Pathophysiology(endocrine)*
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- Combination of hyperthyroidism, nodular goiter & abscence of exopthalmus
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Plummer Dse
-"hot nodules" can be adenomas or non-neoplastic - Ovarian teratoma made of thyroid tissue
- Struma Ovarri
- Assoc. w/ various autoantibodies (Antithyroglobulin,Antithyroid Peroxidase,Anti-TSH receptor,Anti iodine receptor antibodies)
- Hashimoto Thyroiditis
- Focal destruction of thyroid tissue & granuloma inflammation due to viral infxn.(mumps,coxsackie virus)
- Subacute(de Quervain,granulomatous)thyroiditis
- 1 molecule of DIT & Monoiodotyrosine (MIT) combine to form
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T3(triiodothyronine)
-3 to 4 times more active than T4, down regulates TRH receptors & inhibits TSH secretion - Antibodies to TSH receptors w/c incr. T3,T4 secretion & stimulate glandular hyperplasia in Graves Dse.
- Thyroid-stimulating immunoglobulin(TSI) & Thyroid growth immunoglobulin(TGI)respectedly
- Autonomic effects of T3 & T4
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B-andrenergic stimulation
-B-blockers(propranolol) are used in therapy for hyperthyroidism - Metabolic effect of T3 & T4
- Inc. glucose absorption in GIT, Glycogenolysis, Gluconeogenesis, glucose oxidation, lipolysis, & incr. catabolism
- Inversely proportional to the # of unbound thyroid hormone binding sites on TBG
- T3 resin uptake(Thyroid Hormone-binding ratio)
- Benign child tumor of Post. Pituitary charact. by nests & cords of squamous or columnar cells in loose stroma resembling appearance of the embryonic tooth bud enamel organ
- Craniopharyngioma(adamantinoma)
- Prognathism, enlargement of the face, vicera, feet, & hands(sausage-like fingers)
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Acromegaly
-growth hormone hypersecretion caused by somatotroph cell adenoma - Epigastric pain radiating to the back w/ an incr. in serum amylase & lipase
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Acute Pancreatitis
-major assoc. w/ alcoholism and gallstones - Migratory thrombophlebitis(Trousseau Syndrome)
- Carcinoma of the pancreas
- Severe retardation, short stature, coarse facies, protruding tongue, and umbilical hernia
- Cretinism(Hypothyroidism in children)
- Moon facies, hypertention, & accumulation of truncal fat
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Cuching syndrome
-caused by the action of cortisol - Most commonly caused by iatrogenic corticosteroid therapy
- Cushing synd.
- Marked incr. in free water clearance
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Diabetes Isipidus
-caused by lack of ADH - Increased Hemoglobin A1c(HbA1c)
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Diabtetes Mellitus
-HbA1c=serum marker for nonenzymatic glycosylation of proteins - Loss of pain sensation in extremities
- Diabetic neuropathy
- Retinal microaneurysms and cotton-wool spots
- Diabetic retinopathy
- Female w/ staring gaze & exopthalamos
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Graves' disease
-characterized by anti-TSH receptor antibodies in serum - Hypoglycemia & CNS impairment, w/c are reversed upon glucose administration, & increased serum C-peptide
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Insulinoma
-px. surreptitiously administering insulin do not have inc. C-peptide levels in serum - Most common thyroid carcinoma assoc. w/ exposure to ionizing radiation
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Papillary carcinoma of the thyroid
-histologically charact. by papillae lined by "Orphan Annie" nuclei or empty-looking nuclei - Paroxysmal hypertention, tachycardia, sweating, tremor, & hyperglycemia
- Pheochromocytoma
- Causes compression of the optic chiasm resulting in bitemporal hemianopsia
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Pituitary adenoma
-often visualized as radiographic enlargement of the sella turcica -
Hypotension, hyperpigmentation, & dec.
heart rate - Primary adrenal cortical insufficiency(Addisons disease)
- Osteitis Fibrosis Cyctica
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Primary hyperparathyroidism
-cysts, fibrinous accumulation, & focal hemorrhage in bone; also called brown tumor of bone - Premenopausal woman w/ amenorrhea, galactorrhea, loss of libido, & infertility
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Prolactinoma
-most common hyperfunctioning pituitary adenoma - Peripartal hypotension resulting in necrosis & destruction of the ant. pituitary
- Sheehan Synd
- Excessive resorption of free water w/ hyponatremia & cerebral edema, but no peripheral edema
- SIADH(syndrome of inappropriate antidiuretic hormone secretion)
- Tremor, tachycardia,increase in appetite w/ dec. in weight
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Thyrotoxicosis(hyperthyroidism)
-most commonly caused by Graves' dse. - Hypergastrinemia, hyperchlorhydria, & recurrent peptic ulcer dse.
- Zollinger-Ellison Synd.
- Inhibits secretion of Prolactin from ant. pituitary
- Dopamine(PIF),Bromocriptine(dopamine agonist),Somatostatin,Prolactin(neg. feedback)
- Salt-losing hyponatremia leading to hypotension and virilization of female infants
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21-hydroxylase def.
-most common enzymatic defect in congenital adrenal hyperplasia - Ant. pituitary tumor w/c causes galactorrhea, decreased libido, failure to ovulate
- Prolactinoma(excess prolactin)
- Inhibits the iodide(I-)pump
- Thiocyanate & Perchlorate Anions
- Used to reduce thyroid hormone synthesis in tx. of hyperthyroidism by inhibiting "peroxidase"
- Propylthiouracil
- 2 molecules of Diiodotyrosine(DIT) combine to form
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T4(thyroxine)
-synthesized more than T3 - Most common thyroid anomaly
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Thyroglossal duct cyst
-does not lead to alteration in thyroid fxn. - Most common cause of secondary hyperparathyroidism
- Renal failure
- Malignant catecholamine producing tumor of early childhood charact. by amplification of the N-myc oncogene w/ thousands of gene copies per cell(Karyotypic changes)
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Neuroblastoma
-malignant cells may differentiate into benign cells reflective of reduction of gene amplification - Factors w/c stimulate insulin release(tyrosine kinase receptor)
- Inc. bld. glucose, inc. A.A, inc. F.A, glucagon, GIP, GH, cortisol
- Factors w/c stimulate glucagon release(cAMP mechanism)
- Dec. bld.glucose, inc. A.A, CCK(cholecystokinin), norepinephrine, epinephrine, acetylcholine
- Adrenogenital synd. showing inc. aldosterone levels w/ dec. androgen & glucocorticoid levels
- 17 alpha-Hydroxylase Def.
- General apathy, cold intolerance, obesity, & constipation
- Myxedema(hypothyroidism)
- Adrenal insufficiency & vascular collapse due to hemorrhagic necrosis of the adrenal cortex
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Waterhouse-Frederichsen Synd.
-assoc. w/ DIC;due to Meningococcemia in assoc. w/ Meningococcal meningitis - Drug used to inhibit steroid hormone synthesis in tx. of Cushing's Dse.
- Ketoconazole
- Endocrine disorder presenting w/ hypertension, hypokalemia, metabolic alkalosis & inc. serum renin
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Secondary Aldosteronism
-as compared to Conn's Synd(Primary Aldosteronism)in w/c serum renin is low - Malignant tumor of the thyroid w/c originates from C cells & produces calcitonin
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Medullary Carcinoma
-assoc. w/ Multiple Endocrine Neoplasia(MEN)Synd. IIa & IIb(III) - Enzyme stimulated by ACTH to inc. steroid hormone synthesis by inc. conversion of cholesterol to pregnelone
- Cholesterol Desmolase
- Procedure use to test the neg. feedback control of cortisol in the hypothalmic-pituitary-adrenocortical axis
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Dexamethasome Suppression Test
-based on the ability of Dexamethasome(potent synthetic glucocorticoid) to inhibit ACTH secretion - Factors w/c regulate aldosterone secretion
- ACTH, Renin-Angiotensin System(Angiootensin II) & potassium
- Actions of glucocorticoid(cortisol)
- Gluconeogenesis, Anti-inflamatory effects, suppression of immune response, maintenance of vascular responsiveness to catecholamines
- Enzyme synthesized by glucocorticoid w/c inhibits Phospholipase A2, an enzyme w/c provides arachidonate, a precursor for prostaglandin & leukotriene synthesis
- Lipocortin
- Anti-inflammatory effects of glucocorticoids
- Inhibit formation of arachidonate, production of interleukin-2(IL-2) & release of histamine & serotonin
- In determinng the origin of cause for Cushing Synd.,an inc. in ACTH secretion would come from these origin
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Pituitary & Ectopic ACTH production
-as compared to adrenal where ACTH levels are low - Endocrine disorders caused by deficient ACTH, no hyperpigmentation, no volume contracion, no hyperkalemia or metabolic acidosis
- Secondary Adrenocortical insufficiency
- Actions of insulin on liver, adipose tissue & muscle
- Inc. glucose,K,A.A uptake; promote glycogen form. & fat deposition; inhibit glycogenolysis,ketoacid form,lipolysis,protein degradation, gluconeogenesis
- Actions of Somatostatin released from the hypothalmus & delta cells(pancreas)
- Inhibit secretion of GH(hypothalmus) & inhibit secretion of insulin, glucagon, gastrin(pancreas)
- Causes of Cushing's Synd.
- Exogenous corticosteroid medication(most common),hyperproduction of ACTH(by pituitary),adrenal cortical adenoma,adrenal carcinoma,ectopic prod. of ACTH(small cell carcinoma)
- Ca+ resorption of the organic matrix of bone due to PTH is reflected in increased
- Hydroxyproline excretion
- PTH inc. intestinal Ca+ reabsorption by stimulating production of this enzyme in the kidney
- 1,25-dihydroxycholacalciferol
- Pathophysiology of inc. PTH(most commonly caused by Parathyroid Adenoma)
- Hypercalcemia,hypophosphatemia,phosphaturia effect of PTH, inc. filtered load of Ca+, inc. urinary cAMP, inc. bone resorption
- Pathophysio. of chronic renal failure in causing renal osteodystrophy
- Dec. GFR~inc. serum phosphate~dec. ionized Ca+ due to phosphate-Ca complexes;dec. production of 1,25-dihydroxychole. by dse. kidney;inc. PTH due ti dec. serum Ca+ leads to inc. bone resorption & osteomalacia
- Active form of Vit.D
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1,25-dihydroxycolecalciferol
-catalyzed by 1alpha-hydroxylase - Factors w/c inc. 1alpha-hydroxylase activity in the production of Vit. D
- Dec. (Ca+,phosphate,PTH)
- Hormone secreted from the parafollicular cells of the thyroid; stimulated by high serum Ca+; inhibitsbone resorption; used to tx. hypercalcemia
- Calcitonin
- Hormones secreted from the testes(sertoli cells)w/c cause atrophy of the mullerian ducts(become the female internal genital tract)
- Antimullerian Hormone
- Hormones secreted from the testes(leydig cells)w/c stimulate growth & differentiation of the Wolffian ducts(become the male internal genital tract)
- Testosterone
- Hormone found in the accessory sex organs(ex.Prostate) used to convert testosterone to its active form(dihydrotestosterone)
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5 alpha-reductase
-inhibited by Finasteride w/c is used in tx. of BPH - Hormone produced by Sertoli cells in the testes w/c inhibits release of FSH from the ant. pituitary
- Inhibin
- Actions of testosterone
- Differentiation of Wolffian ducts, pubertal growth, spermatogenesis in Sertoli cells, inc. libido
- Effects of FSH & LH on Sertoli cells & Leydig cells in the testes, respectedly
- Maintain spermatogenesis & promote testosterone synthesis
- Effects of FSH & LH on the ovaries
- Steroidogenesis in the ovarian follicle & corpus luteum, follicular involvement beyond the antral stage, ovulation, luteinization
- Actions of estrogen
- Neg.&post. feedback effect(FSH,LH)secretion;maturation & maitenance of(fallopian tubes,uterus,cervix, vagina);develop. female secondary sex charact.at puberty;develop. of breast; upregulates(estrogen,LH,progesterone) receptors;proliferation & devel. of ovarian granulosa cells;maintains preg.;lowers uterine threshold to contractile stimuli during preg,;stimulate prolactin secretion
- Actions of Progesterone
- Neg. feedback effect on(FSH,LH)during luteal phase; maintains secretory activity of uterus during luteal phase; maintaince preg.; raises uterine threshold to contractile stimuli; develop. of breast
- Hormone produced by Theca cells w/c later diffuses granulosa cells
- Testosterone
- Enzyme found in Granulosa cells w/c convert testosterone to 17B-estradiol
- Aromatase
- Benign tumor of the adrenal medulla (chromaffin cells) resulting in inc. renal excretion of catecholamines & their metabolites(metanephrine,normetanephrine,vanillylmandelic acid)
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Pheochromocytoma
-if derived from extra adrenal chromaffin cells, called Paraganglioma - Hormone level of FSH compared to LH during senescence
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FSH>LH
-as compared to childhood(FSH>LH) & puberty(LH>FSH) - In Cushing Synd., a neg. Dexamethasome Suppression Test, signifies the origin of excess production of ACTH comes from
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Adrenal Neoplasm
-if Pituitary in origin, the test would be positive - Adrenogenital Synd. w/c show dec. cortisol & aldosterone levels w/ inc. 17-hydroxyprogesterone & progesterone levels resulting in inc. androstenedione
- 21 Beta-Hydroxylase def.
- Most common cause of hypothyroidism in iodine sufficient areas
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Hashimoto Thyroiditis
-histologically charact. by dense lymphocytic infiltrate & germinal centers in the thyroid - Parathyroid dse. resulting in end-organ resistance to PTH due to a defective Gs protein in the kidney & bone
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Pseudohypoparathyroidism type Ia- Albright's hereditary osteodystrophy
-not correctable by exogenous adm. of PTH; inc. PTH levels, hypocalcemia, hyperphosphatemia