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193 Cards in this Set
- Front
- Back
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What are the basics of Cushing's Sydrome?
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Inc Cortisol from a variety of causes
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4 Main Etiologies of Cushing's?
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1. Pituitary Adenoma (Cushing's Disease)---> Inc ACTH
2. Adrenal Hyperplasia/Neoplasia: dec ACTH 3. Ectopic ACTH production--> inc ACTH 4. Iatrogenic (chronic steroid use)---> dec ACTH |
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Which etiology is most common?
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Iatrogenicity
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Main example of Ectopic ACTH production/
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Small Cell Lung Cancer
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What does a Dexamethasone Suppression Test do in a healthy individual after a low dose?
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Causes a decreased cortisol level (b/c it negatively feeds back on ACTH)
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What does a low dose/high dose Dexamethasone Suppression Test do in a patient w/ an ACTH-producing pituitary tumor?
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Inc Cortisol after low dose test
Dec cortisol after high dose test (it takes a lot of dex to negatively feedback on pituitary |
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What does a low dose/high dose Dexamethasone Suppression Test do in a patient w/ an Ectopic ACTH-producing tumor (like a small cell carcinoma)?
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Inc cortisol after both tests b/c the tumor doesn't care about feedback
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What does a low dose/high dose Dexamethasone Suppression Test do in a patient w/ a Cortisol-Producing Tumor?
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Inc cortisol with both tests cause this tumor really doesn't care about dex
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What are the Sx's of Cushing's?
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HTN
Wt Gain Moon Facies Truncal Obesity Buffalo hump Hyperglycemia (insulin resistance) Skin Changes (thinning, striae) Osteporosis Amenorrhea Immune Suppression |
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What is Conn's Syndrome?
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Primary Hyperaldosteronism
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What causes Primary Hyperaldosteronism?
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Aldo-secreting tumor
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What causes Secondary Hyperaldosteronism?
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Renal Artery Stenosis
Chronic Renal Failure CHF Cirrhosis Nephrotic Syndrome |
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Sx's of Hyperaldosteronism?
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HTN
HypoKalemia Metabolic Alkalosis LOW plasma renin for Primary HIGH plasma renin for Secondary |
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Rx for Hyperaldosteronism?
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Spironolactone
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Why spironolactone?
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its a K-sparing Diuretic that works as an Aldo-Antagonist
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What is Addison's Disease?
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Primary Deficiency of Aldosterone and Cortisol due to Adrenal Atrophy (all three cortext zones) or Destruction by disease
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Sx's of Addison's?
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Hypotension
Skin Hyperpigmentation |
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Why does Addison's pts have hypotension?
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Hyponatremic Volume Depletion
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Why does Addison's pts have hyperpigmentation?
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MSH
its a by-product of inc ACTH production from POMC |
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How do you distinguish Secondary Adrenal Insufficiency from Primary?
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Secondary has Dec pituitary ACTH production
No hyperpigmentation No HyperKalemia |
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What is Waterhouse-Friderichsen Syndrome? cause?
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Acute Adrenocortical Insufficiency due to adrenal hemorrhage associated meningococcal septicemia
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What is Sheehan's Syndrome?
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Postpartum Hypopituitarism
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Etiology of Sheehan's?
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Enlargement of ant pituitary (inc lactotrophs) during pregnancy w/o corresponding Inc in blood supply---> inc risk of infarction following severe bleeding and hypoperfusion during delivery
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Possible Sx's of Sheehan's?
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Fatigue
Anorexia Poor Lactation Loss of pubic and axillary hair |
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What is the most common adult adrenal medulla tumor?
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Pheochromocytoma (still super rare)
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Origin of a Pheochromocytoma?
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Chromaffin Cells arising from NCC
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What do most Pheochromocytomas do?
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Secrete EPI, NE, and DA
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Sx's of Pheochromocytoma?
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5 Episodic P's
Pressure (HTN) Pain (HA) Persipiration Palpitations (Tachycardia) Pallor |
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Breakdown products for Epi, NE, DA?
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Epi---> metanephrine
NE---> VMA DA---> HVA |
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Lab findings for Pheochromocytomas?
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Urinary VMA (from NE)
Inc Plasma catecholamines |
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Rx for Pheochromocytoma?
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Alpha Antagonists
esp phenoxybenzamine |
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Why especially Phenoxybenzamine for Pheo's?
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non-selective, irreversible alpha blocker
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Rule of 10's?
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For Pheo's
10% malignant 10% bilateral 10% extra-adrenal 10% calcify 10% kids 10% familial |
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What conditions/syndromes are Pheo's associated w/?
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Neurofibromatosis
MEN types 2A and 2B |
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What is the most common tumor of the Adrenal Medulla in children?
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Neuroblastoma
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Where are Neuroblastomas located?
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Can occur anywhere along the sympathetic chain
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3 Kickers for Neuroblastomas?
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Less likely to develop HTN
HVA in pee associated w/ N-myc oncogene |
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Characteristics of MEN 1?
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AKA Wermer's Syndrome
Parathyroid Tumors Pituitary Tumors Pancreatic Endocrine Tumors often kidney stones and stomach ulcers |
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What kind of pituitary tumors are associated w/ MEN1?
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Prolactinomas
GH-omas |
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What of Pancreatic Endocrine Tumors are associated w/ MEN1?
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Zollinger-Ellsion Syndrome
Insulinomas VIPomas Glucagonomas (rare) |
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Characteristics of MEN 2A?
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AKA Sipple's Syndrome
Medullary Thyroid Carcinoma Pheochromocytoma Parathyroid Tumors |
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Characteristics of MEN 2B (or 3)?
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Medullary Thyroid Carcinoma
Pheochromocytoma Oral/Intestinal Ganglioneuromatosis |
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What do the medullary thyroid carcinomas of MEN 2A and 2B secrete?
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Calcitonin
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What is associated w/ Oral/Intestinal Ganglioneuromatosis?
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Marfanoid habitus
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What is the inheritance of the different MEN types?
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All are Auto Dom
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What else is associated w/ MEN 2A and 2B?
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ret gene
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Sx's of Hypothyroidism?
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Cold Intolerance
Hypoactivity Wt. Gain Constipation Dec Reflexes Dry, Cool Skin Coarse, Brttle Hair Fatigue, Lethargy dec appetite Myxedema |
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Sx's of Hyperthyroidism
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Heat Intolerance
Hyperactivity Wt. Loss Diarrhea Inc Reflexes Warm Moist Skin Fine Hair chest pain/palpitations arrhythmias |
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what is myxedema?
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facial/periorbital edema
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What is Hashimoto's?
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Hashimoto's Thyroiditis is an autoimmune disorder---> hypothyroidism
can have thyrotoxicosis during follicular rupture |
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Gross morphology of Hashimoto's?
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Moderately enlarged, nontender thyroid
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Microscopic morphology of Hashimoto's?
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Lymphocytic infiltrate w/ germinal centers
Hurthle cells |
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Antibodies in Hashimoto's?
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AntiMicrosomal Ab's
AntiThyroglobulin Ab's |
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What is Subacute Thyroiditis?
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de Quervain's
Self-limited hypothyroidism following flu-like illness can be hyperthyroid early in course |
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Sx's of Subacute Thyroiditis?
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Elevated ESR
Jaw Pain Early Inflammation Very Tender Thyroid Histo: granulomatous inflammation |
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What is Riedel's Thyroiditis?
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Thyroid replaces by fibrous tissue (hypothyroid)
fixed, hard, painless goiter |
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What is Graves' Disease?
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Autoimmune HYPERthyroidism w/ Thyroid stimulating/TSH receptor Ab's
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What type of hypersensitivity is Graves'?
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Type 2
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Sx's of Graves'?
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Exophthalmos
Pretibial Myxedema Diffuse Goiter often presents during stress |
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Serious Graves' complication?
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Stress-induced catecholamine surge---> death by arrhythmia
seen w/ other hyperthyroid disorders too |
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What causes a Toxic Multinodular Goiter?
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Iodine deficiency--->follicular cell hyperplasia
Future Iodine restoration---> hyperthyroidism this is the Jod-Basedow phenomenon |
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5 types of thyroid cancer?
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1. Papillary Carcinoma
2. Follicular Carcinoma 3. Medullary Carcinoma 4. Undifferentiated/Anaplastic 5. Lymphoma |
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Which thyroid cancer is the most common?
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papillary carcinoma
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Px for thyroid cancers?
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1. Papillary Carcinoma: excellent
2. Follicular Carcinoma: good 3. Medullary: ? 4. Anaplastic: very poor 5. Lymphoma: ? |
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Kickers for Papillary Carcinoma of thyroid?
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Ground Glass Nuclei (orphan annie)
Psammoma Bodies Nuclear Grooves |
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What creates an inc risk of Papillary Carcinoma?
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Childhood Irradiation
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origin of Medullary Carcinoma?
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Parafollicular "C" cells
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Kickers for Medullary Carcinoma?
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Produces Calcitonin
Sheets of cells in amyloid stroma |
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What is medullary carcinoma associated w/?
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MEN types 2A and 2B
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Who gets anaplastic carcinoma of thyroid?
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Older Pts
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What is Thyroid Lymphoma associated w/?
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Hashimoto's
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What does severe fetal hypothyroidism-->?
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Cretinism
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Biggest cause of severe fetal hypothyroidism?
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endemic iodine deficiency
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What causes sporadic cretinism?
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defect in T4 formation or developmental failure of thyroid formation
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Findings w/ Cretinism?
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pot-bellied
pale puffy-faced protruding umbilicus protuberant tongue |
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What causes Acromegaly?
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Excess GH in adults
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What causes Gigantism?
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Excess GH in kids
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Findings w/ Acromegaly?
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Large Tongue w/ deep furrows
Deep Voice Large hands and feet Coarse facial features Impaired glucose tolerance (insulin resistance) |
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Rx for Excess GH syndromes?
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Pituitary Adenoma resection followed by Octreotide administration
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When is Increased GH normal?
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Stress
Exercise Hypoglycemia |
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How do you Dx excess GH?
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Inc IGF-1 in serum
Oral Glucose Tolerance Test: fails to suppress serum GH |
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Usual cause of Primary HyperPTH?
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Adenoma
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Findings w/ HyperPTH?
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Stones Bones and Groans
HyperCa HyperCalciuria (renal stones!!) Hypophosphatemia Inc PTH Inc Alkaline Phosphatase Inc cAMP in pee |
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Symptoms of HyperPTH?
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Often asymptomatic
maybe weakness and constipation (groans) |
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What is Osteitis fibrosa cystica?
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von Recklinghausen's Syndrome
cystic spaces fills w/ brown fibrous tissue--->bone pain |
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Causes of Secondary Hyperparathyroidism?
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Secondary Hyperplasia due to dec gut absorption of Ca and inc absorption of Phosphorus
Usually due to Chronic RF--->dec Vit D |
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Findings w/ Secondary HyperPTH?
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HypoCa
HyperPhosphatemia Inc Alkaline Phosphatase Inc PTH |
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What is Renal Osteodystrophy?
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Bone lesions secondary to secondary hyperPTH due to renal disease...geez
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Causes of HypoParathyroidism?
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Surgical excision
Autoimmune destruction DiGeorge Syndrome |
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Findings w/ HypoPTH?
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HypoCa
Tetany |
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Signs of HypoPTH?
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Chvostek's Sign = tapping facial nerve--->contraction of facial nerves
Trousseau's Sign = occlusion of brachial artery w/ BP cuff---> carpal spasm |
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What is PseudoHypoParathyroidism?
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autosomal dominant kidney unresponsiveness to PTH
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Sx's of PseudoHypoParathyroidism?
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HypoCa
Shortened 4th and 5th digits Short Stature |
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Causes of HyperCa? mnemonic?
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CHIMPANZEES
Ca ingestion HyperPTH HyperThyroid Iatrogenic (thiazides) Multiple Myeloma Paget's Disease Addison's Disease Neoplasms Zollinger-Ellison syndrome Excess Vit D Excess Vit A Sarcoidosis |
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Most common pituitary adenoma?
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Prolactinoma
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Sx's of Pituitary Adenoma?
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Bilateral Hemianopia (pushing on optic chiasm
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Rx for Prolactinoma (besides surgery?
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Bromocriptine
Cabergoline they're dopamine agonists that inhibit PRL and cause shrinkage |
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Acute Sx's of Diabetes mellitus?
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Polydipsia
Polyuria Polyphagia Wt loss DKA (type 1) Hyperosmolar coma (type 2) Unopposed secretion of GH and Epi (exacerbates hyperglycemia) |
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Chronic Manifestations of DM?
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Small Vessel disease (diffuse thickening of BM)--->
retinopathy glaucoma nephropathy Large-Vessel athersclerosis CAD Peripheral vascular occlusive disease Gangrene Cerebrovascular Disease Osmotic Damage: Neuropathy Cataracts |
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Primary Defect in Type 1 vs Type 2 DM?
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Type 1
viral or immune destruction of Beta-Cells Type 2: Inc resistance to insulin |
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association of obesity in Type 1 vs Type 2 DM?
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Type 1: no
Type 2: hells yes |
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Genetic Predisposition in Type 1 vs Type 2 DM?
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Type 1: weak, polygenic
Type 2: strong, polygenic |
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HLA association in Type 1 vs Type 2 DM?
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Type 1: HLA-DR3 and DR4
Type 2: no |
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Sx's of DKA?
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Kussmaul respirations (rapid, deep breathing)
N&V Abd Pain Psychosis/Delirium Dehydration Fruity Breath Odor (acetone) |
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Labs for DKA?
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Hyperglycemia
Inc H+ Dec Bicarb (anion gap metabolic acidosis) Inc blood ketone levels Leukocytosis HyperK, but depeleted intracellular K from transcellular shift from dec insulin |
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Complications w/ DKA?
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mucormycosis
Rhizopus infection cerebral edema cardiac arrhythmias Heart Failure |
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Rx for DKA/
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fluids
insulin K+ (for intracellular stores) Glucose to prevent hypoglycemia |
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Types of Diabetes Insipidus? general difference?
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Central = lack of ADH
Nephrogenic = lack of response to ADH |
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Causes of Central DI?
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pituitary tumor
trauma surgery Histiocytosis X |
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Causes of Nephrogenic DI?
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Hereditary
Secondary to: HyperCa Lithium Demeclocycline |
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Dx of DI?
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Water Deprivation Test and urine osmolarity doesn't Inc like it should
Response to Desmopressin differentiates between central and nephrogenic |
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Rx for DI?
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Adequate Fluid intake
Central DI: intranasal desmopressin Nephrogenic DI: Hydrochlorothiazide, indomethacin, or amiloride |
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Findings w/ SIADH?
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Excessive water retention
Hyponatremia Urine Osmolarity > Serum Osmolarity very low Na can--> seizures |
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Causes of SIADH?
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Ectopic ADH (small cell lung cancer)
CNS disorder/head trauma Pulmonary Disease Drugs (e.g. cyclophosphamide) |
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Rx for SIADH?
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Demeclocycline
H20 restriction |
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Etiology of Carcinoid Syndrome?
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Carcinoid Tumors, esp metastatic small bowel tumors, that secrete high levels of Serotonin
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Sx's of Carcinoid Syndrome?
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Diarrhea
Cutaneous Flushing Asthmatic Wheezing Right-sided valvular disease |
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Origin of Carcinoid Tumor?
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Neuroendocrine cells of GI tract
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What is the most common tumor of appendix?
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carcinoid tumor
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"rule" for carcinoid tumors?
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1/3's
1/3 metastasize 1/3 present w/ 2nd malignancy 1/3 are multiple |
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Rx for Carcinoid Syndrome?
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Octreotide
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Lab finding w/ Carcinoid Syndrome?
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Inc 5-HIAA in urine
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What is Zollinger-Ellison Syndrome?
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Gastrin-secreting tumor of pancreas or duodenum
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Findings w/ ZE Syndrome?
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Recurrent Ulcers
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Possible association w/ Z-E syndrome?
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MEN 1
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Rx strategy for Type 1 DM?
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Low-sugar diet
Insulin replacement |
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Rx strategy for Type 2 DM?
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dietary modification
Exercise for wt loss Oral hypoglycemics Insulin replacement |
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Who are the Insulin Drugs? duration of action?
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Lispro (short)
Regular (short) Lente (intermediate) Ultralente (long) Glargine (long) |
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What is the main use for Glargine?
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It has no onset or peak (peakless)--->broad plasma control and ultra-long acting
Great for constant background level control |
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Who are the Sulfonylureas based on generation?
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First Generation = Chlorpropamide
Second Generation = Glipizide Glyburide other first gen: tolbutamide acetohexamide |
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mechanism for insulin release in response to glucose?
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Glucose enters beta-cells
Glucose--->Inc ATP Inc ATP Closes K channels --->Membrane Depolarization ---->Opens Ca Channels Ca Influx--->Insulin Release |
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MOA for Sulfonylureas?
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K Channel Blockers!
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Results of OSU's actions?
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Inc Insulin Release
Dec Glucagon Release Inc Insulin Receptor Sensitivity |
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Who else works on the same K channel as OSU's? mech?
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Thiazides and Diazoxide
Open the K channels-->dec insulin--->hyperglycemia |
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General SE's of OSU's?
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Hypoglycemia (don't miss meals)
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Specific SE for Chlorpropramide?
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Causes release of ADH from post. pit--->SIADH
Disulfiram Rxns |
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Biggest benefit of Second Gen OSU's?
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24 hour duration of action
(don't skip meals) |
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Who are the Biguanides?
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METFORMIN
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Which drugs don't cause hypoglycemia?
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If a drug doesn't change insulin level
OR If a drug only changes insulin in a glucose-dependent manner THEN it doesn't cause hypoglycemia |
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MOA for Metformin?
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Unknown
Dec liver gluconeogenesis Inc glucose uptake into muscle overall is a insulin sensitizer |
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Main SE of Metformin?
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Rare, but Severe Lactic Acidosis
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Which drugs have basically the same fxn's as Metformin?
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Thiazolidinediones (Glitazones)
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Who are the Glitazones?
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Pioglitazone
Rosiglitazone |
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MOA for the glitazones?
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They're insulin sensitizers
dec liver gluconeogenesis inc muscle uptake |
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What does Acarbose do? moa/fxn?
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alpha-Glucosidase Inhibitor
this blocks the intestinal formation of glucose from starch, thus decreasing postprandial glucose levels |
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What does Exenatide do?
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It is a Glucagon-Like Peptide-1 (GLP-1) Analog
GLP-1 is an incretin from SI that augments glucose-dep insulin release Exenatide is a long-acting, GLP-1 receptor full agonist |
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SE's of exenatide?
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hypoglycemia ONLY when combined w/ OSU's (or other drugs...)
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Who are the Glinides and what do they do?
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Repaglinde
they're a new set of drugs that have the same MOA as OSU's (block K channels) They have a fast onset and a shorter duration. |
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Who are the glinides good/bad for?
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Great for patients who want to skip meals since you just have to take the med 30 minutes before a meal
Bad for non-compliant patients b/c if you miss your pill and then you eat--->hyperglycemia |
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Who is the newest Diabetes drug we should know?
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Sitagliptin
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What is sitagliptin?
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Its a Dipeptidyl Peptidase Inhibitor
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What is dipeptidyl peptidase? significance?
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it is the enzyme responsible for the metabolism (breakdown) of GLP-1
So if we inhibit it-->inc GLP-1 levels and Inc glucose-dependent insulin release (i.e. no hypoglycemia) |
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What is Orlistat? MOA?
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Inhibits Pancreatic Lipases--->dec fat digestion--->inc fat excretion
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Uses for Orlistat?
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Long-term obesity management (use w/ dieting)
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Toxicity of Orlistat?
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steatorrhea
GI discomfort HA dec absorption of fat-soluble vitamins |
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What is Sibutramine?
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Sympathomimetic Serotonin and NE reuptake inhibitor
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Uses of Sibutramine?
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Short-term and Long-term obesity management
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Adverse Effects of Sibutramine?
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HTN
Tachycardia |
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Who are the glinides good/bad for?
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Great for patients who want to skip meals since you just have to take the med 30 minutes before a meal
Bad for non-compliant patients b/c if you miss your pill and then you eat--->hyperglycemia |
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Who is the newest Diabetes drug we should know?
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Sitagliptin
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What is sitagliptin?
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Its a Dipeptidyl Peptidase Inhibitor
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What is dipeptidyl peptidase? significance?
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it is the enzyme responsible for the metabolism (breakdown) of GLP-1
So if we inhibit it-->inc GLP-1 levels and Inc glucose-dependent insulin release (i.e. no hypoglycemia) |
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What is Orlistat? MOA?
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Inhibits Pancreatic Lipases--->dec fat digestion--->inc fat excretion
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Uses for Orlistat?
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Long-term obesity management (use w/ dieting)
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Toxicity of Orlistat?
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steatorrhea
GI discomfort HA dec absorption of fat-soluble vitamins |
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What is Sibutramine?
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Sympathomimetic Serotonin and NE reuptake inhibitor
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Uses of Sibutramine?
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Short-term and Long-term obesity management
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Adverse Effects of Sibutramine?
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HTN
Tachycardia |
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Who are the Thiamides and what is their general use?
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Propylthiouracil
Methimazole used for uncomplicated Hyperthyroidism (graves') |
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MOA for the Thiamides?
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Both:
Inhibit organification and coupling of thyroid hormone synthesis PTU also inhibits 5' deiodinase |
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What is the fxn of 5'-deiodinase and thus the added fxn of PTU?
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5'-deiodinase is the enzyme responsible for the conversion of T4--->T3
Ergo, PTU is good for thyroid storm also |
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What is the other main difference between PTU and Methimazole?
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PTU is more highly bound to plasma albumin (92%) and thus doesn't cross the placenta
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What is the significance of placental crossing for thiamides?
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If they cross the placenta, then they can cause Cretinism
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What 4 drugs can inhibit 5'-deiodinase?
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Propylthiouracil
Lithium Propranolol Amiodarone |
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What are 4 drugs used for hypothalamic/pituitary disorders?
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GH
GnRH Prolactin Inhibiting Hormone = PIH (DA) Somatostatin Oxytocin ADH |
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What are the drug names for the hypothalamic/pituitary drugs?
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GH = somatropin
Somatostatin = Ocreotide GnRH=Leuprolide and Nafarelin PIH (DA) = pergolide or bromocriptine oxytocin = oxytocin ADH = desmopressin |
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Uses of GH?
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GH deficiency = pituitary dwarfism
Turner's Syndrome |
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Uses for Ocreotide?
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Acromegaly
Carcinoid tumors/syndrome |
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MOA for Leuprolide or Nafarelin? hence use?
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They're long-acting hormones and thus look like continuous GnRH---> dec FSH and dec LH
uses then are Endometriosis and AR+ Prostate Carcinoma |
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Uses of Pergolide and Bromocriptine for hypothalamic/pituitary issues?
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Used in HyperPRL
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Uses of oxytocin?
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labor induction
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MOA for Desmopressin and uses?
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V2 selective agonist (so won't raise BP)
Rx's Neurogenic DI Mild von Willebrand Syndrome (inc vW factor from endothelium) Primary nocturnal enuresis |
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How is desmopressin administered to kids? why?
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PO
it can cause severe HypoNa in kids--->seizures |
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What can you use for Thyroxine replacement?
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Levothyroxine
Triiodothyronine |
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uses of Levothyroxine and Triiodothyronine
|
Hypothyroidism
Myxedema |
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Adverse effects of Levothyroxine Triiodothyronine
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Tachycardia
Heat intolerance tremors arrhythmias |
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5 big examples of Glucocorticoids?
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Hydrocortisone
Prednisone Triamcinolone Dexamethasone Beclomethasone |
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MOA for Glucocorticoids
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Dec production of LT's and PG's by inhibiting Phospholipase A2
Dec expression (induction) of COX2 |
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uses of Glucocorticoids?
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Anti-inflammatory
Immunosuppressive Asthma Addison's |
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Main SE's of Glucocorticoid uses?
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Suppression of ACTH
Iatrogenic Cushingoid Syndrome (hump, muscle weakness, buising, etc) Hyperglycemia (inc gluconeogenesis) Osteoporosis secondary to hypoCa and GC's competition for Vit D receptor Ulcers (inc gastric acid and pepsin) Na/Water Retention from mineralcorticoid activity (edema and HTN) HypoCa Dec Wound Healing Inc Infections Inc IOP-->glaucoma Inc sorbitol---> inc cataracts Inc ICP?-->mental dysfxn |
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MOA for Demeclocycline?
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ADH Antagonist
its a tetracycline |
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Uses for Demeclocycline?
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DI
SIADH |
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Adverse Effects of Demeclocycline?
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Photosensitivity
Abnormalities w/ bone and teeth (yellow brown discoloration) Contraindicated in Pregnancy (fasT) |
