Flashcards in Endocrine Deck (216):
Where does the thyroid gland develop?
thyroid diverticulum arises from floor of primitive pharynx, descending into neck. It is connected to tongue by thyroglossal duct which norally disappears but may persist as pyramidal lobe of thyroid.
What is the normal remnant of the thyroglossal duct?
What is the most common site of ectopic thyroid tissue?
tongue - lingual thyroid
How does a thyroglossal duct look like?
an anterior midline neck mass that MOVES w/ swallowing. Make sure you remove it b/c it can get infected
Tell me about the fetal adrenal gland?
- consists of an outer adult zone and inner active fetal zone.
- Adult zone is dormant during early fetal life but begins to secrete cortisol late in gestation.
- Cortisol secretion is controlled by ACTH and CRH from fetal pituitary and placenta.
Why is cortisol necessary for the fetus?
- responsible for fetal lung maturation and surfactant production
What is the embryonic derivative of the adrenal cortex and medullar?
- cortex = mesdoerm
- medulla = neural crest
What is produced in the adrenal medulla?
it's stimulated by pregangionlic sympathetic fibers to make catecholamines via chromaffin cells
What is produces in the adrenal cortex?
1. Renin-Angiotensin activates Zone Glomerulosa to make Aldosterone
2. ACTH, hypothalamic CRH stimulates Zone Fasciculata to make cortisol and some sex hormone
3. ACTH, hypothalamic CRH stimulates Zona Reticularis to make sex hormones
How do the adrenal glands drain?
1. Left adrenal --> left adrenal vein -- > left renal vein --> IVC
2. Right adrenal --> right adrenal vein --> IVC
What is the most common tumor of the adrenal medullar for an adult?
What is the most common tumor of the adrenal medulla in kids?
What is stored in the posterior pituitary? (neurohypophysis)
- secretes ADH and oxytocin
- remember derived from neuroectoderm
What is released from the anterior pituitary? (adenohypophysis)
Secretes FSH, LH, ACTH, TSH, prolactin, GH, MSH
- Remember derived from oral ectoderm (Rathke's pouch)
There are some hormones who have alpha and beta subunits. What are they and what is the importance of the subunits?
- FSH, LH, TSH, bhCG
- all the alpha subunits are the same
- the Beta subunits determines hormone specificity
What are the acidophilic hormones?
What are the basophilic hormones?
FSH, LH, ACTH, TSH
What makes up the endocrine pancreas?
1. alpha cells- make glucagon
2. beta cells- make insulin
3. delta cells- make somatostatin
- islets of langerhans are made up of peripheral alpha cells w/ central beta cells and interspersed delta cells
What are all the hormones involved in the HP and HPA axis?
1. TRH --> TSH and prolactin
2. Dopamine inhibits prolactin
3. CRH --> ACTH, MSH, beta-endorphin
4. GHRH --> GH
5. Somatostatin inhibits GH, TSH
6. GnRH --> FSH, LH
7. Prolactin inhibits GnRH
What is the precursor molecule for ACTH?
-POMC which also contains sequences for other hormonal peptides. eg MSH and beta-endorphin
Where is somatostatin made?
throughout the GI Tract notably by delta cells in pancreas and GI mucosa
- also made by nervous system
What effect do somatostatin have?
1. decrease endocrine and exocrine secretions
2. decrease splanchnic blood flow
3. decrease GI motility and gallbladder contraction
What are the clinical uses of somatostatin? eg octreotide
1. pituitary excess - acromegaly, thyroitropinoma, ACTH secreting tumor
2. GI endocrine excess: ZE syndrome, carcinoid syndrome, VIPoma, glucagonoma, insulinoma
3. Need to decrease splanchnic circulation : portal HTN and bleeding peptic ulcers, esophageal varicies
What is the function of prolactin?
1. stimulates milk production in breast
2. inhibits ovulation in females and spermatogenesis in males by inhibiting GnRH synthesis and release
How is prolactin regulated?
1. tonically inhibited by dopamine
2. prolactin in turn inhibits its own secretion by increasing dopamine synthesis and secretion
3. TRH increases prolactin secretion
What can be used to treat prolactinomas?
dopamine agonists - bromocriptine b/c they inhibit prolactin secretion
What can stimulate prolactin secretion?
Dopamine antagonists - most antipsychotics; and estrogens (OCPs, pregnancy)
What happens to females and males when they have hyperprolactinemia?
1. Premenopausal W - hypogonadism, infertility, oligo/amenorrhea, rarely galactorrhea
2. Postmenopausal W - non since they are already hypogonadal
3. Male - hypogonadism (low T) = decreased libido, impotence, infertility, gynecomastia, rarely galactorrhea
What is the function of GH?
Stimulates linear growth and muscle mass through IGF1/somatomedian secretion. Increases insulin resistance (diabetogenic)
How is GH regulated?
- Released in pulses in response to GHRH
- secretion increases during exercise and sleep
- Secretion inhibited glucose and somatostatin
What are all the steps to make aldosterone?
Cholesterol to Pregnenolone (Desmolase)
Preg to Progesterone (3BHSDH)
Prog to 11DOC (21hydroxylase)
11DOC to corticosterone (11Bhydroxylase)
Corticosterone to Also (Aldo synthase)
What are the steps to make Corisol?
Cholesterol to Preg (desmolase)
- essentially you NEED 17 alpha hydroxylase and 3BHSDH to make 17hydroxyprogresterone
- 17 hydroxyprog to 11deoxycortisol (21OHlase)
- 11 deoxycortisol to cortisol (11BOHlase)
What are the steps to make Testosterone?
need 17 hydryoxylase and 3Bhydroxysteroid DH
- to get to DHT you need 5 Alpha reductase
- Use aromatase to make Estrone and estradiol
What happens w/ a 17 alpha hydroxylase deficiency?
- increased mineralcorticoids
- HTN, hypokalemia
XY - decreased DHT = pseudohermaphroditism (variable, ambiguous genitalia, undescended testes)
XX - externally phenotypic female w/ normal internal sex organs, lacks primary sex characteristics
What happens w/ a 21 hydroxylase deficiency?
- increased sex hormones
- hypotension, hyperkalemia, increased renin activity, volume depletion
- masculinization leading to pseudohermaphroditism in females
What happens w/ a 11 B hydroxylase deficiency?
- increased sex hormones
- decreased aldosterone
- increased 11 DOC
HTN and masculinization
What are all of the congenital bilateral adrenal hyperplasia characterized by?
enlargement of BOTH adrenal glands due to increased ACTH stimulation b/c of decreased cortisol
What are all the functions of cortisol?
1. Maintains blood pressure - upregulates alpha1 receptors and increases sensitivity to NE and E
2. decreases bone formation
4. Increases insulin resistance (diabetogenic)
5. Increases gluconeogenesis, lipolysis, proteolysis - catabolic hormone
6. inhibits fibroblasts (causes striae) - decreases collagen synthesis
What are all the anti-inflammatory/immunosuppresive effects of cortisol?
1. inhibits production of LT and PGs
2. inhibits leukocyte adhesion --> neutrophilia
3. blocks histamine release from mast cells
4. reduces esoinophils
5. blocks IL 2 production
How is cortisol regulated?
1. CRH stimulates ACTH causing cortisol production in adrenal zona fasciculata.
2. excess cortisol decreases CRH, ACTH, and cortisol secretion
What are the side effects for excess cortisol?
1. thinning of skin
2. easy bruisability
4. adrenal cortical atrophy
5. peptic ulcers
What are the effects of stress?
2. increased lipolysis - increased FFA
4. higher cortisol levels, more catecholamines
5. affects water absorption
6. proteolysis = poor muscle tone
7. more frequent bowel movements
8. viscous secretions
What hormones use the Gs pathway?
FSH, LH, ACTH, TSH, CRH, hCG, ADH (v2), MSH, PTH, calcitonin, GHRH, glucagon
- FLAT ChAMP
What hormones use the cGMP pathway?
NO and ANP
What hormones use the IP3 pathway?
GnRH, GHRH, oxytocin, ADH (V1), TRH, Angiotensin II, gastrin
What hormones use steroid receptors?
Vit D, Estrogen, T, T3/T4, Cortisol, Aldosterone, Progesterone
What hormones use the intrinsic tyrosine kinase receptor?
Insulin, IGF1, FGF, PDGF, EGF
What hormones use the receptor associated tyrosine kinase?
Prolactin, Immunomodulators (eg cytokines IL2/6/8)
What is the signaling pathway of steroid hormones?
Steroid hormones are lipophilic and therefore must circulate bound to specific binding globulins which increase their solubility.
What happens to T when SHBG increases in men?
lowers free T
What happens to W when SHBG decreases?
raises free T leading to hirsutism
What happens to SHBG during pregnancy?
What is the hormone responsible for controlling the body's metabolic rate?
What is the source of TH?
follicles of thyroid. Most T3 formed in target tissues
What is the function of TH?
1. bone growth (synergism w/ GH)
2. CNS maturation
3. INcrease B1 receeptors in heart = increased CO, HR, SV, contractility
4. Increased basal metabolic rate via Increased NaKAPTase activity = increases O2 consumption, RR, Body temp
5. Increased glycogenolysis, gluconeogenesis, and lipolysis
What regulates TH?
TRH stimulates TSH which stimulates follicular cells.
- negative feedback by free T3 to anterior pituitary decreases sensitivity to TRH
- Thyroid stimulating Igs (TSIs) like TSH stimulates follicular cells -- Grave's
What is the Wolff-Chaikoff effect?
excess Iodine temporarily inhibits thyroid peroxidase = decreases iodine organification = decreases T3/T4 production
What happens to TBG in hepatic failure? in pregnancy?
1. failure = decreased so decrease in total TH
2. pregnancy = increased so increase in total TH
3. OCP = increases TBG
What is better T4 or T3?
T4 is the major thyroid product but it's converted to T3 in peripheral tissues by 5'deiodinase.
- T3 binds receptors w/ greater affinity
What are the steps to make TH?
1. I` is taken into follicular cells and oxidized via peroxidase
2. Then I2 is added to Thyroglobulin to form MIT and DIT = organification (also done by peroxidase), Y residues are added
3. T3/T4 is stored in colloid of thyroid gland
4. Follicular cells proteolyze T3/T4 before sending it out into the blood
What inhibits the initial uptake of I` into the follicular cells?
anions - perchlorate, pertechnetate
What inhibits the organification of TH?
antithyroid drugs - PTU, methimazole
What is Cushing's Syndrome?
increased cortisol due to many reasons
What is the most common cause of Cushing's syndrome?
exogenous steroids = decreased ACTH, both adrenal glands are atrophic
What are some endogenous causes of Cushing's Syndrome?
1. Cushing's Disease (75%)
2. Ectopic ACTH (15%)
3. Adrenal (15%)
What is Cushing's disease?
due to ACTH secretion from pituitary adenoma. Slight increase in ACTH
- both adrenals will be big
What are causes of ecotopic ACTH?
small cell lung cancer, bronchial carcinoids
- high levels of ACTH
What are causes of adrenal Cushings?
adenoma, carcinoma, nodular adrenal hyperplasia (one adrenal is big, other is atrophic)
- here you have decreased ACTH
What are the clinical findings for Cushing's syndrome?
2. WT gain
3. Moon facies
4. Truncal obesity
5. buffalo hump
7. skin changes (thinning, striae)
10. immune suppression
How is the dexamethasone suppression test used to ID cushing's syndrome?
1. Normal - should have suppressed levels of cortisol at high and low doses
2. ACTH pituitary tumor - will only be suppressed at high doses
3. Ecotopic ACTH Tumor and Adrenal producing cortisol tumor - both will have elevated levels of cortisol even at high and low doses of dexamethasone
What is primary hyperaldosteronism?
Caused by adrenal hyperplasia or an Aldosterone secreting adrenal adenoma (Conn) - may be bilateral of unilateral
What are the clinical presentations of primary hyperaldosteronism?
3. metabolic alkalosis
4. Low plasma renin
What is the treatment for a primary hyperaoldosteronism?
Surgery to remove tumor and spironolactone (K sparing diuretic that works by acting as an Aldo antagonist)
What is secondary hyperaldosteronism?
- renal perception of low IV volume results in overactive RAAS
- due to renal artery stenosis, chronic renal failure, CHF, cirrhois, or nephrotic syndrome
- HIGH PLASMA RENIN
What is Addison's Disease?
Chronic primary adrenal insufficiency due to adrenal atrophy or destruction of disease
- deficiency of aldo and cortisol
What are the clinical findings of Addison's Dz?
1. hypotension (hyponatremic volume contraction)
4. skin hyperpigmentation (due to increased MSH from ACTH)
What happens in secondary adrenal insuffiency?
- problem is at the pituitary
- no hyperpigmentation or hyperkalemia
- low cortisol b/c of low ACTH
What happens in tertiary adrenal insufficiency?
abrupt withdrawal of exogenous steroids
- mild HTN
What is Waterhouse Friderichsen syndrome?
Acute primary adrenal insufficiency due to adrenal hemorrhage associated w/ Neisseria meningitidis
What are symptoms of Waterhouse Friderichsen syndrome?
septicemia, DIC, endotoxic shock, petechial rash
What is pheochromocytoma?
Secretes E, NE, and dopamine which can cause episodic HTN
How can a pheochromocytoma be Dxed?
- Urinary VMA, metanephrine, HVA
- plasma catecholamines are elevated
what else is pheochromocytoma associated with?
- neurofibromatosis type 1
- MEN 2A and 2B
What is the treatment for Pheochromocytoma?
remove tumor only after effective alpha and beta blockers is achieved.
- irreversible alpha antagonists must be given first to avoid a hypertensive crisis
- Beta blockers are then given to slow the heart rate
What are the symptoms of a pheochromocytoma?
1. High BP
2. Pain (headache)
What is the rule of 10's for pheochromocytoma?
10% extra-adrenal -- bladder
Where can a neuroblastoma occur?
anywhere along the sympathetic chain
- less likely to develop HTN
What are things associated w/ a neuroblastoma?
1. N-myc oncogene
2. Bombesin tumor marker
3. Neurofilament stain
4. Homer-Wright pseudorosette
What are the signs/symptoms of Hypothyroidism?
1. cold intolerance (decreased heat production)
2. Wt gain, decreased appetite
3. Hypoactivity, lethargy, fatigue, weakness
5. decreased reflexes
6. myxedema (facial/periorbital)
7. dry, cook skin. coarse brittle hair
8. bradycardia, dyspnea on exertion
What are the signs/symptoms of Hyperthyroidism?
1. heat intolerance (increased heat production)
2. wt loss, increased appetite
3. Hyperactivity, sweating
5. increased reflexes
6. pretibial myxedema (grave's)
7. warm, moist skin. fine hair
8. chest pain, palpitations, arrhythmias, increased Beta adrenergic receptors
What are the lab findings for hypothyroidism?
decreased free T4
What are the lab findings for hyperthyroidism?
decreased TSH if primary
increased free/total T4
increased free/total T3
What are some causes of hypothyroidism?
1. Hashimoto's thyroiditis
3. Subacute Thyroiditis (de Quervain's)
4. Riedel's Thyroiditis
5. Other causes - congenital hypothyroidism, iodine deficiency, goitrogens, Wolff-Chaikoff effect, painless thyroiditis
What is Hashimoto's thyroditis?
MCC of hypothyroidism.
- autoimmune disorder (against peroxidase and thyroglobulin)
- may be hyperthyroid early in course. thyrotoxicosis during follicular damage
What is associated a/ Hashimoto's thyroiditis?
- increased risk of non-Hodgkin's lymphoma ( B cell)
What is seen on histology for Hashimoto's thyroiditis?
lymphocytic infiltrate w/ germinal centers
- Hurthle cells: enlarged epithelial cells w/ increased eosinophilic cytoplasm
What are the clinical findings of Hasimoto's thyroiditis?
moderately enlarged, nontender thyroid
What is Cretinism?
- due to severe fetal hypothyroidism
- endemic ones are seen wherever endemic goiters are prevalent (lack of dietary iodine)
- sporadic cretinism is caused by defect in T4 formation or development failure in thyroid formation
What are the clinical findings for Cretinism?
3. puffy face child
4. protruding umbilicus
5. protuberant tongue
short stature, mental retardation, coarse facial features
What is subacute thyroiditis (de Quervain's)?
self-limited hypothyroidism often following a flu-like illness
- may be hyperthyroid early in course
What are the histology findings for De Quervains?
What are the clinical findings for De Quervains?
increased ESR, jaw pain, early inflammation, very tender thyroid
What is Riedel's Thyroiditis?
thyroid replaced by fibrosis tissue
What are the findings for Riedel's thyroditis?
fixed, hard, rock-like , and painless goiter
- macrophages and eosinophils
What is a toxic multinodular goiter?
focal patches of hyperfunctioning follicular cells working independently of TSH due to mutation in TSH receptor
- increase release of T3 and T4
- hot nodule - so takes up radioactive I
What is Jod Basedow phenomenon?
thyrotoxicosis if a pt w/ iodine deficiency goiter is made iodine replete
What is Grave's disease?
Autoimmune hyperthyroidism w/ TSI
- Type III HSR
- Increase T3/T4 but decreased TSH
- scalloped colloid
What are some clinical findings of Grave's?
1. pretibial myxedema
2. ophthalmopathy - proptosis, EOM swelling
3. increased CT deposition
4. diffuse goiter
What is a thyroid storm?
stress induced catcholamine leading to death by arrhythmia (afib)
- serious complication of Grave's and other hyperthyroid disorders
- may see increase ALP due to increase bone turnover
What are some symptoms of thyroid storm?
hyperthermia, vomiting, hypovolemic shock
What is the treatment for thyroid storm?
3. Beta blockers
What is the MC thyroid cancer?
Tell me about papillary carcinoma of thyroid?
1. good prognosis
2. empty- appearing nuclei (ground glass; Orphan Annie eyes)
3. Psammoma bodies - layered calcification
4. nuclear grooves
- increased risk w/ childhood irradiation
5. spreads to nearby lymph nodes
Tell me about follicular carcinoma of thyroid?
1. good prognosis
2. uniform follicles
3. spreads via blood
Tell me about medullary carcinoma of thyroid?
1. from parafollicular C cells - produce calcitonin
2. sheets of cells in amyloid stroma
3. Associated w/ MEN 2A and 2B
What are the various mutations seen w/ thyroid cancers?
1. papillary - Ret
2. follicular -Ras
3. Medullary - Ret
Tell me about undifferentiated/anaplastic thyroid cancer?
older pts, very poor prognosis
- invade local structures= dysphagia or respiratory problems
What are some goitrogens that can cause hypothyroidism?
What is the major regulator of insuline release?
How is insulin made?
it's made as a preproinsulin. The finally product is cleaved into C peptide and insulin.
- Insulin has disulfide bonds b/w alpha and beta chains
How is insulin released from the beta cells of the pancreas?
1. Glu enters via Glut 1
2. Glu undergoes glycolysis and increases the ATP:ADP ratio
3. HIgh levels of ATP close the ATP sensitive K channel
4. The cell is depolarized
5. Voltage gated Ca channels open
6. Ca causes exocytosis of insulin granules
What are all the organs that have insulin- independent glucose uptake?
Brain, RBCs, Intestine, Cornea, Kidney, Liver
Where are Glut 1 receptors found?
- insulin independent
Where are Glut 2 receptors found?
- Beta islet cells, liver, kidney, small intestine
Where are Glut 4 receptors found?
Adipose tissue and skeletal muscle
What are all of the anabolic effects of insulin?
- increase glucose transport in skeletal muscle and adipose
- increase glycogen synthesis and storage
- increase TG synthesis and storage
- increase Na retention (kidneys)
- increase protein synthesis (muscles)
- increase cellular uptake of K and amino acids
- decrease glucagon rlease
What regulates insulin?
1. Hyperglycemia, GH, and Beta2 antagonists - increase insuline
2. Hypoglycemia, somatostatin, and alpha agonists - decrease insulin
What are the effects of glucagon?
Lipolysis and ketone production
When is glucagon released?
in response to hypoglycemia
- inhibited by insulin, hyperglycemia, and somatostatin
What are the acute manifestation of DM?
- polydipsia, polyuria, polyphagia, wt loss, DKA (type I), hyperosmolar coma (type 2), unopposed secretion of GH and E (exacerbating hyperglycemia)
What happens with insulin deficiency and glucagon excess?
1. Decreased glucose uptake = hyperglycemia, glycosuria, osmotic diuresis, electrolyte depletion --> dehyrdation, acidosis --> coma/death
2. Increased protein catabolism -= increased plasma AA, nitrogen loss in urine, and above
3. Increased lipolysis = increased plasma FFAs, ketogenesis, ketonuria, ketonemia --> dehydration and acidosis --> coma/death
What are the chronic manifestations of DM due to?
1. Nonenzymatic glycosylation
2. Osmotic damage
What is affected by nonenzymatic glycosylation?
1. Small vessels - diffuse thickening of basement membranes --> retinopathy ( hemorrhages, exudates, microaneurysms, vessel proliferation), glaucoma, nephropathy (nodular sclerosis, progressive proteinuria, chronic renal failure, arteriosclerosis leading to HTN)
2. Large vessel atherosclerosis, CAD, peripheral vascular occlusive disease, and gangrene --> limb loss, cerebrovascular disease
What is affected by osmotic damage?
- sorbital accumulation in organs w/ aldose reductase
- Neuropathy (motor, sensory, and autonomic degeneration) b/c Schwann cells affected
- Cataracts b/c lens of eye is affected
What are the tests to Dx DM?
Fasting serum glucose
oral glucose tolerance test > 200
What is acanthosis nigracans seen in?
DM and visceral malignancies
What are the special types of nodules seen in DM?
Kimmerlstiel Wilson nodules in the kidneys
what is the primary defect in type 1 DM?
autoimmune destruction of Beta cells of pancreas
What is the primary defect in type 2 DM?
increased resistance to insulin, progressive pancreatic Beta cell failure
What is the age that is associated w/ Type 1 and 2 DM?
Type 1 - less than 30
Type 2 - greater than 40 usually
What is the genetic predisposition with Type 1 and 2 DM?
Type 1 - relatively weak
Type 2 - relatively strong genetic
What type of DM has a HLA association? What is the HLA?
Type 1, HLA DR3 and 4
What is the level of glucose intolerance w/ Type 1 and 2 DM?
Type 1 - severe
Type 2 : mild to moderate
What type of DM has insulin sensitivity?
What type of DM is ketoacidosis common in?
Which type of DM do the classic symptoms of polyuria, polydipsia, polyphagia, and wt loss present in?
What is the histology of type 1 and 2 DM?
Type 1 - islet leukocyte infiltrate
Type 2 - islet amyloid (AIAPP deposit)
What is diabetic ketoacidosis?
one of the most important complications of DM (usually type 1).
- Usually due to increased insulin requirement from increased stress (eg infxn)
- excess fat breakdown and increase ketogenesis from increased FFA which are then made into ketone bodies
What are the main ketone bodies?
B-hydroxybutyrate > acetoacetate
What are the signs and symptoms of Diabetic ketoacidosis?
- Kussmaul respirations
N/V, abdominal pain, psychosis/delirium, dehydration,
- fruity breath order (due to exhaled acetone)
What are kussmaul respirations?
rapid regular deep breathing that is meant to exhale the extra CO2
What are the labs of diabetic ketoacidosis?
-hyperglycemia, increased acid, decreased Bicarb (anion gap metabolic acidosis)
- increased blood ketone levels, leukocytosis, hyperkalemia but depleted intracellular K due to transcellular shift from decreased insulin
What are the complications of Diabetic ketoacidosis?
- life threatening mucormycosis
Rhizopus infxn, cerebral edema, cardiac arrhythmias, heart failure
What is the treatment of diabetic ketoacidosis?
- IV fluids, IV insulin, and K (to replete intracellular stores), glucose if necessary to prevent hypoglycemia.
What is carcinoid syndrome?
- rare syndrome caused by carcinoid tumors (neuroendocrine) especially metastatic small bowel tumors, which secrete high levels of serotonin (5HT)
- not seen if tumor is limited to GI tract (5HT undergoes first pass metabolism in liver
What are the symptoms of carcinoid syndrome?
- recurrent diarrhea, cutaneous flushing, asthmatic wheezing, and right sided valvular disease
What are the labs of carcinoid syndrome?
increased 5HIAA in urine and niacin deficiency
What is the treatment for carcinoid syndrome?
somatostatin analog -- octreotide
What is the rule of 1/3s for carcinoid syndrome?
- 1/3 metastasize
- 1/3 present w/ 2nd malignancy
- 1/3 multiple
- it's the most common tumor of appendix
What is ZE syndrome?
gastrin secreting tumor of pancreas of duodenum
- stomach shows rugal thickening w/ acid hypersecretion
- causes recurrent ulcers
- may be associated w/ MEN type 1
What is MEN 1? (werner's syndrome?
3 P's: Parathyroid, pituitary (prolactin or GH), and pancreatic endocrine tumors (ZE syndrome, insulinomas, VIPomas, glucagonomas
- Commonly presents w/ kidney stones and stomach ulcers
What is MEN 2A? (sipple's syndrome)?
- Medullary thyroid carcinoma (secretes calcitonin)
- parathyroid tumors
What is MEN 2 B?
Medullary thyroid carcinoma
Oral/intestinal glanglioneuromatosis (associated w/ marfanoid habitus) - mucsoal neuroma
What gene mutations is associated w/ MEN 2A and 2b?
What is the mode of inheritance for the MEN syndromes?
What is the treatment strategy for Type 1 DM?
low sugar diet, and insulin replacement
What is the treatment strategy for Type 2 DM?
dietary modification and exercise for wt loss, oral hypoglycemic and insulin replacement
What are the different types of insulin?
1. Lispro (rapid acting
2. Aspart (rapid acting)
3. Glulisine (rapid acting)
4. Regular (short acting)
5. NPH (intermediate)
6. Glargine (long acting)
7. Determir (long acting)
What is the action of insulin for treatment purposes?
1. binds insulin receptor
Liver - increases glucose stores as glycogen
Muscle - increase glycogen and protein synthesis and K uptake
Fat - aids TG storage
What is the clinical use for insulin?
Type 1 DM, type 2 DM, gestational diabetes, life threatening hyperkalemia, stress induced hyperglycemia
What are the toxcities of insulin?
hypoglycemia, very rarely HSR rxn, lipodystrophy, wt gain
MOA of biguanides (metformin)
decreased gluconeogenesis, increased glycolysis, increased peripheral glucose uptake (insulin sensitivity)
- acts in liver
What is the clinical use for metformin?
Oral - first line therapy in type 2 DM
can be used in pts w/out islet function
What are the toxicities of metformin?
LACTIC ACIDOSIS (thus contraindicated in renal failure and IV contrast)
MOA of sulfonylureas?
closes K channel in beta cell membrane so cell depolarizes and triggers insulin release via increase Ca influx
clinical uses of sulfonylureas
stimulates release of endogenous insulin in type 2 DM. Requires some islet function, so useless in type 1 DM
- very useful in early type 2 DM
What are the 1st gen sulfonylureas?
What are the 2nd gen sulfonylureas?
toxicites of 1st gen sulfonylureas
toxicities of 2nd gen sulfonylureas
hypoglycemia can be long lasting
MOA of glitazones/thiazolidinedionines (TZD)
increase insulin sensitivity in peripheral tissues
- binds to PPAR-gamma nuclear transcription regulator
What is the clinical use of TZD?
uses as monotherapy in type 2 DM or combined w/ other hypoglycemics
ADE of TZD?
wt gain, ededma, hepatoxiticity, heart failure
What are examples of TCD?
Pioglitazone and Rosiglitazone
What hypoglycemic increases risk of MI?
MOA of alpha-glucosidase inhibitors?
inhibit intestinal brush border alpha-glucosidase
- delayed sugar hydrolysis and glucose absorptino
- decreased postprandial hyperglycemia
- used in type 2 DM
ADE of alpha-glucosidase inhibitors?
- GI disturbances
Examples of alpha-glucosidase inhibitors
MOA of amylin analog (pramlintide)
decreased glucagon and decrease gastric emptying
- used in type 1 and 2 DM
ADE of amylin analog
hypoglycemia, nausea, diarrhea
MOA of GLP1 analogs
- increase insulin
- decrease glucagon release
- Type 2 DM
ADE of GLP1 analog
examples of GLP1 analogs
1. exenatide - exendin analog
2. liraglutide - synthetic analog
DPP-4 inhibitors MOA
decreases glucagon release
- affects GLP1, prolongs incretin action
- Type 2 DM
DDP4 inhibitors ADE
mild urinary or respiratory infxns
Examples of DDP4 inhibitors?
What is PPAR-gamma used for?
gene activated by PPAR gamma regulate fatty acid storage and glucose metabolism
- increases insulin sensitivity and levels of adiponectin
MOA of PTU
blocks peroxidase, thereby inhibiting organification of iodide and coupling of TH synthesis
- blocks 5'deiodinase = decreases peripheral conversion of T4 to T3
MOA of methimazole
blocks peroxidase, thereby inhibiting organification of iodide and coupling of TH synthesis
clinical use of PTU and methimazole
PTU can be used in pregnancy
skin rash, aganulocytosis, aplastic anemia, hepatoxcity
skin rash, agranulocytosis, aplastic anemia
MOA of levothyroxine and triiodothyronin
clinical uses of levothyroxine and triiodothyronin
hypothyrodism and myxedema
ADE of levothyroxine and triiodothyronin
tachycardia, heat intolerance, tremores, arrhythmias
Clinical use of GH
GH deficiency, Turner syndrome
Clinical use of somatostatin (octreotide)
acromegaly, carcinoid, gastrinoma, glucagonoma, esophgeal varices
Clinical uses of oxytocin
stimulates labor, uterine contractions, milk let down, controls uterine hemorrhage
clinical uses of ADH (desmopressin)
pituitary (central, not nephrogenic) DI
MOA of demeclocyclin
ADH antagonist (member of tetracycline family)
clinical use of demeclocyclin
ADE of demeclocyclin
nephrogenic DI, photosensitivity, abnormalities of bone and teeth
MOA of glucocorticoids?
decrease production of LTs and PGs by inhibiting PLA2 and expression of COX 2
examples of gluocorticoids
Dexamethaosone - long acting
Beclomethasone -long acting
clinical uses of glucorticoids
Addison's dz, inflammation, immune suppression, asthma