Endocrine Flashcards
Dopamineprolactin
Dopamine inhibitsprolactin
Low dopamine= lactogenésis
Arterial supply pituitary
Superior and inferior hypophyseal arteries
Thyroid surgery nerve risk
Protect recurrent laryngeal nerve when lighting inferior thyroid a
Superior laryngeal - superior thyroid a
Congenital hypothyroidism
Course facial features, short stature, mental impairment
“Pot belly” protruding umbilicus
Puffy face, protruding tongue
Pale skin
Thyroid peroxidase
Iodide → iodine
Adds to tyrosine residues on thyroglobulin
Combines MIT + dit or dit x2 to make t3 or t4
Thyroglobulin
Large protein, many tyrosines
Tyrosines → MIT, dit → t3/4
Found in follicular cell lumen
When ready endocytosed into cell and cleave d by proteases
5’ deiodinase
At tissues
T4 → active t3
Wolff chaikoff effect
Excess iodide inhibits TPO
Thyroid binding globulin
Transports almost all t3 and t4 in blood
Inactive whenbound
Increased during pregnancy and with OCPs - bound elevated, free normal
Decreasedhepatic failure, steroids-bound low, free normal
Thyrotoxic crisis
Thyroid storm
Triggered acute physiologic stressors
Agitation, delirium
Fever
Diarrhea
Tachyarrythmia - high output heart failure- A fib
Coma
Antithyroid antibodies graves
Anti tsh-r
Tx hyperthyroid
Propranolol for tachycardia
Antithyroid propylthiouracil or * methimazole - PTU in first tri preg
Prednisone for exophthalmos if present
If failed:
Radioactive ablation
Thyroidectomy
Irregularly enlarged thyroid
Multinodular goiter
Antibodies hashimotos
Anti-tpo, thyroglobulin, microsomal ig G
Hla hashimotos
DR 3/5
Atrophic thyroiditis
Blocking-anti.TSH-R
Absent goiter
Middle age to elderly
Drug induced hypothyroidism
Amiodarone- antiarrythmic
Lithium
Aspirin
Sulfonamide
Myxedema coma
Diminished mental status
Low temp
Hypoglycemia
Hyponatremia
Hypoxia
Hypoventilation
Bradycardia
Hypercapnia
Often neither myxedema nor coma…
Calcitonin tumor marker
Medullary thyroid cancer
Thyroglobulin tumor marker
Papillary or follicular thyroid cancer
CEA tumor marker
Carcinoembryoniz antigen
Medullary thyroid, colon, pancreas, lung, breast
Biopsy hashimotos
Lymphocytes and hurthle cells
Painful enlarged thyroid low thyroid
Subacute granulomatous / de quervain thyroiditis,
Usually precipitated by acute viral infection
Thyroiditishyperthyroid
Silent lymphocytic - May also be asymptomatic - often self- limita and mild- may progress to mild hypothyroid
De quervain thyroiditis
Or transient in ear h ly disease course hashimotos
Riedel thyroiditis
Fibrosis due tochronic inflammation
Low or euthyroid
Painless goiter
Local compressive sx
Methimazole
Preferredantithyroid drug except in pregnancy
Inhibits iodine → tyrosine and iodotyrosine coupling
Propylthiouracil
2nd choiceantithyroid
Preferred inpregnancy first tri
Similar Mx to methimazole
Plus 5’ deiodlinase inhibition of t4→t3
Antithyroid Æs
Agranulocytosis
Liver damage
Anca - antineutrophö cytoplasmic ab
Vasculitis with glomerular injury
More common ptu
Thyroid adenomas
Generally benign
Most nonfunctional, some secretory
No tumor capsule invasion or blood vessel invasion
Papillarythyroid carcinoma
Most commonmalignancy of thyroid
Great prognosis
Likely t4 secretory
Papillary thyroid carcinoma mutations
Ret or braf
Or childhood radiation
Oxytocin production
Mostly PVN of ht
Oxytocin storage
Posterior pituitary
Prolactin sex hormones
Reduces GnRH
Thus _ low T and E
Implicated in infertility
Sheehan syndrome
Postpartum hemmorhage- → pituitary infarction → low prolactin → lactation failure, menstrual irregularities
Thyroid andprolactin
TRH, - → TSH and prolactin
Primary hyperthyroid eg graves or secondary hypothyroid → low prolactin
Pituitary stalk compression prolactin
Hyper prolactinemia
Interrupts inhibitory dopamine signal
Hyper prolactin causes
Dopamine blockers eg. Antipsychotics
Prolactinomas
Pituitary stalk compression
Pregnancy
Primary hypothyroid dt TRH increase
End stage renal disease unknown why
Estrogen prolactin
Directly increases
Progesterone prolactin
Inhibits milk production effects eg pregnancy
G H starvation
-increased t o stabilize blood sugar
By ghrelin
Congenital gh deficiency
Poor linear growth after first few months
Delayed motor muscle Devi
Laron syndrome
Similar to manifestations ofcongenital gh deficiency but gh not → IGF
So high gh low IGF
Childhood gh deficiency
Short stature, doll-like or infantile facial features
Check IGF levels ( more consistent than_gh), bone Age
Ro causes of failure
Testinggigantism
Oral glucose boles would normally decrease gh but not in true gigantism
Dd: marfan, precocious puberty, normal genes
Acromegaly
Adult high gh
Joint pain, muscle aches, gradualoftenunnoticable while happening hand and foot growth c coarse facies
Diabetes, atherosclerosis dt glucose and lipid fx
Causes:
- tumor
- mccune Albright
- men-1
- carney complex
- x linked acrogigantism
Tx Gh excess
Octreotide - somatostatin analog
Somatostatin
Secreted by ht to decrease gh
Hyper prolactin Tx
Cabergoline
Bromocriptine
Note these ore also implicated in hypo when taken for other reasons eg. Pd
Or removal - based on severity. of visual field defects
ACTH deficiency
Mild: postural hypotension and pots
Severe: weight loss, fatigue, low libido, hypoglycemia
Extra bad: fatal vascular collapse - shock
ADH deficiency
Central di
High volume dilute urine
Dehydration, thirst, dizziness
Pituitary apoplexy
Sudden pituitary hemorrhage
Trauma, aneurysm
Emergency
Low ACTH → shock
Sudden excruciating headache, diploma, progressive hypopituitarism
Immediate tx: stabilize bp with fluids and cortisol
Also Tx hypoglycemia
PTH
Increased blood calcium
Low bone density
Low phosphate -renal exchange
Gut uptake, urine reuptake, vitamin D production i bone breakdown
Hyper calcemia sx
Asymptomatic at first
Then:
Fatigue
Irritability
Depression
Memory problems
Decreased bone density if dt high PTH
Then:
Shortened qt_interval
Arrhythmia
Fractures
Kidney stones
Acute pancreatitis
Ulcers
Ab pain, constipation
Stupor, confusion
Seizures,
coma
Men1 and men 2 both cause
High PTH
Men- 1 Gene
Men 1
Men 2a Gene
Ret
High PTH sx
Hypercalcemia
Pain Bones, kidney stones, ab groans, psych moans
Osteitis fibrosis cystica
High PTH → cystic bone lesions
Brown color tumors dt hemorrhage → hemosiderin deposits
Rank-l expression on osteoblasts, rank on osteoclasts
Secondary hyper PTH
Dt chronically * low calcium
Most common CKD dt low vitamin D conversion to active form in renal tubules by 1-a-hydroxylase
Other causes _ malabsorption, vitamin D deficiency
Primary hyperPTH tx
Bisphosphanates eg alendronate decrease bone loss
Cinacalcet mimics ca to turn off PTH
Surgery possible but often fails, tricky
Polyuria calcium
High Ca → polyuria via inhibition of action of ADH in renal tubules = nephrogenic di
Also potentially type I renal tubular acidosis, AKI
Acute hypercalcemia
Most often dt cancer dt:
- pthrp production
- metastasis bone
- ectopic1-a-hydroxylas e→ excess calcitrol vitamin D
Causes hypercalcemia
Parathyroid
Cancer
Granuloma- 1 alpha hydroxylse production
Meds:
-Lithium
- thiazide diuretics
- excess Ca or vit Dsupplement
-Familial hypocalcuric hypercalcemia - defects in ca receptors inparathyroid and kidney
Calcium action potential
Blocks sodium channels
Raises threshold
Weakness
Calcium heart
ReCduced Na movement de Ca blocking channels
Less depolarization → shorter depolarization
Shortened q T interval
Later arrhythmia, St changes
Cv. calcium deposits → valve stenosis, HTN, cardiomyopathy
Loop diuretics ca
Decrease
Loops lose ca
Used in symptomatic hypercalcemia t x
Acute symptomatic hyper Ca Tx
1 fluids
- Loop diuretics
- Bisphosphanates
Calcitonin if severe but resistance if long term
Cancer: denosumab anti-rank-l
High pth: cinacalcet
Granulomatous and lymphoma: prednisone
Resorption
Breakdown of bone
Pancreatitis calcium
Acute pancreatitis can cause low Ca dt deposits forming
High Ca can cause pancreatitis - one of the “groans”
Drugs causing hypocalcemia
Loop diuretics eg furosemide
Bisphosphonates
Cinacalcet
Foscarnet_antiviral
Loop diuretics target
Na-k-2cl transporter thick ascending loop of henle
Chvostek sign,
Hypocalcemia
Tap facial nerve → twitching
Trousseausign
Hypocalcemia
Inflate bp cuff 3 min → hand twitching and contracture
Severe hypocalcomia st
Laryngospasm
Bronchospasm
Seizures
Life threatening
Hypocalcemia reflexes
Hyperreflexia
Hypocalcemia st
Irritability of nerves, muscles, heart
M sk:
Numb/tingle
Twit ching
Hyperreflexia
Tetany
PsyCch:
Anxiety
Depression
Psychosis
Am s
.chronic: Parkinsonism
, dementia, cataracts
Heart
Prolonged qt interval
Torsdades de pointes- potentially fatal
Albumin Ca
Transports
Standard Ca lab is total including albumin bound but only free is active
Free isphysiollogically important
So low albumin means total Ca will be low or normal even if free is normal or high
Acute symptomatic hypocalcemia Tx
Iv calcium gluconate then transition to oral Ca with vit D
Underlying cause
Bisphosphonattes
Prevent bone resorption
Lower serum Ca
Induce apoptosis in osteoclasts
- dronate
AES:
-N/v
- esophageal erosions
- iv: jaw osteonecrosis
Denosumab
Hyper - Ca of malignancy
Prevents resorption
Decreases serum Ca
Anti-rank-l
Blocks osteoclast maturation
Hypo-mg
Causes hypo-ca
Reduces PTH release
Poor diet, alcohol
Sevelamar
Gut phosphate binder
For hyper. Phosphate → hypo-ca of CKD
Calcium acetate
- Gut phosphate binder
Good if Ca supplement also needed but use caution in CKD
Zone glomerulosa adrenal
Outermost
Mineralocorticoid’S
Zone fasciculat a
Middle layer of cortex
Less staining due to high lipid content
Glucocorticoids
Zone reticularis
Innermost oadvenal cortex
Androgens
Chromaffin cells
Adrenal medulla
Catecholamine’S
ACTH cellular targets
Upregulate StAR - steroidogenic acute regulatory protein - rate limiting incortisol formation - transferscholesterol into mitochondria
StimulatesCholesterol desmolase - convertscholesterol to pregnenolone
CBG
Cortisol binding globulin
Transports most of cortisol in blood, prolongs t 1/2
Cortisoltarget
Intracellular gr-glucocorticoid receptor
Complex directly binds glucocorticoid response element of gene
Cortisol bone
Decreases osteoblast ‘ activity
excess → less new bone generation i i weaker bones
Cortisol neutrophils
Demargination
Artificially increases count but decreases function
Cushing disease
Cushing syndrome caused by an ACTH- secreting pituitary adenoma
Syndrome: all cause
Bp cushings
Diastolic htn
Bilateraladrenal_hyperplasia_tx
Cortisol synthesis inhibitors
Metyrapone
Ketoconazale
Mitotane
Hyperaldosterone acid base
Metabolic alkalosis- excess H+ loss
Conn syndrome
Benign aldosterone-secreting adenoma of adrenal gland
Hypokalemia EKG
T wave inversion
Prominent U waves
Main test to distinguish primary from secondary hyper-aldosteronis m
Plasma renin
Renin →aldosterone
So elevated in secondary and low in primary
Hyper-aldosterone Tx
Underlying cause
K sparing diuretics - spironolactone and eplerenone
Spironolactore
Competitive aldosterone receptor antagonist
Cortical collecting duct
K sparing diuretic
AES - androgen t progesterone - gynecomastia
Eplerenone
More specific aldosterone receptor antagonist
K sparing diuretic
Alternative to spironolactone
No gynecomastia
Causes of secondary hyperaldosteronism
Renal artery stenosis - impaired read blood flow
J G cell tumors
Liver cirrhosis
Hear t failure
Nephrotic syndrome
Usually first presenting sign hyper aldosterone
Refractory hypertension
Labs then show hypokalemia and metabolic alkalosis
Congenital adrenal hyperplasia
Autosomal recessive
Usually low cortisol and aldosterone but high sex steroids
Generally masculinizing - external genital ambiguity in female
Most commonenzyme deficient cah
21 -hydroxylase
Classic vs. nonclassic CAH
Classic - salt-wasting, dehydration, adrenal crisis - most common.
Non-classic- non-salt wasting - partial enzyme fx makes aldosterone but still no cortisol
→ less severe
→ may be silent till puberty
→ generally nogenital ambiguity but will have precocious virilizing puberty
Simple virilizing -cortisol andaldosterone present but high DHEA i
Pheochromocytoma MEN
Types 2a and 2b
Neuroblastoma
Abdominaltumor arising from neuralcrest cells
Generally along sympathetic chain or in adrenal medulla
Usually kids <4
Rapid growth
Hypertension from renal artery compression or catecholamine secretion
Rapid involuntary eye movements
Muscle twitchin
Abdominal distention
Palpable mass
Neuroblastoma gene
Usually MYCN Amplification
If present isassociated with more aggressive course with 50%mortality
Without mutation better px with chance of spontaneous regression
Biopsy neuroblastoma
Homer-wright rosettes
Small, round blue cells in circular patterns
Eosinophilic neuropil
IHC bombesin
Suppression testing pheochromocyta
ClonidineSuppression testing if 24 h urine catacholemine and metarephrines is indeterminate
Octreotide
Inhibits insulin and gh release
Chronic hypoglycemia
Acromegaly
Esophageal bleed
Hepatorenal syndrome
HLA T1DM
Dr3 and dr4
Hs type TIDM
. Type 4
Mechanism of microvascular damage in diabetes
Mostly non-enzymatic glycosylation of various cellular proteins. - ages
In eye and Schwann cells - osmotic and oxidative injury from glucose → sorbitol
Rapid insulins
Lispro, aspart, glulisine
Intermediate acting insulin
NPH “
Long acting insulins
detemir, glargine
Metformin
Class: biguanide
Mx: glut 4 phosphorylation → glucose uptake
Also reduced gluconeogenesis and reduced gutreabsorption.
Ae: lactic acidosis. Gi
Ci: renal failure, CHF, hypoxia
-glitazone
Class: thiazolidinediones
Mx: ppar- gamma activation → fatty acid storage → insulin sensitivity
Ae: fluid retention, liver damage, weight gain, low bone density
Ci: CHF
Gly-/gli-
Class: sulfonylureas
Mx: stimulate pancreatic insulin release by closing atp-sensitive k channels
Ae: hypoglycemia, weight gain
Ci: sulfa allergy
_Glinide
Class: meglitinides
Mx:similar tosulfornylureas
Ok in sulfa allergy
- Gliflozin
Class: sglt-2 inhibitors
Mx: inhibit renal glucose reabsorption
Æ: UTI, dehydration, fatigue
Pramlintide
Class: amyline-anoloague
Mx: slow gastric emptying, promote fullness
Use: prevent hyper and hypoglycemia, weight loss, also T1DM
-Tide
Class; GLP -1 agonist
Mx: endogenous incretin mimic
- Increasedpostprandial insulin
-Less glucagon
- delayed gastric emptying
-Fullness
- weight loss
Route: sub Q
A E: gi upset, acute pancreatitis
_Gliptin
Class: Dpp4 inhibitor
Mx: inhibits degradation of glp-1
Similar fx to glp-1 agonists
Route: oral
Hormones inducing insulin release
Glp- 1 and GIP
Glucagonoma
Diabetes
Depression
Declining weight
DVT
Dermatitis - migratory necrolyticerethema
Vip-oma
“Pancreatic cholera”
