endocrine Flashcards
stimulates bone and muscle growth
growth hormone
stimulates milk production
prolactin
stimulates milk secretion during lactation
oxytocin
responsible for female 2° sex characteristics
estrogen (primarily estradiol)
stimulates metabolic activity
thyroid hormone
↑ blood glucose level
↓ protein synthesis
glucocorticoids: cortisol
responsible for male 2° sex characteristics
testosterone
prepares endometrium for implantation/maintenance of pregnancy
progesterone
stimulates adrenal cortex to synthesize and secrete cortisol
ACTH
stimulates follicle maturation in females + spermatogenesis in males
FSH
↑ plasma calcium
↑ bone resorption
PTH
↓ plasma calcium, ↑ bone formation
calcitonin
stimulates ovulation in females + testosterone synthesis in males
LH
stimulates thyroid to produce TH and uptake iodine
TSH
anterior pituitary hormones
FLAT PiG FSH LH ACTH TSH Prolactin intermediate: MSH GH
made in hypothalamus and stored in
posterior pituitary hormones
ADH (supraoptic nucleus)
oxytocin (paraventricular nucleus)
adrenal cortex hormones
deeper you go, sweater it gets:
1) zona glomerulosa (salt): mineralcorticoids (aldosterone: Na+ retention)
2) zona fasciculata (sugar): glucocorticoids (cortisol)
3) zona reticularis (sex): androgens (testosterone)
sex gland hormones
ovaries: estradiol, progesterone, testosterone
placenta: estriol, progesterone
testes: testosterone, estrogen
stimulates production of IGF-1
growth hormone
thyroid hormones
T3/T4
calcitonin: parafollicular cells of thyroid (C cells)
heart hormones
antrial natriuretic hormone (ANH) = atria of heart
pancreatic hormones
α cells: glucagon
ß cells: insulin
delta cells: somatostatin
adrenal medulla hormones
Catecholamines: NE + epi (Chromaffin cells)
fat cell hormones
estrone
formed from rathke’s pouch (ectodermal diverticulum of primitive mouth that invaginates upward)
anterior pituitary
formed from invagination of hypothalamus (neuroectoderm)
posterior pituitary
causes of hyperprolactinemia
pregnancy/nipple stimulation
stress (physical or pyschological)
prolactinoma (associated with bitemporal hemianopia = peripheral vision loss)
dopamine antagonist: antipsychotics (haloperidol, risperidone), domperidone, metoclopramide
premenopause female with hypogonadism sx:
infertility
oligo/amenorrhea
rarely galactorrhea (not hypogonadism sx)
hyperprolactinemia:
↑ prolactin → inhibits GnRH → no FSH, LH
postmenopausal female with hyperprolactinemia presents with
NOTHING (may have galactorrhea) - already hypogonadal (ovaries don’t respond to GnRH anyways - so inhibition of GnRH provides same action)
male with hypogonadism (low T): ↓ libido impotence infertility: low sperm count gynecomastia rarely galactorrhea
hyperprolactinemia:
↑ prolactin → inhibits GnRH → no FSH, LH
most common pituitary adenoma
prolactinoma
cause of: amenorrhea galactorrhea low libido infertilty lesion the optic chiasm: bitemporal hemianopia
hyperprolactinemia from pituitary adenoma:
↑ prolactin → inhibits GnRH → no FSH, LH
treatment of pituitary adenoma
dopamine agonist: bromocriptine or cabergoline
↑ dopamine →↓ prolactin
surgical resection if visual sx severe
large tongue: deep furrows, indentations increase spacing of teeth deep voice large hands + feet coarse facial features (nose, ears) impaired glucose tolerance (insulin resistance) → can lead to diabetes
acromegaly: excess GH in adults
excess bone growth of linear bones
tall + big children
gigantism: excess GH in kids
diagnosis of acromegaly/gigantism
IGF-1 (screening test, stable during day, downstream hormone) if high IGF-1, oral glucose tolerance test (check GH: if ↑ glucose doesn't affect GH level = tumor) not GH (pulsatile, highest at night)
treatment of acromegaly/gigantism
resection of pituitary adenoma
then, octreotide (somatostatin analog)
postpartum hemorrhage → underperfusion of pituitary → pituitary necrosis → hypopituitarism
sheehan syndrome
agalactorrhea (↓ prolactin) amenorrhea after delivery 2° hypothyroidism: fatigue, cold intolerance, weight gain acute hyponatremia (rare)
sheehan syndrome
replacement of tissue in sella turcica (= pituitary) with CSF would cause
called empty sella:
asymptomatic (enough residual pituitary tissue outlining sella turcica) or symptoms of pituitary hormone deficiency (1 or more hormones)
adrenal cortex and medulla derived from
adrenal cortex: mesoderm
adrenal medulla: neural crest = ectoerm
most common tumor of adrenal MEDULLA in adults
pheochromocytoma: chromaffin cell tumor (neural crest cell)→catecholamines: ↑ NE, epi, dopamine
EPISODIC of: sweats severe HTN (episodic) + headache tachycardia palpitations
pheochromocytoma: chromaffin cell tumor →↑ NE, epi, dopamine
most common tumor of adrenal MEDULLA in kids
adrenal neuroblastoma: tumor of sympathetic ganglion cells (can develop anywhere along chain, 40% in adrenals)
secrete little dopamine, VMA, HVA:
kid with mild SUSTAINED HTN
adrenal neuroblastoma: tumor of adrenal medulla
fetal type 2 pneumocytes can’t mature and secrete surfactant without
fetal cortisol (wk 34 GA)
no aldosterone: HYPOTENSION, hyponatremia (salt wasting), hyperkalemia
no cortisol: ↑ ACTH
↑17-OH progesterone
shunt pathway to ↑ androgens: masculinization, virilization
21 α hydroxylase deficiency: congenital adrenal hyperplasia
diagnosis of 21 α hydroxylase deficiency
screening test: ↑↑ 17-OH progesterone
if no screening test is done:
infant girl: masculinization is obvious
infant boy: salt wasting is life-threatening (↓Na, ↑K)
no aldosterone
no cortisol
↑ DOC = deoxycorticosterone (seak MC that causes Na +H20 retention → HTN)
shunt pathway to ↑ androgens: masculinization, virilization
11 ß hydroxylase deficiency: congenital adrenal hyperplasia
no cortisol
no testosterone, estrogen: default pathway: phenotypic female (since default) unable to mature; ambiguous genitalia with undescended testes, if male
ONLY aldosterone: Na + H20 retention →HTN, hypokalemia
17α hydroxylase deficiency: congenital adrenal hyperplasia
complication of 21α hydroxylase, 11 ß hydroxylase deficiency, 17 α hydroxylase deficiency
all cause NO cortisol →↑↑ ACTH → hyperplasia of adrenal gland in order to make more cortisol
no aldosterone: Na+ excretion in urine (salt wasting) → early death if untreated
no cortisol
no testosterone, estrogens: phenotypic female (since default) unable to mature; ambiguous genitalia with undescended testes, if male
↑ pregnenolone, DHEA
3ß-HSD deficiency
causes of cushing syndrome: ↑ cortisol
1) exogenous steroid use (glucocorticoids)
2) Cushing disease: ACTH-producing pituitary adenoma
3) non-pituitary tumor/cancer that produces ectopic ACTH: small cell lung cancer
4) adrenal overproduction of cortisol: adrenal adenoma
symptoms of Cushing syndrome (4 stars)
BAM, CUSHINGOID Buffalo hump Amenorrhea Moon facies Crazy: psychosis, agitation Ulcers (PUD) Skin changes: acne, thinning of skin, bruising, purple striae HTN Infection Necrosis of femoral head Glaucoma, cataracts Osteoporosis Immunosuppresion Diabetes
diagnosis of cause of cushing syndrome requires
dexamethasone suppression test: low dose of dexamethasone (only glucocorticoid that doesn't interfere with cortisol assay) check cortisol in morning high dose of dexamethasone check cortisol next morning
Conn syndrome
aldosterone-secreting adrenal tumor: 1° hyperaldosteronism
triad:
HTN: Na, H20 retention
hypokalemia
metabolic alkalosis: low K+ stimulates H+ urinary excretion + H+ moves intracellularly in exchange for K+ out of cells
low plasma renin: ↑ aldo →↓ renin (- feedback)
aldosterone-secreting adrenal tumor: 1° hyperaldosteronism (Conn syndrome)
kidneys sense low intravascular volume → RAAS system
↑ renin → ↑ aldo
2° hyperaldosteronism
causes of 2° hyperaldosteronism
*(kidneys sense low intravascular volume= ↓ renal perfusion:
renal artery stenosis
low output heart failure: low LV EF
*low protein state, compensatory ↑ renin due to low intravascular volume:
nephrotic syndrome
cirrhosis
treatment of 1° hyperaldosteronism
surgical resection of tumor
if both adrenals secreting or no surgery:
aldosterone antagonist: spironolactone, eplerenone
no cortisol AND aldosterone: hypotension
hyponatremia
hyperkalemia
generalized fatigue
anorexia
weight loss (opposite of excess cortisol)
skin hyperpigmentation: ↑ ACTH → stimulates MSH R
1° adrenal insufficiency: addison disease
causes of 1° adrenal insufficiency: addison disease
1) autoimmune destruction of adrenal cortex
2) met cancer
3) TB
4) Waterhouse-Friderichsen syndrome
skin hyperpigmentation
1° adrenal insufficiency: addison disease ONLY
acute 1° adrenal insufficiency due to adrenal hemorrhage from severe N. meningococcal sepsis (petechial rash) or DIC (coagulopathy)
Waterhouse-Friderichsen syndrome
treatment for 1° adrenal insufficiency: addison disease
treat low cortisol AND aldosterone:
glucocorticoid: prednisone, etc.
mineralcorticoid: fludrocortisone
↓ACTH → ↓ cortisol
NORMAL aldosterone (stimulated by renin!): NO hyperkalemia, hypotension
+ weakness, malaise, weight loss
2° adrenal insufficiency
↓ CRH from hypothalamus due to abrupt withdrawal of long-term exogenous steroid use (must wean)
suppression of HPA axis: ↓ CRH, ACTH, cortisol
NORMAL aldosterone: no hyperkalemia, hypotension
3° adrenal insufficiency
diagnosis of pheochromocytoma
urine test for byproducts: VMA: vanillylmandelic acid ↑serum catecholamines: metanephrine normetanephrine
rule of 90’s for pheochromocytoma
90% benign 90% unilateral 90% adrenal medulla 90% no calcification 90% adults
MEN 2A and 2B AND neurofibromatosis I are associated with what adrenal pathology
pheochromocytoma
EPO-secreting tumors → polycythemia
pheochromocytoma
renal cell carcinoma
hemangioblastoma: vascular tumor of CNS
hepatocellular carcinoma
treatment of pheochromocytoma
surgical resection
before surgery, medically-treat HTN, tachycardia:
epi stimulates α + ß receptors
α blocker for HTN!!! (nonselective, irreversible: phenoxybenzmine)
then, ß blocker for tachycardia!!!
if only ß blocker with α blocker: epi stimulates α R (vasoconstrict) → ↑ bp even more
diagnosis of adrenal neuroblastoma
urinary VMA and HVA
n-myc oncogene
adrenal neuroblastoma
bombesin tumor marker
adrenal neuroblastoma
neurofilament stain
adrenal neuroblastoma
Homer Wright rosettes: radial arrangement of tumor cells around central tangle of fibrils
adrenal neuroblastoma
thyroid gland makes excess T3/T4
hyperthyroidism
general term for excess thyroid hormone due to exogenous drug or thyroid inflammation
thyrotoxicosis
tachycardia palpitations anxiety weight loss heat intolerance hyperactivity warm skin
thyrotoxicosis (includes hyperthyroidism)
diagnosis of thyrotoxicosis (includes hyperthyroidism)
screen: serum TSH (increases exponentially, sensitive)
confirmation/determine extent of disease: free T4/T4 (increases linearly)
autoimmune disorder
TSI (thyroid stimulating immunoglobulin = IgG) binds to TSH receptor on thyroid gland → stimulates free T3/T4 secretion →↓ TSH
may have goiter: swelling of thyroid gland
4:1 female predominance
hyperthyroidism: Graves’ disease
associated with HLA-DR3 and HLA-B8
graves’ disease
diagnosis of hyperthyroidism: Graves’ disease
↑ uptake on radioactive iodine study (diffuse)
thyroid uptakes LOTS of iodine to keep up with T3/T4 production
warm dry skin, thin hair tachycardia, palpitations muscle atrophy weight loss bowel hypermobility ↓ or absent menstrual flow \+/- goiter exophthalmos: abnormal CT deposition in orbit + EOM pretibial myxedema: ↑ deposition of CT components: glycosamino glycans, mucopolysaccharides, thickening of skin on shins thyroid bruit
hyperthyroidism: Graves’ disease
treatment of hyperthyroidism: Graves’ disease
antithyroid: propylthiouracil, methimazole
B blocker: ↓ HR, anxiety
definitive treatment: surgical resection or radioactive iodine: iodine taken up into thyroid gland → destroyed by high dose iodine of next several mo (with need thyroid replacement meds)
causes of hyperthryoidism
Graves disease toxic adenoma (single nodule) /toxic multinodular goiter iodine-induced hyperthryoidism subacute thryoiditis thyroid storm struma ovarii teratoma: thyroid tissue
focal patches of hyperfunctioning follicular cells working independently of TSH due to mutation in TSH R →↑ free T3/T4
hyperthyroidism sx
rarely malignant
toxic adenoma (single)/toxic multinodular goiter
if wasn’t associated with hyperthyroidism - called “non-toxic” adenoma
diagnosis of toxic adenoma/toxic multinodular goiter
radioactive uptake and scan: ↑ iodine uptake only in nodules (“hot nodules”)
goiter
can be hyperfunctioning, hypofunctioning or normal
common if iodine deficiency goiter who receives iodine or iodide (IV iodine contrast agent, amiodirone)
↑ risk if Graves disease or toxic multinodular goiter: ↑ hyperthyroidism
iodine-induced hyperthryoidism (Jod-Basedow phenomenon)
occurs after viral URI: coxsackie, echovirus, adenovirus, measles, mumps
acute fever + rapid PAINFUL goiter
early: transient elevation in T3/T4 - follicular release of pre-stored hormone (HYPERthyroid)
late: HYPOthyroidism (due to focal destruction of thyroid + granulomatous inflammation)
or transient thyroiditis: NEVER progresses to hypothyroidism, SELF-LIMITED
3:1 female predominance
subacute thyroiditis (granulomatous infiltration, hypothyroidism + PAINFUL goiter)
like hoshimoto’s thyroiditis - (lymphocytic infiltration, hypothyroidism + PAINLESS goiter)
both: hyperthyroid → hypothyroid
associated with HLA-B35
subacute thyroiditis
most dangerous type of thyrotoxicosis complication of Graves disease (most common) or other hyperthyroid states SURGE of T3/T4 + catecholamines ↑ body temp AMS tachycardia vomiting diarrhea dehydration coma death
thyroid storm
treatment of thyroid storm
ß blocker: ↓ catecholamine effect
PTU or methimazole: ↓ T3/T4
causes of hypothyroidism
destruction of thyroid gland:
congenital hypothyroidism
autoimmune Ab-mediated destruction (Hoshimoto’s)
iodine deficiency or excess
subacute granulomatous thyroidits (late course)
tx of hyperthyroidism by radiation
surgical removal of thyroid
idiopathic
meds: amiodarone, tyrosine kinase inhibitors (chemo), lithium
CANCER
cold intolerance weight gain constipation menorrhagia slowed mental/physical function dry skin coarse brittle hair reflexes showing slow return phase
hypothyroidism
treatment of hypothyroidism
levothyroxine: T4 (most common)
triiodothyronine: T3
cause of congenital hypothyroidism
thyroid dysgenesis: complete agenesis, hypoplasia, ectopic (failed to descend)
thyroid-related enzyme deficiency
dysfunctional TH production, transport, function
TSH resistance
transfer of anti-thyroid meds or anti-thyroid antibodies from mom
leading cause outside US: iodine deficient mom during pregnancy (supplemented in US diet)
newborn screen for this if untreated child has: impaired physical growth ID enlarged tongue enlarged/distended abdomen
congenital hypothyroidism
autoimmune: infiltrate of lymphocytes into thyroid → eventual destruction of hormone production
hypothyroidism + PAINLESS goiter
early: EUthyroid, + ab, normal TH/TSH, asymptomatic (may never progress to thyroid dysfunction with + ab)
inflammation begins: destruction of thyroid follicle cells → spill T3/T4 = transient HYPERthryoidism (lasts few mo)
destruction of thyroid: HYPOthyroid (goiter → scarred, shrunken gland)
5:1 female
↑ incidence with age
hoshimoto’s thyroiditis: most common cause of hypothyroidism in US
diagnosis of hoshimoto’s thyroiditis
TH TSH thyroglobulin antibodies thyroid peroxidase antibodies presence of Abs doesn't mean will become hypothyroid
HLA-DR5
HLA-B5
hoshimoto’s thyroiditis
autoimmune thyroid diseases can be associated with
other autoimmune diseases: addison's disease type 1 DM pernicious anemia vitiligo sjogren syndrome
↑risk B cell lymphoma of thyroid gland (RAPIDLY enlarging thyroid mass)
hoshimoto’s thyroiditis
treatment of subacute thyroiditis
relief of thyroid pain
NSAID
corticosteriods
if hypothyroidism:thyroid hormone replacement
YOUNG patient with:
chronic inflammation of thyroid → replaced by fibrous tissue (can extend into airway)
histo: fibrosis, MACROPHAGES, EOSINOPHILS
hypothyroid or euthyroid
FIXED, HARD, ROCK-LIKE PAINLESS goiter
riedel thyroiditis
thyroid nodules/goiter
isolated or multiple (multinodular goiter)
can be associated with normal thyroid function, hyperthryoidism, hypothyroidism
evaluation of thyroid nodule
US: size, location, abnormal lymph nodes in neck
can’t determine if benign or malignant
biopsy by fine needle aspirations: determine if benign or malignant
thyroid cancers are never HOT nodules = not making normal or overproducing TH (iodine uptake + scan)
papillary shaped cells
no follicles/colloid
ground glass appearance of cytoplasm with large nuclei with nuclear grooves or empty appearing nuclei “orphan annie nuclei”
“psammoma bodies”: concentric calcifications
papillary thyroid cancer: most common type of thyroid cancer
papillary thyroid cancer risk factors
tobacco use
radiation exposure: treatment dose radiation to neck
possibly hereditary: RET gene mutation or BRAF
activation of tyrosine kinase receptor
papillary and medullary thyroid cancer
30-50 yo "orphan annie nuclei" "psammoma bodies" good prognosis may reoccur 3:1 female predominance
papillary carcinoma of thyroid
treatment of thyroid cancer
1) total thyroidectomy
followed by radioactive
2) papillary or follicular:
iodine treatment (higher dose if treating hyperthryoidism because of increased need for iodine to make TH)
3) medullary: no radioactive iodine (not a carcinoma of thyroid producing cells)
uniform cuboidal cells lining follicles
cancer of follicle cells surrounded by fibrous capsule - cells INVADE fibrous capsule
can spread in blood (unique to thyroid cancer - most carcinomas spread by lymph nodes)
3:1 female prodominance
follicular thyroid carcinoma: 2nd most common type
uniform cuboidal cells lining follicles
follicular adenoma OR follicular thyroid carcinoma (but invasive - invade fibrous capsule)
associated with RET gene mutation or BRAF gene mtuation
papilllary thyroid carcinoma
associated with RAS mutation
or PAX8-PPAR gamma 1 rearragment
follicular thyroid carcinoma
proliferation of parafollicular C cells in medulla (secrete calcitonin)
medullary carcinoma of thyroid
associated with MEN 2A and MEN 2B
medullary carcinoma of thyroid
if have cancer - must remove screened for pheochromocytoma BEFORE removal of thyroid
associated with RET gene mutation
papillary or medullary thyroid carcinoma
undifferentiated neoplasm
more common in elderly
FIXED, HARD, ROCK-LIKE PAINLESS goiter WITH local extensions
very poor prognosis
anaplastic thyroid carcinoma
surgical complications of thyroidectomy
remove/damage parathyroid: ↓ Ca (perioral tingling, myalgia/cramping → tetany, seizures in POST-OP period), can have transient hypoglycemia that recovers over wks
damage to recurrent laryngeal nerves (vagus nerve - innervates thyroid + vocal cords): hoarseness
complications of hypothyroidism
↑ LDL
↑ total cholesterol
complications of hyperthryoidism
atrial fibrillation: need rate-control drug
use ß blocker (not CCB): treat HR + adrenergic sx of hyperthyroidism
tx hyperthyroidism: methimazole
