Goljan Pathology Synopsis - Systemic 2 - Renal to Endocrine Flashcards

Terms Definitions
First sign tubule cell dysfunction
inability to concentrate urine
Fixed specific gravity
chronic renal failure; cannot concentrate or dilute urine
Negative urine bilirubin + trace urobilinogen
normal urine
Positive urine bilirubin, absent urobilinogen
obstructive jaundice
Positive urine bilirubin + increased urobilinogen
Negative urine bilirubin + increased urobilinogen
extravascular hemolytic anemia
Positive urine nitrite + positive urine leukocyte esterase
urinary tract infection
Sterile pyuria
positive urine leukocyte esterase but negative standard culture; TB, C. trachomatis
Prerenal azotemia
↑ BUN and creatinine; ↓ renal blood flow (e.g. heart failure, hypovolemia)
Renal azotemia
↑ BUN and creatinine due to intrinsic renal disease (acute tubular necrosis)
Postrenal azotemia
↑ BUN and creatinine due to obstruction to urine flow
Serum BUN:creatinine ratio
<15:1 (renal failure); >15:1 (prerenal or postrenal azotemia)
BUN 80 mg/dL:creatinine 8 mg/dL
ratio 10/1 - renal failure
BUN 80 mg/dL:creatinine 2 mg/dL
ratio 40/1 - prerenal azotemia or postrenal azotemia
Creatinine clearance
measures GFR
important sign of renal dysfunction
RBC casts
nephritic type of glomerulonephritis
WBC casts
acute pyelonephritis, acute tubulointerstitial nephritis
Fatty casts with Maltese crosses
nephrotic syndrome
Hyaline casts
normal unless associated with proteinuria
Renal tubular cell casts
acute tubular necrosis
Waxy or broad casts
chronic renal failure
hexagonal crystals
Horseshoe kidney
Turner’s syndrome; lower poles fused
Renal dysplasia
MC childhood cystic disease; abnormal development; flank mass
Maternal oligohydramnios
fetal juvenile polycystic kidney disease; Potter’s facies in newborn
Adult polycystic kidney disease
AD; hypertension MC sign; cerebral berry aneurysms
Visceral epithelial cells
synthesize basement membrane
Glomerular BM
negative charge due to heparan sulfate
Nephritic syndrome
oliguria; RBC casts; hypertension; mild to moderate proteinuria
Nephrotic syndrome
proteinuria >3.5 g/day; ascites and pitting edema; fatty casts; fusion of podocytes
linear (anti-glomerular BM antibodies); granular (IC deposition)
MC GN; usually nephritic; episodic hematuria; mesangial IC (lgA-anti-IgA) deposits
Post-streptococcal GN
nephritic; subepithelial deposits; skin/pharyngeal infections; anti-DNAase B
SLE type IV GN
nephritic; subendothelial deposits; anti-DNA antibodies
Crescentic GN
crescents from parietal cell proliferation; worst GN; Goodpasture’s, Wegener’s
nephritic; anti-BM antibodies (glomerular + pulmonary capillary); crescentic GN
young male with hemoptysis progressing to renal failure
Minimal change disease (lipoid nephrosis)
MCC childhood nephrotic syndrome
Lipoid nephrosis
podocyte fusion; loss of negative charge in glomerular BM
Focal segmental glomerulosclerosis
nephrotic syndrome; AIDS and IV heroin abuse
Membranous GN
MCC adult nephrotic syndrome; subepithelial deposits; epimembranous spikes
Causes membranous GN
HBV, ACE inhibitors, cancer
nephrotic; subepithelial deposits; HCV association; tram tracks
nephrotic; C3 nephritic factor; intramembranous ICs (dense deposit disease)
DM nodular glomerulosclerosis
microalbuminuria first sign
DM glomerulosclerosis
nodules with collagen in mesangium; hyaline arteriolosclerosis of arterioles
ACE inhibitors
inhibit angiotensin II vasoconstriction of efferent arterioles
Alport’s syndrome
XD hereditary nephritis with sensorineural hearing loss
Ischemic ATN
prerenal azotemia MCC; renal tubular cell casts; BUN:creatinine ratio <15:1
Ischemic ATN
disruption of BM in proximal tubule and thick ascending limb
Nephrotoxic ATN
aminoglycosides, IVP dye, Pb/mercury poisoning
Nephrotoxic ATN
proximal tubule dysfunction; intact BM
prerenal azotemia, ATN, glomerulonephritis, postrenal azotemia
Acute pyelonephritis
vesicoureteral reflux with ascending infection; WBC casts, fever, flank pain
Chronic pyelonephritis
U-shaped scars overlying blunt calyces
Drug-induced tubulointerstitial nephritis
type I/IV reaction; e.g., penicillin
ARF, fever, rash, eosinophilia, eosinophiluria, WBC casts
Analgesic nephropathy
aspirin plus acetaminophen; renal papillary necrosis; IVP with ring defect
Myeloma kidney
BJ protein produces foreign body reaction in tubules
Urate nephropathy
prevent by giving allopurinol prior to chemotherapy
fixed specific gravity; BUN:creatinine <15:1; waxy and broad casts
Renal osteodystrophy CRF
hypovitaminosis D (no 1-α-hydroxylase); produces osteomalacia
Renal osteodystrophy CRF
osteoporosis from metabolic acidosis
Renal osteodystrophy CRF
secondary HPTH with increased osteoclastic activity
pericarditis, prolonged bleeding time, normocytic anemia, pathologic fractures
Benign nephrosclerosis
kidney of hypertension; shrunken kidneys due to hyaline arteriolosclerosis
Malignant hypertension
renal failure; encephalopathy; BP >210/120 mm Hg; IV nitroprusside
Renal findings
necrotizing arteriolitis; “flea bitten” kidney; hyperplastic arteriolosclerosis
Renal infarction
pale infarcts; hematuria; common in polyarteritis nodosa
renal stone MCC; atrophy of cortex/medulla; postrenal azotemia
Renal stones
most contain calcium (calcium oxalate/phosphate); hypercalciuria MC risk factor
colicky pain radiating into groin, hematuria; x-ray usually shows stone
Staghorn calculus
due to urease producing organisms (Proteus); alkaline urine pH; ammonia smell
hamartoma; associated with tuberous sclerosis
Renal cell carcinoma
smoking MCC; invasion renal vein/vena cava; lung, bone mets; yellow colored
flank mass, hematuria; ectopic hormones (EPO, PTH related peptide), left-sided varicocele
Renal pelvis transitional cell carcinoma
smoking MCC, phenacetin, aniline dyes, cyclophosphamide
Wilm’s tumor
hypertension, unilateral abdominal mass in child; aniridia/hemihypertrophy in AD types
Urine draining from umbilicus
persistent urachus
Retroperitoneal fibrosis
produces hydronephrosis
Bladder extrophy
abdominal wall defect + epispadias
Bladder diverticula
most commonly due to prostatic hyperplasia with urethral obstruction
Acute cystitis
E. coli; females > males; no fever, flank pain, or WBC casts
Bladder transitional cell carcinoma
smoking MCC, aniline dyes, cyclophosphamide; papillary
hematuria; hydronephrosis
Bladder adenocarcinoma
risk factors persistent urachus, extrophy
Bladder squamous cell carcinoma
Schistosoma hematobium infection
ventral opening on penis due to failure closure of urethral folds
dorsal opening on penis due to defect in genital tubercle
Peyronie’s disease
painful curvature penis due to fibromatosis
persistent/painful erection; HbSS
Squamous cell carcinoma penis
HPV and lack of circumcision most important risk factors
undescended testis; risk for seminoma applies to cryptorchid testis and normal testis
mumps usually unilateral (infertility uncommon)
<35 - N. gonorrhoeae, C. trachomatis; >35 - E. coli, P. aeruginosa
scrotal pain relieved by elevation of scrotum (Prehn’s sign)
left-sided scrotal mass; spermatic vein drains into left renal vein; infertility common
may be due to invasion of left renal vein by renal cell carcinoma
persistent tunica vaginalis; scrotum transilluminates
Torsion of testicle
testicle high in canal; absent cremasteric reflex
Testicular cancer
unilateral painless mass that does not transilluminate
Risk factors
cryptorchid testis, Klinefelter’s, testicular feminization
MC cancer; radiosensitive; large cells with lymphoid infiltrate; small percentage have ↑hCG
Spermatocytic variant
>65 yrs of age
Embryonal carcinoma
hemorrhage/necrosis; hematogenous spread before lymphatic; ↑AFP, hCG
Yolk sac tumor
MC testicular cancer in boys; ↑AFP
most aggressive testicle cancer; ↑hCG
more often benign in children than adult
teratoma + embryonal carcinoma
Malignant lymphoma
MC type in elderly; metastasis not primary cancer
DHT derived stimulation embryo; periurethral area - hyperplasia; peripheral area - cancer
perineal pain, fever; WBCs at end of voiding
Benign prostatic hyperplasia
DHT/estrogen-mediated; glandular/smooth muscle hyperplasia
all men develop; urethral obstruction MC (hesitancy, dribbling, nocturia), hematuria, dysuria Rx
Prostate cancer
DHT-mediated; palpable with rectal exam; osteoblastic metastasis (↑ AP)
sensitive but not specific for prostate cancer; ↑ in hyperplasia
Kallmann’s syndrome
absent GnRH, anosmia, absence of taste
failure to sustain an erection; psychogenic in most cases (erections present at night)
parasympathetic response
sympathetic response
Leydig cell failure
↑ LH; ↓ testosterone, sperm count; normal FSH
Seminiferous tubule failure
↑ FSH (↓inhibin); ↓ sperm count; normal LH and testosterone
Leydig and seminiferous tubule failure
↑ FSH and LH; ↓ testosterone and sperm count
Y chromosome
determines genetic sex
develops seminal vesicles, epididymis, vas deferens
Dihydrotestosterone (DHT)
develops prostate and male external genitalia
Male pseudohermaphrodite
genetic male; phenotypically female
Testicular feminization
XR; deficient androgen receptors; MCC male pseudohermaphrodite
Klinefelter’s syndrome
XXY; 1 Barr body; female secondary sex characteristics
Herpes genitalis
recurrent painful vesicles; multinucleated squamous cells with intranuclear inclusions
Human papilloma virus
condyloma acuminata; koilocytosis (wrinkled nuclei surrounded by a halo)
Chlamydia trachomatis
metaplastic squamous cells with vacuoles containing elementary bodies
non-specific urethritis, cervicitis, PID, ophthalmia neonatorum
Neisseria gonorhoeae
urethritis, cervicitis, PID; ophthalmia neonatorum, gram negative diplococcus
Ophthalmia neonatorum first week
N gonorrhoeae
Ophthalmia neonatorum second week
C. trachomatis
Lymphogranuloma venereum
C. trachomatis subtype
scrotal/vulva lymphedema; granulomatous microabscesses; rectal strictures in females
painful ulcer, adenopathy, Hemophilus ducreyi
Granuloma inguinale
Calymmatobacterium granulomatis; raised ulceration but no lymphadenopathy
Treponema pallidum
spirochete; produces vasculitis of arterioles (plasma cell infiltrate)
Primary syphilis
painless chancre
Secondary syphilis
rash on palms/soles; condyloma lata; generalized adenopathy
Tertiary syphilis
neurosyphilis (e.g., tabes dorsalis), aortic arch aneurysm, gummas
reagin antibodies against cardiolipin; ↓ titer with Rx of syphilis
false positive with anticardiolipin antibodies (common in SLE)
confirmatory test for syphilis; not distinguish active from treated disease
remains positive after Rx
Trichomonas vaginalis
flagellate protozoan; cervicitis/vaginitis; Rx metronidazole both partners
Gardnerella vaginalis
vaginal pH >5; bacterial vaginosis; clue cells; Rx metronidazole
Candida vaginitis
white, curd-like discharge; DM, antibiotics, pregnancy; Rx fluconazole
Vulvar squamous cancer
MC vulvar cancer; HPV association
Vulvar leukoplakia
biopsy to R/O squamous dysplasia/cancer
Lichen sclerosis vulva
epidermal atrophy; slight risk for squamous cancer
Squamous hyperplasia vulva
leukoplakia; no cancer risk
Paget’s disease
intraepithelial adenocarcinoma (mucin production) of vulva
Malignant melanoma
vulva location; similar to Paget cells but not mucin positive
Gartner’s duct cyst
lateral wall vagina; persistent mesonephric duct
Embryonal rhabdomyosarcoma
bloody, grape-like vaginal mass young girl
Vaginal adenosis
maternal exposure to DES; precursor clear cell adenocarcinoma vagina
Vaginal squamous cancer
usually extension of cervical cancer
absence of vagina and uterus
Nabothian cysts
endocervical glands covered by metaplastic squamous epithelium
Pathologic cervicitis
trichomonas, HSV-2, C. trachomatis (follicular cervicitis)
Cervical Pap
superficial squamous (estrogen), intermediate (progesterone), parabasal (no hormone)
70% superficial, 30% intermediate
100% parabasal cells
100% superficial cells
100% intermediate cells
Endocervical cells
sign of adequately performed Pap smear
Cervical polyp
bleeding after intercourse; non-neoplastic
Cervical dysplasia
begins in transformation zone; associated with low and high risk HPV
Risk factors cervical dysplasia/cancer
early onset sexual activity; multiple partners; smoking; OC
cervical intraepithelial dysplasia; mild, moderate, severe (in-situ)
Cervical cancer
↓ incidence (Pap smear); 45-yr-old; COD renal failure from obstruction of ureters
cervical discharge; bleeding after intercourse
Sequence to menarche
breast budding, growth spurt, pubic hair, axillary hair, menarche
Proliferative phase cycle
estrogen-dependent; ↑estrogen inhibits FSH and stimulates LH
day 14-I6; LH surge; subnuclear vacuoles; ↑body temperature
Secretory phase cycle
drop in estrogen/progesterone stimulates apoptosis; plasmin prevents clotting
stimulates follicle and aromatase synthesis in granulosa cells
stimulates androgen synthesis in proliferative phase and progesterone synthesis in secretory phase
Day 21
day of implantation of fertilized egg
↑plasma volume > RBC mass; ↑GFR; ↑thyroxine/cortisol (increased binding proteins)
LH analogue produced by syncytiotrophoblast
stimulates corpus luteum of pregnancy to synthesize progesterone for 8-10 weeks
estrogen of postmenopausal woman; aromatization of adrenal androstenedione
estrogen of non-pregnant woman in reproductive life; aromatization of testosterone
estrogen of pregnancy
↑ FSH (best screen; due to ↓estrogen), ↑LH
secondary amenorrhea, hot flushes
↑ hair in normal areas
hirsutism + male secondary sex characteristics (clitoromegaly)
Test for hirsutism/virilization
↑ testosterone - ovarian source; ↑DHEA-sulfate - adrenal source
Polycystic ovarian syndrome (POS)
↑ LH; ↓ FSH; ↑ estrogen and androgens
hirsutism, oligomenorrhea, infertility; enlarged ovaries with subcortical cysts; LH:FSH >2:1
excess menstrual flow; MCC iron deficiency in women
painful menses; 1° PGF2α, 2° endometriosis
bleeding related to hormone rather than anatomic causes
Anovulatory DUB
menarche and perimenopause; estrogen excess without progesterone
Ovulatory DUB
irregular shedding, inadequate luteal phase
Primary amenorrhea
no menses by 16 years old
Secondary amenorrhea
no menses for 3 months
Amenorrhea-hypothalamic/pituitary dysfunction
↓ FSH/LH; e.g., hypopituitarism
Amenorrhea-ovarian dysfunction
↑FSH/LH; e.g., Turner’s syndrome
Amenorrhea-end-organ disease
normal FSH/LH; e.g., imperforate hymen
Asherman syndrome
surgical removal of stratum basalis
Primary amenorrhea-normal secondary sex characteristics
constitutional delay MCC
Primary amenorrhea-lack secondary sex characteristics
Turner’s syndrome
XO; no Barr bodies; XO/XY types have gonadoblastomas; streak gonads (no eggs)
newborn with lymphedema hands/feet; cystic hygroma in neck (web); short stature; 1° amenorrhea
Secondary amenorrhea
pregnancy MCC; prolactinoma; anorexia nervosa; pituitary adenoma
Asherman syndrome
removal of stratum basalis causing scarring; secondary amenorrhea
group B streptococcus; intrauterine device (Actinomyces); chronic - plasma cells
Endometrial polyp
menorrhagia; not a precursor for endometrial cancer
functioning endometrial glands and stroma in myometrium; enlarged uterus
functioning glands and stroma outside uterus; reverse menses; ovary MC site
dysmenorrhea, painful stooling, bowel obstruction; “powder burn” appearance
Endometrial hyperplasia
unopposed estrogen; simple/complex types; precursor endometrial cancer
obesity, estrogen Rx, polycystic ovarian syndrome
Endometrial cancer
obesity, nulliparity, estrogen Rx, early menarche/late menopause; OC protective
bleeding in postmenopausal woman
Leiomyoma uterus
menorrhagia, obstructive delivery; not a precursor for leiomyosarcoma
MC sarcoma
Ectopic pregnancy
PID MC risk factor; intraperitoneal hemorrhage; screen with ß-hCG
Follicular cyst
MC ovarian mass in young woman
Risk factors ovarian tumors
nulliparity and genetic factors; OC protective
Serous ovarian tumors
surface-derived; ↑ bilaterality; psammoma bodies in malignant type
Mucinous ovarian tumors
surface-derived; pseudomyxoma peritonei in malignant type
Endometrioid carcinoma
resembles endometrial cancer; association with endometriosis
Cystic teratoma
MC benign germ cell tumor (<1% malignant); hair/teeth; calcifications
MC malignant germ cell tumor; associated with streak gonads of Turners
Yolk sac tumor
MC germ cell tumor young girl; ↑AFP; Schiller-Duval bodies
Meigs syndrome
ovarian fibroma, ascites, right-sided pleural effusion
Granulosa tumor
low grade malignant; hyperestrinism, Call Exner bodies
benign; yellow color; hyperestrinism
Leydig cell and Sertoli cell tumors
XY phenotype of Turner’s
Krukenberg tumors
metastatic stomach cancer; signet ring cells
Single umbilical artery
↑ incidence congenital defects
lining of villi; produces hCG and human placental lactogen
Human placental lactogen
responsible for mild glucose intolerance in pregnancy
Abruptio placenta
retroplacental clot; painful bleeding; hypertension, cocaine, smoking
Placenta previa
placenta implanted over cervical os; painless bleeding
Placenta accreta
direct implantation into myometrium without intervening decidua; hysterectomy
Twin placenta
monochorionic always identical twins; dichorionic may be identical or fraternal
Siamese twins
monoamniotic monochorionic twin placenta
Enlarged placenta
DM, Rh HDN, syphilis
Complete mole
benign neoplasm of chorionic villi; dilated villi; no embryo; 46 XX (both male)
preeclampsia in first trimester; ↑ incidence choriocarcinoma
Partial mole
embryo present; 68 XXY; no transformation into choriocarcinoma
malignancy of trophoblastic tissue (syncytiotrophoblast, cytotrophoblast)
Risk factors
complete mole (MC), spontaneous abortion, normal pregnancy
↑hCG; lung metastasis; good prognosis
group B streptococcus (S. agalactiae) infection
abnormal placentation causing placental ischemia; ↑ in vasoconstrictors (ATII)
hypertension, proteinuria, pitting edema; begins in third trimester
Spontaneous abortion
50% have karyotype deformity (trisomy 16)
Amniotic fluid
fetal urine
TE fistula, duodenal atresia, open neural tube defects
infantile polycystic disease
↑ Serum AFP
open neural tube defect
↓ Serum AFP
Down syndrome
Urine estriol
fetal adrenal, placental, maternal liver involved in its production
Down syndrome triad
↑ ß-hCG, ↓ serum AFP, ↓ urine estriol
Fibrocystic change
MC breast mass <50-yrs-old; atypical hyperplasia cancer risk; lumpy, painful breasts
Sclerosing adenosis
component of FCC; involves terminal lobules often has microcalcifications
benign stromal tumor; MC movable mass in women <35-yrs-old
Intraductal papilloma
benign tumor lactiferous duct/sinus; MCC bloody nipple discharge <50-yr-old
Invasive ductal cancer
MCC breast mass in woman >50-yrs-old
Breast cancer risk
unopposed estrogen; family history first-degree relatives
Breast cancer
painless mass upper outer quadrant in woman >50-yrs-old
screening test to detect non-palpable masses
Palpable breast mass
order fine needle aspiration (not a mammogram)
Ductal carcinoma in situ
necrotic centers (comedo); microcalcifications common
Paget’s disease of breast
invasive ductal cancer into nipple; Paget’s cells similar to vulvar Paget’s
Medullary carcinoma
bulky tumor with large cells and lymphoid infiltrate; more common in Pt with BRCA 1 mutation
Inflammatory carcinoma
orange peel appearance; lymphatics blocked by tumor (lymphedema)
Lobular cancer
MC cancer of terminal lobule; ↑ bilaterality
Phyllodes tumor
low grade malignant tumor of stroma
ER-PR positive tumors
tumors responding to hormones; candidate for tamoxifen (anti-estrogen)
ERB-B2 oncogene positive breast cancer
aggressive breast cancer
estrogen stimulation of male breast
normal in newborn, puberty (no surgery), old age; (micronodular) cirrhosis MC pathologic cause
Overactive endocrine syndrome
most often adenomas; use suppression tests (most do not suppress)
Tumors that suppress
prolactinoma (bromocriptine), pituitary Cushings (high dose dexamethasone)
Underactive endocrine syndrome
autoimmune destruction MCC; stimulation tests
Hypopituitarism adults
non-functioning adenoma MCC, Sheehan’s postpartum necrosis (stop lactation)
Hypopituitarism in children
craniopharyngioma (Rathke’s pouch remnant) MCC; visual field defects
S/S ↓ FSH and LH
amenorrhea, ↓ testosterone in male
Growth hormone functions
muscle growth, gluconeogenesis; release of insulin growth factor (IGF)
synthesized in liver; bone and cartilage growth
S/S ↓ GH/IGF in children
growth retardation; ↓ height and weight
Sleep and arginine infusion
stimulation tests for GH and IGF
S/S ↓ GH/IGF in adults
secondary hypothyroidism; ↓ T4, ↓ TSH; muscle weakness, dry skin
secondary hypocortisolism; ↓ cortisol, ↓ ACTH; fatigue; hypoglycemia
stimulation test for ACTH reserve
blocks adrenal 11-hydroxylase → ↑ ACTH and 11-deoxycortisol (proximal to block)
Metyrapone test ↓ ACTH and 11-deoxycortisol
pituitary/hypothalamic dysfunction
Metyrapone test ↑ ACTH and 11-deoxycortisol
Addison's disease
Diabetes insipidus
loss ADH (central), refractory to ADH (nephrogenic); always diluting urine
Central diabetes insipidus (CDI)
↓ UOsm and ↑ POsm with water deprivation; vasopressin causes ↑ UOsm > 50%
Causes CDI
pituitary stalk transection, hypothalamic lesion (site for ADH synthesis)
Nephrogenic diabetes insipidus (NDI)
↓ UOsm and ↑ POsm with water deprivation; vasopressin causes ↑ UOsm < 50%
Causes NDI
lithium, demeclocycline, nephrocalcinosis, severe hypokalemia
GH secreting pituitary adenoma before epiphyses have fused
GH secreting pituitary adenoma after epiphyses have fused
S/S acromegaly
cardiomyopathy; large hands, feet, jaw; hyperglycemia
inhibited by dopamine
MC pituitary tumor; secondary amenorrhea and galactorrhea; prolactin inhibits GnRH
surgery or bromocriptine (dopamine analog)
Other causes hyperprolactinemia
primary hypothyroidism, drugs
Inappropriate ADH syndrome
hyponatremia <120 mEq/L; ↑ UOsm (always concentrating urine)
small cell carcinoma lung, CNS injury, chlorpropamide
restrict water; demeclocycline in small cell carcinoma
Serum T4
↑ or ↓ in free hormone or thyroid binding globulin (TBG)
↑ Serum T4 and normal TSH
↑ TBG; due to ↑ in estrogen
↑ Serum T4 and ↓ TSH
↓ Serum T4 and normal TSH
↓ TBG; due to anabolic steroids
↓ Serum T4 and ↑ TSH
primary hypothyroidism
↓ Serum T4 and ↓ TSH
secondary hypothyroidism
negative feedback with T4 and T3; best screening test
I131 uptake
↑ in Graves; ↓ in thyroiditis, patient taking excess thyroid, hypothyroidism
Cold nodule
non-functioning nodule; no uptake I131
Hot nodule
functioning nodule; ↑ uptake I131
Thyroglossal duct cyst
midline cystic mass
Branchial cleft cyst
cyst in anterolateral neck
Acute/subacute thyroiditis
painful thyroid; early thyrotoxicosis; ↓ I131 uptake
Hashimoto’s thyroiditis
MCC hypothyroidism; HLA Dr3/Dr5; inhibitory IgG TSH receptor antibody
Hashimoto’s thyroiditis
↑ anti microsomal and thyroglobulin antibodies
muscle weakness, periorbital puffiness, ↓ reflexes, diastolic hypertension, constipation, dry skin
↓ T4, ↑ TSH
maternal hypothyroidism before fetal thyroid developed, genetic disorder
mental retardation; short stature and increased weight; coarse skin
any cause ↑ thyroid hormone activity; Graves disease, excess hormone, thyroiditis
↑ synthesis thyroid hormone; Graves disease and toxic nodular goiter
Graves disease
autoantibody against TSH receptor (type II reaction); HLA Dr3
S/S unique to Graves
exophthalmos, pretibial myxedema
S/S thyrotoxicosis
tachycardia/atrial fibrillation, systolic hypertension, diarrhea, brisk reflexes
Lab thyrotoxicosis
↑ T4, ↓ TSH, ↑ glucose, ↑ calcium
I131 uptake
↑ Graves, toxic nodular goiter; ↓ thyroiditis, excess hormone, hypothyroidism
Rx Graves disease
ß-blocker; drug to decrease hormone synthesis (propylthiouracil)
Toxic nodular goiter
hyperthyroidism; develops out of a multinodular goiter; no exophthalmos
enlarged thyroid; iodine deficiency MCC; relative thyroid hormone deficiency
rapid enlargement due to hemorrhage into cyst; Rx thyroxine
Solitary thyroid nodule woman
most often benign (cyst)
Solitary thyroid nodule man or child
often malignant
Papillary carcinoma thyroid
MC thyroid cancer; radiation exposure; psammoma bodies
Follicular carcinoma thyroid
invades blood vessels
Medullary carcinoma thyroid
parafollicular cells; calcitonin; amyloid (calcitonin conversion)
MEN I syndrome
3 P's; pituitary tumor, parathyroid adenoma, pancreatic tumor (ZE or ß-islet cell tumor)
MEN IIa syndrome
2 P's; medullary carcinoma thyroid, pheochromocytoma, parathyroid adenoma
MEN IIb syndrome
1 P; medullary carcinoma thyroid, pheochromocytoma, mucosal neuromas
Alkalotic pH
tetany with normal total calcium, ↓ ionized calcium and ↑ PTH
↓ total calcium, normal ionized calcium and PTH
↓ ionized calcium level; threshold potential comes closer to resting potential
thumb adducts into palm, twitching after tapping of facial nerve
maintains ionized Ca2+; ↑ Ca2+ renal reabsorption; ↓ phosphate/bicarbonate reabsorption in kidneys
Primary HPTH
↑ Ca2+, hypophosphatemia, ↑ PTH
adenoma MCC, hyperplasia, cancer
renal stone, peptic ulcers, pancreatitis, hypertension, metastatic calcification
Secondary HPTH
↓ Ca2+, ↑ PTH; hypovitaminosis D from renal failure MCC
Malignancy-induced hypercalcemia
↑ Ca2+, ↓ PTH; all other non-parathyroid causes same results
Causes hypercalcemia
osteolytic lesions, sarcoidosis, ↑ vitamin D, PTH-related peptide, myeloma
Tertiary HPTH
hypercalcemia developing from secondary HPTH
Primary hypoparathyroidism
↓ Ca2+ and ↓ PTH
previous thyroid surgery, autoimmune, DiGeorge syndrome
tetany; calcification basal ganglia
↓ Ca2+ with normal to ↑ PTH; end-organ resistance to PTH
Other causes ↓ Ca2+
hypomagnesemia (↓ PTH), ↓ vitamin D, DiGeorge
↓ Ca2+ and ↓ PTH
primary hypoparathyroidism
↓ Ca2+ and ↑ PTH
secondary hyperparathyroidism
↑ Ca2+ and ↑ PTH
primary hyperparathyroidism
↑ Ca2+ and ↓ PTH
malignancy induced hypercalcemia; other causes hypercalcemia
Waterhouse-Friderichsen syndrome
meningococcemia with bilateral adrenal hemorrhage due to DIC
Addison’s disease
autoimmune destruction adrenal cortex MCC, adrenogenital syndrome, metastasis
hypotension (salt loss), hyperpigmentation (ACTH), hypoglycemia
↓ sodium, ↓ cortisol, ↑ potassium, ↑ ACTH
Adrenogenital syndrome
AR; enzyme deficiency; hypocortisolism; hyperpigmentation from ↑ ACTH
21-Hydroxylase deficiency
↑ 17 KS, ↓ 17 OH, lose salt, hypotension; female pseudohermaphrodite
11-Hydroxylase deficiency
↑ 17 KS, ↑ 17 OH, retain salt, hypertension; female pseudohermaphrodite
17-Hydroxylase deficiency
↓ 17 KS, ↓ 17 OH, retain salt, hypertension; male pseudohermaphrodite
MCC Cushings
long-term corticosteroid therapy
Tests Cushings syndrome
low/high dose dexamethasone suppression; urine free cortisol (best test)
Normal dexamethasone suppression
cortisol analogue; ↓ ACTH and ↑ cortisol
Pituitary Cushings
MCC Cushing’s; ACTH secreting pituitary tumor
low dose dexamethasone not suppress cortisol; high dose suppresses
Adrenal Cushings
adrenal adenoma secreting cortisol; suppressed ACTH
no suppression with low/high dose dexamethasone
Ectopic Cushings
ACTH secreting small cell carcinoma of lung; high ACTH and cortisol levels
no suppression with low/high dose dexamethasone
S/S Cushings
purple stria, truncal obesity, hypertension, DM
Primary aldosteronism
benign adenoma in zona glomerulosa
hypertension and muscle weakness (hypokalemia), no pitting edema
hypernatremia, hypokalemia, metabolic alkalosis, ↑ urine K+ and Na+
benign tumor in adrenal medulla in adults
von Hippel Lindau, neurofibromatosis, MEN IIa and IIb
labile hypertension, anxiety, sweating, headache
↑ 24 hr urine for VMA and metanephrines
malignant tumor adrenal medulla child; widespread metastasis; hypertension
ß-islet cell tumor (insulinoma)
benign tumor; hypoglycemia, ↑ insulin and C-peptide
Patient taking excess insulin
hypoglycemia, ↑ insulin, ↓ C-peptide
malignant α-islet cell tumor; hyperglycemia and rash
Zollinger Ellison syndrome
malignant islet cell tumor secreting gastrin; peptic ulcers
malignant δ islet cell tumor; DM, malabsorption, cholelithiasis, achlorhydria
malignant islet cell tumor; diarrhea, hypokalemia, achlorhydria
organ damage correlates with glycemic control
Type 1
young, thin person; no insulin; HLA DR3/4; insulitis; islet cell antibodies; ketoacidosis
Type 2
older person; obese; relative insulin deficiency (↓ insulin receptors, postreceptor problems)
Type 2
family history; fibrotic islet cells with amyloid; hyperosmolar nonketotic coma
↑ Non-enzymatic glycosylation
glucose attaches to amino acids in basement membranes
Non-enzymatic glycosylation
↑ vessel permeability producing hyaline arteriolosclerosis
Osmotic damage
glucose converted into sorbitol by aldose reductase
Osmotic damage
lens (cataracts), Schwann cell (neuropathy), pericytes retinal vessels (microaneurysms)
Pathogenesis hyperglycemia
↑ gluconeogenesis (most important), glycogenolysis
Pathogenesis hyperlipidemia
no insulin to stimulate capillary lipoprotein lipase; ↑ chylomicrons/VLDL
Pathogenesis ketoacidosis
↑ oxidation fatty acids with excess acetyl CoA; liver synthesis ketone bodies
Most commons due to DM
neuropathy, blindness, CRF, hyperglycemia, non-traumatic amputation
Glycosylated HbA1c
measure of long term glycemic control (8-12 weeks)
Gestational DM
↑ placental size, human placental lactogen
macrosomia (↑ muscle/fat from insulin), RDS, newborn hypoglycemia (↑ insulin)
insulin/oral hypoglycemics MCC, liver disease; carnitine deficiency
Carnitine deficiency
no ß-oxidation of fatty acids; all cells compete for glucose
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