MTB and important from FA Flashcards
increased sex hormone-binding globulin in MEN –>
lowers free testostosterone –> gynecomastia
decreased sex hormone-binding globulin in WOMEN –>
raises free testosteron –> hirsutism
causes of increased sex hormone-binding globulin
OCP
PREGANCY
increased sex hormone-binding globulin - estrogen levels
unchanged
MC ectopic thyroid tissue site is the
tongue (lingual thyroid)
α subunit is common to (hormones)
WHAT DETERMINES THEIR SPECIFICITY
- TSH 2. LH 3. FSH 4. hCG
β subunit determines their hormone specificity
vasopressin and oxytocin production and secretion (where and transportation)
made in hypothalamus (supraoptic and paraventricular nuclei) and transported to posterior pituitary via neurophysins
insulin release regulators (and how)
- glucose (increases)
- GH (increases)
- β2 agonists (increase)
- cortisol (increase)
- α2 agonists –> decrease insulin release
Dopamine function (hypothalamic pituitary)
decreases prolactin and TSH secretion
GHRH analog?
used for
tesamorelin
used to tread HIV lipodystrophy
TRH funtion
- increases TSH secretion
2. increases prolactin secretion
prolactin secretion is regulated by
- TRH (positively)
- dopamine (negatively)
- prolactin (negatively by increasing dopamine secretion)
- estrogen and progesterone (positively, in pregnany)
somatostatin function (on hypothalamic pituitary axon)
decreases secretion of
- GH
- TSH
TSH is regulated by
- T3/T4 (negatively, decrease sensitivity of TRH)
4. dopamine (negatively)
GH secretion is regulated by
- glucose (negatively)
- somatostatin (negatively, release via negative feedaback by somatomedin)
- GHRH (positively)
- Ghrelin (positively, via GH secretagog receptor)
- somatomedin C (negatively, via somatostatin)
TBG - increased (situations)
estrogen (pregnancy or OCP use)
TBG - decreased (situations)
- hepatic failure
2. steroids
etiology of endogenous hepercortisolism (and percentages)
- Cushing disease (Pituitary production) - 70%
- Adrenals - 15%
- Unknown source of ACTH - 5%
- ecropic ACTH (cancer or carcinoid) - 10%
adrenal disorders - diagnostic algorithm - genarally
- establish the presence of hyperctortisolism
2. establish the cause of hypercotisolism
establish the presence of hyperctortisolism - best initial test
24h urine cortisol
if this is not in the choices: answer 1 mg overnight dexamethasone suppression test or late night salivary cortisol levels (normal exclude)
establish the presence of hyperctortisolism - 1 mg overnight dexamethasone suppression test
1 mg should normally suppress the morning cortisol level –> if this suppression occurs, hypercortisolism can be ecxluded
THERE ARE FP
establish the presence of hyperctortisolism - 24 urine vs 1 mg dexamethasone
24h urine cortisol test is a more specific –> if 24h urine cortisol is elevated -> confirm
causes of FP in 1mg overnight suppresson testing
- Depression
- alcoholism
- obesity
establish the cause of hypercortisolism - best initial test
ACTH testing is the best initial test determine the cause (source) or location of hypercrtisolism
- low –> adrenal source or exogenous
- elevated –> pituitary, ectopic production (carcinoid, lung cancer)
enstablish the cause of an high-ACTH hypercortisolism
suppresses with high doses dexamethasone –> pituitary
not suppresses –> ectopic production (carcinoid, lung cancer)
hypercortisolism with low ACTH - next step
means ACTH independence cushing syndrome
–> CT ADRENALS (adrenal mass?)
cushuing with high ACTH that not suppresses on high dose dexamethasone - next step
(ectopic ACTH secreting tumor?)
CHEST CT
cushuing with high ACTH that suppresses on high dose dexamethasone - next step
(pituitary mass)
head MRI –> if not seen any mass (some lsions are to small to be detected on MRI) –> petrosal sinus sampling from ACTH (possibly after CRH stimulation)
–> if not detected –> check for ectopic
cushing - head MRI from the begining
(pituitary mass)
head MRI –> if not seen any mass (some lsions are to small to be detected on MRI) –> petrosal sinus sampling from ACTH (possibly after CRH stimulation)
–> if not detected –> check for ectopic
evaluation of adrenal incidentaloma - steps
4% of the population has. Do not start with a scan or you will remove the wrong organ. STEPS
- metanephrines in blood and urine to exclude (pheo)
- renin + ald levels to exclude hyperaldosteronism
- 1 mg overnight dexamthasone suppression test
the most specific test for adrenal function
- cosyntropin stimulation test (Synthetic ACTH)
- you measure the cortisol level before and after the administration
- in a patient whose health is otherwise normal, there should be rise in corstisol level after giving the drug
all forms of 2ry hypertension are more likely in those whose onset:
- is under age 30 or above age 60
- is not controlled by 2 antihypertensive medications
- has a characteristic finding on the history, physical or labs
hyperaldosteronism - DI
nephrogenic DI due to hypokalemia
primary hyperaldosteronism - best initial test
measure the ratio of plasma aldosterone to plasma renin –> an elevated plasma renin excludes 1ry hyperaldosteronism
primary hyperaldosteronism - the most accurate to confirm test the presence of unilateral adenoma
a sample of the cenous blood draining adrenal –> iw will show a high aldosterone level
primary hyperaldosteronism - CT
should only done after biochemical testing confirms:
- low K+
- High aldosterone despite a high salt diet
- low plasma renin level
primary hyperaldosteronism - treatment
- unilateral adenoma is resected by laparoscopy
2. bilateral hyperplasia is treated with eplerone or spironolactone
pheochromocytoma - best initial test
level of metanephrines in plasma
pheochromocytoma - confirmation
with 24h urine collection for metanephrines
more sensitive that vanillymandelic acid level
pheochromocytoma - imaging
- imaging of the adrenal glands with CT or MRI is done ONLY after biochemical testing
- MIBG: nuclear isotope scan that detects the location of pheochromocytoma that originates outside the adrenal gland
high TSH - when to treat
- when TSH is very high (more than double upper limit of normal) with normal T4 –> replace hormone
- when TSH is less than double the normal (kai nmz normal T4) –> get antirhyroid peroxidase/antithyroglobulin antibodies –> if positive –> replace with thyroid hormone
thyroid disorder - diagnostic tests
all thyroid disorders are best tested first with a TSH
if it is suppressed, measure free T4 levels
TSH levels are markedly elevated if the gland has failed
Hyperthyroidism - etiology
- Graves
- subacute thyroiditis
- painless silent thyroiditis
- exogenous thyroid hormone use
- pituitary adenoma
hyperthiroidism - Graves - unique feature
eye (proptosis (20-40% and skin (5%) findings
Painless silent thyroiditis is aka
- subacute lymphocytic thyroiditis
- lymphocytic thyroiditis with spontaneously resolving hyperthyroidism
- may follow pregnancy
- self-limited / b-blockers for symptoms
graves treatment
- thionamides (methimazole is preferred over PTU)
- radioablation or subtotal thyroidectomy for definitive
- atenolol for symptomatic
- steroids is the best initial therapy for opthalmopathy – . if refractory radiation –> surgery (very rare)
treatment of acute hypothyoridism and thyroid storm
- propranolol: blocks target organ effect, inhibit peripheral conversion of T4 to T3
- Thiourea drugs (methimazole + propylthiouracil)
- Iodinated contrast material: iopanoic acid and ipodate: block peripheral conversion of T4, also blocks the release of existing hormone
- steroids: hydrocortisone
- radioactve iodine: ablates the gland for a permanent cure
- prophylaxis with thiourea drgs
METHIMAZOL IS BETTER
subacute thyroiditis - treatment
self-limited, NSAID or aspirin and β-blockers to treat symptoms
thyroid replacement if hypothyroidism
Job-Basedow phenomenon - definition
thyroitoxicosis if a patient with iodine deficiency and partially autonomous thyroid tissue (eg. autonomous nodule) is made iodine replete
Hashimoto thyroiditis - pathophysiology / HLA
autoimmune disease disorder
antibodies: 1. thyroid peroxidase (antimicrosomal)
2. antithyroglobulin
HLA-DR5
Wolf-Chaikoff effect
thyroid gland downregulation in response to increased iodine
Thyrotoxic vs hypothyroid myopathy
both proximal muscle weakness
thyrotoxic –> normal CK
hypothyroid –> increased CK
hypercalcemia - bone lesions
osteoporosis
hypercalcemia - renal
- nephrolithiasias
- diabetes insibitus (nephrogenic)
- renal insuficiency
acute hypercalcemia - treatment
- saline hydration at high volume
- bisphosphonates: pamidronate, zolendronic acid
- if not respond after saline and biphosponates
- -> calcitonin (rapid action) - in renal failure –> dialysis
- prednisone –> if sarcoidosis or granoulomatous
1ry hyperparathyroidism - treatment
- surgical resection of single adenoma
- for 4 gland hyperplasia –> all glands removed, and a portion of 1 gland is implanted in the muscle of forearm
- if surgery non possible –> cinacalcet
- preoperativ imaging of the neck with sonography or nuclear is helpful in determining the surgical approach
Primary hyperparathyroidism - diagnostic tests
- high calcium and PTH levels
- low P
- EKG with short QT
- sometimes elevated BUN and CR
- ALP from PTH on bone
- bone x-ray is not good test –> dexa is better
hypocalcemia - Mg
- Mg is necessary for PTH to be released from the gland
2. low Mg levels also lead to increased urinary loss of calcium
hypocalcemia - diagnostic tests
- EKG –> prolonged QT –> arrhythmia
2. slit lamp exam –> EARLY CATARACTHS
hypocalcemia - treatment
replace calcium and vit D –> orally if symptoms are mild or absent and IV is severe
orally if symptoms are mild or absent and IV is severe
Pseudohypoparathyroidism - def / treatment
aka ALbright hereditary osteodystrophy (short stature, seizures, poor mental)
- treatment: Ca and VIT D
Ca2+ - QT
hypo –> long GT
hyper –> short QT
pseudopseudohypoparathyroidism - mechanism / presentation
physical exam features of Albright hereditary osteodystrophy (1. short stature 2. shortened 4th/5th digits) but without end-organ PTH resistance –> occurs when the defective Gs protein α-subunit is inherited from father
thyroid cancer - types (MC?)
- papillary carcinoma (MC)
- follicular carcinoma
- medullary carcinoma
- anaplatic/undifferentiated carcinoma
- lymphoma
Papillary carcinoma - histology
- nuclear grooves
- psammoma bodies
- Orphan Annie eyes
- Lymphatic invasion (common)
thyroidectomy - complications
- hoarseness
- hypocalcemia
- transection of recurrent and superior laryngeal nerve
- compressing hematoma
thyroid cancer with BRAF mutation
papillary
thyroid cancer - childhood irradiation
papillary
multiple endocrine neoplasia (MEN) - mode of inheritance
ALL AD
MEN 1 - manifestations
3Ps
- Parathyroid tymors
- Pituitary tumors (prolactin or GH)
- Pancreatic endocrine tumors
MEN 1 - pancreatic endocrine tumors
- Zollinger Ellison syndrome
- insulinomas
- VIPomas
- Glucagonomas
MEN 2A - manifestations
- Parathyroid hyperplasia
- Pheochromocytoma
- Medullary thryroid carcinoma
MEN 2B - manifestations
- Pheochromocytoma
- Medullary thryroid carcinoma
- Oral/intestinal ganglioneuromatosis (mucosal neuromas)
- Marfanoid habitus
glucagonoma symptoms
5 Ds
- Dermatitis (necrolytic migratory erythema)
- Diabetes (hyperglycemia)
- DVT
- Depression
- declining weight
Zolinger-Ellison syndrome - area of tumor / causes / manifestation
- pancreas 2. duodenum
acid hypersecretion –> recurrent ulcers in duodenum and jejunum
manifestation: 1. abdominal pain (peptic ulcer disease, distal ulcers) - diarrhea (malabsorption)
Zollinger -Ellison synsdrome - diagnostic test
secretin stimulation test
positive –> gastrin levels remain elevated after administration of secretin
Carcinoid syndrome - rarely can cause (why)
pellagra niacnin deficiency (increased tryptophan metabolism)
pellagra symptoms p
- Diarrhea
- Dementia
- Dermatitis
somatostatinoma may present with
- diabetes/glucose intolerance
- statorrhea
- gallstones
somatostatinoma - treatment
surgical resection somatostain anglogs (eg. octreotide) for symptom
- T3 vs T4
- TBG leves are influenced by
- T3 more potent but shorter HT
- pregnancy + OCP increase TBG –> normal fT4
- nephrotic syndrome + androgen decrease TBG –> normal fT4
hyperprolactinemia - etiology
- cosecretion with GH (acromegaly)
- hypothyroidism (because high TRH)
- physiologic causes
- drugs
- prolactinoma
hyperprolactinemia - etiology - physiologic causes
- pregnancy
- intense exercise
- renal insufficiency
- increased chest wall stimulation
- also cutting the pituitary gland eliminates dopamine delivery to the anterior pituitary
- cirrhosis
hyperprolactinemia - drugs
- antipsychotic medications
- methyldopa
- metoclopramide
- opioids
- tryciclic antidepressants
- verapamil (the only Calcium channel blocker)
- OCPs
hyperprolactinemia - diagnostic tests after prolactin is found to be high
- thyroid function tests
- pregnancy test (always exclude pregnancy first)
- BUN/creatinine (kidney diseases elevates prolactin)
- liver function tests (cirrhosis elevates prolactin)
- MRI (AFTER)
hyperprolactinemia - MRI - when
- confirmed high prolactin levels
- 2ry causes like medication are excluded
- patient is not pregnant
hyperprolactinemia - treamtent (generally)
- medication (cabergolide is better tolerated than bromocriptine)
- transphenoidal surgery (if no response to meds)
- radiation rarely)
acromegaly - etiology
- almost always by adenoma (i can be associated with one of MEN when it is combined with parathyroid and pancreatic disorders
- rarely is caused by ectopic GH or GHRH production from lymphoma or bronchial carcinoid
- abuse of GH
Acromegaly enlarges soft tissue like cartilage + bone resulting in
- increased hat, ring, and shoe size
- carpal tunnel syndrome and obstructive sleep apnea (from soft tissue enlarging)
- body odor from sweat gland hypertrophy
- coarsening facial features and teeth widening from jaw growth
- deep voice + macroglossia (big tongue)
- colonic polyps and skin tags
- arthralgias from joint growing out of alignment
- hypertension for unclear reasons in 50%
- cardiomegaly + CHF
- erectile dysfunction from increased prolactin cosecreted with pituitary adenoma
acromegaly - diagnostic tests
- glucose intolerance and hyperlipidemia (contribute to cardiac dysfunction)
- best initial test: IGF-1
- most accurate: glucose suppression test
- MRI: only after lab identification of acromegaly
- prolactin levels (cosecretion)
- increased GH 1 to 2 hr following 100 g glucose load (decreases in normal cases
acromegaly - complications
HF, DM (insulin resistance - in 10%), spinal cord compressionm vision loss 2ry to pressure of tumor optic on nerve
acromegaly - medication
- cabergoline: dopamine will inhibit GH release
- octreotide or lanreotide: somatostatin inhibtis GH release
- Pegvisomant: GH receptr antagonists –> inhibit IFG release from liver
GH is an antinsulin - why does it make insulinelike growth factor
only the effect on proteins + aminoacids is inslulinlike
Prolactin deficinecy - presentation in men /women
never symptoms in men
in women: inhibits lactation after childbirth –> cannot lactate normally
GH deficiency - presentation in children vs adults
children: short stature and dwarfism
adults: few symptoms (several other hormones act: catecholamines, glucagon, cortisol), central obesity, reduce muscle mass, increased LDL and ch levels
clinical symptom that distinguish DKA from nonketotic hyperglycemia
Kussmaul breathing
psychiatric disease associated with psychogenic polydipsia
schizophrenia (NOT DEPRESSION)
metastatic tumor that causes CDI
very rare
Breast ca by far the MC
