415 terms

USMLE Endocrine

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thyroid development:
thyroid diverticulum arises from ___ and descends into ___
floor of primitive pharynx
neck
the thyroid, in development, is connected to tongue by ___. what is the fate of this structure?
thyroglossal duct
normally disappears but may persist as pyramidal lobe of thyroid
what is the normal remnant of the thyroglossal duct?
foramen cecum
most common ectopic thyroid tissue site
tongue
thyroglossal duct cyst
presents as anterior midline neck mass that moves with swallowing or protrusion of tongue (vs. persistent cervical sinus leading to branchial cleft cyst in lateral neck)
adrenal cortex is derived from what germ layer?
mesoderm
adrenal medulla embryologic dericative
neural crest
adrenal cortex:
layers from innermost to outer
zona reticularis
zona fasciculata
zona glomerulosa
zona glomerulosa:
primary regulatory control and secretory products
renin-angiotensin
aldosterone
zona reticularis:
primary regulatory control and secretory products
ACTH, CRH
sex hormones (e.g. androgens)
zona fasciculata:
primary regulatory control and secretory products
ACTH, CRH
cortisol, sex hormones
endocrine cells of adrenal medulla
Chromaffin cells
Chromaffin cells:
primary regulatory control and secretory products
preganglionic sympathetic fibers
catecholamines (epi, NE)
adrenal cortex layers mnemonic
"deeper you go, the sweeter it gets"
GFR corresponds with Salt (Na+), Sugar (glucocorticoids), Sex (androgens)
pheochromocytoma
who, where, what (effects)
most common tumor of adrenal medulla in adults
episodic hypertension
neuroblastoma
who, where, what (effects)
most common tumor of adrenal medulla in children
rarely causes hypertension
anterior pituitary hormones mnemonic
B-FLAT:
Basophils: FSH, LH, ACTH, TSH
and
FLAT PiG:
FSH, LH, ACTH, TSH, Prolactin, GH
acidophils of anterior pituitary secrete what hormones?
GH
prolactin
from where is melanotropin secreted?
intermediate lobe of pituitary
anterior pituitary is derived from ___
oral ectoderm (Rathke pouch)
hormonal subunit common to TSH, LH, FSH, GH
alpha
hormonal subunit that determines pituitary hormone specificity
beta
posterior pituitary hormones
vasopressin (ADH)
oxytocin
site of vasopressin (ADH) synthesis
supraoptic nuclei of hypothalamus
site of oxytocin synthesis
paraventricular nuclei of hypothalamus
hormones from the hypothalamus are transported to the posterior pituitary via___
neurophysins (carrier proteins)
posterior pituitary is derived from___
neuroectoderm
pancreatic islets arise from ___
pancreatic buds
pancreatic islet cells: secretion and location
alpha
glucagon
peripheral
pancreatic islet cells: secretion and location
beta
insulin
central
pancreatic islet cells: secretion and location
delta
somatostatin
interspersed
insulin synthesis
preproinsulin synth. in RER--->cleavage of presignal-->proinsulin (stored in secretory granules)--->proinsulin cleavage--->exocytosis of insulin and C-peptide equally
2 conditions in which insulin and C-peptide are both increased
insulinoma
sulfonylurea use
exogenous insulin lacks ___
C-peptide
insulin anabolic functions
inc glucose transport in skeletal muscle, adipose tissue
inc glycogen synth, storage
inc triglyceride synth
inc Na+ retention (kidneys)
inc protein synth (muscles)
inc K+, AA uptake by cells
dec glucagon release
does insulin cross placenta? glucose?
no
yes
insulin binding to receptors stimulates...
tyrosine kinase activity--->glucose uptake via carrier-mediated transport into insulin-dependent tissue
and
--->gene transcription
insulin-dependent glucose transporters
GLUT-4: adipose tissue, striated muscle
insulin and ___ can increase GLUT-4 expression
exercise
insulin-independent transporters
GLUT-1: RBCs, brain, cornea
GLUT-2 (bidirectional): beta islet cells, liver, kidney, SI
GLUT-3: brain
GLUT-5 (fructose): spermatocytes, GI tract
brain's energy source during starvation, when glucose is not available
ketone bodies
why do RBCs always (only) utilize glucose?
lack mitochondria for aerobic metabolism
insulin-independent glucose uptake mnemonic
BRICK-L:
brain
RBCs
intestine
cornea
kidney
liver
insulin regulation:
GH, beta2-agonists
increase insulin
GH causes ___ resistance
insulin
insulin regulation by glucose (pathway)
glucose enters beta cells--->inc ATP generated via glucose metabolism--->K+ channels close (sulfonylurea target)--->beta cell membrane depolarizes--->voltage-gated Ca2+ channels open--->Ca2+ influx--->stimulation of insulin exocytosis
glucagon catabolic function
glycogenolysis
gluconeogenesis
lipolysis
ketone production
glucagon release: stimulation and inhibition
stimulation: hypoglycemia
inhibition: insulin, hyperglycemia, somatostatin
hypothalmic-pituitary hormones: function and clinical notes:
CRH
inc ACTH, NSH, beta-endorphin
dec in chronic exogenous steroid use
hypothalmic-pituitary hormones: function and clinical notes:
dopamine
dec prolactin
dopamine antagonists (e.g. antipsychotics) can cause galactorrhea due to hyperprolactinemia
hypothalmic-pituitary hormones: function and clinical notes:
GHRH
inc GH
analog (tesamorelin) used to treat HIV-associated lipodystrophy
hypothalmic-pituitary hormones: function and clinical notes:
GnRH
inc LH, FSH
regulated by prolactin
tonic GnRH suppressed HPA axis
pulsatile GnRH--->puberty, fertility
hypothalmic-pituitary hormones: function and clinical notes:
prolactin
dec GnRH
pituitary prolactinoma--->amenorrhea, osteoporosis, hypogonadism, galactorrhea
hypothalmic-pituitary hormones: function and clinical notes:
somatostatin
dec GH, TSH
analogs used to treat acromegaly
hypothalmic-pituitary hormones: function and clinical notes:
TRH
inc TSH, prolactin
prolactin source
mainly anterior pituitary
prolactin function
stimulation of milk production
ovulation, spermatogenesis inhibition
(GnRH synth/release inhibition)
excessive prolactin is associated with dec ___
libido
prolactin secretion from ant. pit. is tonically inhibited by ___ from ____
dopamine
hypothalamus
how does prolactin inhibit its own secretion?
inc dopamine synthesis and secretion from hypothalamus
effect of TRH on prolactin secretion
increase
(e.g. in primary or secondary hypothyroidism)
effect of dopamine agonists (e.g. bromocriptine) on prolactin secretion
inhibit
can be used to treat prolactinoma
effect of dopamine antagonisms (e.g. most antipsychotics) and estrogens (e.g. OCPs, pregnancy) on prolactin secretion
stimulation
somatotropin is aka
GH
GH source
ant. pit.
GH function
stimulates linear growth and muscle mass via IGF-1 (somatomedin C)
inc. insulin resistance (diabetogenic)
GHRH stimulates ___
pulsatile release of GH from ant. pit.
secretion of GH ___ during exercise and sleep
inc
inhibitors of GH secretion
glucose
somatostatin release
(via negative feedback by somatomedin)
excess secretion of GH (e.g. pituitary adenoma) causes what in adults? in children?
acromegaly
gigantism
ghrelin function
stimulates hunger (orexigenic effect) and GH release (via GH secretagog receptor
ghrelin production location
stomach
2 causes of increased ghrelin production
sleep loss
Prader-Willi syndrome
leptin function
satiety hormone
dec during starvation
where is leptin produced?
adipose tissue
effect of sleep deprivation on leptin production
decreased
mutation of leptin gene is associated with what?
congenital obesity
andocanabinoids function
stimulate cortical reward centers--->inc desire for high-fat foods
ADH source
synthesized in supraoptic nuclei of hypothalamus
released by post. pit.
ADH function
primary function: dec serum osmolarity, inc urine osmolarity (V2 receptors) via regulation of aquiporin channel insertion in principal cells of CD
secondary: regulation of BP (V1 receptors)
ADH levels in central diabetes insipidus (DI)? nephrogenic DI?
dec
inc
nephrogenic DI can be caused by a mutation in what receptor?
V2
desmopressin acetate is a ___ analog and is used to treat ___
ADH
central DI
adrenal steroids and congenital adrenal hyperplasia:
+ and - regulator of cholesterol desmolase
+ ACTH
- ketoconazole
adrenal steroids and congenital adrenal hyperplasia:
enzyme and location:
cholesterol--->pregnenolone
cholesterol desmolase
zona glomerulosa
products of zona glomerulosa
mineralcorticoids
products of zona fasciculata
glucocorticoids
products of zona reticularis
androgens
adrenal steroids and congenital adrenal hyperplasia:
enzyme and location:
pregnenolone--->progesterone
3beta hydroxysteroid dehydrogenase
zona gomerulosa
adrenal steroids and congenital adrenal hyperplasia:
enzyme and location:
progesterone--->11-deoxycorticosterone
21-hydroxylase
zona glomerulosa
adrenal steroids and congenital adrenal hyperplasia:
enzyme and location:
11-deoxycorticosterone--->corticosterone
11-beta-hydroxylase
zona glomerulosa
adrenal steroids and congenital adrenal hyperplasia:
enzyme and location:
corticosterone--->aldosterone
aldosterone synthase
zona glomerulosa
+ regulator of aldosterone synthase
angiotensin II
adrenal steroids and congenital adrenal hyperplasia:
enzyme and location:
pregnenolone--->17-hydroxyprenenolone
17-alpha-hydroxylase
glomerulosa--->fasciculata
adrenal steroids and congenital adrenal hyperplasia:
enzyme and location:
progesterone--->17-hydroxyprogesterone
17-alpha-hydroxylase
glomerulosa--->fasciculata
adrenal steroids and congenital adrenal hyperplasia:
enzyme and location:
17-hydroxypregnenolone--->17-hydroxyprogesterone
3beta-hyroxysteroid dehydrogenase
zona fasciculata
adrenal steroids and congenital adrenal hyperplasia:
enzyme and location:
17-hyroxyprogesterone--->11-deoxycortisol
21-hydroxylase
zona fasciculata
adrenal steroids and congenital adrenal hyperplasia:
enzyme and location:
11-deoxycortisol--->cortisol
11beta-hydroxylase
zona fasciculata
adrenal steroids and congenital adrenal hyperplasia:
enzyme and location:
12-hydroxypregnenolone--->dehydroepiandrosterone (DHEA)
fasciculata--->reticularis
adrenal steroids and congenital adrenal hyperplasia:
enzyme and location:
17-hydroxyprogesterone--->androstenedione
fasciculata--->reticularis
adrenal steroids and congenital adrenal hyperplasia:
enzyme and location:
DHEA--->androstenedione
3beta-hydroxysteroid dehydrogenase
zona reticularis
adrenal steroids and congenital adrenal hyperplasia:
enzyme and location:
androstenedione--->testosterone
zona reticularis
adrenal steroids and congenital adrenal hyperplasia:
enzyme and location:
androstenedione--->estrone
aromatase
zona reticularis--->peripheral tissues
adrenal steroids and congenital adrenal hyperplasia:
enzyme and location:
testosterone--->estradiol
aromatase
zona reticularis--->peripheral tissues
adrenal steroids and congenital adrenal hyperplasia:
enzyme and location:
testosterone--->dihydrotestosterone (DHT)
5-alpha-reductase
zona reticularis--->peripheral tissues
all congenital adrenal enzyme deficiencies are characterized by enlargement of ___ due to ___
both adrenal glands
inc ACTH stimulation (due to dec cortisol_
adrenal enzyme deficiencies: 17-alpha-hydroxylase:
mineralocorticoids
inc
adrenal enzyme deficiencies: 17-alpha-hydroxylase
cortisol
dec
adrenal enzyme deficiencies: 17-alpha-hydroxylase
sex hormones
dec
adrenal enzyme deficiencies: 17-alpha-hydroxylase
BP
inc
adrenal enzyme deficiencies: 17-alpha-hydroxylase
[K+]
dec
adrenal enzyme deficiencies: 17-alpha-hydroxylase
labs
dec androstenedione
adrenal enzyme deficiencies: 17-alpha-hydroxylase
presentation
XY: pseudohermaphrodism (ambiguous genitalia, undescended testes)
XX: lack secondary sexual development
adrenal enzyme deficiencies: 21-hydroxylase
mineralocorticoids
dec
adrenal enzyme deficiencies: 21-hydroxylase
cortisol
dec
adrenal enzyme deficiencies: 21-hydroxylase
sex hormones
inc
adrenal enzyme deficiencies: 21-hydroxylase
BP
dec
adrenal enzyme deficiencies: 21-hydroxylase
[K+]
inc
adrenal enzyme deficiencies: 21-hydroxylase
labs
inc renin activity
inc 17-hydroxyprogesterone
adrenal enzyme deficiencies: 21-hydroxylase
presentation
most common adrenal enzyme deficiency
presents in infancy (salt wasting) or childhood (precocious puberty)
XX: virilization
adrenal enzyme deficiencies: 11-beta-hydroxylase
mienralocorticoids
dec aldosterone
inc 11-deoxycorticosterone (result: inc BP)
adrenal enzyme deficiencies: 11-beta-hydroxylase
cortisol
dec
adrenal enzyme deficiencies: 11-beta-hydroxylase
sex hormones
inc
adrenal enzyme deficiencies: 11-beta-hydroxylase
BP
inc
adrenal enzyme deficiencies: 11-beta-hydroxylase
[K+]
dec
adrenal enzyme deficiencies: 11-beta-hydroxylase
labs
dec renin activity
adrenal enzyme deficiencies: 11-beta-hydroxylase
presentation
XX: virilization
cortisol
source
adrenal zona fasciculata
bound to corticosteroid-binding globulin
cortisol
function
BIG FIB:
inc BP
inc Insulin resistance (diabetogenic)
dec Glucogenesis, lipolysis, proteolysis
dec Fibroblast activity (causing striae)
dec Inflammatory, Immune responses
dec Bone formation (dec osteoblast activity)
how does cortisol inc BP?
upregulates alpha1 receptors on arterioles--->inc sensitivity to NE, epi
at high conc. can bind to mineralocorticoid (aldosterone) receptors
how does cortisol dec inflammatory and immune responses?
inhibits production of leukotrienes, prostaglandins
inhibits WBC adhesion--->neutrophilia
blocks histamine release from mast cells
reduces eosinophils
blocks IL-2 production
exogenous corticosteroids can cause reactivation of ___ and ___ by blocking IL-2 production
TB
candidiasis
cortisol regulation:
stimulation
CRH (hypothalamus)--->ACTH release (pit)--->cortisol production in z. fasciculata
excess cortisol causes what to happen to CRH?
dec
(= dec ACTH = dec cortisol secretion)
chronic stress does what to cortisol secretion?
induces prolonged secretion
3 forms of plasma calcium
ionized (45%)
bound to albumin (40%)
bound to anions (15%)
affect of inc plasma pH on Ca2+ in plasma
inc affinity of albumin for Ca2+ (inc negative charge)--->hypocalcemia (cramps, pain, parasthesias, carpopedal spasm)
Vit D source
D3 from sun exposure in skin
D2 ingested from plants
vit D3 and D2 are both converted to ___ in liver and ___ in kindey
25-OH (liver)
1,25-OH2 (active form; kidney)
Vit D deficiency causes what in kids? adults?
rickets
osteomlacia
(malabsorption, dec sunlight, poor diet, chronic kidney failure)
Vit D function
inc absorption of dietary Ca2+ and phosphate
inc bone reabsorption--->inc Ca2+ and phosphate
Vit D regulation:
PTH effect
inc PTH = dec [Ca2+], dec phosphate--->inc 1,25OH2 production
Vit D regulation:
effect of 1,25-OH2
feedback inhibition on its own production
24,25-OH2 D3
inactive form of vit D
effect of PTH in kidney
inc Ca2+ and dec phosphate reabsorption
effect of 1,25-OH2 in gut
inc Ca2+ and phosphate absorption
calcium and phosphate homeostasis
diagram
PTH source
chief cells of parathyroid
PTH function
inc bone reabsorption of Ca and Ph
inc kidney reab. of Ca in DCT
dec kindey reab. of Ph on PCT
inc 1,25-OH2 D3 (calcitriol) production (by stimulating kidney 1alpha-hydroxylase in PCT)
inc macrophage CSF and RANK-L
RANK-L
receptor activator of NF-KB ligand)
RANK-L (ligand) is secreted by___ and ____ binds RANK (receptor) on ___ and their precursors to stimulate ___ and inc Ca2+
osteoblasts
octeocytes
osteoclasts
osteoclasts
intermittent PTH release can stimulate ___
bone formation
PTH-related peptide (PTHrP) function and when increased
functions like PTH
increased in many malignancies
PTH regulation:
dec serium Ca2+ =
inc PTH secretion
PTH regulation:
inc serum phosphate =
inc PTH secretion
PTH regulation:
dec serum Mg2+ =
inc PTH secretion
PTH regulation:
big dec serum Mg2+ =
dec PTH production
common causes of Mg2+ decrease
diarrhea
aminoglycosides
diuretics
alcohol abuse
calcitonin source
parafollicular (C) cells of thyroid
calcitonin function
dec bone reabsorption of Ca2+
opposes actions of PTH
not important in normal Ca2+ homeostasis
calcitonin regulation:
inc serum Ca2+ =
calcitonin secretion
signaling pathways of endocrine hormones:
cAMP
FLAT ChAMP:
FSH
LH
ACTH
TSH
CRH
hCG
ADH (V2 receptor)
MSH
PTH
calcitonin
GHRH
glucagon
signaling pathways of endocrine hormones:
cGMP
(think vasodilators)
ANP
BNP
NO
(EDRF)
signaling pathways of endocrine hormones:
IP3
GOAT HAG:
GnRH
Oxytocin
ADH (V1 receptor)
TRH
Histamine (H1 receptor)
Angiotensin II
Gastrin
signaling pathways of endocrine hormones:
intracellular receptor
VETTT CAP:
Vit D
Estrogen
Testosterone
T3/T4
Cortisol
Aldosterone
Progesterone
signaling pathways of endocrine hormones:
intrinsic tyrosine kinase
insulin
IGF-1
FGF
PDGF
EGF
(think growth factors; MAP kinase pathway)
signaling pathways of endocrine hormones:
receptor-associated tyrosine kinase
PIGGlET:
Prolactin
Immunomodulators (e.g. cytokines, IL-2, IL-6, IFN)
GH
G-CSF
Erythropoietin
Thrombopoietin
signaling pathway of steroid hormones
diagram
how to steroid hormones circulate?
are lipophilic, so must be bound to specific binding globulins to inc their solubility
men: inc ____-binding globulin (SHBG) lowers free ___--->gynecomastia
sex hormone
testosterone
in women: dec ____ raises free testosterone, resulting in ____
SHBG
hirstutism
OCPs, pregnancy ____ SHBG levels; free estrogen levels remain ____
SHBG
unchanged
T3/T4 functions
control body's metabolic rate
thyroid hormone source
follicles of thyroid
most T3 formed in target tissues
T3 functions
4 B's:
Brain (CNS) maturation
Bone growth
Beta-adrenergic effects
Basal metabolic rate inc
(inc glycogenolysis, gluconeogenesis, lipolysis)
the bone growth stimulation of thyroid hormones is a result of synergy with what other hormone?
GH
thyroid hormone action on heart
inc beta1 receptors in heart--->
inc CO
inc HR
inc SV
inc contractility
how does T3 increase basal metabolic rate?
inc NA+/K+ ATPase activity--->inc O2 consumption, RR, body temp
what binds most T3/T4 in blood and renders it inactive?
thyroxine-binding globulin (TBG)
only free hormone is active
what results in dec. TBG?
hepatic failure
steroids
what results in inc. TBG?
pergnancy
OCP use
(inc estrogen = inc TBG)
enzyme that converts T4 (the major thyroid product) to T3 in peripheral tissue?
5'-deiodinase
does nuclear receptor have greater affinity for T3 or T4?
T3
what enzyme is responsible for oxidation and organification of iodine, as well as coupling of monoiodotyrosine (MIT) to di-iodotyrosine (DIT)?
peroxidase
what inhibits both peroxidase and 5'-deiodinase?
propylthiouracil
methimazole inhibits peroxidase in what pathway?
oxidation and organification of iodine, as well as coupling of monoiodotyrosine (MIT) to di-iodotyrosine (DIT)
thyroid hormone regulation
(+)
TRH (hypothalamus)-->TSH (pituitary)-->stimulation of follicular cells of thyroid
thyroid hormone regulation
(-)
free T3/T4--->acts on ant pit to dec sensitivity to TRH
thyroid-stimulating Igs (e.g. TSH) stimulate follicular cells in what diseases (an example)?
Graves disease
Wolff-Chaikoff effect
excess iodine temporarily inhibits thyroid peroxidase---> dec iodine organification--->dec T3/T4 production
anions that have a negative regulatory effect on iodine oxidation to I2 in the thyroid
perchlorate
pertechnetate
thiocyanate
Cushing syndrome
etiology
inc cortisol due to variety of causes:
1. exogenous corticosteroids
2. primary adrenal adenoma, hyperplasia, carcinoma
3. pseudohyperaldosteronism
4. ACTH-secreting pituitary adenoma (Cushing disease)
5. paraneoplastic ACTH secretion (e.g. small cell lung cancer, bronchial carcinoids)
what is responsible for the majority of endogenous cases of Cushing syndrome?
Cushing disease (ACTH-secreting pituitary adenoma)
how do exogenous corticosteroids cause Cushing syndrome?
dec ACTH, bilateral adremal atrophy
most common cause of Cushing syndrome
exogenous corticosteroids
how do primary adrenal ademona, hyperplasia, carcinoma, and pseudohyperaldosteronism cause Cushing syndrome?
dec ACTH-->atrophy of uninvolved adrenal gland
how do Cushing disease (ACTH-secreting pituitary adenoma) and paraneoplastic ACTH secretion result in Cushing syndrome?
inc ACTH--->bilateral adrenal hyperplasia
Cushing syndrome findings
hypertension
weight gain
moon facies
truncal obesity
buffalo hum
skin changes (thinning, striae)
osteoporosis
hyperglycemia (insulin resistance)
amenorrhea
immunosuppression
Cushing syndrome diagnosis:
screening tests
inc free cortisol on 24-hr urinalysis
inc midnight salivary cortisol
no suppression with overnight low-dose dexamethasone test
Cushing syndrome diagnosis:
what to suspect if ACTH is dec
adrenal tumor
Cushing syndrome diagnosis:
what to suspect if ACTH is inc
Cushing disease or ectopic ACTH secretion
tests used to distinguish Cushing disease from ectopic ACTH secretion
1. high-dose (8mg) dexamethasone suppression test
2. CRH stimulation test
Cushing syndrome diagnosis:
if ACTH is not decreased with high-dose (8mg) dexamethasone test___
ectopic ACTH secretion
(source is resistant to negative feedback)
Cushing syndrome diagnosis:
if ACTH is not increased with CRH stimulation test ___
ectopic ACTH secretion
(pituitary ACTH is suppressed)
adrenal insufficiency
inability of adrenal glands to generate enough mineralo- +/- glucocorticoids
adrenal insufficiency symptoms
weakness
fatigue
orthostatic hypotension
muscle aches
weight loss
GI disurbances
sugar and/or salt cravings
adrenal insufficiency diagnosis
measurement of serum electrolytes
morning/random serum cortisol and ACTH
response to ACTH stimulation test
metyrapone stimulation test
for adrenal insufficiency diagnosis
metyrapone blocks last step of cortisol synthesis (11-deoxycortisol-->cortisol)
normal: dec cortisol, compensatory inc ACTH
+: ACTH remains dec after test
primary adrenal insufficiency
loss of gland function = dec aldosterone and cortisol--->hypotension (hyponatremic vol contraction), hyperkalemia, metabolic acidosis, skin/mucosal hyperpigmentation
what causes hyperpigmentation of skin/mucosa in primary adrenal insufficiency?
MSH, a byproduct of inc ACTH production from pro-opiomelanocortin
primary adrenal insufficiency
acture
sudden onset (e.g. due to massive hemorrhage)
may present with sock and acute adrenal crisis
primary adrenal insufficiency
most common cause in Western worls
autoimmunity
esp. associated with autoimmune polyglandular syndromes
primary adrenal insufficiency
chronic
aka - Addison disease
Addison disease
chronic primary adrenal insufficiency
due to adrenal atrophy or destruction due to disease (e.g. autoimmune, TB, metastasis)
Waterhouse-Friderichsen syndrome
acute primary adrenal insufficiency due to adrenal hemorrhage associated with septicemia (usually N. meningitidis), DIC, endotoxic shock
secondary adrenal insufficiency
dec pituitary ACTH production
no skin/mucosal hyperpigmentation
no hyperkalemia (aldosterone synthesis preserved)
tertiary adrenal insufficiency
in patients with chronic exogenous steroid use, precipitated by abrupt withdrawal
aldosterone synthesis unaffected
neuroblastoma
most common adrenal tumor in children <4yo
originates in neural crest cells
Homer-Wright rosettes characteristic
occurs anywhere along sympathetic chain
neuroblastoma presentation
abdominal distension with firm, irregular mass that can cross midline (vs. Wilms tumor - smooth and unilateral)
opsoclonus-myoclonus syndrome (dancing eyes-dancing feet)
bombesin and neuron-specific enolase +
there is an increased presence of what in urine associated with a neuroblastoma?
1. homovanillic acid (HVA; product of dopamine breakdown)
2. vanillylmandelic acid (VMA); NE breaskdown product)
neuroblastoma is associated with overexpression of what gene?
N-myc oncogene
neuroblastoma is associated with decreased likelihood to develop what?
hypertension
pheochromocytoma
etiology
most common tumor of adrenal gland in adults
derived from chromaffin cells (arise from neural crest)
rule of 10s
pheochromocytoma
etiology: rule of 10s
10% malignant
10% bilateral
10% extra-adrenal
10% calcify
10% kids
pheochromocytoma
symptoms
most tumors secrete epi, NE, dopamine-->episodic hypertension
associated with neurofibromatosis type 1, von Hippel Lindau disease, MEN 2a,2B,
symptoms occur in spells
episodic hyperadrenergic symptoms
pheochromocytoma
episodic hyperadrenergic symptoms
5 Ps:
Pressure (in BP)
Pain (headache)
Perspiration
Palpitations (tachycardia)
Pallor
pheochromocytoma
findings
inc catecholamines and metanephrines in urine and plasma
pheochromocytoma
treatment
irreversible alpha-agonists (e.g. phenoxybenzamine) followed by beta-blockers prior to tumor resection
(must be alpha then beta to avoid hypertensive crisis)
hypothyroidism
signs/symptoms
cold intolerance (dec heat production)
weight gain, dec appetite
hypoactivity, lethargy, fatigue, weakness
constipation
dec reflexes
myxedema (facial, periorbital)
dry, cool skin; coarse, brittle hair
bradycardia, dyspnea on exertion
hypothyroidism
lab findings
inc TSH (sensitive test for primary hypothyroidism)
dec free T3, T4
hypercholesterolemia (dec LDL receptor expression)
hyperthyroidism
signs/symptoms
heat intolerance (inc heat production)
weight loss, inc appetite
hyperactivity
diarrhea
inc reflexes
pretibial myxedema (Graves disease); periorbital edema
warm, moist skin; fine hair
chest pain, palpitations, arrhythmias
inc #/sensitivity of beta-adrenergic receptors
hyperthyroidism
lab findings
dec TSH (if primary)
inc free or total T3, T4
hypocholesterolemia (inc LDL receptor expression)
hypothyroidism: Hashimoto thyroiditis
most common cause of hypothyroidism in iodine-deficient regions
autoimmune (anti-thyroid peroxidase, antimicrosomal, antithyroglobulin Abs)
associated with HLA-DR5 and inc risk non-Hodgkin lymphoma
may be hyperthyroid early due to thyrotoxicosis during follicular rupture
hypothyroidism: Hashimoto thyroiditis
histologic findings
Hurthle cells
lymphoid aggregate with germinal centers
hypothyroidism: Hashimoto thyroiditis
findings
moderately enlarged, nontender thyroid
hypothyroidism: congenital (cretinism)
severe fetal hypothyroidism due to maternal hyperthyroidism, thyroid agenesis, thyroid dysgenesis (most common cause in US), I deficiency, dyshormonogenetic disorder
hypothyroidism: congenital (cretinism)
findings
6 P's:
Pot-bellied
Pale
Puffy-faced child
Protruding umbilicus
Protuberant tongue
Poor brain development
hypothyroidism: subacute thyroiditis (de Quervain)
self-limiting
follows flu-like illness
may be hyperthyroid early in course
hypothyroidism: subacute thyroiditis (de Quervain)
histology
granulomatous inflammation
hypothyroidism: subacute thyroiditis (de Quervain)
findings
inc ESR
jaw pain
early inflammation
tender thyroid
hypothyroidism: Riedel thyroiditis
thyroid replaced by fibrous tissue (hypothyroid), which may extend to local structures (e.g. airway)
mimics anaplastic carcinoma
is a manifestation of IgG4-related systemic disease (e.g. autoimmune pancreatitis, retroperitoneal fibrosis, noninfectious aortitis)
hypothyroidism: Riedel thyroiditis
findings
fixed, hard (rock-like), painless goiter
hypothyroidism: other causes
iodine insufficiency
goitrogens
Wolff-Chaikoff effect (thyroid gland downregulation due to inc iodine)
hyperthyroidism: most common cause
Graves disease
hypertyroidism: Graves disease
IgG stimulates TSH receptors on...
1. thyroid (hyperthyroidism and diffuse goiter)
2. retro-orbital fibroblasts (exophthalmos proptosis, extraocular muscle swelling)
3. dermal fibroblasts 9pretibial myxedema)
often presents during stress (e.g. childbirth)
hyperthyroidism: toxic multinodular hoiter
focal patches of hyperfunctioning follicular cells working indepenedently of TSH (mutated TSH receptor)
inc T3, T4 release
hot nodules are rarely malignant
hyperthyroidism: thyroid storm
stress-induced catecholamine surge as serious complication of thyrotoxicosis due to disease and o/ hyperthyroid disorders
thyroid storm presentation
agitation
delirium
fever
diarrhea
coma
tachyarrhythmia (cause of death)
inc ALP due to inc bone turnover
thyroid storm treatment
3 P's:
beta-blockers (e.g. Propranolol)
Propylthiouracil
corticosteroids (e.g. Prenisone)
hyperthyroidism: Jod-Basedow phenomenon
thyrotoxicosis if patient with iodine defiency goiter is made iodine replete
thyroidectomy is an option for___
thyroid cancer and hyperthyroidism
complications of thyroidectomy
hoarseness (recurrent laryngeal nerve damage)
hypocalcemia (parathyroid gland removal)
transection of recurrent and superior laryngeal nerves (during ligation of inferior thyroid artery and superior laryngeal artery, respectively)
papillary carcinoma
most common thyroid cancer; excellent prognosis
empty-appearing nuclei with central clearing (Orphan Annie eyes)
psammoma bodies
nuclear grooves
lymphatic invasion common
inc risk w/ childhood radiation, RET and BRAF mutations
follicular carcinoma
thyroid cancer w/ excellent prognosis
invades capsule (unlike follicular adenoma)
uniform follicles
medullary carcinoma
a thyroid cancer
from parafollicular "C" cells--->produces calcitonin, sheets of cells in an amyloid stroma
hematogenous spread common
associated with MEN 2A and 2B (RET mutations)
undifferentiated/aplastic carcinoma of thyroid
older patients
local structures
very poor prognosis
lymphoma of thyroid
associated with Hashimoto thyroiditis
hypoparathyroidism
diagram
hypoparathyroidism causes
accidental surgical excision
autoimmune destruction
DiGeorge syndrome
hypoparathyroidism findings
hypocalcemia
tetany
Chvostek sign
Trousseau sign
Chvostek sign
tapping facial nerve (tap Cheek) -->facial muscle contraction
Trousseau sign
occlusion of brachial artery with BP cuff--->carpal spasm
pseudohypoparathyroidism
aka - Albright hereditary osteodystrophy
unresponsiveness to kidney PTH
hypocalcemia, shortened 4th/5th digits, short stature
AD
familial hypocalciuric hypercalcemia
defective Ca2+-sensing receptor on parathyroid cells
PTH cannot be suppressed by inc [Ca2+]---->mild hypercalcemia with normal/inc PTH levels
PTH and Ca2+ pathologies:
low calcium, low PTH
hypoparathyroidism
PTH and Ca2+ pathologies:
low calcium, high PTH
secondary hyperparathyroidism
(Vit D deficiency, chronic renal failure)
PTH and Ca2+ pathologies:
high calcium, low PTH
PTH-independent hypercalcemia
(excess Ca2+ ingestion, cancer)
PTH and Ca2+ pathologies:
high calcium, high PTH
primary hyperparathyroidism
(hyperplasia, adenoma, carcinoma)
hyperparathyroidism: primary
causes
parathyroid adenoma or hyperplasia
hyperparathyroidism: primary
presentation
hypercalcemia
hypercalciuria (renal stones)
hypophosphatemia
inc PTH
inc ALP
inc cAMP in urine
weakness and constipation
abdominal/flank pain (kidney stones, acute pancreatitis)
depression
osteoitis fibrosa cystica
cystic bone spaces filled with fibrous brown tissue
("brown tumor of deposited hemosiderin from hemorrhages; bone pain)
associated with primary hyperparathyroidism
hyperparathyroidism: secondary
causes

Add...
secondary hyperplasia due to dec Ca2+ absorption or inc phosphate
most often chronic renal disease (causes hypovitaminosis D-->dec Ca2+ absorption)
hyperparathyroidism: secondary
presentation
hypocalcemia
hyperphosphatemia in chronic renal failure (hypophasphatemia in most other causes)
inc ALP
inc PTH
renal osteodystrophy
one lesions due to secondary or tertiary hyperparathyroidism (mainly due, in turn, to renal disease)
pituitary adenoma
most commonly benign prolactoma
adenoma may be hormone-producing (functional) or silent (non-functional)
presentation of nonfunctional tumors associated with pituitary adenoma
mass effect (bitemporal hemianopia, hypopituitarism, headache)
presentation of functional tumors associated with pituitary adenoma
based on hormone produced, e.g.:
1. prolactinoma: amenorrhea, galactorrhea, low libido, infertility
2. somatotropic adenoma: acromegaly
hyperparathyroidism: tertiary
refractory (autonomous)
resulting from chronic renal disease
big inc PTH
inc Ca2+
acromegaly
excess GH in adults
gigantism
excess H in children
inc linear bone growth
most common cause of death associated with gigantism
HF
acromegaly
findings
large tongue with deep furrows
deep voice
large hands, feet
coarse facial features
impaired glucose toelrance (insulin resistance)
increased risk colorectal polyps, cancer
acromegaly
diagnosis
inc serum IGF-1
failure to suppress serum GH following oral glucose tolerance test
pituitary mass on brain MRI
acromegaly
treatment
resection of pituitary adenoma
of not cured: octreotide (somatostatin analog) or pegvisomant (GH receptor antagonist)
diabetes insipidus characteristics
intense thirst
polyuria
inability to concentrate urine
lack of ADH (central) or failure to respond to circulating ADH (nephrogenic)
central DI:
etiology
pituitary tumor
autoimmune
trauma
surgery
ischemic encephalopathy
idiopathic
central DI:
findings
dec ADH
urine SG < 1.006
serum osmolality: >290 mOsm/kg
hyperosmotic volume contraction
central DI:
water deprivation test
>50% inc in urine osmolality only after ADH analog administration
central DI:
treatment
intranasla desmopressin acetate
hydration
water deprivation test
for diagnosis of DI
no water intake 2-3 hours followed by hourly measurements of uring vol/oslmolarity and plasma Na+ conc. and osmolarity
if normal values are not clearly reached: administer ADH analog (desmopressin acetate)
nephrogenic DI:
etiology
hereditary (ADH receptor mutation)
secondary to hypercalcemia, lithium, demeclocycline (ADH antagonist)
nephrogenic DI:
findings
normal ADH levels
urine SG< 1.006
serum osmolality > 290 mOsm/kg
hyperosmotic volume contraction
nephrogenic DI:
water deprivation test
minimal change in urine osmolality, even after administration of ADH analog
nephrogenic DI:
treatment
HCTZ, indomethacin, amiloride
hydration
SIADH
syndrome of inappropriate ADH secretion:
excessive water retention
euvolemic hyponatremia with continued urinary Na+ excretion
urine osmolality > serum osmolality
SIADH causes
extopic ADH (e.g. small cell lung cancer)
CNS disorders/head trauma
pulmonary disease
drugs (e.g. cyclophosphamide)
SIADH treatment
fluid restriction
IV hypertonic saline
conivaptan
tolvaptan
demeclocycline
SIADH:
body response to the abnormal ADH secretion and consequences of response
dec aldosterone (hyponatremia) to maintain near-normal volume
--->cerebral edema, seizures
SIADH
correct slowly or quickly? why?
slowly
need to prevent osmotic demyelination syndrome (aka central pontine myelinosis)
hypopituitarism causes
nonsecreting pituitary adenoma
craniopharyngioma
Sheehan syndrome
Empty Sella syndrome
Pituitry Apoplexy
brain injury
radiation
hypopituitarism treatment
hormone replacement therapy:
corticosteroids
thyroxine
sex steroids
human GH
Sheehan syndome
ischemic infarct of pituitary following postpartum bleeding
failure to lactate, absent menstruation, cold intolerance
(cause of hypopituitarism)
empty sella syndrome
atrophy or compression of pituitary
often idiopathic
common in obese women
(cause of hypopituitarism)
pituitary apoplexy
sudden hemorrhage of pituitary, often in presence of existing pituitary adenoma
(cause of hypopituitarism)
acute manifestations of diabetes mellitus
diagram
maifestations of diabetes mellitus
polydipsia
polyuria
polyphagia
weight loss
DKA (type I)
hyperosmolar coma (type 2)
rarely: unopposed GH and epi secretion
what two conditions may cause unopposed secretion of GH and epi?
diabetes mellitus (rarely)
glucocorticoid therapy (steroid diabetes)
chronic complications of diabetes mellitus:
nonenzymatic glycation
1. small vessel disease --->retinopathy (hemorrhage, exudates, microaneurysms, vessel proliferation), glaucoma, neuropathy, nephropathy
2. large vessel atherosclerosis, CAD, peripheral vascular occlusive disease, angrene--->limb loss, cerebrovascular disease--->MI/death (most commonly)
nephropathy due to diabetes mellitus causes____
nodular goleruloscerosis (Kimmelsteil-Wilson nodules)--->progressive proteinuria and atherosclerosis--->hypertension and chronic renal failure
diabetes mellitus diagnosis
fasting serum glucose
oral glucose tolerance test
HbA1c (reflects average blood glucose over prior 3 months)
Diabetes mellitus: type 1 vs. type 2:
primary defect
1. autoimmune beta cell dstruction
2. increased insulin resistance; progressive pancreatic beta cell failure
Diabetes mellitus: type 1 vs. type 2:
insulin necessary for treatment?
1. always
2. sometimes
Diabetes mellitus: type 1 vs. type 2:
age (exceptions common)
1. <30 yrs
2. >40 yrs
Diabetes mellitus: type 1 vs. type 2:
obesity association?
1. no
2. yes
Diabetes mellitus: type 1 vs. type 2:
genetic predisposition
1. weak (50% concordance w/ identical twins); polygenic
2. strong (90% " "), polygenic
Diabetes mellitus: type 1 vs. type 2:
association w/ HLA system
1. yes (HLA-DR3, -DR4)
2. no
Diabetes mellitus: type 1 vs. type 2:
glucose intolerance
1. severe
2. mild-moderate
Diabetes mellitus: type 1 vs. type 2:
insulin sensitivity
1. high
2. low
Diabetes mellitus: type 1 vs. type 2:
ketoacidosis
1. common
2. rare
Diabetes mellitus: type 1 vs. type 2:
beta cell #s in islets
1. dec
2. variable (with amyloid deposits)
Diabetes mellitus: type 1 vs. type 2:
serum insulin level
1. dec
2. variable
Diabetes mellitus: type 1 vs. type 2:
classic symptoms (polyuria, polydipsia, polyphagia, weight loss)
1. common
2. sometimes
Diabetes mellitus: type 1 vs. type 2:
histology
1. islet leukocytic infiltrate
2. islet amyloid polypeptide (IAPP) deposits
diabetic ketoacidosis
causes
inc insulin requirements from inc stress (e.g. infection)
excess fat breakdown, ketogenesis from inc FAs--->ketone bodies
usually type 1 diabetes (endogenous insulin in type 2 prevents lipolysis usually)
ketone bodies
beta-hydroxybutyrate
acetoacetate
diabetic ketoacidosis
signs/symptoms
Kussmaul respirations (rapid, deep breathing)
nausea/vomiting
abdominal pain
psychosis/delirium
dehydration
fruity breath odor (due to exhaled acetone)
diabetic ketoacidosis
labs
hyperglycemia
inc H+
dec HCO3- (inc anion gap metabolic acidosis)
inc blood ketone levels
leokocytosis
kyperkalemia (depleted intracellular K+ due to shift from dec insulin; so total body is actually K+ depleted)
diabetic ketoacidosis
complications
life-threatening mucormycosis (usually Thizopus infection)
cerebral edema
cardiac arrhythmias
HF
diabetic ketoacidosis
treatment
IV fluids
IV insulin
K+ (to replete intracellular stores)
glucose if necessary to prevent hypoglycemia
glucagonoma (cause and signs/symptoms)
tumor of pancreatic alpha cells--->
glucagon overproduction
dermatitis (necrolytic migratory erythema), diabetes (hyperglycemia), DVT, depression
insulinoma
tumor of pancreatic beta cells-->insulin overproduction--->hypoglycemia
may see Whipple triad
dec. blood glucose, inc C-peptide levels (vs. exogenous insulin use)
Whipple triad
1. low blood glucose
2. symptoms of hypoglycemia (e.g. lethargy, syncope, diplopia)
3. resolution of symptoms after normalization of glucose levels
insulinoma treatment
surgical resection
carcinoid syndrome
causes
caused by carcinoid tumors (neuroendocrine cells), esp metastatic bowel tumors, which secrete hig levels of serotonin (5-HT)
not seen if tumor is only in GI tract (5-HT undergoes first-pass metabolism in liver)
carcinoid syndrome
presentation
recurrent disrrhea
cutaneous flushing
asthmatic wheezing
right-sided valvular disease
inc 5-hydroxyindoleacetic acid (5-HIAA) in urine
niacin deficiency (pellagra)
carcinoid syndrome treatment
surgical resection
somatostatin analog (e.g. octreotide)
most common malignancy of SI
carcinoid syndrome
carcinoid syndrome:
rule of 1/3s
1/3 metastasize
1/3 present with 2nd malignancy
1/3 are multiple
Zollinger-Ellison syndrome
gastrin-secreting tumor (gastrinoma) of pancreas or duodenum
acid hypersecretion--->recurrent ulcers in duodenum, jejunum
abdominal pain (peptic ulcer disease, distal ulcers)
darrhea (malabsorption)
+ secretin stimulation test
may be associated with MEN-1
secretin stimulation test
for Zollinger-Ellison syndomre
+ if gastrin levels remain elevated after secretin administration (normally inhibits gastrin release)
multiple endocrine neoplasias (MEN) inheritance
AD
MEN-1
characteristics
3 P's:
Parathyroid tumors
Pituitary tumors (prolactin or GH)
Pancreatic endocrine tumors (Zollinger-Ellison syndrome, insulinomas, VIPomas, glucagonomas (rare)
MEN1 gene mutation
MEN1 gene function
menin (tumor suppressor) encoded
MEN2A
characteristics
2P's:
Parathyroid hyperplasia
Pheochromocytoma
medullary thyroid carcinoma (secretes calcitonin)
RET gene mutation (tyrosine kinase receptor)
MEN2A and 2B are associated with ___
marfanoid habitus
MEN2B
characteristics
1 P:
Pheochromocytoma
medullary thyroid carcinoma (secretes calcitonin)
oral/intestinal ganglioneuromatosis (mucosal neuromas)
RET gene mutation (tyrosine kinase receptor)
MEN 2A vs 2B
(medullary thyroid cancer at center of both shapes)
diabetes treatment:
type 1
low-carb diet
insulin replacement
diabetes treatment:
type 2
dietary modification and exercise for weight loss
if lifestyle changes fail: insulin replacement
diabetes treatment:
gestational diabetes mellitus (GDM)
dietary modifications
exercise
insulin replacement if lifestyle changes fail
insulin preparations: rapid acting
examples
aspart
glulisine
lispro
insulin preparations: rapid acting
action
binds insulin receptor (tyrosine kinase activity)
Liver: inc glucose stored as glycogen
Muscle: inc glycogen, protein synthesis, K+ uptake
Fat: TG storage
insulin preparations: rapid acting
clinical use
type 1 DM
type 2 DM
DM (postprandial glucose control)
insulin preparations: rapid acting
toxicities
hypoglycemia
rare hypersensitivity rxn
insulin preparations: short acting (regular)
clinical use
type 1 DM
type 2 DM
GDM
DKA (IV)
hyperkalemia (+glucose)
stress hyperglycemia
insulin preparations: intermediate acting (NPH)
clinical use
type 1 DM
type 2 DM
GDM
insulin preparations: long acting
examples
detemir
glargine
insulin preparations: long acting
clinical use
type 1 DM
type 2 DM
GDM (basal glucose control)
oral hypoglycemia drugs: biguanides
examples
metformin
oral hypoglycemia drugs: biguanides
acting
exact mechanism unknown
dec gluconeogenesis
inc glycolysis
inc peripheral glucose uptake
(inc insulin sensitivity)
oral hypoglycemia drugs: biguanides
clinical use
oral
first-line therapy in type 2 DM
causes modest weight loss
can be used in pts without islet function
oral hypoglycemia drugs: biguanides
toxicities
GI upset
lactic acidosis (contraindicated in renal insufficiency; most serious side-effect)
oral hypoglycemia drugs: sulfonylureas
examples
First generation: chloropropamide, tolbutamide
Second generation: glimepiride, glipizide, glyburide
oral hypoglycemia drugs: sulfonylureas
action
close K+ channel in beta cell membrane--->depolarization--->insulin release via inc Ca2+ influx
oral hypoglycemia drugs: sulfonylureas
clinical use
stimulate release of endogenous insulin in type 2 DM
cannot be used for type 1 DM because some islet cell function is required
oral hypoglycemia drugs: sulfonylureas
toxicities
risk of hypoglycemia inc in renal failure
1st generation: disulfiram-like effects
2nd generation: hypoglycemia
oral hypoglycemia drugs: glitazones/thiazolidinediones:
examples
piolitazone
rosiglitazone
oral hypoglycemia drugs: glitazones/thiazolidinediones:
action
inc insulin sensitivity in peripheral tissue
binds PPAR-gamma nuclear transcription regulator
oral hypoglycemia drugs: glitazones/thiazolidinediones:
clinical use
monotherapy for type 2 DM or combined with biguanides/sulfonylureas
oral hypoglycemia drugs: glitazones/thiazolidinediones:
toxicity
weight gain
edema
hepatotoxicity
HF
inc fracture risk
PPAR-gamma genes encode transcription factors that activate genes for ___
FA storage
glucose metabolism
PPAR-gamma activation causes inc ___ sensitivity and inc levels of ___
insulin
adiponectin
oral hypoglycemia drugs: GLP-1 analogs
examples
exenatide
liraglutide
oral hypoglycemia drugs: GLP-1 analogs
action
dec insulin relase
inc glucagon release
oral hypoglycemia drugs: GLP-1 analogs
clinical use
type 2 DM
oral hypoglycemia drugs: GLP-1 analogs
toxicities
nausea
vomiting
pancreatitis
oral hypoglycemia drugs: DPP-4 inhibitors
examples
linagliptin
sexagliptin
sitagliptin
oral hypoglycemia drugs: DPP-4 inhibitors
action
inc insulin release
dec glucagonrelease
oral hypoglycemia drugs: DPP-4 inhibitors
clinical use
type 2 DM
oral hypoglycemia drugs: DPP-4 inhibitors
toxicities
mild urinary or respiratory infections
oral hypoglycemia drugs: amylin analogs
example
pramlinitide
oral hypoglycemia drugs: amylin analogs
action
dec gastric emptying
dec glucagon
oral hypoglycemia drugs: amylin analogs
clinical use
types 1 and 2 DM
oral hypoglycemia drugs: amylin analogs
toxicities
hypoglycemia
nausea
diarrhea
oral hypoglycemia drugs: SGLT-2 inhibitors
example
canagliflozin
oral hypoglycemia drugs: SGLT-2 inhibitors
action
block glucose reabsorption in PCT
oral hypoglycemia drugs: SGLT-2 inhibitors
clinical use
type 2 DM
oral hypoglycemia drugs: SGLT-2 inhibitors
toxicities
glucosuria
UTIs
vaginal yeast infections
oral hypoglycemia drugs: alpha-glucosidase inhibitors
examples
acarose
miglitol
oral hypoglycemia drugs: alpha-glucosidase inhibitors
action
inhibit brush border alpha-glucosidases
delayed carb hydrolysis and glucose absortion---> dec postprandial hyperglycemia
oral hypoglycemia drugs: alpha-glucosidase inhibitors
clinical use
monotherapy for type 2 DM or combined with other oral hypoglycemic drugs
oral hypoglycemia drugs: alpha-glucosidase inhibitors
toxicities
GI disturances
propylthiouracil, methimazole:
mechanism
block thyroid peroxidase-->I oxidation/organification (coupling) inhibited--->inhibition of thyroid hormone synthesis
propylthiouracil also blocks 5'-deiodinase--->dec T4 to T3 conversion in peripheral tissues
propylthiouracil, methimazole:
clinical use
hyperthyroidism
propylthiouracil used in pregnancy
propylthiouracil, methimazole:
toxicities
skin rash
agranulocytosis (rare)
aplastic anemia
hepatotoxicity (propylthiouracil)
teratogen (methimazole; aplasia cutis)
levothyroxine (T4), triiodothyronine (T3):
mechanism
thyroid hormone replacement
levothyroxine (T4), triiodothyronine (T3):
clinical use
hypothyroidism
myxedema
used off-label as weight-loss supplements
levothyroxine (T4), triiodothyronine (T3):
toxcitity
tachycardia
heat intolerance
tremors
arrhythmias
hypothalamic/pituitary drugs: ADH agonists
examples
conivaptan
tolvaptan
hypothalamic/pituitary drugs: ADH agonists
clinical use
SIADH
block action of ADH at V2 receptor
hypothalamic/pituitary drugs: desmopressin acetate
clinical use
central (not nephrogenic) DI
hypothalamic/pituitary drugs: GH
clinical use
GH deficiency
Turner syndrome
hypothalamic/pituitary drugs: oxytocin
clinical use
stimulates labor, uterine contractions, milk let-down
controls uterine hemorrhage
hypothalamic/pituitary drugs: somatostatin (octreotide)
clinical use
acromegaly
carcinoid syndrome
gastrinoma
glucagonoma
esophageal varices
demeclocycline:
mechanism
ADH antagonist (member of tetracycline family)
demeclocycline:
clinical use
SIADH
demeclocycline:
toxicity
nephrogenic DI
photosensitivity
bone/teeth abnormalities
glucocorticoids:
examples
beclomethasone
dexamethasone
fludrocortisone (also has mineralcorticoid activity)
hydrocortisone
methylprednisone
prednisone
triamcinolone
glucocorticoids:
mechanism
metabolic, catabolic, anti-inflammatory, immunosuppresive effects mediated by interactions w/ glucocorticoid response elements
phospholipase A2 inhibition
inhibition of transcription factors such as NK-kB
glucocorticoids:
clinical use
Addison disease
inflammation
immunosuppression
asthma
glucocorticoids:
toxicity
Iatrogenic Cushing syndrome
adrenalcortical atrophy
peptic ulcers
steroid diabetes
steroid psychosis
adrenal insufficiency (when drug stopped abruptly after chronic use)
presentation of Iatrogenic Cushing syndrome
hypertension
weight gain
moon facies
truncal obesity
buffalo hump
thinning of skin
striae
osteoporosis
hyperglycemia
amenorrhea
immunosuppression
cinacalcet:
mechanism
sensitizes Ca2+-sensing receptor (CaSR) in parathyroid gland to circulated Ca2+ ---> dec PTH
cinacalcet
clinical use
hypercalcemia due to primary or secondary hyperparathyroidism
cinacalcet
toxicity
hypocalcemia
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