Flashcards in Endocrinology Deck (142)
What receptors on what cells lead to NO release when stimulated?
Muscarinic receptors on endothelial cells
Most pituitary hormones act via cAMP-linked receptors. Which ones dont and how do they work?
GnRH, Oxytocin, and ADH act via IP3 system. Prolactin and GH act via JAK/STAT tyrosine kinases
Steroid hormones bind their receptors in the cytoplasm and translocate to the nucleus. What is the exception to this?
Thyroid hormones bind their receptor in the nucleus
What inhibits uptake and organification of iodide?
Anions (perchlorate, pertechnetate) inhibit uptake and excess iodine (Wolff-Chaikoff effect) inhibits organification
Why are beta blockers helpful in hyperthyroidism?
Combat sympathetic effects (except increased o2 demand and weight loss) and they decrease peripheral T4 to T3 conversion
Give the change in cortisol levels in the following conditions during a dexamethasone test (give low dose first then high dose): normal, ACTH-pituitary tumor, ectopic ACTH-producing tumor, cortisol-producing tumor
Normal - up (high dose not done). ACTH-pituitary tumor - up down. Ectopic ACTH-producing tumor - up up. Cortisol producing tumor - up up.
Causes of waterhouse-friederichsen syndrome
Neisseria meningitidis septicemia, DIC, endotoxic shock
Test of choice to diagnose pheochromocytoma
Urinary VMA or metanephrines
Treatment for pheochromocytoma
Alpha antagonists (esp phenoxybenzamine) and surgery
Most common extracranial neoplasm in children
Non-rhythmic eye movements with myoclonus (opsoclonus-myoclonus) in child
Test of choice for neuroblastoma
HVA (breakdown product of dopamine)
What genetic change is associated with neuroblastoma
N-myc overexpression signals rapid tumor progression
Spinal cord compression, pancytopenia, hepatomegaly, palpable nodules, proptosis, truncal ataxia
Hypotension, tachycardia, hypoglycemia, with existing history of vomiting abdominal pain and weight loss
Acute adrenal crisis (will occur in patients with adrenal insufficiency during stress)
Increased risk of what cancer in hashimotos thyroiditis
Histology of Hashimotos thyroiditis
Lymphocytic infiltrate with germinal centers with Hurthle cells. Thyroid will be moderately enlarged and nontender
Defect in T4 formation or developmental failure in thyroid formation
Pot-bellied, pale, puffy-faced child with protruding umbilicus and protuberant tongue
Self-limited hypothyroidism following flulike illness
Subacute (de Quervain) thyroiditis. Will see granulomatous inflammtion, jaw pain, tender thyroid
Thyroid replaced by fibrous tissue (hypothyroid). Will find fixed, hard painless goiter
What do you have to rule out if you suspect Riedels thyroiditis?
Iodine deficiency, thyroglossal duct cyst, goitrogens, Wolff-Chaikoff effect
Treatment for Graves
Glucocorticoids to reduce inflammation
What is another name for De Quervains Thyroiditis?
Granulomatous thyroiditis. (also subacute thyroiditis)
Give the histology of each of the following thyroid cancers: papillary, follicular, medullary
Papillary - ground glass nuclei, psammoma bodies, nuclear grooves. Follicular - uniform follicles. Medullary - sheets of cells in amyloid stroma
What type of bone changes do you see in hyperparathyroidism?
Subperiosteal reabsorption with cystic degeneration
What is osteitis fibrosa cystica associated with?
What GI abnormality is primary hyperparathyroidism associated with?
What is required to diagnose complete central DI?
An increase of 50 percent or greater in urine osmolality on DDAVP administration
Lab findings in prolactinoma
Decreased GnRH, decreased LH, decreased testosterone
One difference in symptoms between pheochromocytoma and neuroblastoma
Pheochromocytoma causes episodic hypertension
To where do the left and right adrenal veins respectively drain?
Left - left renal. Right - IVC
What do neurophysins do and what does their deficiency cause?
Carry ADH and oxytocin from hypothalamus to posterior pituitary. Deficiency leads to central DI
What are the posterior and anterior pituitary respectively derived from?
Posterior (neurohypophysis) - Neuroectoderm, Anterior (adenohypophysis) - Oral ectoderm (Rathkes pouch)
What do the acidophils and basophils of the pituitary gland make?
Acidophils - GH, prolactin. Basophils - FSH, LH, ACTH, TSH
What organs dont need insulin for glucose uptake?
Brain, RBCs, Intestine, Cornea, Kidney, Liver
What type of transport do GLUT transporters carry out, and what is their specificity for?
Facilitated diffuse for D-glucose
What type of receptor is the insulin receptor?
What protein gets activated as a result of insulin receptor stimulation in hepatocytes?
Protein phosphatase (which phosphorylates glycogen synthase)
Which glucose transporter is insulin dependent?
Give the pituitary hormones secreted or inhibited by each of the following hypothalamic secretions: TRH, Dopamine, Somatostatin, Prolactin
TRH - stim TSH and prolactin. Dopamine - inhibits prolactin. Somatostatin - inhibits GH and TSH. Prolactin - Inhibits GnRH
What substance acts counter to ACTH in synthesis of adrenal hormones?
Ketoconazole (inhibits cholesterol to pregenolone conversion by desmolase, which is stimulated by ACTH)
Inhibits cortisol formation by 11B-hydroxylase. Leads to decreased cortisol and increased ACTH (reflexively)
Relative levels of mineralocorticoids, cortisol, and sex hormones in 17a-hydroxylase deficiency
MC - high, cortisol - low, sex hormones - low
Relative levels of mineralocorticoids, cortisol, and sex hormones in 21-hydroxylase deficiency
MC - low, cortisol - low, sex hormones - high
Relative levels of mineralocorticoids, cortisol, and sex hormones in 11b-hydroxylase deficiency
MC - Aldosterone low but 11-deoxycorticosterone high, cortisol - low, sex hormones - high
Hypertension, hypokalemia, male pseudohermaphroditism if XY or female with lacking secondary sex characteristics if XX
Hypotension, hyperkalemia, increased renin, volume depletion, masculinization, female pseudohermaphroditism
11b-hydroxylase deficiency. Contrast with 21-hydroxylase deficiency, which is masculinization with HYPOtension
What is the most common congenital adrenal hyperplasia?
What does prolonged ACTH stimulation do to the adrenal gland histologically?
Causes hyperplasia of the fasiculata
Treatment of congenital adrenal hyperplasias
Suppress ACTH with exogenous corticosteroids
What effect does GH have on IGF-1 production?
Stimulates IGF-1 production in liver (no effect on hypothalamic activity)
Amenorrhea, galactorrhea, low libido, infertility
Prolactinoma (pituitary adenoma)
What secondary effect can a prolactinoma have in women?
Hypogonadism which leads to osteoporosis (prolactin inhibits GnRH release)
Medical treatment for prolactinomas
Bromocriptine or cabergoline (dopamine agonists)
Medical treatment for acromegaly
What factors cause increased GH release
Stress, exercise, and hypoglycemia
Serum sodium in DI
Greater than 142
Water deprivation test results in DI
Urine osmolality fails to increase (stays less than 300-500)
Treatment for DI
Central - desmopressin. Nephrogenic - HCTZ, indomethacin, or amilioride
Typically where is the dysfunction in central DI?
Hypothalamus. Usually posterior pituitary problems only cause transient DI
Treatment for SIADH
Demeclocycline or water restriction
Causes of SIADH (4)
Ectopic ADH (small cell), 2) CNS disorders/head trauma, 3) Pulmonary disease, 4) Drugs (eg cyclophosphamide)
Complication of pituitary adenoma
Pituitary apoplexy (bleeding into existing pituitary adenoma)
What type of insulin is the preferred treatment for DKA?
Regular (not short acting)
What factors tend to increase or decrease blood glucose in type 1 diabetics?
Infection, pain, and sleep deprivation tend to increase blood glucose. Exercise decreases blood glucose
What compounds are central in the pathogenesis of T2DM?
FFAs and serum TGs
What are the tests of choice for T1DM, T2DM, and gestational diabetes respectively?
T1 and T2 DM - fasting blood sugar (in the US). Gestational - OGTT
What are potassium levels like in DKA?
Hyperkalemia is present, but intracellular levels of K are very low due to transcellular shift from decreased insulin
What is your first step in management if you suspect mucormycosis in a DKA patient?
Biopsy and look at it under the microscope
Pathogenesis of fetal macrosomia in gestational diabetes
Maternal glucose crosses placenta, hyperplasia of fetal islets, fetal hyperinsulinemia followed by fetal hypoglycemia, fetal macrosomia
Rule of thirds for carcinoid
One third metastasize, One third present with second malignancy, one third present as multiple
Treatment for carcinoid syndrome
Test of choice for Zollinger-Ellison
Infusion of secretin (will see increased gastrin secretion in Z-E syndrome)
Pituitary (prolactin or GH), Parathyroid, Pancreas (ZES, insulinoma, VIPoma, glucagonoma). Kidney stones and stomach ulcers. Draw a diamond
Medullary thyroid carcinoma (calcitonin), Pheochromocytoma, Parathyroid tumors. Draw a square
Medullary thyroid carcinoma (calcitonin), pheochromocytoma, oral/intestinal ganglioneuromatosis (neuromas). Marfinoid habitus. Draw a triangle.
How does pheochromocytoma often present
Genetic mutation associated with MEN 2A and 2B
List the insulins and include their duration of action
Rapid - lispro and aspart. Short acting - insulin. Intermediate - NPH. Long-acting - Glargine and detemir
Treatment for gestational diabetes
Sulfonylurea (first generation)
Sulfonylurea (first generation)
Sulfonylurea (second generation)
Sulfonylurea (second generation)
Sulfonylurea (second generation)
Glitazone (aka thiazolidinedione)
Glitazone (aka thiazolidinedione)
Mimetic (diabetes drug)
Closes K channel in beta cell membrane, triggering insulin release via increased Ca influx
Mechanism of biguanides (metformin)
Unknown. Decreased gluconeogenesis, increased glycolysis, increased peripheral insulin sensitivity
Mechanism of Glitazones/Thiazolidinediones
Increased insulin sensitivity via PPAR-gamma binding
Alpha-glucosidase inhibitor mechanism
Inhibits intestinal brush border alpha-glucosidases leading to decreased glucose absorption
Mimetics (pramlinitide) action
Amylin analogue. Leads to decreased glucagon secretion and delayed gastric emptying and promotes satiety
Exenatide (GLP-1 analog) effects
Increased insulin, decreased glucagon release
What does activation of PPAR-gamma do and what drugs activate it?
Increases insulin sensitivity and levels of adiponectin. Glitazones/thiazolidinediones
Contraindications of metformin
Renal failure (can cause lactic acidosis)
Toxicities of glitazones/thiazolidinediones
Weight gain, edema, hepatotoxicity, heart failure
PTU and methimazole
Block peroxidase and inhibit iodide organification. PTU also blocks 5-deiodinase (decreasing peripheral conversion of T4 to T3).
Toxicities of PTU and methimazole
Rash, agranulocytosis, aplastic anemia, hepatotoxicity (PTU), teratogen (methimazole)
Necrolytic migratory erythema, elevated erethematous rash on groin, hyperglycemia, stomatitis, cheilosis, abdominal pain, anemia
Uses of GH
GH deficiency and Turner syndrome
Uses of octreotide
Acromegaly, carcinoid, gastrinoma, glucagonoma, hepatorenal syndrome
Uses of oxytocin
Stimulate labor, uterine contractions, milk let down, and controlling uterine hemorrhage
ADH anatgonist, use in SIADH. May cause nephrogenic DI, photosensitivity, abnormalities of bone and teeth
What effect do glucocorticoids have on liver sugar metabolism?
Stimulate gluconeogenesis (have an anti-insulin effect)
Uses of glucocorticoids
Addisons, inflammation, immune suppression, asthma, Graves
What is the bone finding in Cushings?
3 tumors secreting stuff you cannot suppress
Parathyroid adenoma making PTH, adrenal adenoma making cortisol, adrenal tumor secreting aldosterone
Most common cause of hypopituitarism in adults
Nonfunctioning pituitary adenoma
What type of necrosis occurs in Sheehans syndrome?
Coagulative (pituitary is not part of the brain)
Second most common cause of hypopituitarism in adults
Most common cause of hypopituitarism in kids
First signs of hypopituitarism
Amenorrhea or impotence (due to loss of gonadotropins)
Test of choice for pituitary dwarfism
Sleep GH and IGF-1 levels
What amino acids stimulate growth hormone release?
Histidine and arginine
Order in which hormone production disappears in hypopituitarism
(first to go) Gonadotropins, GH, TSH, ACTH, prolactin (last to go)
Stimulators of prolactin synthesis
OCPs, hydralazine, Ca channel blockers, psychotropic drugs, primary hypothyroidism
What non-thyroid related symptom is seen in women with primary hypothyroidism and why?
Galactorrhea. Low thyroid hormones levels increase synthesis of TSH and TRH. TRH stimulates prolactin synthesis
Prolactin level above what value always means prolactinoma?
Increased T4 with a normal TSH
Estrogens such as OCPs or pregnancy (due to increase in TBG)
Use of I-131 test
Distinguishes Graves from exogenous thyroid supplementation
Cardiac abnormality associated with Graves
Most common symptom of hypothyroidism
Proximal muscle weakness (cannot get out of chairs, serum CK will be high)
Give the rule for cold thyroid nodules
Any cold nodule in a man or child is cancer until proven otherwise. Cold nodules in (esp older) women are often benign
Thyroid cancer prognosis
(Best) Papillary then follicular then medullary (worst)
Most common cause of hypocalcemia
Hypoalbuminemia (albumin carries about 40 percent of total Ca)
Why is alkalosis associated with tetany?
Because albumin is made of acidic AAs, and thus will bind more free calcium (lowering ionized calcium levels) in alkalotic state. Will not have hypocalcemia on labs but will have tetany and functional hypocalcemia
Purple striae, obesity, thin extremities
What type of Cushings can you suppress with high dose dexamethasone?
What will the low dose dexamethasone suppression test result be in all types of Cushings?
Failure to suppress. You will, however, see suppression at low doses in normal patients
Why do Cushings patients have thin exremities and central obesity?
Cortisol encourages protein (muscle) breakdown, but leads to hyperglycemia, which leads to insulin release, which causes fat and sugar storage centrally. Essentially we are moving tissue from our muscles centrally
Why are the striae in Cushings purple?
Cortisol decreases collagen synthesis
Why will patients with Conns syndrome have tetany?
Metabolic alkalosis causes functional hypocalcemia
Patient with neurofibromatosis and HTN
Suspect pheochromocytoma. Check VMA and metanephrines