Endocrine Flashcards
thyroid axis
thyrotropin-releasing hormone TRH (hypothalamus) –>
TSH (pituitary) –> T3/T4 (thyroid)
- Neg Feedback: if thyroid hormone levels become too high, they inhibit secretion of both TRH (hypothal) and TSH (pituitary)
- Pos Feedback: low blood levels of T3/T4 are sensed by hypothalamus –> inc TRH –> inc release of TSH
adrenal axis
corticotropin-releasing hormone CRH (hypothalamus) –>
adrenocorticotropic hormone ACTH (pituitary) –>
cortisol (adrenal gland)
sex hormones axis
gonadotropin-releasing hormone GRH (hypothalamus) –>
FSH + LH (pituitary) –> estrogen, progesterone + some testosterone (ovaries) + testosterone (testes)
tertiary disorder
HYPOTHALAMUS IS THE PROBLEM
-LABS IN SAME DIRECTION
secondary disorder
PITUITARY IS THE PROBLEM
-LABS IN SAME DIRECTION
- pituitary adenoma:
- inc TSH + inc T4/T3
- inc ACTH + inc cortisol
-hypopituitarism - low pituitary hormones and low target organ hormones (both low)
primary disorders
TARGET ORGAN IS THE PROBLEM
-LABS IN OPPOSITE DIRECTIONS
- thyroid:
- graves, toxic goiters, toxic adenoma: inc T4/T3, dec TSH
- hashimoto’s, thyroiditis: dec T4/T3, inc TSH
- adrenal:
- addison’s: dec cortisol + inc ACTH
- adrenal adenoma: inc cortisol + dec ACTH
- ovaries:
- menopause: dec estrogen + inc FSH/LH
thyroid function tests
TSH - BEST THYROID FX SCREENING TEST
Free T4 - FREE THYROXINE, ordered when TSH abnormal to determine hyper/hypo
- elevated TSH, low FT4 = PRIMARY HYPO
- elevated TSH, normal FT4 = SUBCLINICAL HYPO
- elevated TSH, high FT4 = TSH MEDIATED HYPER (2/3ry)
- low TSH, low FT4 = 2ry/3ry HYPO (RARE)
- low TSH, normal FT4 = SUBCLINICAL HYPER
- low TSH, high FT4 = PRIMARY HYPER, THYROTOXICOSIS
Thyroid AB
-ANTI-THYROID PEROXIDASE AB, ANTI-THYROGLOBULIN AB –> DX HASHIMOTO’S OR AUTOIMMUNE
-THYROID STIMULATING AB –> GRAVE’S DZ
Free T3 - serum triiodothyronine
-useful to dx hyperthyroidism when TSH is low and T4 normal
thyroid - radioactive iodine test (RAIU)
diffuse uptake –> grave’s dz or TSH-secreting pituitary adenoma
decreased uptake –> thyroiditis (hashimotos, postpartum, dequervain)
hot nodule –> toxic adenoma
multiple nodules –> toxic multinodular goiter
cold nodule –> r/o malignancy
subclinical hypothyroidism
inc TSH, normal T4/T3
-tx- LEVOTHYROXINE IF SX (pt devo hyperlipidemia, hypothyroid sx, TSH >20)
HYPOthyroid
-sx- weight gain, cold intolerance, dry skin, hair loss (outer eyebrow), goiter, nonpitting edema, fatigue, memory loss, dec DTR, constipation, bradycardia, menorrhagia, hypoglycemia
HYPERthyroid
-sx- weight loss, inc app, heat intolerance, warm, moist, skin, easy bruising, hyperactive, anxiety, tremors, diarrhea, tachy, palpitations, high output heart failure, scant periods, hyperglycemia
cretinism
CONGENITAL HYPOTHYROIDISM due to maternal hypothyroidism or infant hypopituitarism
- sx- macroglossia, hoarse cry, coarse facial features, umbilical hernia, weight gain
- mental devo abnormalities if not corrected
-tx- LEVOTHYROXINE
euthyroid sick syndrome
abnormal thyroid hormone levels w/ normal thyroid function seen w/ NONTHYROIDAL ILLNESS (surgery, malignancies, sepsis, heart dz)
- DEC FREE T3/T4, DEC TSH (T3 abnormally low)
- INCREASED REVERSE T3
thyroid storm (thyrotoxicosis crisis)
POTENTIALLY FATAL COMPLICATION OF UNTREATED THYROTOXICOSIS USUALLY AFTER A PRECIPITATING EVENT (surgery, trauma, infx, illness, pregnancy)
-RARE (1-2% w/ hyperthyroid, high mortality 75%)
- sx- HYPERMETABOLIC STATE: PALPITATIONS, TACHY, A-FIB, HIGH FEVER, N/V, PSYCHOSIS, TREMORS
- dx- INC FREE T3/T4, DEC TSH (may be undetectable)
Treatment is:
1) beta blocker (propranolol)
2) thionamide (propylthiouracil or methimazole)
3) iodine solution
4) glucocorticoids (supportive - inhibits peripheral conversion of t4 to t3 and impairs thyroid hormone production)
- AVOID ASPIRIN (causes increased T3/T4)
myxedema crisis
EXTREME FORM OF HYPOTHYROIDISM
-MC IN ELDERLY WOMEN W/ LONG STANDING HYPOTHYROIDISM IN WINTER
- patient will have acute precipitating factor (infx, CVA, CHF, sedative/narcotics) AND undiagnosed HYPO, noncompliance w/ HYPO meds
- patient will show severe signs of HYPO: BRADYCARDIA, obtunded, hypothermia, hypoventilation, HYPOGLYCEMIA, HYPONATREMIA, HYPOTN
-labs will look like HYPO –> inc TSH, dec T4/T3
- tx- IV LEVOTHYROXINE (give even w/ high suspicion)
- ICU ADMIT, treat underlying, PASSIVE WARMING
grave’s disease
AUTOIMMUNE - MC CAUSE HYPERTHYROID
-TSH receptor AB cause inc thyroid hormones + thyroid growth (worse w/ stress like illness, pregnancy)
-patient will be female, with enlarged thyroid, clinical hyperthyroid sx, THYROID BRUITS, EXOPHTHALMOS/PROPTOSIS, PRETIBIAL MYXEDEMA (nonpitting, edematous pink to brown plaques/nodules shin)
-labs will show + THYROID-STIM IMMUNOGLOBULINS AB,
maybe thyroid peroxidase and anti-TG-AB
-inc T3/T4, dec TSH
-RAIU: DIFFUSE UPTAKE
- MC therapy: RADIOACTIVE IODINE + HORMONE REPLACE
- METHIMAZOLE OR PROPYTHIOURACIL (PTU)
- BB for symptoms
- Thyroidectomy if radioactive iodine c/i (pregnancy)
*PTU PREFERRED IN PREGNANCY, ESP 1ST TRIMESTER
toxic multinodular goiter (plummer’s disease)
OR toxic adenoma (one nodule)
autonomous functioning nodules
toxic adenoma - one autonomous functioning nodule
- patient will be ELDERLY, with clinical hyperthyroidism, diffusely enlarged thyroid, NO SKIN/EYE CHANGES, +/- palpable nodules
- COMPRESSIVE SX: DYSPNEA, DYSPHAGIA, STRIDOR, HOARSENESS
- labs will show inc T3/T4, dec TSH
- RAIU: PATCHY AREAS OF INC AND DEC UPTAKE or HOT NODULE (in TA)
- TX RADIOACTIVE IODINE
- surgery if compressive symptoms
- METHIMAZOLE OR PROPYTHIOURACIL (PTU)
- BB for symptoms
TSH secreting pituitary adenoma
autonomous TSH secretion
-patient will have clinical HYPERthyroidism, diffusely enlarged thyroid, BITEMPORAL HEMIANOPSIA, mental disturbances
- labs: INC T3/T4 AND TSH (SAME DIRECTION)
- RAIU: DIFFUSE UPTAKE
- MRI shows adenoma
-TRANSPHENOIDAL SURGERY TO REMOVE ADENOMA
hashimoto’s thyroiditis
autoimmune (chronic lymphocytic)
-patient will have clinical HYPO, painless, enlarged thyroid
- labs: +THYROID AB: THYROGLUBULIN AB, ANTIMICROSOMIAL & THYROID PEROXIDASE AB
- DEC T3/T4, INC TSH
-LEVOTHYROXINE
silent thyroiditis OR postpartum thyroiditis
autoimmune (+/- temporary)
-patient will have painless, enlarged thyroid
THYROTOXICOSIS –> HYPOTHYROID (depends on when they present)
- labs: +THYROID AB
- TFTs: hyper or hypo (depends on when present)
- RAIU: decreased uptake
- 80% return to euthyroid state w/in 12-18 mo w/out treatment
- ASPIRIN
- NO ANTI-THYROID MEDS
de Quervain’s throiditis (granulomatous)
MC POST-VIRAL or inflam rx
-patient will have PAINFUL, TENDER NECK/THYROID, CLINICAL HYPERTHYROID (thyrotoxicosis –> hypothyroid) present at w/ Hyper sx bc of neck pain
- labs: INC ESR, NO THYROID AB
- TFTs: USUALLY HYPER
- decreased uptake RAIU
- most return to euthyroid state w/in 12-18 mo w/out treatment
- ASPIRIN
- NO ANTI-THYROID MEDS
med induced thyroiditis
AMIODARONE (contains iodine)
LITHIUM
ALPHA INTERFERON
thyrotoxicosis –> hypothyroid
-often returns to euthyroid when med stopped
acute thyroiditis (suppurative)
MC STAPH AUREUS
- patient will have PAINFUL, FLUCTUANT THYROID, appear ill, FEBRILE
- labs: inc WBC, left shift
- abx; I+D if abscess
Riedel’s thyroiditis
FIBROUS thyroid
FIRM, HARD, “WOODY” NODULE, may devo HYPO
+/- surgery
MC cause of hypothyroidism
in US: hashimoto’s
in world: iodine deficiency
thyroid nodules
RF: extremes of age, history of head/neck irradiation
- 90% in women are benign (papillary ca mc women)
- most found in children or men are malignant
- sx- most asymptomatic, +/- compressive symptoms
- if functional (rare) –> +/- thyrotoxiciosis
- exam: benign nodules vary (smooth, firm, irregular, discrete, painless) MALIGNANT: RAPID GROWTH, FIXED, NO MOVEMENT W/ SWALLOW
- most patients euthyroid
- dx- FINE NEEDLE ASPIRATION W/ BX BEST TO EVAL
- Radioactive Iodine Uptake Scan (if FNA +/-) –> COLD NODULES ARE HIGHLY SUSPICIOUS FOR MALIG
- ultrasound
- tx- SURGERY IF CANCER SUSPECTED (or indeterminate FNA w/ cold scan) –> total vs partial thyroidectomy
- OBSERVATION OF NODULES Q6-12MO W/ US
-FOLLICULAR ADENOMA MC TYPE OF THYROID NODE
thyroid cancer
- about 5% nodules malignant
- INC SUSPICION IN PT <20, COLD NODULE ON RAIU
- most patients are euthyroid
- PAPILLARY + FOLLICULAR ARE WELL DIFFERENTIATED (BETTER PROGNOSIS), ANAPLASTIC POORLY DIFF (WORSE PROGNOSIS)
- PAPILLARY - 80% MC TYPE
- MC AFTER RADIATION EXPOSURE, YOUNG FEMALES
- LEAST AGGRESSIVE; CERVICAL METS COMMON, DISTANT METS UNCOMMON
- HIGH CURE RATE
- tx- surgery: total vs partial (w/ radioiodine therapy +/- thyroid suppression)
- FOLLICULAR - 10%
- inc w/ iodine deficiency; mc 40-60yo
- more aggressive but slow-growing
- DISTANT METS COMMON (LOCAL LESS COMMON)
- HIGH CURE RATE
- tx- surgery: total vs partial (w/ radioiodine therapy +/- thyroid suppression)
- MEDULLARY 10%
- MC W/ MEN2 (NOT ASSOC W/ RADIATION)
- MORE AGGRESSIVE - ARISES FROM PARAFOLLICULAR CELLS - SECRETE CALCITONIN
- local cervical lymph node involved early, distant mets occur late
- poorer prognosis - don’t take up iodine
- tx-TOTAL THYROIDECTOMY + NECK DISSECTION (LYMPH NODES AND FATTY TISSUE)
- CALCITONIN LEVELS USED TO MONITOR
- ANAPLASTIC <5%
- may occur years after radiation exposure
- MC MALES >65
- MOST AGGRESSIVE - RAPID GROWTH +/- COMPRESS
- MAY INVADE TRACHEA, local + distant mets
- POOR PROGNOSIS (most don’t live 1 yr after dx)
- MOST NOT AMENABLE TO SURGICAL RESECTION –> radiation, chemo, +/- PALLIATIVE TRACHEOSTOMY
calcium
- vit D required for intestinal Ca absorption
- Ca range maintained by 3 hormones:
- HYPOCALCEMIA stimulates INC PTH + INC CALCITRIOL (VIT D) secretion –> increases blood Ca via inc GI/kidney Ca absorption and inc bone Ca resorption (via osteoclasts)
- PTH also inhibits phosphate reabsorption
-HYPERCALCEMIA stimulates INC CALCITONIN SECRETION –> DECREASES BLOOD CA (dec Ca absorption in GI/kidney and inc bone mineralization (osteoblasts)
hyperparathyroidism
Primary:
- MC - EXCESS PTH PRODUCTION
- PARATHYROID ADENOMA MC CAUSE - 80%
- PARATHYROID HYPERPLASIA/ENLARGE - 15-20%
- occurs in 20% of patients taking LITHIUM, MEN1 + 2a
- sx- STONES, BONES, ABDOMINAL GROANS, PSYCHIC MOANS + DEC DTR
- dx- HYPERCA + INC PTH + DEC PHOS
- INC 24h URINE CALCIUM EXCRETION, inc Vit D
- osteopenia on bone scan, imaging to detect adenoma
- tx- PARATHYROIDECTOMY (subtotal/3/5 gland) or total w/ autotransplantation of parathyroid tissue in forearm
Secondary:
- INC PTH DUE TO HYPOCA OR VIT D DEFICIENCY (parathyroid tries to compensate by inc PTH)
- CHRONIC KIDNEY FAILURE (MC CAUSE 2RY)
- severe Ca or Vit D deficiency
- tx- vit D / Ca supplementation
Tertiary:
- prolonged PTH stimulation after 2ry hypoparathyroidism
- -> autonomous PTH production; can be seen post-transplant too
hypoparathyroidism
RARE –> either low PTH or insensitivity to its action
-MC CAUSE SURGICAL (ACCIDENTAL DAMAGE/REMOVAL) OR AUTOIMMUNE DESTRUCTION, radiation tx, hypomagnesemia (req to produce PTH), cong
- sx- HYPOCALCEMIA –> carpopedal spasms, TROUSSEAU’S + CHVOSTEK’S SIGNS, INC DTR
- dx- HYPOCALCEMIA, DEC PTH, INC PHOS
- tx- CA SUPPLEMENT + VIT D (IV calcium gluconate if severe)
HYPOcalcemia
hypoCa w/ dec PTH –> HYPOPARATHYROID MC
hypoCa w/ inc PTH –> CHRONIC RENAL DZ, LIVER DZ
- VIT D DEFICIENCY
- HYPOMAGNESEMIA, inc phosphate, hypoalbuminemia
- high citrate states (blood transfusions), acute pancreatitis, rhabdo
- meds: PPIs
- sx-
- hypoCa decreases excitation threshold for heart, nerves, muscle –> LESS STIM NEEDED FOR ACTIVATION/CONTRACTION
- NEURO: cramping, bronchospasm, syncope, seizures, FINGER/CIRCUMORAL PARESTHESIAS
- TETANY: CHVOSTEK’S, TROUSSEAUS SIGN, INC DTR
- CARDIO: CHF, arrhythmias
- skin: dry, psoriasis
- GI: D, abd pain
- skeletal: abn dentition, osteomalacia, osteodystrophy
-labs: DEC IONIZED CA + total serum Ca (<8.5)
+/- inc phosphate, dec magnesium
-check PTH, BUN, Cr
-ECG - PROLONGED QT INTERVAL
-tx- SEVERE: IV CALCIUM GLUCONATE or cal carbonate
-mild: PO CA + VIT D, K + Mg repletion may be needed
-CORRECTED CA IN PT W/ LOW SERUM ALBUMIN:
[0.8 X (normal albumin (4.4) - pt’s albumin)] - serum Ca
HYPERcalcemia
-90% of cases due to primary hyperparathyroidism or malignancy
PTH-mediated:
-PRIMARY HYPERPARATHYROIDSM MC CAUSE OVERALL: INC CA, INC PTH, DEC PHOSPHATE
PTH-independent:
- MALIGNANCY (SECRETES INC PTH-RELATED PROTEIN), DEC PTH
- Vit D excess, Vit A excess, THIAZIDES, LITHIUM
- hyperCa increases excitation threshold for heart, nerves, muscles –> STRONGER STIM NEEDED FOR ACTIVATE/CONTRACT
- MOST PT ASYMPTOMATIC +/- arrhythmias
- STONES: KIDNEY STONES, POLYURIA
- BONES: PAINFUL BONES, FRX (INC REMODELING)
- ABD GROANS: ILEUS, CONSTIPATION
- PSYCHIC MOANS: weakness, fatigue, AMS, dec DTR, depression or psychosis, blurred vision
- labs: INC IONIZED CA (most accurate), inc total serum Ca (>10), PTH-related protein, 1,25 Vit D levels, 24 urinary Ca
- ECG: SHORTENED QT INTERVAL (prolonged PR interval, QRS widening)
- tx- SEVERE: IV SALINE –> FUROSEMIDE 1ST LINE (loops enhance renal excretion), AVOID HCTZ (INC CA)
- CALCITONIN, BIPHOSPONATES, STEROIDS
- mild: no tx needed, tx underlying cause
osteoporosis
LOSS OF BONE DENSITY –> due to inc absorption or decreased formation
-LOSS OF BOTH MINERAL AND MATRIX
- PRIMARY: I - POSTMENOPAUSAL + SENILE
- RF: cauc, asian, thin, smoking, steroids, kidney dz, ETOH, low Ca or vit D diets, inactivity
- SECONDARY: due to CHRONIC DZ OR MEDS
- hypogonadism, PROLONGED HIGH DOSE CORTICO USE, Cushing’s syndrome, thyrotoxicosis, hyperparathyroidism, DM, liver disease, low estrogen, malignancy, immobilization, heparin, anticonvulsants
- sx- usually asymptomatic - 1st sx may be frx, back pain
- PATHOLOGIC FRX: MC VERTEBRAL, HIP, DISTAL RADIUS
- postmeno: mostly trabecular bone loss –> inc vertebral compression + wrist fractures
- senile: travecular and cortical bone loss –> hip/pelvic
- SPINE COMPRESSION: MC UPPER LUMBAR AND THORACIC; LOSS Of VERTEBRAL HEIGHT
- dx- DEXA - best to show extent of demineralization
- OSTEOPOROSIS: T SCORE < -2.5
- OSTEOPENIA: T SCORE < -1.0-2.5
- labs: serum Ca, phos, PTH + ALP usually normal, dec vit D
- xray: shows demineralization; mostly axial skeleton
- tx-BISPHOSPHONATES 1ST LINE
- VIT D ASSOC WITH SLOWER PROGRESSION +/- Ca
- SELECTIVE ESTROGEN RECEPTOR MODULATOR: RALOXIFENE (reduce progress, protect vs breast ca, not inc risk of endo cancer)
- ESTROGEN - also helps w/ sx menopause; inc risk endo + breast ca, CAD, stroke, venous thromboembolism
osteogenesis imperfecta
genetic mutation for type 1 collagen (necessary for bone integrity) - assoc w/ severe osteoporosis, spontaneous frx in childhood, BLUE-TINTED SCLERAE + PRE-SENILE DEAFNESS
renal osteodystrophy
bone disorders (OSTEITIS FIBROSIS CYSTICA + OSTEOMALACIA) assoc w/ CKD -failing kidneys don't eliminate phosphate properly + poorly synthesize vit D --> HYPOCALCEMIA --> INC PTH --> OSTEOIDS (DEC MINERALIZATION)
-sx- BONE + PROXIMAL MUSCLE PAIN (IN CONTEXT OF UREMIA) +/- pathological fractures, chondrocalcinosis
- dx- 2ry HYPERPARATHYROIDISM
- labs: dec Ca, inc phos, inc PTH
- inc PO4 (not able to excrete it), hypoCa (due to dec vit D production by kidney) = inc PTH
- xray: OSTEITIS FIBROSIS CYSTICA = PERIOSTEAL EROSIONS, BONY CYSTS “SALT + PEPPER APPEARANCE ON SKULL” - due to osteoclast activity (stim by inc PTH)
- CYSTIC BROWN “TUMORS” on bx (not actual tumors)
- tx- PHOSPHATE BINDERS: CALCIUM CARBONATE, CALCIUM ACETATE, SEVELAMER goal < 5.5
- active Vit D = calcitriol + calcium
osteomalacia + rickets
VIT D DEFICIENCY –> dec Ca AND phosphate –> DEMINERALIZATION –> SOFT BONES
-dec of mineralization only (osteoporosis is mineral + matrix proportionally)
- sx-
- RICKETS (CHILDREN): DELAYED FONTANEL CLOSURE, GROWTH RETARD, DELAYED DENTITION, COSTAL CARTILAGE ENLARGE, BOWING LONG BONES
- OSTEOMALACIA (ADULTS): BONE PAIN, MUSCLE WEAKNESS, BOWING OF LONG BONES
- dx- DEC VIT D, DEC CALCIUM AND PHOSPHATE, INC ALK PHOS
- xray: LOOSER LINES (ZONES): transverse “pseudo fracture” lines
-tx- VITAMIN D (ERGOCALCIFEROL) 1ST LINE
adrenal zones
GFR for layers, ACE for hormones they produce
- Zona Glomerulosa –> Aldosterone (outer layer cortex)
- Zona Fasciculata –> Cortisol (middle layer cortex)
- Zona Reticularis –> Estrogens/Androgens (inner layer cortex)
Primary chronic adrenocortical insufficiency / Addison’s Disease
ADRENAL GLAND DESTRUCTION (LACK OF CORTISOL AND ALDOSTERONE)
- AUTOIMMUNE: MC CAUSE INDUSTRIALIZED COUNTRIES –> CAUSES ADRENAL ATROPHY
- INFECTION: MC CAUSE WORLDWIDE (TB, HIV) –> CAUSES ADRENAL CALCIFICATION
- vascular: thrombosis or hemorrhage in adrenal gland
- metastatic dz
- medications: KETOCONAZOLE, RIFAMPIN, PHENYTOIN
- sx-
- HYPERPIGMENTATION (inc ACTH stimulation of melanocyte-stim hormones))
- Dec Aldosterone: ORTHOSTATIC HYPOTENSION, HYPONATREMIA, HYPERKALEMIA, NON-GAP META ACIDOSIS, HYPOGLYCEMIA
- Dec Sex Hormones in Women: loss of libido, amenorrhea, loss of axillary + pubic hair
- dx-
- screen w/ am cortisol??
- SCREEN FOR ADRENAL INSUFFICIENCY: HIGH DOSE ACTH (COSYNTROPIN) STIM TEST (blood or urine cortisol measured before and after IM injection ACTH)
- normal –> rise in blood/urine cortisol levels after ACTH
- ADRENAL INSUFFICIENT –> LITTLE/NO INC IN CORTISOL
- CRH STIMULATION TEST: differentiates btw causes of adrenal insufficiency
- PRIMARY/ADDISON (ADRENAL) –> INC ACTH BUT LOW CORTISOL (opposite)
- secondary (pituitary) –> low ACTH and cortisol
-tx- HYDROCORTISONE 1ST LINE + FLUDROCORTISONE
(hormone replace = synth glucocorticoid and synth mineralocorticoid)
-replace TT for women (adrenals only place it comes from, men have testes)
secondary chronic adrenocortical insufficiency
Secondary: PITUITARY FAILURE OF ACTH SECRETION
( = lack of cortisol)
-EXOGENOUS STEROID USE MC CAUSE esp w/ abrupt cessation
- sx- usually have normal mineralocorticoids (aldosterone) fx
- weakness/muscle ache, myalgias, fatigue, WL, anorexia, N/V/D, abd pain, HA, sweat, abnormal periods, mild hypoNa, HYPOTENSION
- dx-
- SCREEN FOR ADRENAL INSUFFICIENCY: HIGH DOSE ACTH (COSYNTROPIN) STIM TEST (blood or urine cortisol measured before and after IM injection ACTH)
- normal –> rise in blood/urine cortisol levels after ACTH
- ADRENAL INSUFFICIENT –> LITTLE/NO INC IN CORTISOL
- CRH STIMULATION TEST: differentiates btw causes of adrenal insufficiency
- PRIMARY/ADDISON (ADRENAL) –> INC ACTH BUT LOW CORTISOL (opposite)
- secondary (pituitary) –> low ACTH and cortisol
-tx- HYDROCORTISONE 1ST LINE (synthetic glucocorticoid = cortisol)
glucocorticoid vs mineralocorticoid
glucocorticoid = cortisol (synthetic = hyrdorcortisone, prednisone, dexamethasone)
mineralocorticoid = aldosterone (synthetic = fludrocortisone)
chronic adrenal insufficiency considerations (stress/surgery)
- must be treated w/ IV glucocorticoids + IV isotonic fluids before and after surgical procedures (mimics body’s natural response)
- during illness/surgery/high fever, oral dosing needs to be adjusted to recreate the normal adrenal gland response to stress (ex. triple normal dose)
- should carry medical alert tag and injectable form of cortisol for emergencies
adrenal (addisonian) crisis
-sudden worsening of adrenal insufficiency due to “stressful” event (normal response is 3x inc cortisol)
- ABRUPT W/DRAWL OF GLUCOCORTIOIDS MC (in pt not gradually tapered off steroids)
- previously undiagnosed pt w/ Addison’s dz, exacerbation of known Addison’s dz w/ no increase in glucocortico, bilateral adrenal infarction (hemorrhage)
- sx- SHOCK –> HYPOTENSION, HYPOVOLEMIC
- ab pain, N/V, fever, weakness, lethargy, coma
-dx- labs: BMP (HYPONATREMIA, HYPERKALEMIA, HYPOGLYCEMIA), cortisol levels, ACTH, CBC
- tx-
- FLUIDS (NRML SALINE FOR HYPOTN), D5-NS IF HYPOGLYCEMIC
- IV HYDROCORTISONE (if Addison’s), dexamethasone if undiagnosed
- reverse electrolyte disorders
- FLUDROCORTISONE (synthetic mineralocorticoid)
cushing’s syndrome
cushing’s SYNDROME = SIGNS/SX RELATED TO CORTISOL EXCESS
cushing’s DISEASE = CUSHING’S SYNDROME CAUSED SPECIFICALLY BY PITUITARY INC ACTH SECRETION
- exogenous: IATROGENIC –> LONG TERM TX (MC CAUSE)
- endogenous: CUSHING’S DZ (BENIGN PITUITARY ADENOMA OR HYPERPLASIA –> SECRETES ACTH)
- ECTOPIC ACTH (secretes ACTH - small cell lung cancer)
- ADRENAL TUMOR - cortisol-secreting adrenal adenoma
- sx- 2ry to excess cortisol + glucocorticoids
- CENTRAL (TRUNK) OBESITY, MOON FACIES, BUFFALO HUMP, SUPRACLAVICULAR FAT PADS
- WASTING OF EXTREMITIES, PROXIMAL MUSCLE WEAKNESS, SKIN ATROPHY, STRIAE, inc infx, hyperpigmentation
- HTN, WEIGHT GAIN, HYPOKALEMIA, ACANTHOSIS NIG
- depression, mania, psychosis
- ANDROGEN EXCESS: hirsutism, oily skin, acne, inc libido, amenorrhea
-dx-
-SCREEN:
-LOW-DOSE DEXAMETHASONE SUPPRESSION: nrml response is cortical suppression;
NO SUPPRESS = CUSHING’S SYNDROME
-24 HOUR URINE FREE CORTISOL
-SALIVARY CORTISOL (usually at night)
- DIFFERENTIATING:
- HIGH-DOSE DEXAMETHASONE SUPPRESS –>
- SUPPRESSION = CUSHING’S DZ
- NO SUPPRESSION = ADRENAL OR ECTOPIC ACTH-producing TUMOR
ACTH LEVELS:
- DECREASED ACTH –> ADRENAL TUMORS (produce high levels of cortisol, suppressing ACTH levels via HPA axis)
- NORMAL/INCREASED ACTH –> CUSHINGS DZ OR ECTOPIC ACTH-PRODUCING TUMOR (secrete ACTH independent of HPA axis)
-tx-
-Cushing’s Dz (pituitary) –> TRANSPHENOIDAL SX (alt radiation)
-Ectopic ACTH-secreting or adrenal tumors –> SURGERY
(KETOCONAZOLE in inoperable pt, dec cortisol product)
-Iatrogenic steroid therapy –> GRADUAL STEROID TAPER
hyperaldosteronism
Primary: RENIN-INDEPENDENT
- idiopathic or bilateral adrenal hyperplasia, MC, women
- CONN’S SYNDROME: ADRENAL ALDOSTERONOMA
Secondary: DUE TO INCREASED RENIN
- INC RENIN –> 2ry INC IN ALDOSTERONE VIA RAAS
- MC DUE TO RENAL ARTERY STENOSIS or dec renal perfusion (CHF, hypovolemia, nephrotic syndrome)
- sx-
- HYPOKALEMIA: muscle weakness, polyuria, fatigue, dec DTR, hypoMg
- HYPERTENSION: HA, flushing, NOT EDAMATOUS
- dx-
- labs: HYPOKALEMIA W/ METABOLIC ACIDOSIS (due to dumping K and H in exchange for Na)
- Screen: ALDOSTERONE:RENIN RATIO
- Definitive: Saline Infusion Test
- CT/MRI - look for adrenal or extra-adrenal mass
- tx-
- Conn’s Syndrome: EXCISION + SPIRONOLACTONE (blocks aldosterone)
- Hyperplasia: SPIRONOLACTONE, ACEI, correct electros
- Secondary (renovascular htn): ANGIOPLASTY DEFINITIVE, ACEI
pheochromocytoma
CATECHOLAMINE-SECRETING ADRENAL TUMOR –> SECRETES NOREPI AND EPI AUTONOMOUSLY AND INTERMITTENTLY
- triggers: sx, exercise, pregnancy, meds
- 90% benign
- sx- HYPERTENSION!!!
- “PHE” - PALPITATIONS, HEADACHES, EXCESSIVE SWEAT
- dx- INC 24h URINARY CATECHOLAMINES
- MRI/CT to visualize adrenal tumor
- labs: hyperglycemia, hypoK
- tx- COMPLETE ADRENALECTOMY
- PREOP a-BLOCKADE: PHEnoxybenzamine or PHEntolamine x7-14d –> followed by BB to control HTN
- DON’T INITIATE THERAPY W/ BETA-BLOCKADE to prevent unopposed a-constriction during catecholamine released triggered by surgery or spontaneously (life threatening HTN)
*cocaine mimics same effect, same tx
anterior hypopituitarism
- pituitary destruction or deficient stim from hypothalamus, tumor, bleeding into pituitary, infarxtion
- deficient in GROWTH HORMONE, TSH, GONADATROPIN (FSH/LH/GnRH), ACTH
- tx- hormone replacement
anterior pituitary tumors
most benign MICROadenomas that are: FUNCTIONAL, NON-FUNCTIONAL, COMPRESSIVE (may cause mass effect on optic chiasm –> bitemporal hemianopsia)
- PROLACTINOMAS: MC TYPE
- women: oligomenorrhea, amenorrhea, galactorrhea, infertile
- men: impotence, dec libido, hypogonadism, infertility
- tx- CABERGOLINE or BROMOCRIPTINE 1ST LINE (dopa agonists inhibit prolactin) - NOT SX
- SOMATOTROPINOMA: secretes growth hormone
- ACROMEGALY IN ADULTS, GIGANTISM IN CHILDREN
- DM AND GLUCOSE INTOLERANCE
- dx- INSULIN-LIKE GROWTH FACTOR (SCREEN); confirm w/ ORAL GLUC SUPPRESSION TEST (inc GH levels)
- ADRENOCORTICOTROPINOMAS: secrete ACTH
- CUSHING’S DZ + HYPERPIGMENTATION
- TSH-SECRETING ADENOMAS
- THYROTOXICOSIS (T3/T4 + TSH all increased)
- dx- MRI - look for SELLAR LESIONS/PIT TUMORS
- endocrine studies
- tx- TRANSSPHENOIDAL SURGERY TX OF CHOICE for removal of ACTIVE or compressive tumors (EXCEPT PROLACTINOMAS)
- acromegaly: TSS + BROMOCRIPTINE; OCTREOTIDE (somatostatin analogue that inhibits GH secretion)
- prolactinoma: CABERGOLINE or BROMOCRIPTINE 1ST LINE (dopa agonists inhibit prolactin) - NOT SX
hyperprolactinemia
PROLACTINOMAS MC CAUSE, hypothyroid, acromegaly, cirrhosis, renal failure
- DOPAMINE ANTAGONISTS (bc dopa inhibits prolactin) - metoclopramide, promethazine, prochlorperazine, SSRIs, TCAs, cimetidine, estrogen)
- pregnancy, stress, exercise
- increased prolactin inhibits gonadotropinRH –> dec FSH/LH
- women: oligomenorrhea, amenorrhea, galactorrhea, infertile
- men: impotence, dec libido, hypogonadism, infertility
-dx- TSH, BUN/Cr, LFTs, B-hCG, prolactin, +/-MRI
- tx- stop offending drugs
- CABERGOLINE or BROMOCRIPTINE 1ST LINE (dopa agonists inhibit prolactin)
- surgical tx in select pt
gynecomastia
increased effective estrogen (inc production or dec degradation) or decreased androgens
- Infants: due to high maternal estrogen
- Puberty: esp 10-14y (lasts about 6mo-2y)
- Older men: due to decreased androgen production
- idopathic, cirrhosis, testicular tumors, hyperthyroid, CKD, klinefelter syndrome, alcoholism
- meds: spironolactone, ketoconazole, cimetidine, 5-alpha reductase inhibitors, digoxin, GnRH agonists (leuprolide)
-dx- clinical, check TT levels
- tx- stop offending meds, observe if early (most regress spontaneously), ideal tx should be in first 6 mo (after 12 mo, tissue may start fibrosis)
- meds: TAMOXIFEN (estrogen modulator), aromatase inhibitors, androgens in hypogonadism
- surgical if all else fails
diabeties mellitus - complications
Type 1: autoimmune beta cell destruction; onset <30y
Type 2: insulin resistance + relative impairment of insulin secretion –> due to genetic + enviro factors, esp WG + dec physical activity MC >40y
-RF: family hx, 1ry relative, Hispanic, AA, pacific island, HTN, HLD, delivery of baby >9lbs, syndrome X, atherosclerosis, obesity, stroke
NEUROPATHY:
- Sensorimotor: paresthesia, dec proprioception “STOCKING GLOVE” PATTERN, pain, dec DTR
- Autonomic: ORTHOSTATIC HYPO, N/V/D/C, incontinence
- CN3 palsy: but pupil size remains normal
RETINOPATHY: painless deterioration of sm retinal vessels
- dx- fundoscopy, angiography
- Nonproliferative (background) - microaneurysms –> hard exudates form lipoproteins, dot or flame hem from blood
- Proliferative: neovascularization
- Maculopathy: macular edema, blurred vision, central loss
NEPHROPATHY: kidney deterioration leading to microalbuminuria (fist sign)
- dx- ALBUMINURIA, anemia, acidosis
- kidney bx - KIMMELSTIEL WILSON (nodular glom-scler)
- tx- ACE
MACROVASCULAR
-artherosclerosis –> coronary artery dz, periph vascular dz, stroke
*inc risk infections bc of vascular insufficiency + immunosuppression from hyperglycemia
HYPOGLYCEMIA
- Autonomic sx: sweating, tremors, palp, nervous, tachy
- CNS sx: HA, lightness, confusion, slurred speech, dizzy
- mild <60 –> 10-15g fast-acting carb, recheck 15 min
- severe/unconscious <40 –> IV bolus of D50 or inject glucagon SQ
diabetes mellitus - diagnosis
FASTING PLASMA GLUCOSE: fasting at least 8 hours on 2 occasions - GOLD STANDARD
- impaired tolerance: 110-125
- DM: >126
2-Hour GTT - (3Hr GTT gold standard in gestational)
- impaired tolerance: >140-199
- DM: >200
Hemoglobin A1C
- impaired tolerance: 5.7-6.4%
- DM: >6.5%
Random Plasma: in pt w/ classic DM sx or complications
-DM: >200
SCREENING:
ADA: all adults >45 every 3 years OR any adult w/ BMI >25 and 1 additional risk factor
USPSTF: any 40-70yo that is overweight or obese (q 3y)
diabetes mellitus - management
- diet, exercise + lifestyle change should be tried 1st in type II –> oral antihyperglycemic agents
- Diet: 50-60% Carbs, 15-20% Protein, 10% Unsat Fats
- Insulin preferred for gestational DM
- A1C goal: <7.0 (check q3 mo if not controlled, q6 mo if controlled)
- pre-meal BG goal: 80-130
- post-meal BG goal: <180
- Lipids: LDL <100, HDL >40, TG <150
- Neuropathy: gabapentin, foot care, +/- TCAs
- Retinopathy: DM control, laser photocoag, bevacizumab (proliferative), yearly eye screen
- Nephropathy: DM control, ACEI if microalbumin, HTN control, yearly BUN/Cr checks
- Type I –> most need 0.5-1.0 units/kg each day (divide between long-acting and meals)
DKA
INSULIN DEFICIENCY + counterregulatory hormonal excess in DM as RESPONSE TO STRESSFUL TRIGGERS:
-INFECTION MC, INFARCTION, NONCOMPLIANCE W/ INSULIN, dose change, undiagnosed
- cortisol stress hormone –> inc glucose + patients can’t meet demand of inc insulin requirements
- YOUNGER PT W/ TYPE 1 DM
insulin deficiency –> hyperglycemia, dehydration, ketonemia (high anion gap meta acidosis), potassium deficit
-sx- HYPERGLYCEMIA, ABD PAIN, KETOTIC BREATH, KUSSMAUL’S RESPIRATIONS, weak, fatigue, confusion, tachy, hypoTN, decreased turgor
-dx- PLASMA GLUCOSE: >250 Arterial pH: <7.3 mild --> <7.0 severe Serum Bicarb: 15-18 mild --> <10 severe Ketones: POSITIVE Serum Osmolarity: varies
-tx-
initial: ABC, mental status, vitals, vol status, screen for precipitating event
-IV FLUIDS CRITICAL 1ST STEP –> ISOTONIC 0.9% NS UNTIL HYPOTN RESOLVES –> 0.45% NS –> D5 0.45 NS to prevent hypoglycemia from insulin tx
-when the blood glucose is < 200 mg/dL, treatment involves adding dextrose to the intravenous fluids
-INSULIN (REG) - lower serum gluc –> dec gluconeogenesis, recuced ketone production
-POTASSIUM: despite serum K levels, pt is always total body K deficient (correction of DKA will cause hypokalemia) If serum K high, wait til normal and then replete
+bicarb if severe acidosis
hyperosmolar hyperglycemia (HHS)
INSULIN DEFICIENCY + counterregulatory hormonal excess in DM as RESPONSE TO STRESSFUL TRIGGERS:
-INFECTION MC, INFARCTION, NONCOMPLIANCE W/ INSULIN, dose change, undiagnosed
- cortisol stress hormone –> inc glucose + patients can’t meet demand of inc insulin requirements
- OLDER PT W/ TYPE 2 DM (higher mortality)
usually some illness leading to reduced fluid intake (mc infx) –> dehydration, increased osmolarity, hyperglycemia, potassium deficit, absence of severe ketosis (type 2 typically make enough insulin to prevent ketogenesis)
-sx- HYPerGLYCEMIA, MENTAL STATUS CHANGE, fever, weak, fatigue, confusion, tachy, hypoTN, decreased turgor
-dx- PLASMA GLUCOSE: >600 Arterial pH: >7.3 Serum Bicarb: >15 Ketones: Small Serum Osmolarity: >320
-tx-
initial: ABC, mental status, vitals, vol status, screen for precipitating event
-IV FLUIDS CRITICAL 1ST STEP –> ISOTONIC 0.9% NS UNTIL HYPOTN RESOLVES –> 0.45% NS –> D5 0.45 NS to prevent hypoglycemia from insulin tx
-INSULIN (REG) - lower serum gluc –> dec gluconeogenesis, reduced ketone production
-POTASSIUM: despite serum K levels, pt is always total body K deficient (correction of DKA will cause hypokalemia) If serum K high, wait til normal and then replete
+bicarb if severe acidosis
multiple endocrine neoplasia I (MEN 1)
Rare inherited disorder of 1+ overactive endocrine gland tumors (3 P’s) - most tumors are benign (esp <30yo)
PARATHYROID (90%), PANCREAS (60%), PITUITARY (55%)
- sx-
- HYPERPARATHYROIDISM - MC
- PANCREATIC TUMORS - 2nd MC - highest malig pot’l
- Gastrinomas (zes) –> multiple peptic ulcers
- Insulinomas –> WHIPPLE’S TRIAD: fasting/exertional hypoglycemia, low bg during attach, relieved w/ glucose (inappropriate insulin w/ fasting) –> sx removal
- Glucagonomas –> NECROLYTIC MIGRATORY ERYTHEMA, TYPE 2 DM –> sx removal
- VIPomas (vasoactive intestinal peptide tumors) . –> watery diarrhea, hypoK, achlorhydria, dehyrdration
- Somatostatinomas –> steatorrhea, cholelithiasis, type 2 DM
- PITUITARY ADENOMAS
- Prolactinomas MC
- Somatotropinomas –> acromegaly (excessive GH)
- Corticotropinomas –> cushing’s disease (excess ACTH)
- Screening for MEN 1:
- genetic testing –> DEFECT IN MENIN GENE
- PTH + CA (hyperparathyroid often 1st sign)
- GASTRIN (mc pancreas manifestation)
- PROLACTIN (mc pituitary tumor)
multiple endocrine neoplasia 2 (MEN 2)
Rare autosomal dominant (RET proto oncogene) disorder of multiple endocrine gland tumors
-MEN 2a (90%): MEDULLARY THYROID CARCINOMA, PHEOCHROMOCYTOMA, HYPERPARATHYROIDISM
- MEN 2b (5%): medullary thyroid carcinoma, pheochromocytoma, NEUROMAS, MARFANOID
- assoc w/ presence of mucosal neuromas, and have a more aggressive form of thyroid cancer (presents in infancy)
-FAMILIAL MTC: MEDULLARY THYROID CARCINOMA
- sx-
- Medullary Thyroid Carcinoma: usually first feature
- cells SECRETE CALCITONIN
- palpable neck mass, compressive sx –> TOTAL THYROIDECTOMY (prophylactically in 1st 6mo for MEN2b)
- Pheochromocytoma: usually appears btw 10-30yo
- adrenal medullary tumor w/intermittent secretion of catecholamines (epi/norepi) –> palp, HA, sweating
- dx- 24h urine catecholamines, adrenal CT or MRI
- tx- complete adrenalectomy
- Hyperparathyroidism (only MEN 2a!) - not usually presenting feature as in MEN1; screen MEN2a yearly
- hypercalcemia “stones, bones, abd groans, psych moans”
- tx- parathyroidectomy (3.5 or 4 w/ transplantation)
SEEN IN 2B ONLY:
- Neuromas: mucosal of the lips, tongue, eyelids, conjunctiva, nasal/laryngeal mucosa
- Marfan-Like Body: high arched palate, pectus excavatum, scoliosis
Screening:
- genetic testing for RET PROTO-ONCOGENE
- routine labs: CALCITONIN, EPINEPHRINE, PTH/CALCIUM
metabolic syndrome (syndrome x, insulin resistance syndrome)
syndrome of multiple metabolic abnormalities that inc risk for complications like DM and CVD
-pathophysiology: INSULIN RESISTANCE –> free fatty acids released, causes an increase in trigs and glucose production an reduction of insulin sensitivity –> insulin resistance and hyperinsulinemia (high levels of insulin cause sodium resabsorption leading to HTN)
- dx - at least 3 of the following:
- dec HDL: <40 men, <50 women
- inc BP: >135 systolic or >85 diastolic (or meds for BP)
- inc fasting trigs: >150 (or meds for trigs)
- inc fasting blood sugar: >100 (or drug tx)
- inc abdominal obesity: waist circ >40” men, >35” women
- tx-
- lifestyle
- weight loss:
- PHENTERMINE (3 mo only), PHENTERMINE/TOPIRAMATE (no restriction on duration)
- LORCASERIN - selective serotoninagonist induces satiety
- ORLISTAT - inhibits fat absorption
- bariatric sx
- LDL: statins, Exetimibe, bile acid sequestrants
- Trigs: FIBRATES, nicotinic acid, omega3
- HDL: NICOTINIC ACID, statins, fibrates, bile acid seq
- BP: diet, exercise, ACE/ARBs
- Insulin resistance: metformin
growth hormone deficiency
Most common cause: pituitary tumor ↓ Muscle mass ↓ Bone density ↑ Lipids ↓ Memory dx: ↓ IGF-1
diabetes insipidus
Patient will be complaining of polyuria and polydipsia
Labs will show increase in plasma osmolality and a decrease urine osmolality
Central DI: Most commonly caused by a decrease in ADH production
Diagnosis is made by vasopressin challenge test: > 50% increase in urine osmolality and decrease urine volume
Treatment is intranasal DDAVP
Nephrogenic DI: Patient with a history of taking lithium
Most commonly caused by renal unresponsiveness to ADH
Diagnosis is made by water deprivation test: no change in urine osmolality
Treatment is HCTZ, amiloride, indomethacin
