Endocrine

Help!

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

🗑

Review the information in the table. When you are ready to quiz yourself you can hide individual columns or the entire table. Then you can click on the empty cells to reveal the answer. Try to recall what will be displayed before clicking the empty cell.

To hide a column, click on the column name.

To hide the entire table, click on the "Hide All" button.

You may also shuffle the rows of the table by clicking on the "Shuffle" button.

Or sort by any of the columns using the down arrow next to any column heading.
If you know all the data on any row, you can temporarily remove it by tapping the trash can to the right of the row.

Embed Code - If you would like this activity on your web page, copy the script below and paste it into your web page.

Normal Size Small Size show me how

Created by: bscaryp