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Pathology block IV
Endocrine
| Question | Answer |
|---|---|
| Common endocrine diseases | diabetes mellitus (1), hyperthyroidism (2), hyperparathyroidism (3) |
| Hypopituitarism - deficiency | polytropic deficiency is more common than monotropic pituitary hormone deficiency |
| Pituitary adenoma | causes hypopituitarism; may be secretory/space-occupying or non-secretory/space-occupying lesion |
| Ischemic infarction near pituitary | causes hypopituitarism; can be postpartum pituitary infarction (Sheehan Syndrome), arteriosclerotic emboli, systemic vasculitis |
| Autoimmune hypophysitis | causes hypopituitarism |
| Less common causes of hypopituitarism | craniopharyngioma, empty sella syndrome, primary glioma, metastatic tumor (breast/lung), suprasellar intracranial germ tumor, sarcoidosis, wegener's, hemochromatosis, histiocytosis, radiation, encephalomeningitis, hypothalamic dx |
| Pathophysiology of hypopituitarism | usu at least 2 hormonal deficiencies (rarely involves all); greatest effect on GH and ACTH d/t glandular anatomy |
| Temporal sequence of clinical manifestations of hypopituitarism | Gonadotropin deficiency (rapid in premenopausal women), GH deficiency, thyrotropin, corticotropin, prolactin |
| Pathophysiology of congenital or acquired GH deficiency | body is proportional but smaller than nml; lack of secondary sex traits if deficit is b/f puberty d/t associated gonadotropin deficiency; if other tropic hormones remain, pt can develop and become fertile |
| Pathophysiololgy of adult acquired GH deficiency | mc cause is iatrogenic pituitary surgery; Hypoglycemia d/t absence of gluconeogenic effect; poor wound healing; generalized muscle weakness and atrophy |
| Pathophysiology of adult acquired ACTH deficiency | selective reduction in glucocorticoid secretion by adrenals w/preservation of mineralcorticoid (aldosterone secretion depends on RAAS not pituitary); no hyperpigmentation, hypotension or hypovolemia; Hyponatremia; dec pubic/axillary hair d/t androgen def. |
| Pathophysiology of adult acquired gonadotropin deficiency in men | hypogonadism (dec testicular size/softening, dec libido, erectile dysfxn, dec vol of ejaculate, weakness, dec hair, gynecomastia); osteoporosis |
| Pathophysiology of adult acquired gonadotropin deficiency in premenopausal women | anovulatory periods, amenorrhea, hot flashes, dec libido, breast atrophy, vaginal dryness (a/w dyspareuria); osteoporosis |
| Pathophysiology of adult acquired gonadotropin deficiency in postmenopausal women | very difficult to dx; significantly dec libido, accelerated breast atrophy and vaginal dryness; osteoporosis |
| Presentation of pt with hypopituitarism | low target hormone levels with low levels of corresponding trophic hormones (ex: low T4/T3 --> low TSH; low cortisol --> low ACTH, etc) |
| Morbidity a/w hypopituitarism | commonly a/w congenital cases d/t profound systemic adverse effects on growth and development of multiple hormone deficiencies |
| Sheehan syndrome | variant of hypopituitarism d/t physiologic hyperplasia during pregnancy (causes stress on blood supply leading to coagulative necrosis d/t ischemic infarction); infarction a/w prepartum anemia & significant peripartum hemorrhage/hypotension; no lactation |
| Primary Empty Sella Syndrome Pathology | defective diaphragma sella (composed of dura mater); elevated intracranial pressure deforms leptomeninges & compresses pituitary (circulation may be compromised causing hypopituitarism) |
| Primary Empty Sella Syndrome Clinical Synopsis | few pts are symptomatic; frontal headache; visual disturbances; hypertension; amenorrhea; elevated ICP; CSF rhinorrhea d/t transphenoidal fistula from hi ICP; |
| Primary Empty Sella Syndrome Lab findings | hyperprolactinemia (mc); hypopituitarism (various combos - global "sheehan-like" presentation, or selective - a/w GH deficiency in kids); central diabetes insipidus |
| Monotropic pituitary deficiency | very rare; usu genetic/familial & a/w other congenital anomaly syndromes; usu d/t deficiency in corresponding hypothalamic releasing factor (not intrapituitary failure); similar to target organ primary deficiency |
| Monotropic GH deficiency | children fail to grow; adults (hypoglycemic, generally weak/muscle atrophy; poor wound healing) |
| Monotropic ACTH deficiency | very rare; selective reduction of cortisol secretion (not mineralcorticoids); hypoglycemia; no hyperpigmentation, hypotension, or hypovolemia |
| Monotropic FSH deficiency | amenorrhea in females; infertility in both sexes; limited 2* sex traits if deficient b/f puberty (fertile eunuch syndrome in males d/t nml FSH); possibly a/w Kallmann syndrome |
| Monotropic Prolactin deficiency | mc cause is from postpartum pituitary necrosis (Sheehan); females have inability to lactate postpartum (alactia), menstural disorders, delayed puberty, infertility/subfertility; males have infertility |
| Isolated GH deficiency pathophysiology | usu idiopathic from dysfxn of pituitary or hypothalamus; systemic deficiency of circulating GH has numerous physiological effects |
| Isolated GH deficiency lab findings | dec somatotropin (GH), dec serum insulin-like growth factor (IGF-I) and its binding ptn 3; hypoglycemia; dyslipidemia |
| Growth Hormone Stimulation Test - isolated GH deficiency | GH release can be stimulated via GH-releasing hormone, arginine infusion, etc; alw stimulated by istrogenic hypoglycemia; lack of ability to reach serum level of 10mg/mL |
| Isolated pediatric GH deficiency pathophysiology | most are idiopathic; few pts have developmental anomalies of pituitary gland & sella; few w/genetic auto dom abnormality of GH gene or GH receptor gene; leads to deficiency of somatomedin C (ILF-I from liver/pituitary) |
| Isolated pediatric GH deficiency clinical findings | short stature, delayed puberty w/retained fertility; hyperglycemia; inc incidence of atherosclerosis and osteoporosis |
| Isolated adult GH deficiency | usu a/w preceding dx that damaged pituitary fxn (tumor, leukemia, radiation, trauma, histicytosis, infxn); weak, hypoglycemic, poor healing, atherosclerosis, osteoporosis |
| Isolated ACTH deficiency | rare; cause can be pituitary or suprapituitary; weak, hypoglycemic, hyponatremic?, hypercalcemic; low blood/urine 17-OH corticoid; low serum/urine cortisol; low serum ACTH --> causes dehydration, hypotension, hyponatremia ; Responds to ACTH infusion |
| Isolated Gonadotropin deficiency pathophysiology | lack of FSH and LH leads to either ovarian or testicular failure w/resultant hypogonadism (lack of 2* sex traits, delayed/absent puberty, infertility, oligo/azospermia, etc); low FSH, LH, estradiol, testosterone |
| Female isolated gonadotropin deficiency | primary amenorrhea, dyspareuria d/t lack of mucosal thickening, lack of breast development |
| Male isolated gonadotropin deficiency | lack of libido, erectile dysfxn, generalized muscle weakness/low mass, high-pitched voice, no body hair, small testicles, small penis |
| Kallmann Syndrome | hypogonadism w/anosmia; congenital GnRH deficiency from hypothalamus leading to deficiencies in FSH and LH; causes infertility (mc), hearing loss, no 2* sex traits & few are fertility |
| Kallmann Syndrome and GnRH Stimulation Test | shows diminished gonadotropin responses (normal response is 2-5x inc in LH levels and smaller inc in FSH) |
| Isolated thyrotropin deficiency | absence of TSH allows thyroid gland to stop fxning and atrophy; markedly reduced T3/T4 secretion by follicular cells |
| Adult Isolated thyrotropin deficiency | hypotonia, hoarse cry, weakness, enlarged tongue, constipation, potbelly, umbilical hernia, strabismus, edematous subcutaneous tissue (myxedema), motor & cognitive development delay (autistic-like), microcephaly |
| Adult isolated thyrotropin deficiency | low core temp, dec cognitive ability/slow mentation, chronic fatigue (low cardiac EF), constipation (slow), hoarse (dysphonia), weak pulse/slow HR, wt gain, dry skin/mucosa, thinning of hair, hard edema/myxedema, pericard effusion, no goiter; lo TSH T3/T4 |
| Causes of Hyperpituitarism | benign adenoma (mc), pituitary carcinoma, non-neoplastic pituitary hyperplasia, paraneoplastic syndrome related to non-pituitary malignancy; hypothalamic disorder |
| Microadenoma | causes hyperpituitarism; usu a few mm - 1cm in diameter; small size precludes appearance of localized symptoms |
| Macroadenoma | causes hyperpituitarism, >1cm in diameter; often causes localized symptoms d/t size |
| Pathophysiology of cortitroph adenoma | mc functioning adenoma of pituitary gland; mc cause of Cushing's; secretes ACTH which causes hyperplastic adrenals that secrete inc amounts of cortisol and aldosterone |
| Pathophysiology of Somatotroph/GH adenoma | if b/f adolescence pt becomes very tall (gigantism); degeneration of islets of langerhans d/t excessive GH stimulation leading to diabetes mellitus; can develop panhypopituitarism d/t destruction of pituitary gland by the expanding adenoma |
| Somatotroph/GH adenoma after puberty | pt cannot grow in height; causes acromegaly; membranous bone becomes thicker (jaw - micrognathial; prominant supraorbital ridge; cranial bossing; kyphosis); thick long bones in hands/feet; macroglossia; hyperglycemia/DM; arthropathy; ptn anabolism |
| Uncommon causes of elevated GH | inc GHRH from hypothalamic tumor; ectopic GH secretion from neuroendocrine paraneoplastic tumor (lung, pancreas); ectopic GHRH from nonendocrine tumor (carcinoid, lung, pancreas, kidney) |
| Pathophysiology of lactotroph adenoma (prolactinoma) | neoplasm of prolactin-secreting pituitary cells; hyperprolactinemia inhibits FSH and LH that effects genders differently; inc incidence of MEN type I |
| Prolactinoma in females | amenorrhea usu 2* amenorrhea in adults, 1* if prior to puberty; galactorrhea; infertility; loss of libido; mastodynia (breast pain) |
| Prolactinoma in males | hypogonadism; erectile dysfxn; decreased libido; galactorrhea |
| Pathophysiology of Gonadotroph Adenoma | usu a macroadenoma that causes localized symptoms d/t size; chronically elevated FSH and LH leading to amenorrhea |
| Pathophysiology of Thyrotroph Adenoma | increased secretion of TSH leading to hyperthyroidism |
| Pituitary microadenoma pathophysiology | <9mm in diameter; may or may not secrete pituitary hormones (if silent = "incidentaloma"); prolactinoma is mc secreting form (a woman w/galactorrhea and 2* amenorrhea has 30% chance of this condition); TSH-secretor and gonadotropinoma are least common |
| Other reasons why a woman has elevated prolactin levels | pregnancy, chronic renal failure, cirrhosis of liver, excessive exercise, side effect from drugs, hypothyroidism |
| Pituitary Macroadenoma | if large it causes CNS effects including chronic HAs & visual field defects d/t pressure on optic chiasm; can cause panhypopituitarism if entire gland is compressed |
| Pituitary apoplexy | sequelae of pituitary macroadenoma; rapid growth of tumor causes ischemia/necrosis & many acute pituitary deficiencies that can be lethal from hypoadrenalism (fatigue, slow mentation, death) |
| Iatrogenic Pituitary Apoplexy | GnRH from prostatic carcinoma causes pituitary hyperplasia/neoplasia at a fast rate followed by hemorrhage/infarction leading to pituitary crisis |
| Nelson Syndrome | bilateral adrenalectomy (d/t Cushing's) leads to high levels of pituitary ACTH resulting in pituitary adenoma |
| Ectopic Pituitary Adenoma | vanishingly rare; usu located in peri-sella region d/t presence of ectopic nests of pituitary cells in leptomeninges |
| Measurement of pituitary hormones in pituitary adenoma patient | one will be elevated (usu prolactin) and a deficiency in the others d/t compression of surrounding pituitary tissue; elevated prolactin may be d/t secretion from tumor or from disruption of inhibition from hypothalamus d/t compression of pituitary stalk |
| ADH/Vasopressin/AVP origin in hypothalamus | made by neurons in supraoptic and paraventricular nuclei of anterior hypothalamus; stored w/neurophysin in secretory granules in posterior pituitary |
| Control of ADH release | osmoreceptors in supraoptic nucleus detect changes in ECF; if serum osmolarity increases ADH is released; decreased osmolarity causes decreased ADH; Baroreceptors in carotid sinus/aortic arch/LA respond to changes in plasma vol (dec vol increases ADH) |
| Common causes of syndrome of inappropriate ADH secretion (SIADH) | CNS dx (trauma; Paraneoplastic Syndrome (ectopic ADH d/t bronchogenic carcinoma or pancreatic adenocarcinoma); Pulm TB; bacterial pneumonia; Pituitary induced Addisons (ACTH def); hypothyroidism; EtOH withdrawal; HIV; drugs (NSAIDs, anti-dep, thiazide...) |
| Pathophysiology of SIADH | excess secretion from post pituitary causes excess water retention, inc plasma vol, HTN, hyponatremia; if ADH supply is exhausted, acute diabetes insipidus ensues; natiuresis d/t atrial natiuretic peptide (ANP) suppresses prox tubule Na reabs d/t inc vol |
| Clinical findings of SIADH | sx d/t hypnatremia & deranged intracellular water; anorexia; N/V; chronic HA; altered cognition; muscle weakness; wt gain; possible oliguria; edema is UNCOMMON until late as is acute hyponatremic encephalopathy or seizure w/babinski sign |
| Clinical note about persistant hyponatremia without identifiable cause | consider a marker for undiagnosed malignancy until proven otherwise |
| Lab findings in SIADH | hyponatremia; dec serum osmolarity (<280mOsm/kg); elevated plasma ADH by immunoassay (>14picograms/mL) |
| SIADH differential and clinical sequelae | Pseudohyponatremia (lab artifact d/t hyperlipidemia or hyperproteinemia); Central Pontine myelinolysis (aka CPM) can occur w/agressive fluid replacement & is manifested by paraparesis/quadriparesis, seizures, persistant vegitative state |
| Diabetes Insipidus pathology | absence of ADH; inc water excretion (low osmolality polyuria); dec water resorption & compensatory polydipsia; inc serum osmolality if polydipsia doesn't match urine; hypovolemia, hypotension w/excess loss; can be d/t head trauma to post hypothalamus |
| Diabetes Insipidus clinical | polyuria (>40ml/kg/day); inc thirst & water intake (polydypsia); FTT in children d/t bad water balance; abnml labs only if pt cannot drink enough water to maintain plasma osmolality |
| Diabetes Insipidus hypernatremia | usu 150mEq/L or more |
| Diabetes Insipidus inc plasma osmolality | usu 300mOsm/kg or more |
| Diabetes Insipidus dec urine osmolality | always below the normal plasma osmolality of 290mOsm/kg and often 200mOsm/kg or less |
| Water deprivation test | used for diagnosis of Diabetes Insipidus; pt cannot drink for 14hrs; if pt has DI, their urine volume does not decrease and the urine remains dilute (low osmolality) |
| Vasopressin/desmopressin test | used to dx Diabetes Insipidus; if central DI, administration of IV ADH causes >50% inc in urine osmolality; If nephrogenic DI, IV ADH has no effect on urine osmolality |
| Differential diagnosis of hypernatremia | dehydration, aggressive IV Rx w/saline solution; excess salt intake |
| Causes of central diabetes insipidus | Idiopathic (mc); usu d/t autoimmune destruction of hypothalamic ADH neurons |
| Nephrogenic diabetes insipidus | X-linked (mc) mutation of vasopressin receptor gene (AVPR2); or auto recessive mutation in aquaphorin gene (AQP2) on 12q |
| Wolfram Syndrome | DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, deafness) |
| Thyroglossal duct cyst | usu midline in subhyoid bone; filled w/milky fluid; usu asymptomatic, but can enlarge creating mass effect of become infected or contain neoplastic functional thyroid tissue |
| Ectopic Thyroid Tissue | thyroid tissue found below cricoid cartilage in midline of neck |
| Lingual ectopic thyroid | d/t failure of thyroid migration, possibly a/w other ectopic sites or hypothyroidism depending on total vol of fxnl tissue; can undergo goitrous enlargement/mass or neoplastic formation; inc incidence of thyroglossal duct cysts |
| Substernal ectopic thyroid | located in anterior or superior mediastinum; may have continuity with cervical thyroid tissue, may undergo goitrous enlargement or neoplastic transformation |
| Ovary ectopic thyroid | aka struma ovarii; not a developmental abnormality, rather a teratromatous neoplasm w/thyroid tissue that surpassed the other elements of a mature teratoma; rarely a/w hyperthyroidism |
| Hypothyroidism causes | Autoimmune thyroid disease/thyroiditis/hashimoto's/lymphocytic (mc); post-thyroid ablative Rx; thyroidectomy; endemic iodine deficiency; cystinosis (lysosomal storage dx) |
| Pathophysiology of autoimmune thyroiditis | anti-thyroid cell autoantibodies bind follicular cells, cause inflam response & destroy parenchyma; causes dec synth of thyroxine (T4) and thriiodothyronine (T3); elevated TSH d/t lack of feedback inhib & growth of goiter |
| Progression of autoimmune thyroiditis | early parenchymal destruction causes transient hyperthyroidism as stored hormones are liberated from follicles; lymphocyte infiltration of gland causes diffuse goiter, thyroid atrophy and hypothyroidism |
| Pathophysiology of secondary (central) hypothyroidism | identical pathophys to 1* hypothyroidism, but includes decreased levels of TSH d/t pituitary failure |
| Clinical synopsis of hypothyroidism | low temp; slow mental state; fatigue from low ejection fraction; constipation; weakness; dysphonia; weak pulse, low HR; wt gain; dry skin/mucosa; thinning of hair; hard edema of subcut tissue w/inc mucins in fluid (myxedema); hi TSH, low T4/T3; autoantibo |
| Autoantibodies in hypothyroidism | thyroid peroxidase Abs (binds membrane antigen involved in hormone synth); Thyroglobulin Abs; TSH receptor-blocking autoantibodies |
| Congenital hypothyroidism/myxedema/cretinism | developmental hypoplasia or agenesis (mc); thyroid gland is small and located in abnml places (base of tongue, mediastinum, etc); |
| Pathophysiology of dyshormonogenesis | inherited genetic defect in one of the enzymes needed to make thyroid hormones resulting in significantly reduced thyroid hormone synthesis; mc defect is in thyroid peroxidase activity - results in failure of oxidation (organification) of iodide to iodine |
| Clinical synopsis of developmental hypothyroidism | hypotonia, hoarse cry, weakness, large tongue, constipation, potbelly, umbilical hernia, strabismus, myxedema, motor/cognitive developmental delay; low T4/T3; high TSH; must be dx early to prevent MR/DD |
| Myxedema Coma | life-threatening encephalopathy w/stupor or coma d/t chronic hypothyroidism d/t infxn, CVA, traumatic injury, or hypothermic episode; hi TSH, low T4/T3; hypoxia d/t hypoventilation; hypoglycemia; lactic acidosis; hypnatremia (H20 retention); hypercalcemia |
| Myxedema coma - clinical synopsis | a/w winter; acute encephalopathy can progress from stupor to coma; dry/coarse/scaly skin, hair; nonpitting myxedema; macroglossia; dysphonia; delayed deep tendon reflexes; seizures; bowel ileus; pleural effusion; cardiomegaly; bradycardia |
| Primary Hyperthyroidism | d/t disorder originating in thyroid gland not pituitary; generalized overactivity of gland to local hyperactive nodule or circulating Ab which stimulates the gland (long acting thyroid stimulator: LATS); inc BMR; S/Sx resemble state of catecholamine exces |
| Secondary hyperthyroidism | d/t stimulation of thyroid gland by an excess of thyrotrophin (TSH) secreted by pituitary gland |
| Tertiary hyperthyroidism | d/t stimulation of thyroid gland via TSH by an excess of thyrotrophin-releasing hormone from the hypothalamus |
| Common causes of hyperthyroidism | Graves disease (mc) autoantibodies possess TSH-like effects; functioning thyroid adenoma/carcinoma; pituitary (TSH-producing) adenoma --> 2* |
| Clinical synopsis of hyperthyroidism | goiter, palpitations, tachycardia, cardiac arrhythmias (a-fib is mc); exopthalmos d/t retro-orbital edema; wt loss; hyper-reactive DTRs; hyperactivity, nervousness, heat intolerance, emotional labile, insomnia |
| Hyperthyroidism - labs, course, sequelae | hi T4/T3, low TSH, elevated circulating TSH receptor-stimulating autoantibodies; if not treated, increasing T3/T4 secretion leads to thyroid crisis (thyrotoxic storm) and death d/t cardiac arrhythmias |
| Graves disease | variant of hyperthyroidism; circulating anti-thyroid autoantibodies (LATS) that bind TSH receptors in thyroid gland to promote thyroid follicle hyperplasia & goiter; inc secretion of T3/T4 leading to elevated tissue levels and significantly raised BMR |
| TSH-producing adeoma | 2* hyperthyroid; neoplasm of pituitary thyrotrophs produce excess TSH; stimulation of thyroid leads to goitrous hyperplasia, inc thyroid hormone secretion; rarely the pituitary is thyroid resistant causing thyrotrophs to over-produce TSH w/o neg feedback |
| Toxic nodular goiter | aka plummer's disease; multinodular goiter that produces excess thyroid hormones; circulating Abs are NOT present |
| Toxic adenoma | aka Plummer's nodule; neoplastic nodule that is autonomous in secreting thyroid hormones; possibly d/t mutation in TSH receptor; removal of nodule allows rest of thyroid gland to fxn normally |
| T3 thyrotoxicosis | 20% of hyperthyroid cases; d/t cautoimmune thyroiditis (mc), toxic adenoma, toxic multinodular goiter; considered very early stage of hyperthyroidism that will progress; tachycardia, hyperactive, DTRs, tremors; low TSH, nml T4, hi T3 |
| Subactue thyroiditis | onset after a viral URTI; thyroid gland manifests transient edema/tenderness & elevation in circulating thyroid hormones d/t follicular epithelial leakage from inflammation; Sx of hyperthyroidism are proportional to level of hormone elevation |
| Toxic thyroiditis | aka: spontan. resolving hyperthyroid; lymphocytic (hashimoto's-like) thyroiditis inducdes temporary rise in thyroid hormone levels d/t follicular inflam/destruction; followed by slow progressive hypothyroidism; elevated autoAbs (except TSH receptor stimu) |
| Masked hyperthyroidism | aka: apathetic hyperthyroidism; usu in elderly; hyperthyroidism w/o nml clinical manifestations d/t co-morbidities including CNS disease |
| Amiodarone hyperthyroidism | iodine-containing anti-dysrhythmic heart medication which promotes increased secretion of thyroid hormones |
| HCG-related hyperthyroidism | high levels of HCG can stimulate the thyroid gland to overproduce thyroid hormones because of the molecular homology to TSH; can be seen in molar or nml pregnant women |
| Facticious hyperthyroidism | aka thyrotoxicosis factitia; elevated circulating thyroid hormone d/t pt surreptitiously ingesting large amounts of exogenous thyroxine; no goiter, depressed serum TBG level |
| Interferon-induced hyperthyroidism | interferon Rx for chronic viral hepatitis can induce TSH-receptor autoantibodies leading to iatrogenic Grave's disease |
| Pediatric Hyperthyroidism | Graves disease (mc) cause; also: thyroid adenoma (toxic adenoma), pituitary TSH-producing adenoma |
| Pediatric Graves disease pathophysiology | caused by thyroid-stimulating immunoglobulins: IgG1 (TSIs); binding to extracellular domain of TSH causes follicular growth & thyroid hormone release; Thyroid receptor antibodies (TRAs) may also be present; initiating event - bacterial or viral (yersinia) |
| Pediatric Graves disease: clinical findings | deterioration of behavior/school performance; goiter, palpitations, tachycardia, exopthalmos, wt loss; hyperactivity, nervous, emotional labile, insomnia, heat intolerance, menstrual irregularities, resting tremors; low TSH, hi T4/T3; TSI autoAbs; hyperCa |
| Neonatoal Graves Disease | usu d/t circulating maternal TSH Abs (IgG) and transplacental passage of antibodies by binding fetal thyroid cells (occurs in 1/70 of Grave's dx moms); Sx resolve w/in months; incidence of premature, craniosynostosis, congenital thyrotoxic cardiomyopathy |
| McCune-Albright Syndrome | presence of polyostotic fibrous dysplasia, cafe-au-lait spots, and various endocrinopathies (mostly precocious puberty), also hyperthyroidism; d/t mutation in alpha subunit of G-ptn that links TSH receptor to adenylate cyclase (constitutive activation) |
| Thyrotoxic Storm/Crisis; Acute thyrotoxicosis | acute exacerbation of Sx of hyperthyroidism following a precipitating cause: usu d/t infxn, CVA, trauma, surgery, radioactive iodine Rx for hyperthyroidism; childbirth; |
| Lab findings in thyrotoxic storm | dec TSH, hi T4; nml or hi T3; leukocytosis, hyperglycemia, hypercalcemia (bone resorption), hi AST/ALT liver enzymes, hi cortisol, hi catecholamines, dehydration (if vomiting/diarrhea is severe; elevated BUN, Na, hyper or hypokalemia) |
| Clinical course of thyrotoxic storm | high risk of death d/t cardiac arrhythima; inc transient muscle weakness (thyrotoxic periodic paralysis or chronic thyrotoxic myopathy d/t dysfnxnl NaK pump); inc risk of CHF and seizures |
| Apathetic/masked thyrotoxicosis | varient of thyrotoxic storm; chronic thyrotoxicosis in elderly and debilitated; can progress w/o nml hypermetabolic symptoms w/presentation of collapse; CHF, cognitive depression; low TSH, hi T4, nml or hi T3; higher morbidity than typical presentation |
| Thyroid masses | 95% are benign; 1/20,000 are malignant |
| Nodular goiter | may or may not be a/w hyperthyroidism; if at least one or more nodules are functioning, it is toxic (inc circulatin T3/T4 and low TSH) |
| Thyroid adenoma | benign neoplasm; may or may not be functioning; (fxnl - toxic adenoma or plummer nodule; inc circulating T3/T4 and low TSH) |
| Thyroid papillary carcinoma | most common type of thyroid malignancy; accounts for most thyroid cancers |
| Thyroid follicular carcinona | usu present in older adults; arises from follicular cells; more aggressive than papillary carcinoma (1 in 5 cases are metastatic to bone or lung); 20YS 80% (2x mortality rate of papillary) |
| Anaplastic thyroid carcinoma | rare; usu older adults; arises from follicular cells; very aggressive w/early widespread mets (brian, lung, bone); <1% 5YS w/pts dying in 10mo of dx |
| Medullary thyroid carcinoma | 1 in 28,000/yr; sporadic in older adults; familial in teens & a/w MEN syndromes; arises from parafollicular cells (calcitonin-producers; neuroendocrine); may be a/w paraneoplastic syndromes b/c parafollicular cells produce other hormones |
| Paraneoplastic syndromes a/w medullary thyroid carcinoma | d/t elevated calcitonin production; carcinoid syndrome; cushing syndrome d/t inappropriate ACTH secretion |
| Thyroid masses in children | d/t radiation exposure to the neck of adolescents; most nodules are benign, but high rate of malignancy in pediatric masses than in adults; if malignant, papillary type is most common (except in MEN syndrome where medullary carcinoma predominates); |
| Subacute (lymphocytic) thyroiditis | usu follows viral URTI; parenchymal injury d/t autoimmune response from antigen cross-reactivity ; may be a/w multinucleate giant cells (subacute granulomatous thyroiditis); painfully large thyroid |
| Lab findings in subacute thyroiditis | transient elevated T4 d/t parenchymal damage; elevated ESR; hi circulating cytokines (IL-6, TNF-alpha), anti-thyroid antibodies |
| Clinical course of subacute thyroiditis | usu spontaneous resolution; may be a/w hyperthyroidism if enough hormone enters circulation; few develop chronic autoimmune thyroiditis and subsequent hypothyroidism |
| Riedel thyroiditis | a/w dense fibrous induration & adhesion to adjacent structures that can cause tracheal compression; probably autoimmune rxn a/w dysregulation of repair process; mononuclear infiltrates (not giant cells) destroys follicles w/fibrous spread beyond capsule |
| Postpartum thyroiditis | autoantibodies and cell-mediated immune response damages thyroid parenchyma; causes painless goiter; low T4, hi TSH, hi anti-thyroid autoantibodies (anti-peroxidase, etc) |
| Euthyroid sick syndrome | thyroid producesT3/T4 but effects are blocked in post-thyroid paths (ex: low or blocked uptake; inappropriate conversion of T4 to rT3 (rT3 has no action); impaired type I deiodinase enzyme lowers peripheral tissue T3 levels; selenium def=no diodinase fxn) |
| Other causes of euthyroid sick syndrome | chronically elevated cortisol &/or inflam cytokines (IL-1, IL-6, TNF) that inhibit TSH, T4/T3 synth; or, prolonged physiological stress=cortisol inhibition of T4-->T3 conversion causing systemic hypometabolism from low T3 |
| Primary Euthryoid sick syndrome (ESS) clinical synopsis | chronic mild hypothermia (core temp <98.0F) and chronic fatigue; Low total and free T3; elevated rT3 (d/t inhibition of enzyme path responsible for breaking down rT3) |
| Hyperparathyroidism - pathophysiology of elevated PTH | inc Ca absorption by bowel; inc Ca reabsorption from renal tubules (inc PO4 excretion & hypophosphatemia); inc osteoclastic fxn (osteopenia, osteitis fibrosa cystica, pathologic fx, osteoblasts cannot keep up w/bone loss); NET: Hi serum Ca and Low PO4 |
| Osteitis fibrosa cystica | subperiosteal bone resorption followed by formation of cysts that distort bony architecture; commonly in phalanges & distal clavicles; if hemorrhage into a cyst, it is followed by giant cell reparative granulomas known as "brown tumors" |
| Lab findings in hyperparathyroidism | elevated PTH; hypercalcemia, hypercalciruia, hypophosphatemia; metabolic acidosis (d/t PTH-enhanced bicarb urinary excretion) |
| Clinical course of hyperparathyroidism | inc Ca load to kidneys promotes nephrolitiasis esp if urine is alkaline; elevated serum Ca causes: dec CNS fxn (lethargy), muscle weakness, constipation d/t dec peristaltic activity, dec diastolic relaxation of heart (CHF), metastatic calcification) |
| Common causes of primary hyperparathyroidism | parathyroid adenoma (mc); parathyroid hyperplasia; parathyroid carcinoma |
| Common causes of secondary hyperparathyroidism | chronic renal failure (mc) - chronic Ca loss in urine leads to chronic stimulation of parathyroid glands; hypercalcemia is usu not a problem b/c of Ca loss thru kidneys |
| Ectopic PTH hyperparathyroidism | PTH production by extraparathyroid malignant tumor leads to paraneoplastic hyperparathyroidism; the secreted molecule may be different than nml PTH, but has same activity (aka: parathyroid hormone-related ptn); a/w small cell of lung &renal cell carcinoma |
| Hypoparathyroidism | mc is acquired from surgical removal or injury; lack of circulating PTH leads to dec Ca absorption from GI, inc Ca excretion in urine, dec bone resorption; Dec serum Ca levels leads to neuromuscular excitability and tetany |
| Pseudohypoparathyroidism | heterogeneous grp of disorders characterized by hypocalcemia, hyperphosphatemia, inc serum PTH and insensitivity to biological activity of PTH; various levels of end-organ resistance to PTH effects (seizure, muscle cramps, migrating parasthesias) |
| Lab findings in pseudohypoparathyroidism | hypocalcemia, hyperphosphatemia, nml or hi PTH, abnml Ca/PO4 serum/urinary response pattern to admin of biosynthetic PTH fragment |
| Endocrine pancreas: alpha cells | produce glucagon that causes rapid breakdown of glycogen, esp in liver, and its transformation into glucose; also produces amylin |
| Endocrine pancreas: beta cells | mc; produce insulin and amylin |
| Endocrine pancreas: enterochromaffin cells | produce serotonin; sparse w/in islets of langerhans; neoplasms of these cells are: Carcinoid tumors (secreting excess serotonin) |
| Insulin | produced by islet beta cells; pre-pro-hormone cleaved to A, B, & C(mid)-peptides; secretion regulated by plasma glucose (responding to influx of Ca) |
| Binding of insulin in liver | binds receptors (tyrosine kinase); inc storage of glucose, decrease glycogenolysis/glucose release, decrease gluconeogenesis |
| Binding of insulin to non-hepatic tissues | binds receptors and increases cellular uptake of glucose |
| Fasting blood surgar | supplied by gluconeogenesis by liver |
| Effects of insulin | dec blood glucose via uptake in muscle/fat; promote conversion of glucose to glycogen (glycogenesis); inhibit release of glucose from liver glycogen (glycogenolysis); inhibit fat breakdown to FA, TGs, ketones; inhibit ptn breakdown gluconeogenesis |
| During fasting states | low insulin, high glucagon, increased liver gluconeogenesis, inc glycogenolysis in liver/other tissues; net effect to maintain blood sugar |
| After a meal | inc insulin levels (direct stim of beta cells by rising blood sugar); low glucagon; dec hepatic gluconeogenesis; uptake of glucose in muscle and adipose; excess glucose turned into glycogen or lipid |
| Glucagon | produced by islet alpha cell and in CNS; stimulates hepatic gluconeogenesis/glycogenolysis; levels vary inversely with insulin; maintains euglycemia in fasting state |
| Pathophysiology of insulin insufficiency | catabolic state (effects on glycogen stores (glycogenolysis in liver, inc hyperglycemia), lipids (inc lipolysis w/FA entering blood not turned into TGs, oxidized to ketones, glycerol->glucose in blood), ptns (muscle->AAs, gluconeogenes, inc hyperglycemia) |
| Adequate insulin levels | promote glycogen synthesis, prevents lipolysis (by inhibiting lipase), promotes muscle absorbing AAs |
| Type I Diabetes | 10% of cases; autoimmune dx (Tcells destroy islet beta cells); high levels of anti-islet antigen Abs; inability to synthesize & secrete insulin; mononuclear infiltration of islets (insulitis) |
| Lab findings for Type I Diabetes | glucosuria, high blood sugar (>200mg/dL); low serum C-peptide; low serum insulin; high plasma glucagon; beta-cell autoantibodies; high HbA1c; high fructosamine |
| Types of beta cell autoantibodies | Glutamic acid decarboxylase (GAD65); Islet cell (cytoplasmic or surface antigen) Abs (ICA, ICCA, ICSA); anti-insulin; anti-insulin receptor; anti-tyrosine phosphate; |
| Common causes of secondary Type I DM | Cushings (1* hypercortisolism); Iatrogenic hypercortisolism; hemochromatosis; chronic pancreatitis; CF; pancreatic adenocarcinoma; pheochromocytoma; pituitary neoplasm producing GH |
| Clinical course and sequelae | even w/treatment; if blood sugar is not tightly controlled, pt has veneralized vasculopathy/end organ damage; lifespan is shortened for 1in7 to 4th decade (diabetic ketoacidosis, diabetic kidney dx, accelerated coronary atherosclerosis) |
| Microvascular and macrovascular vasculopathy in diabetics | onset 10-15yrs after dx; diabetic glomerulosclerosis; Diabetic retinovasculopathy; Peripheral neuropathy; Accelerated central & peripheral vascular atherosclerosis |
| Diabetic glomerulosclerosis | nodular; mc end-stage renal dx in US; starts w/excess albumin in urine (microalbuminuria >300mg/day) |
| Kimmelstiel-Wilson Syndrome | combination of nephrotic syndrome and hypertension in diabetics a/w diabetic glomerulosclerosis |
| Diabetic retinovasculopathy | mc cause of blindness in US adults |
| Peripheral neuropathy | vasculopathy of small vessels that supply peripheral nerves leading to ischemic injury of peripheral nerves |
| Accelerated central and peripheral vascular atherosclerosis | coronary atherosclerosis; peripheral arterial insufficiency leading to ischemic injury of extremities and ultimately distal amputation |
| Increased incidence of infection in diabetes | chronically elevated blood sugars create good environment for microbial growth; pts develop immunodeficiencies including chemotactic/phagocytic defects in phagocytes |
| NOTE: type I DM pts w/no complications for 20yrs after onset | a/w high probability of long-term good health |
| Benign glycosuria | variant of type I DM; may be d/t defect in renal tubular glucose transporter causing glucose in urine, but normal blood levels; may be d/t altered renal glucose threshold in pregnancy; may be d/t chronic renal disease |
| Gestational diabetes mellitus | levels of placental steroid & peptide hormones induce tissue insulin resistance in mom; inc maternal demand for insulin w/feeding (if not met w/inc islet insulin secretion, mom gets hyperglycemia); transferred to fetus & fetal pancreas produces insulin |
| Pathophysiological effects of gestational DM on mom | inc incidence of polyhydraminos (premature rupture of membranes & labor); inc incidence of pyelonephritis; inc incidence of failure to progress/difficult labor/c-section |
| Pathophysiological effects if gestational DM on fetus | inc incidence of: macrosomia, fetal anomalies, neonatal hypoglycemia (a/w brain damage); intrauterine death |
| Clinical course of gestational DM | most cases resolve; few manifest continued DM; marked inc incidence of subsequent Type 2 DM in mom |
| Latent autoimmune diabetes in adults pathophysiology | autoimmune attack on beta-cells in pancreas is slow; significant destruction (w/accompanying insulin deficiency) may take many years; pts usu do NOT have HLA antigens commonly seen w/type I DM |
| Brittle Diabetes Mellitus | type I DM w/marked fluxes in blood sugar predisposing to episodes of hypo and hyperglycemia; probably d/t dysfxnl beta-cells undergoing episodes of insulin production and deficiency |
| Bronze Diabetes Mellitus | a/w hemochromatosis; d/t deposition of iron in pancreas that destroys islets and causes insulin-dependent DM; iron is also deposited in skin giving pt a bronze discoloration |
| Diabetic Ketoacidosis - initiating events | infxn causing physiologic stress & inc insulin requirement not met by maintenance of nml insulin dose (mc); acute insulin deficiency (disruption of nml insulin Rx, ineffective Rx, new onset of DM) |
| Pathophysiology of diabetic ketoacidosis | d/t insulin deficiency, energy shifts from nml CHO metabolism to fasting state of fat metabolism (fat-->FAs-->beta oxidation-->ketones/ketoacids); w/excess ketone bodies for energy or excretion the body becomes acidic |
| Lab findings in diabetic ketoacidosis | High blood/urine glucose; metabolic acidosis; ketonemia/ketonuria; inc anion gap |
| Clinical findings and sequelae in diabetic ketoacidosis | malaise, polyuria, polydysia, N/V, acute encephalopathy (lethargy, delirium, coma, seizures); mortality of <2% w/Rx and >90% w/o Rx; risk of permanent post-DKS CNS damage |
| Type 2 Diabetes Mellitus | 1/20 in US; usu >45yo; >120% of IBW; family Hx; hispanic, native american, Afr-Amer, Asi-Amer, Pac-Islander; Hx of elevated glucose; HTN (>140/90); dyslipidemia (HDL<40, TGs>150); Hx of gestational DM or child >9lbs at birth; Polycystic ovarian syndrome |
| Pathogenesis of type 2 DM | combo of peripheral insulin resistance w/inability of pancreatic b-cells to inc insulin production to maintain euglycemia in face of peripheral insulin resistance; familial & environmental factors; resistance of cells to insulin is 1* event |
| Pathogenesis of type 2 cont'd | not a/w damage to pancreas or ciruculating insulin deficiency; skeletal muscle/adipose does not absorb excess glucose from meals; gluconeogenesis in liver continues dispite rising blood sugar; pancreas produces more insulin (hyperinsulinemia); obese pts |
| Pathology of type 2 DM | islets demonstrate significant amyloid-like material which is composed of amylin (insulinoma amyloid polypeptide); co-secreted with insulin by b-cells in response to food intake |
| Lab findings a/w type 2 DM | random blood sugar >200; fasting plasma glucose >125; HbA1c >7%; fasting serum C-peptide >1ng/dL (hyperinsulinemia); Serum insulin may be nml, low or high |
| Clinical findings of type 2 DM | fatigue, wt loss, polyuria, polydipsia, nocturia; many have end-organ damage (retinopathy, peripheral neuropathy, diabetic glomerulopathy); most have 4-7yrs of subclinical form of disease |
| Clinical course of type 2 DM | peripheral vascular ischemia (skin ulcers/gangrene of feet); renal insufficiency/failure; CHF (1* dysfxn from hyperglycemia or 2* to atherosclerosis, HTN, renal insuff); infxns/sepsis (hyperglycemia inhibits Bcell & PMN fxn (acquired immune deficiency) |
| Additional course of type 2 DM | general microvasculopathy a/w infxn; Malignant otitis externa (Pseudomonas), Rhinocerebral meningitis, Emphysematous pyelonephritis (G- gas producers: E.coli/Klebsiella); Retinopathic amblyopia; peripheral neuropathy |
| Non-proliferative diabetic retinopathy | hemorrhages & exudates d/t retinal microvasculopathy |
| Proliferative diabetic retinopathy | neovascularization of retina in response to retinal injury and infarction |
| Maturity-onset diabetes of the young | a/w family Hx of type 2 DM; pathogenesis unknown; impaired Bcell fxn a/w peripheral insulin resistance; most pts transform into insulin dependent DM d/t beta-cell failure |
| Hyperosmolar non-ketotic syndrome | chronic hyperglycemia d/t peripheral tissues are resistance to insulin; chronically elevated insuling induces liver to produce more glucose; serum insulin nml or high; absence of ketones b/c pt has nml insulin & lipolysis is suppressed |
| Hyperosmolar state in non-ketogenic syndrome | initiated by illness (UTI, URTI, etc) that cause N/V, anorexia, dec fluid intake & mild dehydration (pt stops eating or stops anti-glycemic Rx); physiologic stress favor high glucose (cortisol, epi/NE, glucagon); osmotic diuresis & hi serum osmolality |
| Lab findings in Hyperosmolar non-ketotic syndrome | marked elevated blood sugar (600-1000); hyperosmolarity (>330); hypernatremia d/t plasma vol contraction; hypokalemia; high BUN (d/t dehydration); high lactic acid (d/t generl hypoperfusion); pH nml or acitodic; no ketones; nml serum insulin |
| Clinical findings/course in Hyperosmolar non-ketotic syndrome | most pts have Hx of DM; polyuria, polydypsia, malaise, tachycardia (dehydration & stressors), acute encephalopathy (lethargy, delirium, seizures), <20% mortality d/t age/systemic metabolic probs, (NOT a/w cerebral edema) |
| Metabolic syndrome | cluster of pathophys abnormalities; "deadly quartet" = obesity, type 2 DM, hyperlipidemia, hypertension; basis is probably insulin resistance and its compensatory hyperinsulinemia; predisposes pts to CVD |
| Pathogenesis of Metabolic Syndrome | a/w peripheral insulin resistance & elevated resting plasma insulin; inc free FAs promote insulin-resistance; inc adipose synthesis/secretion of adipokines (TNF-a, IL-6) & plasminogen activator inhibitor which promotes thrombosis esp in vulnerable plaques |
| Clinical findings in Metabolic syndrome | most pts have central obesity, HTN, type 2 DM; inc incidence in CVD (40%); hyperglycemia, microalbuminuria, high TGs, low HDL |
| Mineralcorticoids | promote resorption of Na from nephron in exchange for K secretion; promotes H2O reabsorption thru osmotis & H+ secretion |
| Glucocorticoids | has mineralcorticoid effects; promotes gluconeogenesis (hyperglycemia); ptn catabolism frees AAs for gluconeogenesis; inhibits ptn synth; mobilizes FAs; promotes hepatic AA uptake; antiinflamm (stabilizes lysosomes, dec WBC respose, blocks cytokine produ) |
| Androgens | weaker androgenic effect than testosterone |
| Catecholamines | effects on organs depends on type of adrenergic receptors in organ; Epi (alpha/beta receptor activation; inc heart contractility, inc cell metab); NE (high level of alpha receptor activation; vasoconstriction) |
| Adrenal insufficiency (Addison's Disease) | adrenocortical insufficiency; causes fatigue, electrolyte imbalance, low BP, low plasma vol, wt loss, inc melanin pigment of skin/mucosa, anorexia, N/V; w/o therapy it can cause acute adrenocortical insufficiency |
| Pathophysiology of Adrenal Insufficiency | deficiency secretion of glucocorticoid, mineralocorticoid & adrenal androgen secretion; hypoglycemia; hyponatremia; hyperkalemia; dec plasma vol (hypotension, dec CO, pseudopolycythemia); metabolic acidosis (aldosterone usu promotes H+ excretion) |
| Primary Addison's Disease Pathophysiology | symptomatic only when >75% of adrenal cortex is damaged; usu d/t autoimmune destruction of both cortices (sparing medulla); a/w polyglandular autoimmune endocrinoapthy |
| Uncommon causes of Primary Addison's Disease | adrenal TB; metastatic neoplasm; Waterhouse-Friderichson Syndrome (sepsis-related hemorrhage); Systemic fungal infxn/mycotic adrenalitis (aspergillosis); Sarcoidosis; Wegener's granulomatosis; Congen adrenal hyperplasia; amyloidosis, hemochromatosis |
| Pathology of Primary Addison's disease | autoimmune-mediated destruction characterized by parenchymal cell loss & atrophy a/w patchy lymphocytic infiltrate; presence of granulomatous inflammation should suggest either TB, sarcoidosis, etc |
| Clinical findings in Primary Addison's Disease | chronic or slowly progressive dx; acute onset depends on adrenal fxn; physiological stress can precipitate adrenal crisis; skin hyperpigment w/vitiligo; fatigue, weak, anorexia, wt loss, N/V, cogn impair, dehydration, thin axillary/pubic hair in women |
| Lab findings in Primary Addison's disease | hyponatremia (mc); hyperkalemia, hypoglycemia, metabolic acidosis, hypercalcemia, low plasma vol (weak/fatigue, hypotension, dec CO); high adrenal gland Abs (anti-21-hydroxylase (mc); anti-17-hydroxylase, anti-P450); low cortisol; high ACTH |
| Paraclinical findings of Addison's disease | lack of response to exogenous corticotropin administration (ACTH); lack of elevation of cortisol is diagnostic |
| Clinical course/sequelae of Primary Addison's disease | adrenal crisis w/in days of losin complete fxn OR chronic state (hypovolemic shock, electrolyte imbalance, abdominal pain, hyperpyrexia, death) |
| Schmidt Syndrome | variant of primary Addison's disease; combo of idiopathic autoimmune addison's and autoimmune thyroiditis (hashimoto's disease); used to be classified as multiple endocrine deficiency syndrome |
| Secondary Addison's Disease | d/t chronic exogenous CCstroid Rx w/abrupt discontinuance leading to acute adrenal insufficiency; chronic CCsteroid use leads to cortical atrophy & when pt has physiologic stress the cortex cannot respond & pt gets hypocortisolism; |
| Pathophysiology of Central Addison's Disease | 1. deficiency in hypothalamus & low ACTH w/low plasma cortisol (pituitary response to CRH is nml; hypothalamus may be damaged by neoplasm; 2. deficiency of pituitary & low ACTH w/low cortisol (pituitary response to CRH not intact; pituitary is damaged) |
| Lab findings in Central Addison's Disease | depressed plasma cortisol; plasma ACTH may be elevated or depressed depending on pathophys; if the cause is ACTH deficiency, the serum K is nml b/c aldosterone is regulated independent of ACTH via RAAS |
| Common Causes of Hypercortisolism/Cushings | exogenous CCsteroid Rx (mc); ACTH-producing pituitary adenoma; adrenal adenoma/carcinoma |
| Pathophysiology of Cushings Syndrome | high cortisol; enhanced gluconeogenesis & hyperglycemia; ptn catabolism (muscular atrophy/weakness; low Ig (acquired immune def); osteoporosis (no osteoid in new bone formation); mild plasma expansion d/t mineralocorticoid effects of cortisol (mild HTN) |
| Pathophysiology of Cushings Disease | a/w pituitary adenoma producing ACTH; inc cortisol (hyperglycemia & ptn catabolism); nml mineralcorticoid levels (aldosterone not controlled by ACTH): nml Na, K, pH, BP |
| Pathophysiology of Iatrogenic Cushings Syndrome | synthetic CCsteroids used for many diseases; chronic use suppresses/atrophies adrenal cortex; ACTH may remain nml or be suppressed d/t neg. feedback; can suffer adrenal crisis w/o drugs |
| Clinical synopsis of Cushings | mild chronic HTN; progressive trunkal obesity & muslce wasting in limbs; moon face swelling; adipose buffalo hump; thin skin/purple striae; irregular period; hirsutism |
| Lab findings in Cushings | hyperglycemia; inc plasma cortisol; inc 24hr urine free cortisol; hypochloremia; metabolic acidosis; hypercholesterolemia; hypokalemia (d/t plasma expansion); hi testosterone; low ACTH (1*adrenal hypercortisol); high ACTH (cushings or ectopic ACTH source) |
| Dexamethasone suppression test | paraclinical test for Cushings; nighttime dose of Dex, measure plasma cortisol in A.M.; plasma cortisol should be <2 to indicate that the adrenals can be suppressed; only useful in diagnosing mild cases; cannot distinguish from pseudocushings |
| Clinical course of Cushings | inc incidence of: osteoporosis, opportunistic infx, peptic ulcer disease; mortality is low w/accurate diagnosis and Rx |
| Pathophysiology of Hyporeninemic Hypoaldosteronism | **dec renin levels** (d/t dec angiotensin I/II) leads to dec aldosterone levels; d/t chronic interstitial renal dx (mc; sickle cell or analgesic nephropathy); Iatrogenic (b-blockers, ACE-i, COX-i); diabetic glomerulopathy |
| Pathophysiology of Hyporeninemic Hypoaldosteronism: dec renal tubular fxn | dec Na resorption (Na loss in urine; serum hyponatremia); dec K secretion (serum hyperkalemia); dec H+ secretion (metabolic acidosis); no effect on glucocorticoid secretion |
| Pathophysiology of Isolated Hypoaldosteronism | **renin levels are nml**; dec aldosterone secretion (nml cortisol); hyponatremia, hyperkalemia; metabolic acidosis |
| Clinical course of hypoaldosteronism | generalized fatigue & weakness; hypovolemia; lack of aldosterone normally causes hypotension BUT in context of chronic renal failure hypERtension wins; (hypotention a/w iatrogenic causes...orthostatic hypotension/valsalva syncope) |
| Lab findings in hypoaldosteronism | hyperkalemia, metabolic acidosis, dec plasma renin (difficult to measure/validate); dec serum aldosterone |
| Clinical course of hypoaldosteronism | inc incidence of cardiac arrhythmias; in hyporeninemic cases the outcome follows course of chronic renal failure |
| Hyperaldosteronism | a/w 1 in 100 essential HTN; mc cause of 2* HTN; inc aldosterone d/t autonomou aldosterone production; inc tubular resorption of Na (hypernatremia, hypervolemia); hypokalemia; metabolic alkalosis; hypocalcemia (inc binding in basic environ); low renin |
| Pathophysiology of Primary Hyperaldosteronism | d/t: 1. fxning adenoma (aldosteronoma; Conn's syndrome); 2. idiopathic uni/bilat adrenocortical hyperplasia; 3. adrenal carcinoma; 4. ectopic secretion from non-adrenal malignancy (kidney/ovary) |
| Pathophysiology of Secondary Hyperaldosteronism | d/t CHF (mc); reduced renal blood flow leads to activation of RAAS axis & elevated aldosterone; pathophysiological effects are similar to 1* condition which exacerbates CHF |
| Clinical synopsis of hyperaldosteronism | generalized weakness; mild refractory HTN: constipation (d/t hypokalemia); expanded plasma vol (subcut edema, exacerbation if CHF) |
| Lab findings in hyperaldosteronism | hypokalemia, metabolic alkalosis; elevated serum aldosterone; elevated 24hr urine aldosterone; low plasma renin; possible hypernatremia |
| Clinical course of hyperaldosteronism | chronic treatment-resistant HTN occurs in 1* cases; inc incidence of: cerebrovascular accidents; CHF; sudden death; low morbidity/mortality w/Rx |
| Adrenal Hemorrhage/Apoplexy | d/t sepsis, trauma, toxemia of pregnancy, DIC, chronic anticoagulant Rx, antiphospholipid antibody syndrome, idiopathic |
| Pathophysiology of Adrenal Hemorrhage | adrenal gland has rich arterial supply & poor single-vein drainage; when stressed, ACTH secretion inc leading to inc blood flow that can exceed capacity of vein; venous spasm d/t high catecholamines (venous stasis, venous thrombosis, arterial hemorrhage) |
| Clinical course of adrenal hemorrhage | leads to adrenal insufficiency (Addison's dx); pt requires steroid replacement Rx; the highest mortality rate is a/w bacterial sepsis |
| Waterhouse-Friderichsen Syndrome | variant of adrenal hemorrhage; caused by Neisseria meningitidis septicemia; mostly in children; a/w purpura d/t vasculitis & systemic inflammatory response; hypotension d/t hypoadrenalism |
| strep pneumoniae w/hyponatremia and low cortisol levels | adrenal hemorrhage w/need to amputate lower limb |
| Pathophysiology of adrenal adenoma/nodular adrenal hyperplasia | true neoplasm that compresses surrounding adrenal cortex; >80% are non-fxnl; If fxnl, pt can have inc glucocorticoids/cortisol (Cushing), Inc mineralcorticoids/aldosterone (Conn syndrome; low K, Hi Na/BP, hi aldosterone); Estrogen or Androgens |
| Pathophysiology of Adrenal Carcinoma | bigger than adenoma; usu fxnl; inc glucocorticoid (mc) causing cushings; Inc androgen in female (virilization or precocious puberty); Risk of inherited cancer (Gardner, Beckwith-Wiedemann, Li-Fraumeni syndromes) |
| Pathophysiology of Pheochromocytoma | arises from adrenal medulla; if a/w inc Epi/NE (hi BP, fast HR, neuroendocrine granules w/episodes of very hi BP, palpitations, tacycardia) |
| Pheochromocytoma description | member of paraganglioma neoplasms arising from specialized chemoreceptor tissues of symp nervous system; benign or malignant; related to chemodectoma (extra-adrenal paragliomas or non-chromoffin) in carotid/aortic body tumor, glomus jugulare tumor... |
| Risk factors for pheochromocytoma | presence of other endocrine neoplasms (as part of multiple endocrine neoplasia syndromes); neurofibromatosis type I; von Hippel-Lindau disease |
| Pathophysiology of pheochromocytoma | tumor that secretes Epi & may be a/w hypotension d/t a predominance of B2-receptor blockade in skeletal muscle (leads to vasodilation) over alpha-adrenergic stimulation in peripheral vessels; metabolized to metanephrine & normetanephrine |
| Clinical features of pheochromocytoma | most pts have Sx a/w excess catecholamines; episodic HTN, tachycardia, diaphoresis; recurrent HAs, episodic skin flushing |
| Lab findings in pheochromocytoma | elevated plasma metanephrines (via HPLC test); hi urine metanephrine (random & 24hr); hi urine spot vanillymandelic acid (random & 24hr) |
| Clinical course of pheochromocytoma | inc incidence of CVA, sudden HTN w/anesthesia, biopsy, surgery, trauma, iodine contrast (to prevent hypertensive crisis, pretreat pt w/alpha-adrenergic blocker) |
| Multiple endocrine neoplasia (MEN) type 2A | variant of pheochromocytoma; aka: Sipple syndrome; onset in youth; medullary thyroid carcinoma, bilateral pheochromocytoma, few w/parathyroid hyperplasia/adenoma |
| Multiple endocrine neoplasia (MEN) type 2B | variant of pheochromocytoma; medullary thyroid carcinoma; bilat pheochromocytoma; does NOTmanifest parathyroid disease |
| Congenital adrenal hyperplasia | a group of inherited autosomal recessive disorders; complete or partial deficiency of enzyme for cortisol or aldosterone synth leading to their deficiency & abnml accumulation of precursor adenocortical hormones |
| Hydroxylase deficiency | mc cause of congenital adrenal hyperplasia; 4 different forms: Virilizing form (affects androgens only); Salt-wasting form (lo Na, lo K, Addisonion form); Nonclassic/late-onset form (aka attenuated/acquired form); Cryptic form |
| 11-Hydroxylase deficiency | 2nd most common cause of congenital adrenal hyperplasia |
| Pathology of congenital adrenal hyperplasia | enlarged adrenals w/diffuse or nodular hyperplasia; cortex hyperplasia usu in zona fasciculata & reticularis (glomerulosa is nml) |
| Pathophysiology of 21-hydroxylase deficiency | stops cortisol and aldosterone from being made; pt will die in a few days (90% of all CAH); |
| Simple virilizing form of CAH | 21-hydroxylase deficiency; female ambiguous genitalia at birth or changes at precocious pugerty (axillary hair/pubic hair); Males w/precocious puberty get hair, phallic enlargement, accelerated growth |
| Salt-wasting form of CAH | addisonian form; cortisol & aldosterone deficiency d/t 21-hydroxylase deficiency; hyponatremia; hyperkalemia; dec plasma vol & hypotension |
| Pathophysiology of 11-hydroxylase deficiency | aka C-11 beta hydroxylase deficiency; 6% of all CAH; single enzyme defect in glucocorticoid & androgen pathway (dec cortisol w/inc ACTH; dec androgens); adrenal insufficiency does not occur b/c of elevated corticosterone; but gonads cannot make sex hormon |
| Inc deoxycorticosterone (mineralocorticoid) | a/w 11-hydroxylase deficiency; Na retention w/inc plasma vol leading to HTN; hypokalemia; renin suppression (aldosterone suppression) |
| Gonadal inability to synthesize sex hormones | a/w 11-hydroxylase deficiency; dec estrogen, progesterone, testosterone; all pts are phenotypically female (XY are pseudohermaphroditic) w/no secondary sex traits at pubery & primary amenorrhea |
| Clinical course for congenital adrenal hyperplasia | adrenal crisis shortly after birth or during childhood; infertility; chronic hypertension |
| Carcinoid tumor | tumors that can arise in multiple organs (esp bowel; appendix is mc) from primitive mucosal stem cells that differentiate along neoneuroendocrine cell lines; Risk factors: MEN1; Peutz-Jeghers Syndrome |
| Carcinod syndrome | a combo of symptoms produced by release of seratonin from carcinoid tumors; not all carcinoid tumors are a/w the syndrome |
| Sporadic carcinoid tumors | MEN1 gene at 11q13 is deleted (MEN1 normally acts as tumor suppressor gene) |
| Pathophysiology of carcinoid tumors | from neuroendocrine stem cells in gut, liver, pancreas, bronchus, ovaries; classified by primitive structure (ex: foregut (1* or 2*), midgut, hindgut); Can secrete seratonin, histamine, NE/Epi, ACTH, gastrin, somatostatin, insulin, glucagon |
| Clinical findings in carcinoid tumor | variable symptoms manifests w/metastasis; episodes of flushing (carcinod flush) in most pts upper body w/heat & itch d/t seratonin or histamine & precipitated by EtOH, food, stress; recurrent diarrhea/colicky abdominal pain; tricuspid/pulm valv stenosis |
| less common findings in carcinoid tumors | recurrent wheezing d/t bronchial spasm; mental aberration; hypercortisolism d/t inc ACTH (HTN, hyperglycemia, abdominal striae, trunkal obesity); acromegaly d/t inc GH; flat angiomas on skin |
| Malignant carcinoids | may not produce carcinoid syndrome even with metastasis |
| Lab findings in carcinoid tumors | diagnostic biomarkers; elevated whole blood or serum seratonin; elevated whole blood/plasma histamine; inc urine serotonin (5-hydroxytryptamine, -tryptophan, -indoleacetic acid); urine histamine, substance P, neuropeptide K, chromogranin |
| Clinical course of carcinod tumors | variable w/each tumor; carcinoid-related heart disease; inc incidence of carcinoid crisis w/anesthesis or surgery |
| Carcinoid-Related Heart Disease | occurs in most pts; endocardial fibrosis of ventricular surface of tricuspid valve/tendinous cords; dysfxn/stenosis/regurgitation causes RHF (less commonly pulm or mitral valve); d/t inc circulating GF |
| Carcinoid crisis w/surgical procedures | usu a/w foregut carcinoid tumors; d/t high levels of 5-HIAA; intense flushing, sudden diarrhea, acute abdominal pain, tachycardia, marked hypo or HTN, altered mental status, coma |
| Foregut carcinoid tumors | in bronchus, stomach, prox duodenum, pancreas; low serotonin; secrete: 5-hydroxytrypophan, histamine, polypeptide hormones; benign or malignant; a/w atypical carcinoid synd, acromegaly, cushing, skin telangictasia/hypertrophy in face/neck |
| Common secondary cause of foregut carcinoid tumor | chronic achlorhydria (gastric mucosa destroyed cannot make acid) |
| Midgut carcinoid tumors | mc type in adults; in 2nd part of duodenum, jejunum, ileum, Rcolon, appendix; argentaffin positive stain; secretes: serotonin, kinins, prostaglandins, substance P, vasoactive peptides; *usu benign; a/w cushings d/t ACTH production |
| Hindgut Carcinoid Tumors | in transverse colon, descending colon or rectum; rarely secretes: serotonin, 5-hydroxytryptophan, vasoactive peptides; may be benign or malignant; usu asymptomatic |
| Any patient with a single gland syndrome (ex: hypothyroidism, addison's dx, etc) | these pts have high incidence of other subsequent endocrine gland failures |
| Multiple Endocrine Neoplasia Syndromes | group of diseases in which endocrine glands are affected by neoplasia in specific patterns; auto dom mutation in MEN1 tumor suppressor gene on chrom 11 OR MEN2 gene responsible for protooncogene RET on chrom 10q |
| Pathophysiology of MEN Type 1 | most pts hyperparathyroid d/t hyperplasia or adenoma (neoplastic is de novo w/o prodrome); pituitary tumors (prolactinoma); adrenal (adenoma, hyperplasia, fxnl, carcinoma), thymic/bronchial carcinoids; scattered multiple lipomas or angiofibromas |
| Pathophysiology of MEN type 2A | mc varient of MEN type 2; neoplasia arises from pre-existing hyperplasia; Medullary thyroid carcinoma (usu bilat; child onset; inc calcitonin); Adrenal Neoplasia (usu bilat pheochrom); minority have hyperparathyroidism d/t hyperplasia/adenoma |
| Pathophysiology of MEN type 2B | very rare; neoplasia only arises from pre-existing hyperplasia; Medullary thyroid carcinoma (usu bilat; onset in youth; inc calcitonin); Adrenal neoplasia (usu pheochrom); Marfanoid appearance; Inc ganglioneuromas; *NOT a/w parathyroid neoplasia* |
| Clinical course for MEN syndromes | morbitity/mortality a/w different diseass (peptic ulcer disease/Zollinger-Ellison Syndrome; metastases of endocrine pancreas; Severe hypercalcemia w/arrhythmias from hyperparathyroidism; Metastatic medullary thyroid carcinoma; Catecholamine arrhythmias |
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