglycemia
causes gluconeogenesis, glyconeolysis
glucose from cells to blood
type 1 DM causes
immune mediated (90%)
idiopathic
circulating levels of insulin are negligible, insulinogenic stimuli elicit no response from pancreas
typically appears in children, teens
immune mediated T1DM
autoantibodies attack islet cells (that produce insulin)
idiopathic T1Dm
unknown stimulus cause death/dysfunction of beta cells
symptoms of T1DM
polyphasia (with weight loss, despite normal intake)
polyuria (increased urinatoin due to osmotic diuresis)
polydipsia (increased thirst due to osmotic diuresis)
Type 2 DM basic
gradual development of insulin resistance
pancreas tries to make more, but not enough. B cells die and glucose toxicity increases causing more rapid destruction
symptoms of T2DM
asymptomatic
hyperglycemia or glucosuria found on routine lab
may report increased thirst or urination
pathophysiology of T2DM
hyperinsulemia, hyperglycemia, increased free fatty acids results in
- endothelial cell dysfunction (impaired relaxation and proliferation of smooth muscle cells)
- inflammation (low grade inflammation, worsens resistance and arteriosclerosis, promotes clotting
treatment options for T2DM (list classes) (5)
- metformin
- sylfonylureas
- incretin mimetics
- thiazolidineodiones
- SGLT2 inhibitors
metformin
class, MOA, brand
brand: glucophage
no class
decreases glucose output by liver, sensitizes peripheral cells to insulin
1st line
doesn’t cause hypoglycemia, promotes weight loss
side effect: diarrhea (must discontinue if presents)
glipizide
class, MOA, brand
Glucotrol
class: sylfonylureas
stimulates pancreatic beta cells to make more insulin
cheap, powerful BUT causes hypoglycemia and weight gain
incretin mimetics
2 types:
- GLP-1 Agonists
- DPP4 inhibitors
don’t cause hypoglycemia and may cause weight loss
eventide
class, MOA, brand
Byetta
class: incretin mimetics
synthetic GLP-1 (replaces what diabetic no longer makes)
inhibits glycogen release, slows gastric emptying, increases glucose dependent insulin secretion
patient fells full, eats less
MUST be injected :(
Sitagliptin
class, MOA, brand
Januvia
class: incretin mimetics
inhibits dipeptidyl peptidase (which degrades GLP-1) therefore inhibiting GLP-1 breakdown
pioglitazone
Actos
class: TZD
lower glucose by increasing glucose uptake in muscle and fatty tissue
decreases hepatic glucose production
multiple CI, cause weight gain
canagliflozin
Invokana
Class: SGLT-2 inhibitor
inhibits glucose reabsorption after filtration by kidney
may cause weight loss, increases risk of UTI/DKA
4 insulin options for diabetics
genetically engineered
- rapid acting insulin (insulin lisper)
- regular insulin
- NPH insulin
- Long acting insulin (insulin glargine/Lantus)
rapid acting insulin
acts faster than endogenous insulin
two roles: mealtime coverage, insulin pump
pts must eat within 20 minutes and front load cards to avoid hypoglycemia
regular insulin
slower onset, wears off in 5-7 hrs
not common used: primarily used as drip to treat severe hyperglycemia and DKA
NPH insulin
slow onset (2x daily)
basal coverage
can be mixed with rapid acting insulin for mealtime and basal coverage
Long acting insulin
inulin glargine (Lanthus)
basal Insulin, once daily injection
why do we have multiple types of insulin to treat diabetes?
so that we can best mimic the physiologic activity of the pancreas
T1DM is caused by
complete lack of insulin
only treatment option is to replace insulin
T2DM caused by
insulin resistance, so many different options
diabetic emergencies
- diabetic ketoacidosis
2. nonketotic hyperosmolar coma
diabete ketoacidosis
common T1DM (young patients0
- lack of insulin causes body to break down ketoacids in blood (decreasing blood pH – from 7.35 to 7.2) therefore impact enzyme function
- patient develops dehydration from osmotic diuresis and hypokalemia
triggered by: n/v, surgery, stressor
develops rapidly, treated by giving insulin
non-ketotic hyperosmolar coma
T2DM (older patients with poor access to fluids)
patient has enough insulin to prevent ketosis, but can’t satisfy cellular needs
severe osmotic diuresis occurs (need to get urine out so sucks up all water)
develops slowly, treated by hydration
