Flashcards in Endocrinology Deck (144):
In a patient complaining of recent weight gain, easy fatiguability, high bp, high glucose, and high 24 hr urinary cortisol excretion, if cortisol levels can be suppressed by low-dose dexamethasone, what three conditions are possible?
Adrenal adenoma, adrenal malignancy, exogenous glucocorticoid intake.
In a patient complaining of weight gain, easy fatiguability, high bp, high glucose, and high 24 hr urinary cortisol excretion, if cortisol levels can be suppressed by HIGH dose dexamethasone, what condition is likely?
In a patient complaining of weight gain, easy fatiguability, high bp, high glucose, and high urinary 24 hr cortisol excretion, if cortisol levels are NOT suppressed by high dose dexamethasone, what condition is likely?
Ectopic ACTH production.
What is the difference in presentation between a patient with a cortisol secreting pituitary adenoma vs adrenal adenoma?
Adrenal- low to normal ACTH, pituitary- high ACTH.
What is the plasma concentration of sodium in patients with Diabetes Insipidus?
Greater than 142 mEq/L due to high water loss.
In a patient with low serum sodium levels and low urine osmolality, what is the likely diagnosis?
What should normal urine osmolality after dehydration challenge be?
Greater than 800 mOsm/L.
In a patient with primary polydipsia, how should urine osmolality change in a water deprivation test?
It should demonstrate a significant increase in urine osmolality- water restriction normalizes osmolality.
What is the difference between proteins synthesized on ribosomes in the cytosol compared to on ribosomes in the RER?
Ribosomes in the RER synthesize lysosomal, membrane bound, and secretory proteins; free ribosomes synthesize proteins used in the cytosol or for free organelles. RER is well developed in protein secreting cells.
What is the function of the smooth endoplasmic reticulum?
To function in lipid synthesis, carbohydrate metabolism, and detoxification of harmful substances.
What is the most common cause of primary hyperparathyroidism?
By what three mechanisms is excess serum calcium produced in hyperparathyroidism?
By an increase in renal absorption of calcium, by an increase in the GI absorption of calcium by vitamin D formation, and by an increase in bone resorption by osteoclast activation. Serum phosphorus is low due to decrease in phosphate resorption in the proximal renal tubule.
What is the classic bone finding in hyperparathyroidism?
Subperiosteal thinning (radiologically- subperiosteal erosions in the medial side of the second and third phalanges of the hand, granular salt and pepper appearance of the skull)
What are the classic findings in a patient with hyperparathyroidism?
Bone loss, renal stones, GI upset, psych disorders.
How is Vitamin D deficiency defined histologically?
Excessive unmineralized osteoid and widened osteoid seams.
Stimulation of what autonomic receptors increases insulin secretion?
M3 and beta2
Stimulation of what autonomic receptors decreases insulin secretion/ inhibit release?
Alpha2; this is the dominant effect causing sympathetic stimulation overall to inhibit insulin secretion.
Following glucocorticoid administration, what types of cells increase due to demargination of leukocytes previously attached to the vessel wall?
Neutrophil counts. Eosinophil counts decrease significantly as do lymphocytes, monocytes, and basophils.
What pathologic changes cause exopthalmos?
Increased soft tissue mass within the bony orbit due to increased muscle mass and fibroblast proliferation/ ground substance proliferation.
Name three presenting symptoms of glucagonoma.
Necrolytic migratory erythema (erythematous papules/ plaques on the face, perineum, extremities, lesions that enlarge and coalesce leaving a bronze coloured central indurated area with peripheral blistering/ scaling); DM, and GI sx (anorexia, diarrhea, abdominal pain). Often normocytic normochromic anemia is seen.
What type of anemia is seen in anemia of chronic disease?
Name three sx of primary mineralocorticoid excess (hyperaldosteronism).
HTN, suppressed plasma renin, weakness/parasthesias.
What is aldosterone escape?
The compensatory rise in ANP and natruiesis due to increased extracellular volume- this counteracts increased Na resorption due to aldosteronism leading to only a slight increase in ECF vol which manifests as hypertension without significant edema or hypernatremia. Increased excretion of K+ and H+ also occurs.
What plasma mineral levels characterize primary mineralocorticoid excess (hyperaldosteronism)?
Hypertension, hypokalemia, metabolic alkalosis, low renin levels.
What hormone is elevated in patients with klinefelters?
Increased urinary VMA is indicative of what condition?
The genetic defect associated with MEN2A and 2B is associated with what mutation?
Mutation of RET protooncogene.
What is the tissue origin of endocrine organs?
Neural crest cells.
Name two endocrine cell types that arise from neural crest.
Chromaffin cells of the adrenal medulla and parafollicular cells (C-cells) of the thyroid
In patients with some testicular tumors (namely non-seminomatous germ cell tumors i.e. teratomas), what symptoms are common and what serum marker is elevated?
Elevated hCG; symptoms of hyperthyroidism.
What are symptoms of subacute granulomatous thyroiditis (de Quervain's thyroiditis)?
Usually caused by viral infection; causes thyrotoxicosis, tenderness over the thyroid gland, increased ESR, markedly reduced radioactive iodine uptake.
How does subacute thyroiditis present histologically?
Patchy initial neutrophil infiltration followed by infiltration of lymphocytes, histiocytes and multinucleated giant cells surrounding fragmented colloid.
What is the difference between transient central DI and permanent central DI?
Permanent central DI is caused by damage to the hypothalamic nuclei; transient central DI is caused by isolated damage to the posterior pituitary.
What is the function of thyroid peroxidase?
Oxidation of inorganic iodide, formation of monoidodtyrosine/ diiodotyrosine, coupling of idotyrosines.
What is the mechanism of action and function of methimazole?
Antithyroid drug which acts by inhibiting thyroid peroxidase.
Name two drugs in the thionamide class.
Methimazole, propylthiouracil (used as antithyroid medications)
What is the difference in action between methimazole and propylthiouracil?
Propylthiouracil decreases peripheral conversion of T4 to T3 also.
What is the typical presentation of a male patient with 5a reductase deficiency?
Feminized external genitalia at birth that typically masculinizes at puberty.
What is the most common thyroid malignancy?
Describe the histology of papillary carcinoma of the thyroid.
Characteristically large cells with overlapping nuclei containing finely dispersed chromatin giving them a ground glass appearance (orphan annie eyes). There are numerous intranuclear inclusions and grooves due to invagination of the nuclear membrane. Psammoma bodies are also found.
Describe the histology of medullary thyroid cancer.
Polygonal to spindle shaped cells with a slightly granular cytoplasm that stains for calcitonin; adjacent amyloid deposits are seen. It arises from parafollicular c-cells.
What three strategies are used to minimize symptoms of thyrotoxicosis?
1. minimize thyroid hormone synthesis and release; 2. minimize peripheral conversion of T4 to more active T3; 3. minimize sympathetic outflow/ actions on target organs.
What is the mechanism of action of beta blockers in therapy for thyrotoxicosis?
Reduction of heart rate, reduction of anxiety/ agitation, reduction of peripheral conversion of T4-T3 by inhibiting iodothyronine deiodinase
What is the mechanism of action of thiazolidinediones?
Glucose lowering due to reduction of insulin resistance by binding PPAR-gamma.
What are the main side effects of thiazolidinediones?
Fluid retention, weight gain, precipitation of CHF; fluid retention is worse with concurrent insulin use.
How is exopthalmos characterized on histology?
Edema and infiltration of lymphocytes into the extraocular muscles and connective tissue with accumulation of glycosaminoglycans.
What is the effect of hypothyroid myopathy on creatine kinase?
What lab values distinguish menopause?
Elevated FSH due to loss of estrogen negative feedback. LH levels are also elevated but this is seen later in menopause.
Metformin is contraindicated in what patient population?
Patients with renal failure due to risk of lactic acid accumulation (or in any situation where lactic acidosis may be precipitated- liver dysfunction, CHF, sepsis, alcoholism, etc.)
What two reactions are catalyzed by 21-hydroxylase?
Conversion of progesterone to 11-deoxycorticosterone in zona glomerulosa; conversion of 17-hydroxyprogesterone to 11 deoxycortisol in the zona fasciculata.
How is c-peptide formed and secreted?
Formed from proinsullin in the pancreatic b-cell golgi apparatus and is packaged along with insulin in islet cell secretory granules and secreted in equimolar concentrations with insulin.
What induces negative feedback on LH? FSH?
Testosterone- LH; Inhibin B- FSH
What type of mutations are common in follicular thyroid cancer and in some follicular adenomas? Anaplastic thyroid cancer?
RAS mutations; p53 mutations in anaplastic thyroid cancer.
What are the three symptoms of MEN1?
Parathyroid tumor (hypercalcemia), pancreatic tumor (gastrin), pituitary adenoma (prolactin, ACTH).
What are the three symptoms of MEN2a?
Medullary carcinoma of thyroid (calcitonin), Pheochromocytoma, parathyroid tumor
What are the three symptoms of MEN2b?
Medullary carcinoma of thyroid (calcitonin), Pheochromocytoma, Marfanoid habitus/mucosal neuromas.
What is the difference in patients with complete central DI compared to those with partial central DI?
In complete central DI, rise in urine osmolality is typically more than 50%.
What is Conn's syndrome?
Name the three basal, long acting insullins.
NPH, Glargine, Detemir (once or twice daily)
What insulin is best for IV short acting use postprandially?
Name three insulins that are best for posptrandial post-meal hyperglycemia.
Lispro, Aspart, Glulisine.
What is the mechanism of action of thiazolidinediones?
Glucose lowering by improving insulin resistance; bind to PARR gamma (intracellular nuclear receptor) causing conformational change which allows binding to another coactivator to cause transactivation.
Which three drugs prevent the reduction of folic acid to tetrahydrofolate by inhibition of dihydrofolate reductase?
Trimethoprim, methotrexate, pyrimethamine.
What is the mechanism of action of sulfamethoxazole?
Competes with PABA to inhibit dihydrofolic acid synthesis (intermediate step in the formation of tetrahydrofolate)
What is the pregnancy 'triple test'?
Used to determind AFP, hCG, and estriol levels between 16 and 18 weeks of gestation.
What is the most common cause of elevated AFT levels during triple test?
Dating error- underestimation of gestational age which can be confirmed by fetal USG.
What AFP levels are characteristic of Downs?
Low AFP levels.
When are estriol levels decreased in a fetus?
Name three conditions in which hCG is elevated, not including conventional pregnancy.
Multiple gestation, hydratiform mole, choriocarcinoma.
Describe the presentation of a female born with 11-hydroxylase deficiency.
Ambiguous genitalia, hypertension, hypokalemia.
What is the typical presentation of males and females respectively born with classic, non-salt wasting 21-hydroxylase deficiency?
Males- Early virilization, increased linear growth, eleavated 17-hydroxyprogesterone and androgens; females- ambiguous genitalia at birth.
How is congenital adrenal hyperplasia treated?
Administration of low (physiologic doses) of exogenous corticosteroids to suppress ACTH secretion; this allows exogenous corticosteroids to decrease androgen production by the adrenal cortex.
C peptide is present in endogenous or exogenous insulin?
ENDOGENOUS only. C-peptide is LOW in exogenous administration.
How do you tell the difference between insulinoma and sulfonurea or meglitnide abuse?
By testing the urine or blood for hypoglycemic agents
What is characteristic of sulfonurea or meglitinide abuse and insulinoma?
Increased insulin, c-peptide, and pro-insulin levels.
Exogenous administration of corticosteroids causing Cushing's syndrome has what characteristics?
Suppression of the entire HPA axis; this causes low endogenous CRH, ACTH, and cortisol production and atrophy of the bilateral adrenal cortices. If the patient stops taking corticosteroids, adrenal crisis can result.
What is the medication of choice for the treatment of gestational diabetes melitus?
What hormone is deficient in Kallman syndrome and from where is it secreted?
GnRH from the hypothalamus.
What is the mechanism of action of Finasteride?
5-alpha reductase inhibitor that suppresses peripheral conversion of testosterone to dihydrotestosterone. (Used for BPH and androgenic alopecia).
What is the mechanism of action of flutamide?
Non-steroid antiandrogen used for the treatment of prostate cancer; it competes with testosterone and DHT for their receptors in the target cells. In treatment of prostate cancer, it is used in combination with GnRH agonists to suppress testosterone.
What is the function of anion inhibitors (perchlorate, pertechnetate) in iodine absorption?
Block iodine absorption by thyroid gland via competitive inhibition.
What is the mechanism of action of thionamides (methimazole and propylthiouracil)?
Decrease formation of thyroid hormones by inhibition of thyroid peroxidase.
What is the mechanism of action of iodide salts?
Inhibition of synthesis and release of thyroid hormones.
What is the most common type of tumor arising from Rathke's pouch in childhood?
What is the difference in presentation between males and females with 17-a-hydroxylase deficiency?
Males- appear phenotypically female at birth (no internal female genitalia); females develop normal internal and external genitalia. At puberty, secondary sex characteristics are not developed (no menarche in females).
What changes are seen around puberty in patients with 17-a-hydroxylase deficiency?
Hypertension, hypokalemia, low renin.
What is the common presentation of male infants with classic salt-wasting 21-hydrocylase deficiency?
Normal male genetalia; 1-2 weeks after birth present with vomiting, hypotension, hyponatremia, hyperkalemia (females present with ambiguous genitalia).
Name the three findings that characterize mineralocorticoid excess.
Hypertension, hypokalemia, metabolic alkalosis without marked hypernatremia and low renin levels due to hypervolemia.
What hormone abnormalities are characteristic of Klinefelter syndrome?
Low testosterone, low inhibin, high FSH, high LH.
What is iodide trapping?
The first step in the formation of thyroid hormone; it is an energy dependent transport of inorganic iodide into the thyroid follicular cell and is carried bout by the sodium iodide symporter (NIS) on the basolateral membrane of the thyroid follicular cell.
What ions are taken up by the sodium iodide symporter (NIS)?
Inorganic iodide, perchlorate, pertechnetate, radioactive iodine. All of these chemicals competitively inhibit each other.
What should be administered to prevent thyoid absorption of radioactive iodine isotopes?
In a nonmedical setting, how should loss of consciousness brought about by severe hypoglycemia be treated?
IM glucagon; this should be followed by IV dextrose in the medical setting.
How do methimazole and propylthiouracil (PTU) differ?
PTU decreases peripheral conversion of T4 to T3, has a shorter half life, and is the drug of choice in pregnancy (methimazole is teratogenic).
In a mother with poor glucose control, how does the fetus respond to high glucose and what are the consequences?
Increasing insulin causes beta cell hyperplasia. Once free from the mother, the infant continues to overproduce insulin and experiences severe hypoglycemia
Why do thiasolidinediones used to treat diabetes take days to weeks to observe reduction in glucose levels?
Because it results in alteration in gene transcription and protein production.
How does glucagon increase serum glucose?
By increasing production from the liver through glycogenolysis and gluconeogenesis
Name four symptoms strongly suggestive of adrenal crisis.
Shock, hyponatremia, hyperkalemia, hypoglycemia.
What is Waterhouse-Friderichsen syndrome?
Meningococcal septicemia causing adrenal hemorrhage which leads to acute adrenal crisis.
What is menotropin and how does it induce ovulation?
Human menopausal gonadotrophin; acts like FSH and leads to the formation of a dominant ovarian follicle. Ovulation is then induced by a large dose of hCG which stimulates the LH surge.
How is DKA treated?
IV infusion of regular insulin with IV fluids and correction of electrolyte imbalances (esp. potassium repletion)
What are the pharmacokinetic properties of regular insulin?
It is short acting with a half life of 5 minutes, allowing rate of infusion to be adjusted based on glucose levels.
What are the pharmacokinetic properties of subcutaneous short acting regular insulin?
Starts working in 30 minutes, peaks at 2-4 hours, lasts 5-8 hours.
What is the most common cause of death in patients with DM?
Coronary heart disease.
What is the metyrapone stimulation test?
Sensitive indicator of HPA integrity; it blocks cortisol synthesis by inhibiting 11-b-hydroxylase which converts 11-deoxycortisol to cortisol in the zona fasciculata. This reduces cortisol levels, causes an increase in pituitary ACTH and 11-deoxycortisol which is metabolized to 17-hydroxycorticosteroids which accumulate in urine.
Failure of serum 11-deoxycortisol and urine 17-hydroxycorticosteroid to rise in response to metyrapone indicates what condition?
Primary or secondary adrenal insufficiency
What are chromaffin cells?
Modified postganglionic sympathetic neurons derived from neural crest that receive sympathetic input. They are stimulated by Ach released by preganglionic neurons and secrete catecholamines (80% Epi, 20% NE) into the bloodstream to amplify SNS activity.
What effect does estrogen have on thyroid activity?
Increases total T4 and total T3 due to increases in thyroid binding globulin (TBG). Free hormone levels remain the same.
Describe the relationship between insulin and glucagon.
Insulin inhibits glucagon release
What type of drug is acarbose?
Alpha glucosidase inhibitor used in DM2
What is the mechanism of action of alpha-glucosidase inhibitors?
Decrease activity of membrane-bound disaccharidases on the intestinal brush border which prevents breakdown of disaccharides to allow delay in carbohydrate absorption
Describe the five manifestations of SIADH.
Low plasma sodium, low plasma osmolality, inappropriately concentrated urine, increased urinary sodium, clinically normal body fluid volume
What drug is most commonly used to treat hirsutism in women?
Spironolactone; less commonly flutamide and finasteride
What is desmopressin (DDAVP)?
Synthetic analog of vasopressin (ADH)
How does DDAVP act on vWF?
It induces endothelial procoagulatory protein release (including vWF); it is used in patients with vW disease during minor surgeries.
Which two drug classes improve blood glucose levels by increasing secretion of insulin from pancreatic b cells?
Sulfonylureas and meglitinides
Glucocorticoids increase synthesis of what proteins?
Liver proteins, especially enzymes involved in gluconeogenesis and glycogenesis (this contributes to hyperglycemia)
What type of drug is Canagliflozin?
SGLT2 inhibitor- causes urinary glucose loss
What side effects are associated with SGLT2s?
Urinary tract sx, genital mycotic infections due to glucosuria, symptomatic hypotension; contraindicated in patients with moderate to severe renal impairment due to lack of efficacy and increased risk of side effects; must assess renal function before beginning these drugs.
What is pituitary apoplexy and what most often causes it?
Acute hemorrhage into the pituitary gland; usually associated with preexisting pituitary adenoma. It presents with severe headache, CN involvement, signs of meningeal irritation. Tx is glucocorticoids to prevent hypotension and surgical decompression.
What is the effect of prolonged ACTH stimulation of the zona fasciculata and reticularis?
HyperPLASIA of the zona fasciculata and reticularis
How do medullary thyroid cancers present microscopically?
Cancer arises from parafollicular calcitonin-secreting-C-cells; microscopically there are uniform polygonal or spindle shaped cells with extracellular amyloid deposits; amyloid stains with congo red.
Describe the typical histological findings of Hashimoto's thyroiditis.
Mononuclear, parenchymal infiltration of lymphocytes and plasma cells with well developed germinal centers; Hurthle cells (large, oxyphilic cells with granular cytoplasm) are also present due to metaplastic change.
What is the difference between prolactin secretion and other pituitary hormone secretion?
Prolactin is under constant INHIBITION by dopamine secretion by the hypothalamus; thus hypothalamic destruction causes increased levels of prolactin secretion.
What is another name for somatomedin C?
Insulin-Like-Growth factor 1
What is the mechanism of action of anastrozole?
Selective inhibitor of aromatase (used in breast cancer)
What is the most common cell type in the pituitary gland?
Somatotrophs (secrete growth hormone)
What happens to serum calcium and serum phosphorus in vitamin D deficiency?
Decresed Ca and PO43- absorption from the GI tract; this causes increased PTH.
How do elevated PTH levels affect urinary phosphate excretion?
Increase urinary phosphate excretion.
How does aromatase deficiency manifest?
With maternal virilization during pregnancy; newborn girls have normal internal genitalia and ambiguous or male type external genitalia. At puberty- primary amenorrhea, osteoporosis, tall stature. Men have tall stature and osteoperosis but no genital abnormalities.
What is aromatase deficiency?
AR disorder manifesting early in embryonal life with high androgen and low estrogen in the female fetus.
Describe the electrolyte abnormalities in patients with primary adrenal insufficiency.
Hyponatremia, hyperkalemia, hyperchloremia, non-anion gap metabolic acidosis (caused by decreased H+ excretion and low serum levels of HCO3-)
What is the response of PTH, calcitonin, and Vit. D synthesis in response to calcium loading?
Decreased PTH and vit D. synthesis; increased calcitonin.
What causes pretibial myxedema?
Accumulation of glycosaminoglycans within affected tissues.
What is the most common cause of adrenal crisis and insufficiency?
What hormone levels characterize adrenal crisis due to glucocorticoid use?
Low CRH, ACTH, low cortisol.
In secondary hyperparathyroidism in patients with chronic renal failure, what is the effect on levels of PTH, calcium, and phosphorus?
High PTH, low calcium, high phosphorus
Name two classes of medication that often cause medication induced body fat redistribution syndrome.
HIV-1 protease inhibitors and glucocorticoids.
What transient conditions may occur in neonates of diabetic mothers?
Transient hypoglycemia and hypertrophic cardiomyopathy.
What is the mechanism of action of Leuprolide in the treatment of prostate cancer?
Long acting GnRH analog that causes continuous GnRH activity to ultimately suppress the pituitary gonadal axis after an initial start up flare with an increase in both testosterone and DHT levels.
What is the difference in alteration of hormone levels between Leuprolide and Finasteride in the treatment of prostate cancer?
Leuprolide is a GnRH agonist that causes a transient increase then decrease in both testosterone and DHT levels; finasteride causes a discordant decrease in DHT levels.
Increases in serum levels of what two products increase insulin resistance in overweight individuals?
Free Fatty acids and serum triglycerides.
During hyperglycemia, what is excess plasma glucose converted into?
To sorbitol by aldose reductase