Endocrine Flashcards
(59 cards)
1
Q
thyroid axis
A
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
2
Q
adrenal axis
A
corticotropin-releasing hormone CRH (hypothalamus) –>
adrenocorticotropic hormone ACTH (pituitary) –>
cortisol (adrenal gland)
3
Q
sex hormones axis
A
gonadotropin-releasing hormone GRH (hypothalamus) –>
FSH + LH (pituitary) –> estrogen, progesterone + some testosterone (ovaries) + testosterone (testes)
4
Q
tertiary disorder
A
HYPOTHALAMUS IS THE PROBLEM
-LABS IN SAME DIRECTION
5
Q
secondary disorder
A
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)
6
Q
primary disorders
A
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
7
Q
thyroid function tests
A
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
8
Q
thyroid - radioactive iodine test (RAIU)
A
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
9
Q
subclinical hypothyroidism
A
inc TSH, normal T4/T3
-tx- LEVOTHYROXINE IF SX (pt devo hyperlipidemia, hypothyroid sx, TSH >20)
10
Q
HYPOthyroid
A
-sx- weight gain, cold intolerance, dry skin, hair loss (outer eyebrow), goiter, nonpitting edema, fatigue, memory loss, dec DTR, constipation, bradycardia, menorrhagia, hypoglycemia
11
Q
HYPERthyroid
A
-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
12
Q
cretinism
A
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
13
Q
euthyroid sick syndrome
A
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
14
Q
thyroid storm (thyrotoxicosis crisis)
A
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)
15
Q
myxedema crisis
A
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
16
Q
grave’s disease
A
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
17
Q
toxic multinodular goiter (plummer’s disease)
OR toxic adenoma (one nodule)
A
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
18
Q
TSH secreting pituitary adenoma
A
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
19
Q
hashimoto’s thyroiditis
A
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
20
Q
silent thyroiditis OR postpartum thyroiditis
A
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
21
Q
de Quervain’s throiditis (granulomatous)
A
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
22
Q
med induced thyroiditis
A
AMIODARONE (contains iodine)
LITHIUM
ALPHA INTERFERON
thyrotoxicosis –> hypothyroid
-often returns to euthyroid when med stopped
23
Q
acute thyroiditis (suppurative)
A
MC STAPH AUREUS
- patient will have PAINFUL, FLUCTUANT THYROID, appear ill, FEBRILE
- labs: inc WBC, left shift
- abx; I+D if abscess
24
Q
Riedel’s thyroiditis
A
FIBROUS thyroid
FIRM, HARD, “WOODY” NODULE, may devo HYPO
+/- surgery
25
MC cause of hypothyroidism
in US: hashimoto's
| in world: iodine deficiency
26
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
27
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
28
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)
29
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
30
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)
31
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
32
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
33
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
34
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
35
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
36
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
37
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)
38
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)
39
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)
40
glucocorticoid vs mineralocorticoid
```
glucocorticoid = cortisol
(synthetic = hyrdorcortisone, prednisone, dexamethasone)
```
```
mineralocorticoid = aldosterone
(synthetic = fludrocortisone)
```
41
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
42
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)
43
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
44
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
45
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
46
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
47
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
48
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
49
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
50
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
51
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)
52
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)
53
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
54
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
55
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)
56
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
57
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
58
growth hormone deficiency
```
Most common cause: pituitary tumor
↓ Muscle mass
↓ Bone density
↑ Lipids
↓ Memory
dx: ↓ IGF-1
```
59
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
