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Endocrinology

STUDY
PLAY
features of polypeptide/protein hormones
large >500kDa
hydrophilic
circulate unbound
Serum T1/2 = minutes
receptors on cell surfaces
second messengers that alter activity of other molecules within cells
examples of polypeptide/protein hormones
LH, FSH, catecholamines, ACTH, TSH, prolactin, GH, GHRH, CRH, GnRH, AVP, PTH, VIP, glucagon, insulin, somatostatin, IGF-I
features of steroid/thyronine hormones
small <500kDa
hydrophobic
circulate bound to proteins
serum T1/2 = hours
receptors are located in the cytoplasm and nucleus
have direct nuclear action
examples of steroid hormones
testosterone, E2 (estrogen), progesterone, T4, T3, cortisol, aldosterone, vitamin D, thyroxine
the endocrine organs are
hypothalamus
pituitary gland
thyroid gland
parathyroid gland
pancreas
adrenal glands
testes/ovaries
this endocrine organ is considered the control center of the other endocrine organs
the hypothalamus
describe the negative feedback system
high levels of a hormone DECREASE hormone synthesis and secretion
low levels STIMULATE
describe the positive feedback system
high levels of a hormone STIMULATE, low levels INHIBIT
what happens to cell receptors if excess hormones are present
the receptors are down-regulated
the decreases receptor availability decreases the target tissue response to the excess hormone
what happens if the circulating hormone is depleted
the receptors are up-regulated
the increased receptor availability increases the likelihood of target tissue response
in primary hyper/hypo-function...
the alteration is in the function of a hormone-secreting gland
in secondary hyper/hypo-function...
the alteration is in pituitary or hypothalamic function
ectopic hyper/hypo-function
a hormone is secreted from a tissue other than its usual source
adenoma
benign enlargement of a cluster of cells
neoplasm
abnormal new growth of tissue: generally considered MALIGNANT
hyperplasia
benign enlargement of the entire gland
the pituitary gland is
an extension of hypothalamic neurons
what do hypothalamic nuclei synthesize
ADH & Oxytocin
where are ADH and Oxytocin synthesized
in the hypothalamus
where are ADH and Oxytocin stored
in the posterior pituitary
ADH is also known as
AVP - arginine vasopressin
what is the neurohypophysis
the posterior pituitary
how does ADH maintain water balance
inhibits diuresis
where does ADH act
on renal tubules (increases permeability @ collecting ducts) to cause water reabsorption -> urinary concentration
what regulates ADH secretion
osmoreceptors in the hypothalamus (detects osmolality of blood)
atrial & carotid barorecptors (detects circulating blood volume)
what hormones stimulate ADH secretion
angiotensin II, epi, cortisol, estrogen, progesterone
what inhibits the secretion of ADH
alcohol EtOH
what drugs stimulate the secretion of ADH
hydrochlorothiazide(HCTZ), chlorpropamide, morhine, propanolol, barbituates, nicotine, oxytocin, carbamazapine(tegretol)
stimuli for the secretion of ADH
hemoconcentration
hypovolemia/hypotention
increasing temoerature
nausea/vomiting
hormones
drugs
what is the thresh-hold for ADH release and thirst stimulation
plasma osmolality >285 osm/L
normal osmolality 275 - 300 osm/L
a differential diagnosis for a patient with polyuria should include
diabetes mellitus (DM)
Cushing's syndrome
glucocorticoid therapy (corticosteroid use)
psychogenic polydypsia
nocturnal polyuria of Parkinson's disease
lithium use
diabetes insipidus (DI)
hypercalcemia
pt presents with excess urine volume >2L/day w/low specific gravity (decreased osmolality)
intense polydipsia - fluid intake of 2-20L/day
may have hypernatremia, dehydration, hypotension, vascular collapse
diabetes insipidus
when ADH is not present or inactive where can water not be conserved
the distal collecting tubules
causes of central DI (diabetes insipidus) include
hypothalamic or pituitary surgery
trauma to pituitary stalk
infections (encephalitis, syphilis, TB)
tumors of the pituitary or metastases to the pituitary
pituitary infarction (postpartum hemorrhage - Sheehan's syndrome)
pituitary inflammation (autoimmune hypophysitis)
causes of nephrogenic DI include
medications; lithium, demeclocycline, methicilin, foscarnet, EtOH, caffiene
chronic renal disease
pyelonephritis
hypokalemia
chronic hypercalcemia
sickle cell anemia
myeloma
what should you suspect in patients with persistent urinary incontinence/bedwetting
partial DI
symptoms are less intense
what tests will aid in the diagnosis of diabetes insipidus
plasma and urine osmolality
water deprivation test
24 hour urine- volume, glucose creatinine,osmolality
serum- glucose, BUN, calcium, uric acid, sodium, potassium, creatinine, osmolality
history and physical
how do you preform the Vasopressin Challenge Test
1.measure urine volume 12hrs prior to admin of dDAVP
2.give dDVAP- IV, SubQ, or intranasally
3.measure urine volume 12hrs after dDVAP is given
4.measure serum sodium if signs of hyponattremia are present
5. MRI of pituitary and hypothalamus
if a patient has central DI and you administer the Vasopressin Challenge test, what will you see?
decreased thirst
decreased urin output
increased urine osmolality
if you measure serum vasopressin (ADH) in a patient you suspect has DI, and you find elevated levels, what is that indicative of
nephrogenic DI
this is complication of nephrogenic DI
hypernatremia
treatment of central DI
refer to neurologist & endocrinologist
desmopressin acetate
-lowest dose possible
-many dosing routes: oral, IV, IM, SubQ, intranasal, metered-dose inhaler
pt presents with acute nephrogenic DI
treat with indomethacin
50mg q8hrs
what might a nephrologist do for a pt with nephrogenic DI
indomethacin combined with HCTZ, desmopressin, or amiloride (potassium sparing diuretic)
how do HCTZ and amiloride help in nephrogenic DI
they produce a hyperosmolar urine while decreasing urine output
treatment for chronic/mild DI
maintain adequate water intake
characteristics of SIADH
normal vascular volume with hyponatremia
inappropriate ADH secretion in the absence of ANY osmotic stimulus
-decreased plasma osmolaity
-inappropriate concentration of the urine
some causes of ADH are
tumors secreting ectopic ADH
medications/drug induced
lesions in the pathway of receptors
80% of lung tumors are associated with
SIADH
medications/drugs that can induce SIADH
antidepressants
antineoplastic agents
MDMA (ecstacy)
NSAIDs
Narcotics
Cytotoxic therapy
hypothyroidism/hypoadrenalism
lesions in the pathway of receptors that can cause ADH
CNS disorders: stroke, subarachnoid hemorrage, meningitis, encephalitis, trauma, brain tumor
pulmonary disease: TB, bacterial pneumonia
pain, physical stress, postoperative state
pt presents with; fatigue, headache, nausea & anorexia which progress to nausea and vomiting and eventually neurogenic impairment due to hyponatremia
SIADH
normal serum sodium is 135-145 mEq/L at what point must you urgently treat hyponatremia
<120 mEq/L
clinical presentations of SIADH include
hyponatremia
low plasma osmolality/decreased osmolality <280mosml/kg
inappropriately high urine osmolality for plasma osmolality
urine sodium >20mEq/L (elevated)
hypouricemia & low BUN
normal plasma volume (euvolemia)
where does excess fluid go in patients with SIADH
2/3 into the cells (ICF)
1/3 into ECF
what determines the treatment od SIADH
the severity and duration of hyponatermia
hyponatermia occurs over time and pt is asymptomatic
correct slowly with water restriction over time
if your pt with SIADH is euvolemic treat by
water restriction (500-1000mL/day - so as not to dilute sodium)
insure adequate sodium intake
Demeclocycline- for pts that can't adhere to water restriction (inhibits the effects of ADH on distal renal tubules)
if your SIADH pt is hypovolemic treat by
provide isotonic fluids (NS or LR) - surpresses hypovolemic stimulus for ADH release
at what serum sodium level is symptomatic hyponatremia seen
<120 mEq/L
a pt presents with hyponatremia and CNS symptoms, how do you treat them
IV saline + furisemide (Lasix)
~ when serum sodium is <115 mEq/L use hypertonic saline 3%
Demeclocycline
what are the syndromes of increases oxytocin secretion
none have been defined
what does oxytocin do
stimulates uterine contraction at time of labor and delivery
stimulates smooth muscle contraction in the breast during suckling
what are the cell types of the anterior pituitary
somatotrophs (50%)-GH
corticotrophs (15%)-ACTH
lactotrophs (15-20%)-PRL
gonandotrophs (10%)-LH & FSH
thyrotrophs (5%)-TSH
are pituitary tumors usually malignant
no, they are rarely malignant and seldom metastasize
what are the effects of a pituitary tumor
excess hormone productio + sequela
loss of function of the remaining gland
space-occupying effects
GnRH (gonadotropin releasing hormone) acts on which anterior pituitary hormone(s)
FSH
LH
GHRH (growth hormone releasing hormone) acts on which anterior pituitary hormone(s)
GH
TRH (thyrotropin releasing hormone) acts on which anterior pituitary hormone(s)
TSH
Prolactin
VIP PHI-27 (vasoactive intestinal polypeptide) acts on which anterior pituitary hormone(s)
prolactin
CRH (corticotropin releasing hormone) ADH (antidiuretic hormone-vasopressin) act on which anterior pituitary hormone(s)
ACTH
B-lipotrophin
B-endorphin
somatostatin is a hypothalamic inhibitory hormone that acts on
GH
TSH
Dopamine is a hypothalamic inhibitory hormone that acts on
TSH
Prolactin
GH is inhibited by
somatostatin
TSH is inhibited by
somatostatin
dopamine
prolactin is inhibited by
doamine
a pituitary hormone is most likely to result in excess secretion of
prolactin (60%)
the second most likely hormone secreted in excess due to a pituitary tumor is
GH (20%)
the third most likely hormone secreted in excess due to a pituitary tumor is
ACTH (10%)
what keeps prolactin in check
dopamine
what is the major function of the pituitary
support lactation in the postpartum period
concentrations of prolactin increase 10 fold during pregnancy and lactation
things other than pregnancy and nursing that can cause increased prolactin secretion
nipple piercing, breast augmentation, mastectomy
chronic chest wall stimulation
hypothyroidism
stress
pituitary stalk lesion
pituitary tumors that secret prolactin
dopamine antagonists (phenothiazines)
prolactin is secreted continuously unless
it is actively inhibited by dopamine
decreased prolactin secretion is caused by
dopamine agonist (cabergoline, bromocriptine, pergoglide)
dopamine
who are prolactinomas most common in
women
are prolactinomas usually micro-(<1cm) or macro- (>1cm) adenomas
most are micro <1cm in diameter
premenopausal women with prolactinomas may present with
galactorrhea
amenorrhea
headache
oligomenorrhea
infertility
visual field abnormalities
postmenopausal women with prolactinomas may present with
headaches and visual field disturbances are common
space occupying effects
men with prolactinomas may present with
erectile dysfunction, diminished libido, and occasionally gynecomastia
space occupying effects of pituitary tumors
CSF rhinorrhea (sella turcica or sphenoid sinus)
unilateral defects CN III, IV, VI and ophthalamic & maxillary branches of V (cavernous sinuses)
bi-temporal heminopsia (optic chiasm)
headaches and pituitary insufficiency
when do you order an MRI evaluation of the pituitary on a patient with hyperprolactinemia
when all other possible causes have been ruled out
first thing you treat in a patient with prolactinoma
the underlying problem
ie- if TSH is increased, fix that 1st... then continue on
what is the medical treatment of choice for prolactinomas
cabergoline and bromocriptine
dopamine agonist
80% of patients will experience normal prolactin levels with therapy
when would you utilize the surgical option of traanssphenoid surgery on a patient with a prolactinoma
tumors are unresponsive to medical therapy
tumors affect visual field
tumor exhibits apoplexy
pt is intolerant or refuses medical therapy
when should radiation therapy be utilized on a patient with a prolactinoma
pt has a macroadenoma that enlarges despite medical therapy
what is the risk of radiation therapy in the treatment of prolactinomas
panhypopituitarism
10 - 15% of patients
what stimulates the release of IGF-1
GH stimulates the release of IGF-1 in the liver and other tissues
what increases the release of GH
GHRH
sleep- associated w/GH peaks
exercise
trauma - stress to the body
acute illness- stress to the body
hypoglycemia
what decreses the release of GH
somatostatin - inhibitory peptide
hyperglycemia/ingestion of food
hypothyroidism
glucocorticoids
increased levels of IGF-a - affects feedback loop
GH increases the following
linear growth in children
overgrowth of bones in acral areas
soft tissue growth
fatty acid release from adipose tissue
insulin resistance at peripheral tissues to maintain blood glucose in normal range
muscle growth
increased BMR and increased lean body mass
increased hepatic gluconeogenesis
induces Na+ and water retention->swollen hands and feet
GH will decrease
glucose uptake at muscle cells
peripheral glucose utilization
in adults a GH producing pituitary adenoma will cause
acromegaly (almost always caused by an adenoma)
children with a GH producing adenoma will have
gigantism and tall stature (occurs before epiphyseal plate closes
most are macroadenomas
less than 1% are malignant
musculoskeletal signs of acromegaly include
increased stature
prognathia
macroglossia
frontal bossing
spade like hands w/widened fingers
sweaty palms
large feet
osteoarthritis (abnormal joint loading)
other than the obvious musculoskeletal signs what are some other signs/symptoms of acromegaly
dilated cardiomyopathy->cardiomegaly-> cardiac failure
hypertension
impaired glucose tolerance;diabetes mellitus (30%)
headaches, tiredness, excessive sweating
temporal hemainopsia
why do you not measure GH when trying to diagnose acromegaly
GH levels fluctuate, measure IGF-1
if you measure IGF-1 levels and they are abnormal, what do you do next
order fasting IGF & Prolactin
if your patients fasting IGF level is elevated, give 75 g of glucose, then measure GH
if GH is elevated ( >2mU/L) after 60 minutes acromegaly is confirmed
(glucose normally suppresses GH)
what is the imaging study of choice for diagnosing acromegaly
MRI with contrast for hypothalamic or pituitary tumor
(tumor is seen in 90% of pts)
a CT scan be used if MRI is contraindicated
what should be included in your differential diagnosis if there is elevated GH and IGF-1
recent exercise
eating immediately before IGF-1 assay is drawn
acute illness or agitation
diabetes mellitus
malnutrition
some complications of acromegaly are
hypopituitarism, hypertension, impaired fasting glucose, dibetes mellitus, cardiac enlargement, cardiac failure, carpal tunnel syndrome, arthritis
the treatment of choice for acromegaly
pituitary microsurgery
endoscopic transnasal, transsphenoidal resection
symptom remission in 70% of patients
is mediacl treatment alone sufficient in treating acromegaly
not usually options include:
dopamine agonist:cabergoline, bromocriptine (Parlodel)
somatostatin analogue:octreotide and lanreotide
GH recptor antagonist: Pegvisomant
what and when is stereotactic radiosurgery used
when pts with acromegaly fail surgical or medical therapy
describe Cushing's disease
ACTH hypersecretion by a benign pituitary adenoma
3X more frequent in women
excess ACTH from the pituitary -> increased cortisol release from zona fasiculata of the adrenal cortex
pt presents with: central obesity, facial plethora, hypertension, hirsutism, menstrual irregularity, muscle weakness, abdominal striae, thin skin w/easy bruising, and glucose intolerance (or diabetes)
hypercortisolism
diagnosis of Cushing's disease is done by what test
24 hour urinary free cortisol level + plasma ACTH level
if your patient's UFC is elevated and their ACTH is suppressed
an adrenal tumor is likely
if your patient's UFC is elevated and their ACTH is normal or elevated
Cushing's disease or ectopic ACTH
perform high dose dexamthasone suppression test
if one pituitary hormone os found to be deficient what should you do
measure levels of the other pituitary hormones
you may see isolated deficiencies in these pituitary hormones
LH/FSH
TSH
ACTH
GH
panhypopituitarism
global failure of the pituitary gland
invasion, injury, and infarction are
major causes of pituitary insufficiency
sheehan's syndrome
postpartum necrosis
failure to lactate as well as amenorrhea
s/s of hypothyroidism and/or glucocorticoid insufficiency
symptoms could be delayed up to 15 years
the main cause of pituitary insufficiency is
apoplexy (infarction)
acute hemorrhage in a preexisting adenoma
if patient presents with severe headache and visual field deficits
acute hypopituitarism
treat with glucocorticoids immediately
pt requires immediate surgery for decompression of the pituitary fossa
ordered gradual loss of pituitary hormone secretion
GH
LH
FSH
TSH & ACTH
if there is an ACTH deficiency
adrenal glands fail to secret sufficient amounts of cortisol
a sudden deficiency in in cortisol will cause
hypotension
may cause cardiovascular collapse
a chronic deficiency in cortisol may cause
weakness, fatigue, weight loss, hypotension
if there is a TSH deficiency
the thyroid gland fails to secret sufficient amounts of T4 and T3
weakness, fatigue, and weight change are vague symptoms associated with
hypothyroidism
a deficiency in gonadotropins (FSH & LH)
in childhood- failure to enter normal puberty
in adult females- breast atrophy, loss of pubic hair, infertility, amenorrhea
in adult males- testicula atrophy, decreased libido, loss of body hair, E.D., infertility
a GH deficiency or a defect in a GH receptor
in infants/children- growth retardation, short stature, fasting hypoglycemia
in adults- abd adiposity, reduced strength, decreased lean body mass, impaired psychosocial well-being, increased systolic BP, increased LDL
prolactin deficiency
usually asymptomatic in non-pregant women
loss of lactation in postpartum period
in hypopituitary labs if T4 is low what will TSH be
it will NOT be elevated in response
treatment of pituitary tumor
transsphenoidal resection
treatment for ACTH deficiency
3-7.5 mg of prednisone or 15-30 mg hydrocortisone /day
2/3 in AM and 1/3 in PM
increase dose in stress (acute illness, surgery, trauma)
treatment for TSH deficiency
synthroid (levothyroxine 0.025-0.3 mg daily
treatment for gonadotropin (LH & FSH)
estrogen/progesterone treatment in females
testosterone for males
fertility:
males-hCG injections, clomiphene
females-clomiphene (induces ovulation)
treatment for GH deficiency
asymptomatic adults: No treatment
somatotropin(hGH) injections for adults
hGH injections for children
treatment excess prolactin causing hypogonadism
dopamine agonist
cabergoline, bromocriptine
what is the major secretory product of the thyroid
T4 - thyroxine
where is T3 mainly produced
90% in peripheral tissues from circulating T4
this hormone is physiologically active
T3
T3's physiological effects
INCREASED: O2 consumption, metabolic rate, heat production, plasma levels of free fatty acids, protein synthesis & degradation, cholesterol excretion to bile, glucose absorption
DECREASED: plasma cholesterol
ACCELERATES: cellular oxidation of free fatty acids
ENHANCES: gluconeogenesis
UP-REGULATES: catecholamine receptors
is most thyroid hormone free or bound to protein
99% of circulating thyroid hormone is bound to protein
TGB
thyroxine-binding prealbumin
Albumin
what hormone levels are measured to evaluate thyroid function
TSH & Free T4
the following tests are used to evaluate thyroid function
serum thyroid hormones
thyroid antibodies (autoimmunity)
ultrasound
RALU-123 & Scan
FNA
what is the single most useful test in the evaluation of the thyroid
serum TSH
low TSH and high T4 indicates
primary hyperthyroidism
low TSH is indicative of
primary hyperthyroidism
exogenous thyroid hormone administration
other conditions/medications
elevated TSH and low T4 indicates
primary hypothyroidism
elevated TSH is indicative of
primary hypothyroidism
secondary hyperthyroidism
other conditions/medications
what screening test should be used in addition to TSH
serum free T4
is serum free T4 affected by variations in protein binding
no
in primary hypothyroidism the lab results will be
TSH: elevated
T4: low
in primary hyperthyroidism the lab results will be
TSH: low
T4: high
T3: high
hyperthyroidism
overproduction of thyroid hormones by the THYROID gland
thyrotoxicosis
excess thyroid hormone from ANY cause acting on peripheral tissues
elevated levels of these antibodies can be found in Hashimoto's thyroiditis
anti-thyroid peroxidase antibodies
anti-thyroglobulin antibodies (elevated early and then disappear)
thyroid-stimulatin Ig activates _____ which results in hyperthyroidism
TSH receptors
the main use for serum thyroglobulin is
a marker in pts w/thyroid CA
elevates levels may indicate CA recurrence
what antibody is elevated in Grave's disease
anti-thyroglobulin antibodies
this test is helpful in narrowing down the differential Dx in pts w/symptoms of hyperthyroidism
RAIU-123 and scan
how is RAI-123 given to patients
orally
after giving RAI-123 how long do you wait before measuring
6-24 hours
a normal thyroid uptakes about how much iodine
10-30%
what does a RAIU scan look like in a pt with thyroiditis
virtually no iodine up-take
inflammation prevents thyroid from working properly
acute suppurative thyroiditis is often caused by
streptococcus bacteria
subacute thyroiditis is the most common cause of thyroid pain, its cause is
viral
RAIU scan of a thyroid with graves disease
is very densely colored. it is diffusely overactive
Graves' disease is more common in
women
8:1
primary hyperthyroidism
on physical exam you find a smooth diffuse goiter and hear bruit in the goiter. you also notice exophthalmos
Graves' disease
you get the following la values
TSH: low
T4/T3: high
antibodies + (anti-thyroglobulin)
how do you treat this patient
Graves' disease
propanolol - B-blocker
methimazole (Tapazole) - antithyroid drug
if pregnant/nursing use propylthiouracil (PTU)
the treatment choice for Graves' disease for adults in the US is
radioactive iodine 131
it destroys the thyroid tissue
who might you use a subtotal thyroidectomy on
pregnant women not controlled with low doses of antithyroid drugs
or if there is a significant chance of malignancy
if you have an elderly person that presents with; weight loss, fatigue, lethargy, depression, and angina pectoris
apathetic hyperthyroidism
treatment for subacute thyroiditis
NSAIDS or ASA
Prednisone can be used if NSAIDs are ineffective for inflammation
Beta blocker (hyperthyroid phase)
iodinated contrast agent (thyrotoxic symptoms)
Synthyroid (hypothyroid state)
silent or painless thyroiditis is AKA
postpartum thyroiditis
this stony thyroiditis is the rarest form
Riedel's (usu in middle aged/elderly women)
caused by a fibrous infiltration of the thyroid gland
treatment for Riedel's thyroiditis is
surgery to relieve tracheal & esophageal compression
as well as tamoxifen (Nolvadex)
this is an elargement of the thyroid gland
could be caused by increased stimulation of the thyroid by TSH or by thyroid stimulating IGs
Goiter
what are the 2 types of goiter
diffuse sime nontoxic
benign multinoular
goiter treatment
supression with levothyroxine (Synthyroid)
-only fpr pts w/normal or elevated TSH (provides T4 so the thyroid doesn't have to)
these labs are diagnostic of
FT4: elevated
T3: elevated
TSH: suppressed
RAIU- diffuse patchy uptake (multiple functioning nodules)
toxic multinodular goiter
treatment for toxic multinodular goiter
propanolol (Inderal) - for symptoms
anti-thyroid drugs - to reverse hyperthyroidism
RAI ablation of thyroid
Surgey - pressure symptoms and cosmetics
if the thyroid is removed provide Synthyroid
single thyroid nodules could be
benign adenoma (most common)
cyst
malignancy (primary or metastatic)
multiple thyroid nodules could be indictive of the following
multinodular goiter
thyroiditis
MALIGNANCY
iodine deficiency
Graves' disease
Hasimoto's thyroiditis
Subacute thyroiditis
if you have a pt with a history of hypothyroidism and thye have not been taking their medicine (Synthyroid) what medical emergency do you need to consider
myxedema coma
this rare condition (with a high mortality rate) is most often seen in patients with Grave's disease
Thyroid storm
where are the adrenal glands located
on top of the kidneys
describe benign thyroid nodules
soft
mobile
no associated cervical lymphadenopathy
describe malignant thyroid nodules
firm or hard
fixed/adherent (to underlying muscles or the trachea)
cervical lymphadenopathy is common
what are the steps in evaluating thyroid nodules
1. asses function TSH and FT4
2. thyroid ultrasound
3. FNA (cell "biopsy" for malignancy)
4. thyroid scan RAI-123
treatment of benign nodules
regular examinations w/ultrasound
if size increases FNA again
Rx Synthyroid if serum TSH is elevated or pt is hypothyroid
most frequent and least aggressive type of thyroid cancer
Papillary
many pts have microscopic metastases to cervical lymph nodes
absorbs iodine "hot nodule"
2nd most frequent thyroid cancer
Follicular
metastases to neck nodes, bone, lung
absorbes iodine "hot nodule"
3rd most frequent thyroid cancer that originates from parafollicular cells
Medullary
pt may present w/flushing & persistent diarrhea
1/3 sporadic, 1/3 familial, 1/3 associated w/ MEN 2a and 2b
does not absorb iodine
4th most frequent thyroid cancer and most aggressive
Anaplastic
poor prognosis most pts die <12 months after Dx
usu older pts, rapidly growing mass
does not absorb iodine
pt has:
palpable, firm, non tender, fixed thyroid mass
symptoms of hypothyroidism
Thyroid function tests normal
CEA is elevated
thyroid cancer
thyroglobulin elevated in papillary & follicular
calcitonin is elevated in medullary
what is the treatment of choice for thyroid cancer
surgery
treatment for anaplastic thyroid cancer
local resection w/radiation therapy (not RAI)
treatment for medullary thyroid cancer
surgery only
treatment for papillary and follicular thyroid cancer
surgery followed by RAI
do papillary and anaplastic thyroid cancers respond to RAI-131
no
only effective for papillary and follicular CAs
primary hypothyroidism is a failure of
the thyroid gland to secret T4 and T3
secondary hypothyroidism is a failure of
the pituitary to secret TSH
myxedema
fluid retention is hallmark
interstitial accumulation of hydrophilic mucopolysaccharides causing lymphedema
hyponatremia (impaired renal tubular Na reabsorption due to decreased Na-K-ATPase)
what is the most common cause of primary hypothyroidism
Hasimoto's thyroiditis AKA chronic lymphocytic thyroiditis
Amiodarone has a high iodine content and can cause
Hashimoto's thyroiditis
(can cause clinically significant hypothyroidism)
you receive the following lab values on your patient:
TSH: elevated
FT4: low end of normal
Cholesterol: elevated
Prolactin: elevated
RAIU- low uptake
Hashimoto's thyroiditis
primary hypothyroidism
what catecholamines are secreted by the adrenal medulla
epinephrine
norepinephrine
pt c/o: fatigue, lethargy, constipation, depression, weight gain, cold intolerance, and weakness
you suspect
hypothyroidism
complications of hypothyroidism
mostly cardiac
increased susceptibility to infection
Megacolon
organic psychoses with paranoid delusions
myxedema coma
levothyroxine (Synthroid) is a T4 replacement in which patients would you want to use caution
patients over 60
those with ischemic heart disease
-start low 25mcg/daily and increase 1-3 weeks until pt is euthyroid
Synthroid
3-4 weeks after therapy near normal levels
25-75 mcg/day starting dose
maintainance dose ~175 mcg/day
monitor dose w/TSH
6-8 weeks after start or change before checking TSH
too much thyroid hormone -> a-fib
at what time of day should your patient take throid hormone
in the morning on an empty stomach
Amiodarone is a concomitant with thyroid hormone and therefore
will require close monitoring with use
what interferes with the absorption of thyroid hormone
iron
calcium supplements
bile acid resins
antacids
soy
PPI's (T4 specifically)
what women may require a higher dose of thyroid hormone
pregnant women
women on estrogen therapy
congenital hypothyroidism (hypothyroidism in infancy)
cretinism
5 month old baby presents with a thickened tongue, poor muscle tone and has deaf-mutism
cretinism
etiology: aplasia or hypoplasia of the thyroid or failure of the thyroid gland to migrate to its normal anatomical location
childhood (acquired) hypothyroidism is usually from
Hashimoto's thyroiditis
TSH insufficiency
secondary hypothyroidism
causes of secondary hypothyroidism
pituitary tumor
pituitary hemorrhage
pituitary infection
what labs can you expect in secondary hypothyroidism
serum TSH is low or low normal
T4 is at the lower limit of normal
TRH will be elevated - this will increase prolactin levels as well
this rare but severe and life threatening hypothyroid condition is more common in older women who have had a stroke or stopped taking medication (they usually have a history of hypothyroidism, often poorly controlled)
Myxedema Coma (crisis)
factors that precipitate myxedema coma
sepsis
exposure to cold
central nervous system depression
trauma
you have a bradycardic with an altered mental status, weakness, they are hypothermic and hypoventilating w/hypoxia and hypercapnia. They also have hypotension, hyponatremia, and hypoglycemia
clinical presentations of Myxedema coma
management of the myxedema patient
intubation and mechanical ventilation
blankets only for hypothermia
IV fluids for volume expansion (hypertonic saline for hyponatremia)
Synthroid
corticosteriods IV for adrenal insufficiency
extreme hyperthyroidism /thyrotoxicosis is also known as
thyroid storm
high mortality rate
rare, but when it occurs it's often in patients with Grave's Disease
thyroid storm precipitating factors
Stressful illness
Thyroid surgery
Radioactive iodine administration
Discontinuing anti-thyroid drugs
pt presents with:
Marked delirium, Severe tachycardia or atrial fibrillation, Vomiting, Diarrhea, Dehydration
Very high fever - hyperpyrexia out of proportion to other clinical findings is the hallmark of thyroid storm ( > 103), Sweating, tremors, restlessness
you suspect
THYROID STORM
treatment of the patient with Thyroid Storm
Admit to ICU
Anti-thyroid drugs, potassium iodide, Inderal (propanolol), hydrocortisone
Definitive treatment: 131I ablation or surgery
these hormones are synthesized in the adrenal cortex
Glucocorticoid hormones: Cortisol
Mineralocorticoids: Aldosterone
Androgens:
Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS)
Testosterone and androstenedione
the inner medulla of the adrenal glands is
Extension of sympathetic nervous system
~Catecholamines
Corticotropin-releasing hormone (CRH) is produced in the hypothalamus and stimulates _____
ACTH synthesis
Corticotropin-releasing hormone (CRH) is produced in the hypothalamus and is inhibited by_____
cortisol (via negative feedback)
Secretion of CRH is increased in stressful events like
Major illness, surgery, injury, exercise, hypoglycemia, starvation
Adrenocorticotropic hormone (ACTH) is produced by the pituitary corticotrophs (anterior) and secreted how
pulses with a diurnal rythm
highest in the early AM 0400-0600(2/3)
lowest at night (1/3)
ACTH stimulates ______ to secrete_____
adrenal glands / cortisol
what inhibits ACTH secretion
cortisol via negative feedback
besides cortisol what else does ACTH stimulate
adrenal aldosterone secretion
melanocytes to produce melanin
what bis the major gluco-corticoid secreted by the adrenal cortex
cortisol
in what pattern is cortisol secreted
Secreted in a diurnal pattern:
highest at awakening
lowest at bedtime
exercise, acute trauma, infection, stress and lead to increased secretion of
cortisol
how does cortisol effect carbohydrate metabolism
Inhibits insulin secretion
Inhibits glucose uptake by muscle and fat (= insulin resistance and elevated blood glucose level)
Increases hepatic gluconeogenesis
how does cortisol effect fat metabolism
Increases lipolysis and quantity of free fatty acids
how does cortisol effect protein metabolism
Increases protein breakdown which increases the amount of amino acids available for conversion to glucose
Major Biologic Effects of an Increased Cortisol Level
Weight gain and truncal obesity
Inflammation is suppressed
Immune system is suppressed
Suppresses bone formation and decreases calcium absorption
There are catabolic effects on bone, connective tissue and muscle:
Loss of connective tissue, thin skin, easy bruising, development of abdominal striae (stretch marks), impaired wound healing

• Sodium and water retention

• Growth failure in children may occur

• Altered mood, behavior and cognition may occur
a common cause of excess cortisol is
Long-term high-dose exogenous glucocorticoids:
Prednisone, dexamethasone, hydrocortisone
ACTH-producing pituitary tumor (Cushing's disease) (43%) causes
excess cortisol
excess cortisol can come from
long term high dose exogenous glucocorticoids
ACTH pituitary tumor
adrenal adenomas or carcinomas
ACTH by non pituitary tumors
weight gain, round facies, truncal obesity, weakness, HTN, and cutaneous striae are common signs of
Cushing's syndrome
if you suspect your patient has cushing's syndrome what test would you order
24 hr urine free cortisol (UFC)
describe a 24 hr UFC
Should be collected on 2-3 different occasions over 24 hours
A 24-hour urine creatinine level should be obtained as well
These results should be within 10% of each other (confirms completeness of the urine collections)
An elevated urine cortisol confirms state of hypercortisolism
normal or moderately elevated ACTH (52-200 pg/ml)
-MRI of the pituitary gland confirms this condition
Cushing's Disease (pituitary tumor/adenoma)
ACTH-dependent causes of hypercortisolism - will have _______- ACTH level
elevated (> 52 pg/ml)
very elevated ACTH (200-1000 pg/ml)
Ectopic ACTH secretion
-CT scan of chest and abdomen may reveal a mass lesion responsible for ectopic ACTH secretion
*small cell lung cancer
ACTH-independent causes of hypercortisolism - a suppressed ACTH level (< 9 pg/ml) will be observed:
Exogenous glucocorticoid use
Adrenal adenoma or adrenal corticocarcinoma
• CT of adrenal glands confirms either of these conditions
if exogenous corticosteroid is the cause of cushing's syndrome
reduce the dose if possible
if an adrenal adenoma or carcinoma has been determined to be the cause of cushing's syndrome
surgery to remove the mass
if cushing's sydrome (specifically disease) is caused by an ACTH-producing pituitary adenoma
remove the tumor via a selective transsphenoidal pituitary resection
a tumor that secretes ectopic ACTH is treated by____ or ____based on histology and location
surgery or chemotherapy
pharmacological treatment of Cushing's syndrome is
cortisol synthesis can be blocked by use of metyrapone, aminoglutethimide, or ketoconazole
Addison's Disease
primary adrenal insufficiency
uncommon disorders
~Pts present with weakness, fatigue, hyperpigmentation, nausea, vomiting, anxiety, etc
Autoimmune adrenalitis (80%)
primary adrenal insufficiency (Addison's Disease)
Due to the autoimmune nature adrenal function decreases over years as it progresses to adrenal failure
non autoimmune causes of Addison's Disease
tuberculosis, bilateral adrenal hemorrhage, congenital adrenal hypoplasia, or surgical removal of the adrenal glands
pt presents with weakness & fatigue, hyperpigmentation, unexplained weight loss, A/N/V, HOTN, and hyponatremia (hyperkalemia)
you suspect
primary adrenal insufficiency (Addison's Disease)
Inadequate secretion of ACTH by the pituitary gland
secondary adrenal insufficiency
(pituitary)
the most common cause of secondary adrenal insufficiency
Sudden/rapid withdrawal of long-term exogenous corticosteroid treatment that has suppressed ACTH
common etiologies of secondary adrenal insufficiency
Pituitary tumors causing suppression of pituitary function
Postpartum pituitary infarction
Pituitary irradiation or surgery
Head trauma
pt presents with weakness & fatigue, pallor, unexplained weight loss, A/N/V, HOTN, ACTH low, electrolytes normal
you suspect
secondary adrenal insufficiency
Low AM cortisol level (usually < 3 mcg/dl) and elevated plasma ACTH (usually > 200 pg/ml)
Dx: Primary Adrenal Insufficiency
•Proven by simplified cosyntropin (ACTH) stimulation test:
Inject cosyntropin (synthetic ACTH)
Measure cortisol levels between 30 and 60 minutes after cosyntropin is administered
A normal response is an increased cortisol level > 20 mcg/dl (rules out Addison's disease)
•The test may be administered any time of the day
what is the normal response to the cosyntropin (ACTH) stimulation test
•A normal response is an increased cortisol level > 20 mcg/dl (rules out Addison's disease)
primary adrenal insufficiency:
hyperpigmentation
hyperkalemia/hyponatremia
elevated ACTH
low cortisol level w/ACTH stimulation
secondary adrenal insufficiency
NO hyperpigmentation
normal electrolyte levels
low or inappropriately normal ACTH
increased cortisol level w/ACTH stimulation
Sick Day Rules
Double glucocorticoid dose for as short a time as possible for stress, trauma, acute illness, surgery, etc.
Treatment of Addison's Disease
Replace mineralcorticoids and corticosteroids to physiologic levels:
15-30 mg hydrocortisone per day or 3-6 mg prednisone per day in divided doses (2/3 in AM and 1/3 in PM)
Florinef (fludrocortisone) - has a potent sodium-retaining effect
"Sick day rules": Double glucocorticoid dose for as short a time as possible for stress, trauma, acute illness, surgery, etc.
Emergency steroid kit - 100 mg hydrocortisone vial for IM use
Educate patient about risk of stopping glucocorticoid therapy
MedicAlert bracelet - "Adrenal insufficiency - takes hydrocortisone"
treatment of Secondary adrenal insufficiency
Glucocorticoid (cortisone, dexamethasone, etc.)
Treat the underlying pituitary disorder
Emergency steroid kit, MedicAlert bracelet, "sick day rules" (as above)
Precipitating situations for adrenal crisis include
stress (infection, trauma, surgery), sudden withdrawal of glucocorticoid therapy, bilateral adrenalectomy, adrenal trauma, or pituitary necrosis. Also can be seen following the use of etomidate (used for rapid intubation)
pt has
extreme weakness, dehydration, hypotension, fever, nausea, vomiting, hypoglycemia, headache, confusion, coma
acute adrenal insufficiency (Adrenal Crisis)
Draw a blood sample for an immediate cortisol assay
Must distinguish adrenal insufficiency from other causes of shock
Also perform ACTH, electrolyte, BUN, creatinine and glucose assays
A normal response to stress is increased secretion of
CRH, ACTH, and cortisol
diagnosis of acute adrenal insufficiency (adrenal crisis)
administering a simplified cosyntropin stimulation test:
Obtain a cortisol level 30-60 minutes after giving cosyntropin (synthetic ACTH)
A normal cortisol level is >20 mcg/dl
The cosyntropin will be unable to stimulate a normal increase in serum cortisol in adrenal crisis, so the cortisol will remain low.
The ACTH level will be elevated (> 200 pg/ml) if the patient has primary adrenal disease
treatment of acute adrenal insufficiency
High doses of a glucocorticoid:
Hydrocortisone 100-300 mg immediately, then give hydrocortisone 100 mg IV every 6 hours
As pt tolerates oral meds, continue to dose with oral medication and taper off slowly over weeks.
Broad-spectrum antibiotics:
Empiric therapy - many cases of adrenal crisis are precipitated by a bacterial infection
Obtain bacterial cultures based on history and physical
Treat the cause of the underlying stress if possible
where is aldosterone secreted from
the adrenal cortex
what stimulates the secretion of aldosterone
angiotensin II and hyperkalemia
Low renal perfusion pressure stimulates _____ secretion by the kidneys
renin
Renin converts angiotensinogen from the liver into
angiotensin I
Angiotensin-converting enzyme from the lungs converts angiotensin I to
angiotensin II
Angiotensin II stimulates
adrenal aldosterone secretion
where is the major effect of aldosterone
renal tubules
There is re-absorption of sodium in exchange for potassium and hydrogen ions
Helps regulate both volume status and potassium balance
In healthy individuals aldosterone secretion is stimulated by
Increased plasma potassium - small increases in the plasma potassium concentration causes a several-fold increase in aldosterone secretion
Low renal perfusion pressure - hypovolemia or renal artery stenosis
Increased sympathetic nervous system activity
primary etiology of hyperaldosteronism
Excess aldosterone production from adrenal glands (unilateral adrenocortical adenoma, bilateral adrenal hyperplasia, adrenal cancer)
secondary etiologies of hyperaldosteronism
Excess renin production by the kidneys
Most common cause: renal artery stenosis
May also be caused by hypovolemia and congestive heart failure
Primary hyperaldosteronism
increased aldosterone level leads to increased sodium retention and this causes suppressed plasma renin Increases renal potassium excretion.
Secondary hyperaldosteronism
increased renin (etiology of the increased aldosterone to begin with)
treatment for hyperaldosteronism
Adenoma: unilateral adrenalectomy
Bilateral adrenal hyperplasia: Aldactone (spironolactone) (aldosterone antagonist and diuretic)
Renal artery stenosis:
Angioplasty
Revascularization procedures
Hyperkalemia occurs in _______deficiency
aldosterone
common etiologies of hypoaldosteronism are
diabetic nephropathy and hypertensive nephrosclerosis
adrenal androgens in women can cause:
acne, hirsutism, virilization
excess adrenal androgens can come from
Exogenous androgens taken in excess
Adrenal carcinomas
Congenital adrenal hyperplasia (CAH):
Most common type - deficiency of 21-hydroxylase
Lack of cortisol causes elevated ACTH which causes more 17- hydroxyprogesterone to be converted into androgens
the adrenal medulla secretes
catecholamines
Epinephrine & Norepinephrine
these signal for the release of catecholamines
Decreased blood pressure
Decreased blood volume
Decreased blood glucose
Severe illness
Severe emotional stress
Pheochromocytoma
A catecholamine-secreting tumor of chromaffin cells arising from the adrenal medulla or any location along the sympathetic nervous chain (paragangliomas)
Rare: found in 0.1 - 1% of patients with hypertension
Peak prevalence in 30-40 year olds
this classic triad can be seen in pheochromocytoma
Headache (80%)
Sweating (70%)
Palpitations (60%)
other than the classic triad what are some signs of pheochromacytoma
Anxiety and nervousness
Tremor
Facial pallor and mottled cyanosis, then flushing
Tachycardia with or without precordial pain
Angina
Nausea, vomiting, and abdominal pain
Stimuli causing paroxysmal catecholamine release
Activity (exertion, postural change)
Meals, alcohol use, smoking
Urination and straining at stool
Emotional stress, trauma, pain
General anesthesia and barbiturates
Hormones/drugs: glucagon, adrenocorticotropic hormone (ACTH), histamine
diagnosis of pheochromocytoma
Obtain screening labs: free T4, TSH, CBC, ESR, glucose
24-hour urine for catecholamines (dopamine, epinephrine, norepinephrine)
24-hour urine for metanephrines:
Metabolites of catecholamines
VMA (vanillymandelic acid)
It is best to obtain urine samples during or immediately following an episode if episodes are paroxysmal
you are trying to Dx a pt with pheochromocytoma and they have just had an attack and experience paroxysmal HTN
Direct blood and urine assays for epinephrine and norepinephrine OR plasma free metanephrine or plasma free catecholamines immediately after an attack are likely to be abnormal
if lab analysis indicates a probable pheochromocytoma, what localization studies would you use
CT adrenal glands, if negative then:
• CT of entire abdomen, pelvis and chest
Abdominal MRI may also be used
123 I-mIBG (Iodine 123 scintigraphic localization)
Used if CT and/or MRI scans are inconclusive
Somatostatin receptor imaging (head and neck paragangliomas)
PET scan may also be used
Related to hypertension: stroke and/or sudden blindness
Cardiomyopathy
Cardiac arrhythmias
are complications related to
pheochromocytoma
management of the patient with pheochromocytoma
Pre-op alpha-blockade (phenoxybenzamine) or calcium channel blockers
Beta-blockers may also be used for persistent tachycardia or arrhythmias but ONLY after use of an alpha-blocker if the patient remains tachycardic
~Use of a beta-blocker initially can actually increase the blood pressure
Surgery (laparoscopic removal) is the treatment of choice
pheochromocytoma treatment hypertensive crisis
IV labetalol, nitroprusside, or phentolamine
Pheochromocytoma post-operative check
check urine for catecholamines and check blood pressure regularly
For inoperable or metastatic pheochromocytomas
metyrosine administration reduces catecholamine synthesis
adrenal incidentalomas
Cortisol-producing - 9.2%
Pheochromocytoma - 4.2%
Mineralocorticoid-producing (aldosteronoma) - 1.6%
Metastatic disease
evaluation of adrenal incidentalomas
24-hr urine for metanephrines and catecholamines
24-hr urinary free cortisol
Serum potassium and aldosterone
Plasma renin activity
If labs are all show no functionality of incidentaloma, then serial CT scans at 3 and 12 months for patients with nonfunctional incidentalomas < 4 cm, then every 2-3 years if the mass does not increase in size
"Red flags" for the presence of secondary hypertension
Hypokalemia without diuretic Rx
Presentation at an early age without a family history of HTN
New presentation of HTN in patients > 50 years old
A higher degree of severity (diastolic > 110 mmHg)
Well-controlled HTN suddenly refractory to therapy
Increased blood pressure is paroxysmal in nature
Absence of obesity
New or unusual symptoms suggestive
Secondary (endocrine and non-endocrine etiologies) of HTN
Thyroid dysfunction
Hyperaldosteronism
Pheochromocytoma
Cushing's syndrome
Renal artery stenosis
Coarctation of the aorta
Others: estrogen use, sleep apnea, diabetic nephropathy, pregnancy, etc.
you suspect thyroid dusfunction as the cause of HTN, you test
TSH T4
you suspect hyperaldosteronism as the cause of HTN, you test
serum K+, aldosterone, renin
you suspect pheochromocytoma as the cause of HTN, you test
24 hr urine catecholamines, metanephrines
you suspect cushing's syndrome as the cause of HTN, you test
objective clinical findings + 24 hr urine free cortisol
you suspect renal artery stenosis as the cause of HTN, you test
US, doppler study of renal arteries
you suspect coarctation of the aorta as the cause of HTN, you test
check BP in all extremities