Copy Of Investigation Of Endocrine Disease

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Copy Of Investigation Of Endocrine Disease

  1. 1. Investigation of endocrine disease
  2. 2. Endocrinology is Easy <ul><li>Diseases are due to </li></ul><ul><ul><li>TOO MUCH hormone </li></ul></ul><ul><ul><li>TOO LITTLE hormone </li></ul></ul><ul><li>Hormone levels vary physiologically </li></ul><ul><li>Testing needs to be dynamic </li></ul><ul><ul><li>If the hormone is too high SUPPRESS IT </li></ul></ul><ul><ul><li>If the hormone is too low STIMULATE IT </li></ul></ul>
  3. 4. Pituitary Gland <ul><li>Anterior: hormone secretion of thyroid, adrenal cortex, gonads </li></ul><ul><li>Posterior: water balance, salt balance </li></ul>
  4. 5. Two Major Divisions of Pituitary <ul><li>Each has a distinct role to play in hormone regulation </li></ul>Anterior “ Adenohypophysis” Posterior “ Neurohypophysis”
  5. 7. Diagnosis of PD by PH stimulation test Peak value >5 mu/ml TRH 500 ng TSH Doubling of baseline TRH 100-500 metoclopramide Prl Serum GH > 10ng/ml at any time I H test 0.1 uint L-dopa 250-500 Arginine 0.5 gm Clonidine test Glucagon test G H N response Test agent Hormone
  6. 8. Pituitary stimulation test 2 Peak serum cortisol >20 ng/dl Serum 11-deoxycortisol level >8 ng/dl I H TEST (short ACTH stimulation test cosyntropin test) Metyrapone test 2-3 gm po ACTH Doubling of the base line LH@FSH GnRH 100mmg IV LH @FSH N response Test agent hormone
  7. 9. Laboratory finding in acromegaly <ul><li>Plasma glucose may be elevated </li></ul><ul><li>Increase serum insulin </li></ul><ul><li>Elevated serum phosphate </li></ul><ul><li>Hypercalciuria </li></ul><ul><li>Elevated GH </li></ul>
  8. 10. Diagnosis of acromegaly <ul><li>Glucose suppression test </li></ul><ul><li>IGF-1 </li></ul><ul><li>Tumor localization </li></ul><ul><li>MRI </li></ul>
  9. 11. Posterior pituitary hormone (ADH vasopressin) <ul><li>ADH acts through tow receptors V1 @ V2 </li></ul><ul><li>V1 receptors mediate vascular smooth muscle contraction @stimulate prostaglandin synthesis </li></ul><ul><li>V2 receptors produce renal action by increase the water permeability of the luminal membrane of collecting duct epithelium </li></ul><ul><li>In the absence of ADH permeability of the epithelium is decrease leading to polyuria </li></ul>
  10. 13. Laboratory finding <ul><li>A large urinary volume >3 l /per day </li></ul><ul><li>Urine osmolality less than 200 mosm/kg </li></ul><ul><li>Slightly elevated plasma osmolality </li></ul><ul><li>Low serum ADH in CDI </li></ul><ul><li>High or normal ADH in NDI </li></ul>
  11. 14. Diagnosis of DI <ul><li>Water deprivation test (method) </li></ul><ul><li>Deprivation from water for 4-18 hr </li></ul><ul><li>Hourly measurements of urine osmolality </li></ul><ul><li>Continues until urine osmolality of 3 consecutive sample varies by less than 30 mosml/kg </li></ul><ul><li>5 unite of AVP or 1 mg of desmopression injected @ urine and plasma osml measure 30,60,120 m later </li></ul>
  12. 15. Interpretation of WDT low Normal or high low Plasma ADH increase No change increase Urine osmol after vasopressin Increase >750 No change <300 No change <300 Urine osmol after wdt psychogenic NDI CDI
  13. 16. Thyroid gland
  14. 17. Thyroid <ul><li>Growth, development </li></ul><ul><li>Metabolic rate </li></ul>
  15. 18. Thyroid Function Tests <ul><li>Free serum thyroxine (T4) </li></ul><ul><li>Free serum T3 </li></ul><ul><li>TSH </li></ul>
  16. 19. Scans/Ultrasound <ul><li>Radioiodine uptake (RAIU) </li></ul><ul><li>Thyroid Scan </li></ul><ul><li>Ultrasound </li></ul><ul><li>Fine needle Aspiration </li></ul>
  17. 20. Radioiodine Uptake <ul><li>Useful in differentiating non-pituitary thyrotoxic states (i.e., low TSH, high free thyroxine) </li></ul><ul><li>No use in hypothyroidism </li></ul><ul><li>A set dose of radioactive iodine (usually I123) is given and 24hrs later a radiation detector is placed over the thyroid to determine % of dose taken up by thyroid </li></ul>
  18. 21. RAIU <ul><li>RAIU is increased in </li></ul><ul><ul><li>Graves Disease </li></ul></ul><ul><ul><li>Hot nodules </li></ul></ul><ul><ul><ul><li>Multi-nodular goiters </li></ul></ul></ul><ul><ul><ul><li>Toxic Solitary Nodule </li></ul></ul></ul><ul><ul><ul><li>hCG secreting tumors </li></ul></ul></ul>
  19. 22. RAIU <ul><li>RAIU is decreased in </li></ul><ul><ul><li>Amiodarone </li></ul></ul><ul><ul><li>Factitious Thyroiditis </li></ul></ul><ul><ul><li>Self limited thyroiditis-induced thyrotoxic state </li></ul></ul><ul><ul><ul><li>Painless chronic thyroiditis </li></ul></ul></ul><ul><ul><ul><li>Postpartum thyroiditis </li></ul></ul></ul><ul><ul><ul><li>Subacute thyroiditis </li></ul></ul></ul>
  20. 23. Thyroid Scan <ul><li>Also called scintiscan or radionuclide scan </li></ul><ul><li>A dose of radioiodine or Tc99m is given </li></ul><ul><li>Scintillation scanner produces a rough picture indicating how these isotopes localize in the thyroid </li></ul><ul><li>Thyroid scan is only used for nodular disease---useful for determining whether a nodule is hot or cold </li></ul><ul><li>Again---RAIU produces a number, scan produces a picture </li></ul>
  21. 24. Ultrasound <ul><li>U/S can provide information about its size and texture </li></ul><ul><li>Used for determining whether a nodule is cystic or solid </li></ul><ul><li>Follow the size of a nodule or goiter over time. </li></ul>
  22. 25. Parathyroid gland And calcium metabolisms
  23. 26. CALCIUM HOMEOSTASIS DIETARY CALCIUM INTESTINAL ABSORPTION ORGAN PHYSIOLOGY ENDOCRINE PHYSIOLOGY DIETARY HABITS, SUPPLEMENTS BLOOD CALCIUM BONE KIDNEYS URINE THE ONLY “IN” THE PRINCIPLE “OUT” ORGAN PHYS. ENDOCRINE PHYS. ORGAN, ENDOCRINE
  24. 27. VITAMIN D SYNTHESIS SKIN LIVER KIDNEY 7- DEHYDROCHOLESTEROL VITAMIN D 3 VITAMIN D 3 25(OH)VITAMIN D h  25-HYDROXYLASE 25(OH)VITAMIN D 1,25(OH) 2 VITAMIN D ( ACTIVE METABOLITE ) 1  -HYDROXYLASE TISSUE-SPECIFIC VITAMIN D RESPONSES
  25. 28. CALCIUM, PTH, AND VITAMIN D FEEDBACK LOOPS NORMAL BLOOD Ca RISING BLOOD Ca FALLING BLOOD Ca SUPPRESS PTH STIMULATE PTH BONE RESORPTION URINARY LOSS 1,25(OH) 2 D PRODUCTION BONE RESORPTION URINARY LOSS 1,25(OH) 2 D PRODUCTION
  26. 29. Adrenal gland
  27. 31. Synthesis of Adrenocortical Hormones <ul><li>Zona glomerulosa: aldosterone </li></ul><ul><li>Zona fasciculata: glucocorticoids (cortisol) </li></ul><ul><li>Zona reticularis: androgens (DHEA and androstenedione) </li></ul>
  28. 32. Regulation of Adrenocortical Hormones <ul><li>Hypothalamus </li></ul><ul><ul><li>CRH-containing neurons are stimulated </li></ul></ul><ul><ul><li>CRH delivered to anterior pituitary </li></ul></ul><ul><ul><li>CRH binds to receptors on corticotrophs, causing synthesis and secretion of ACTH </li></ul></ul>
  29. 33. Pathways of Steroid Biosynthesis
  30. 34. Cushing’s Syndrome <ul><li>Diagnosis of Cushing’s syndrome </li></ul><ul><ul><li>History </li></ul></ul><ul><ul><ul><li>Weight gain, fatigue </li></ul></ul></ul><ul><ul><ul><li>Infertility, impotence, changes in menstruation </li></ul></ul></ul><ul><ul><ul><li>Diabetes, polyuria, polydypsia </li></ul></ul></ul><ul><ul><ul><li>Depression, headache </li></ul></ul></ul><ul><ul><ul><li>Signs of underlying tumor (weight loss, appetite) </li></ul></ul></ul><ul><ul><li>Physical exam </li></ul></ul><ul><ul><ul><li>Obesity, fat distribution </li></ul></ul></ul><ul><ul><ul><li>Proximal muscle weakness/wasting </li></ul></ul></ul><ul><ul><ul><li>Palpation of abdominal mass </li></ul></ul></ul>
  31. 35. Cushing’s Syndrome <ul><li>Diagnosis of Cushing’s syndrome </li></ul><ul><ul><li>Labs </li></ul></ul><ul><ul><ul><li>24 hour urinary cortisol </li></ul></ul></ul><ul><ul><ul><ul><li>2-3 consecutive days </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Verify with creatinine values </li></ul></ul></ul></ul><ul><ul><ul><li>Spot AM/PM serum cortisol </li></ul></ul></ul><ul><ul><ul><ul><li>Circadian variation </li></ul></ul></ul></ul><ul><ul><ul><ul><li>AM ACTH surge causes increased cortisol </li></ul></ul></ul></ul><ul><ul><ul><ul><li>PM should see at least 50% drop in cortisol level </li></ul></ul></ul></ul><ul><ul><ul><li>Low-dose dexamethasone suppression test </li></ul></ul></ul>
  32. 36. Cushing’s Syndrome <ul><li>Diagnose cause of Cushing’s syndrome </li></ul><ul><ul><li>History (steroid use?) </li></ul></ul><ul><ul><li>Serum ACTH </li></ul></ul><ul><ul><ul><li>Elevated : Cushing’s disease, ectopic ACTH </li></ul></ul></ul><ul><ul><ul><li>Suppressed: primary adrenal source </li></ul></ul></ul><ul><ul><ul><li>Correlate with cortisol levels </li></ul></ul></ul><ul><ul><li>High-dose dexamethasone suppression test </li></ul></ul><ul><ul><li>Metyrapone test </li></ul></ul>
  33. 37. Cushing’s Syndrome <ul><li>Dexmethasone suppression test </li></ul><ul><ul><li>Synthetic glucocorticoid (30x more potent as inhibitor) </li></ul></ul><ul><ul><li>Low dose </li></ul></ul><ul><ul><ul><li>0.5mg po q6 hours x48 hours </li></ul></ul></ul><ul><ul><ul><li>Measure cortisol, 17-hydroxycorticosteroid, creatinine </li></ul></ul></ul><ul><ul><ul><li>Fall in all steroid levels in pseudo-Cushing and normals </li></ul></ul></ul><ul><ul><ul><li>Differentiates presence/absence of Cushing’s syndrome </li></ul></ul></ul><ul><ul><li>Alternative dosing </li></ul></ul><ul><ul><ul><li>1mg po at midnight and measure 8am cortisol </li></ul></ul></ul><ul><ul><ul><li>Much less sensitive </li></ul></ul></ul>
  34. 38. Cushing’s Syndrome <ul><li>Dexmethasone suppression test </li></ul><ul><ul><li>High Dose </li></ul></ul><ul><ul><ul><li>2mg po q6 hours x48 hours </li></ul></ul></ul><ul><ul><ul><li>Measure cortisol and urinary free cortisol </li></ul></ul></ul><ul><ul><ul><li>Ectopic ACTH and adrenal tumors- no suppression </li></ul></ul></ul><ul><ul><ul><li>Cushing’s disease- suppress to <50% of baseline </li></ul></ul></ul><ul><ul><ul><li>Usually only used if ACTH/Cortisol assays unavailable or equivocal </li></ul></ul></ul>
  35. 39. Cushing’s Syndrome <ul><li>Metyrapone test </li></ul><ul><ul><li>Inhibits 11-B-hydroxylase </li></ul></ul><ul><ul><li>Blocks conversion of 11-deoxycortisol to cortisol </li></ul></ul><ul><ul><li>Plasma cortisol levels fall and ACTH increases </li></ul></ul><ul><ul><li>Marked increase in 17-hydroxycorticosteroid levels and 11-deoxycortisol levels </li></ul></ul><ul><ul><ul><li>Cushing’s Disease- normal or supernormal increase in levels </li></ul></ul></ul><ul><ul><ul><li>Ectopic ACTH or adrenal sources- no response </li></ul></ul></ul><ul><ul><li>Risks adrenal insufficiency </li></ul></ul>
  36. 40. Cushing’s Syndrome <ul><li>Petrosal vein sampling </li></ul><ul><ul><li>Measure petrosal venous sinus ACTH level and correlate to plasma levels </li></ul></ul><ul><ul><li>Invasive with morbidity </li></ul></ul><ul><ul><li>Usually not used </li></ul></ul><ul><li>Adrenal venous sampling </li></ul><ul><ul><li>Measure cortisol and aldosterone </li></ul></ul><ul><ul><li>Not used anymore </li></ul></ul>
  37. 41. Cushing’s Syndrome <ul><li>Radiographic Localization </li></ul><ul><ul><li>CT of sella turcica </li></ul></ul><ul><ul><ul><li>Unenhanced and gadolinium enhanced MRI </li></ul></ul></ul><ul><ul><ul><li>Radionuclide imaging for somatostatin receptors </li></ul></ul></ul><ul><ul><ul><li>>60% sensitive </li></ul></ul></ul><ul><ul><ul><li>1 st study if diagnosed with Cushing’s syndrome </li></ul></ul></ul><ul><ul><li>CT of chest/abdomen with 3mm cuts through adrenal </li></ul></ul><ul><ul><ul><li>Adrenal hyperplasia </li></ul></ul></ul><ul><ul><ul><ul><li>Thickening and elongation of adrenal rami bilaterally </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Multinodularity of cortex bilaterally </li></ul></ul></ul></ul>
  38. 42. Cushing’s Syndrome <ul><li>Radiographic Localization </li></ul><ul><ul><li>CT of adrenal glands </li></ul></ul><ul><ul><ul><li>Adenomas- usually >2cm but <5cm </li></ul></ul></ul><ul><ul><ul><ul><li>Low attenuation (lipid content) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Atrophy of opposite gland </li></ul></ul></ul></ul><ul><ul><ul><li>Carcinoma- indistinguishable from adenomas </li></ul></ul></ul><ul><ul><ul><ul><li>>5cm </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Necrosis, calcifications, irregularity, invasion </li></ul></ul></ul></ul><ul><ul><li>MRI of adrenal- usually not needed </li></ul></ul><ul><ul><ul><li>Signal intensity much higher than in spleen = carcinoma </li></ul></ul></ul><ul><ul><ul><li>Adjacent organ and/or vascular involvement </li></ul></ul></ul>
  39. 43. Cushing’s Syndrome <ul><li>Radiographic Localization </li></ul><ul><ul><li>CT of adrenal glands </li></ul></ul><ul><ul><ul><li>Adenomas- usually >2cm but <5cm </li></ul></ul></ul><ul><ul><ul><ul><li>Low attenuation (lipid content) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Atrophy of opposite gland </li></ul></ul></ul></ul><ul><ul><ul><li>Carcinoma- indistinguishable from adenomas </li></ul></ul></ul><ul><ul><ul><ul><li>>5cm </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Necrosis, calcifications, irregularity, invasion </li></ul></ul></ul></ul><ul><ul><li>MRI of adrenal- usually not needed </li></ul></ul><ul><ul><ul><li>Signal intensity much higher than in spleen = carcinoma </li></ul></ul></ul><ul><ul><ul><li>Adjacent organ and/or vascular involvement </li></ul></ul></ul>
  40. 45. DIAGNOSIS <ul><li>Basal Cortisol Level </li></ul><ul><ul><li>Avoid random level: low sensitivity </li></ul></ul><ul><ul><li>Check morning cortisol </li></ul></ul><ul><ul><ul><li>Greater than 18 µg/dL indicates an intact axis </li></ul></ul></ul><ul><ul><ul><li>Less than 3 µg/dL strongly suggests insufficiency </li></ul></ul></ul><ul><ul><li>Intermediate values: perform cosyntropin stimulation test </li></ul></ul>
  41. 46. DIAGNOSIS <ul><li>Low-Dose Cosyntropin Test </li></ul><ul><ul><li>Cosyntropin doses as low as 0.5 to 1 ug will give a maximal response within 15 to 30 mins </li></ul></ul><ul><ul><li>Possibly superior to high-dose test for diagnosing secondary insufficiency because ACTH level closer to physiologic level </li></ul></ul><ul><ul><li>Normal response: peak plasma cortisol level > 18 µg/dL </li></ul></ul><ul><ul><li>Like high-dose test, low sensitivity when ruling out mild or recent secondary insufficiency; confirm with more sensitive tests (insulin tolerance, metyrapone) </li></ul></ul>
  42. 47. DIAGNOSIS <ul><li>Insulin Tolerance Test </li></ul><ul><ul><li>Hypoglycemia induced by the IV injection of reg insulin stimulates the entire HPA axis. </li></ul></ul><ul><ul><li>Plasma glucose and cortisol are measured after injection of insulin. </li></ul></ul><ul><ul><ul><li>Normal response: cortisol increases to at least 18ug per dL </li></ul></ul></ul><ul><ul><li>E xpensive and contraindicated in patients with coronary heart disease or seizures </li></ul></ul>
  43. 48. DIAGNOSIS <ul><li>Metyrapone Test </li></ul><ul><ul><li>Metyrapone inhibits conversion of 11-deoxycortisol to cortisol </li></ul></ul><ul><ul><li>Give at midnight and measure the concentration of 11-deoxycortisol and cortisol at 8am </li></ul></ul><ul><ul><li>In normal subjects, the plasma 11-deoxycortisol concentration increases to at least 7ug per dL. In patients with adrenal insufficiency, the increase is smaller and is related to the severity of the corticotropin deficiency </li></ul></ul>
  44. 49. Hyperaldosteronism <ul><li>Causes </li></ul><ul><ul><li>Adenoma (most common) </li></ul></ul><ul><ul><ul><li>F>M </li></ul></ul></ul><ul><ul><ul><li>4 th -5 th decades of life </li></ul></ul></ul><ul><ul><li>Bilateral adrenal hyperplasia </li></ul></ul><ul><ul><li>Adrenocortical carcinoma (rare) </li></ul></ul><ul><ul><li>Glucocorticoid remedial aldosteronism </li></ul></ul><ul><ul><ul><li>Aldosterone producing adenoma </li></ul></ul></ul><ul><ul><ul><li>Responsive to renin </li></ul></ul></ul>
  45. 50. Hyperaldosteronism <ul><li>Diagnosis </li></ul><ul><ul><li>History, HTN, symptoms </li></ul></ul><ul><ul><li>Laboratory </li></ul></ul><ul><ul><ul><li>Serum K+ (<3.0) </li></ul></ul></ul><ul><ul><ul><li>Serum aldosterone </li></ul></ul></ul><ul><ul><ul><ul><li>Salt load patients (suppresses aldosterone) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Level >14 micrograms/d diagnostic of primary hyperaldosteronism </li></ul></ul></ul></ul><ul><ul><ul><li>Serum renin </li></ul></ul></ul><ul><ul><ul><ul><li>If >1.0 then unlikely primary hyperaldosteronism </li></ul></ul></ul></ul>
  46. 51. Pheochromocytoma, Diagnosis <ul><li>24hr urinary catecholamines (NE, Epi, Dop) and metabolites (metanephrine, normetanephrine, VMA) </li></ul><ul><li>Plasma catecholamine or metabolites during episode </li></ul><ul><li>Elevated serum epinephrine suggests pheo in medulla or Organ of Zukerkandl </li></ul><ul><li>NO FNA! (can precipitate hypertensive crisis) </li></ul>
  47. 52. Pheochromocytoma, Diagnosis <ul><li>Localizing studies: CT, MRI, MIBG scan </li></ul><ul><ul><li>Thin cut CT detects most lesions: 97% intraabdominal </li></ul></ul><ul><ul><li>MRI: 90% pheos bright on T2 weighted scan </li></ul></ul><ul><ul><li>MIBG: used for extraadrenal, recurrent, multifocal, malignant disease </li></ul></ul><ul><li>Malignant disease </li></ul><ul><ul><li>Local invasion, disease outside of adrenal/paraganglionic tissue </li></ul></ul><ul><ul><li>No histological or clinical criteria can differentiate malignant disease </li></ul></ul>

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