Endocrinology Flashcards
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?
Pituitary adenoma.
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?
Polygenic polydipsia.
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?
Parathyroid adenoma.
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?
Normocytic, normochromic
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?
FSH.
Increased urinary VMA is indicative of what condition?
Pheochromocytoma.
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?
Papillary carcinoma.
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?
- 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?
Elevated.
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%.