Endocrine Flashcards
MEN syndromes* w/ path*
1: 3P’s ==> parathyroid adenoma > pituitary tumor > pancreatic islet tumors (Zollinger-Ellison gastrinoma, insulinoma, VIPomas)
RET autosomal dominant:
2A: MPP ==> medullary thyroid cancer > pheochromocytoma > parathyroid hyperplasia
2B: MPN ==> medullary thyroid cancer > pheochromocytoma > neuromas and/or marfanoid habitus
Adrenal insufficiency path w/ ddx, presentation, dx*
Primary: inadequate gluco- and mineralcorticoid production. Addison’s (autoimmune), infection (TB*, histoplasmosis, sarcoid), congenital
Secondary: low ACTH production due to pituitary dysfunction, usually 2/2 cessation of glucocorticoids ==> only glucocorticoids affected
Hypotension
Fatigue, weakness, weight loss, n/v
Addison’s: hyperpigmentation, vitilogo
Hyponatremia
Eosinophilia
Hypoglycemia
Primary only: mineralcorticoid insufficiency ==> low Na+ reabsorption + low H/K+ secretion @ DCT = non-gap acidosis, hyperkalemia
—–
Primary: high ACTH + AM plasma cortisol < 3
Secondary: low ACTH + low AM cortisol
Both: cortisol < 18 after cosyntropin (synthetic ACTH) administration
Thyroidectomy complication, dx*
Hypoparathyroidism
Fatigue, anxiety, cramping
Trousseau’s sign
Chvostek sign
Hypocalcemia ==> QT prolongation
Diabetes (DM) type 1 path, presentation, dx, tx
Autoimmune (HLA-DR3/4) beta cell destruction
Polydipsia/phagia
Rapid weight loss
DKA
Anti-islet or anti-glutamic acid decarboxylase (Gad)
2 fasting glucose > 125
Random glucose > 200
If equivocal: oral glucose tolerance > 200
Hbg A1c > 6.5
Short acting (lispro / aspart) = immediate onset Insulin = 2 hr peak NPH = 6 hr peak Detemir, glargine = no peak, 24 hour baseline control
Dawn & somagyi effect w/ treatment
Dawn: AM hyperglycemia 2/2 nocturnal growth hormone & glucagon ==> pm NPH
Somagyi: AM hyperglycemia 2/2 pm NPH that stimulates excess nocturnal counter regulatory hormones (cortisol, epinephrine) ==> decrease pm NPH
DKA path*, presentation, dx, tx
Ketone release 2/2 inability to uptake glucose w/ massive hyperosmolarity causing fluid loss & electrolyte imbalance
DM type 1 (!!!) Vomiting MS changes Kussmaul breathing (compensatory respiratory alkalosis)
Anion gap acidosis pH <7 Hyponatremia Paradoxical hyperkalemia (total body K+ low due to urinary loss but K+ shifts extracellularly 2/2 insulin insufficiency and acidosis)
Fluids
Bicarb
Insulin w/ dextrose & K+ (prevent severe hypokalemia!!)
*Monitoring: pH or anion gap is most sensitive monitor
Hyperosmolar non-ketotic syndrome (HONK) path, presentation, dx, tx
Hyperglycemia without ketosis
DM type 2, usually with preceding infection or trauma
NORMAL pH
Paradoxical hyperkalemia (low K+ 2/2 urinary loss but extracellular shift 2/2 insulin insufficiency)
Hyponatremia
1st: NS ==> 0.45% saline
2nd: Insulin w/ K+ and dextrose
Diabetes type 2 path, presentation, dx, tx in order of preference w/ mechanism & s/e**
Peripheral insulin resistance ==> may lead to beta cell dysfunction
Obesity
Polyuria, polydispia, polyphagia etc.
2 fasting glucose > 125
Random glucose > 200
OGT > 200
Hgb a1c > 6.5
Behavioral 1. Metformin ==> decrease gluconeogenesis & increase insulin sensitivity ==> lactic acidosis, NO w/ renal failure 2. Sulfonylurea (glipizide) ==> increase endogenous insulin ==> weight gain & hypoglycemia 3. TZDs (-glitazone) ==> increase insulin sensitivity ==> weight gain & heart failure 3. alpha-glucosidase inhibitor ==> decrease GI carb uptake 3. DDP-IV inhibitor (sitagliptin) ==> inhibit DDP degradation of GLP1 thus decreasing glucagon release ==> weight neutral 3. GLP-1 agonist "incretin" (exenatide) ==> increase GLP thus decreasing glucagon ==> weight LOSS, pancreatitis risk 4. Insulin ==> only for patients > 8.5 HbA1C
Diabetes complications, tx, health maintenance*
Highest cardiac risk factor:
aspirin after 40 y/o
statins after 40 y/o: LDL < 100, TGL < 150
ACE-i or ARB if CKD, heart failure, microalbuminuria or BP > 140
Neuropathy:
MSK: stocking glove pain/numbness ==> amitryptiline or gabapentin (NSAIDs too, but only if not renal failure)
Cardiac: tachycardia, postural hypotension
GI: gastroparesis (delayed emptying), diarrhea ==> metoclopramide prokinetic
GU: incomplete emptying, erectile dysfunction
Annual filament exam
Nephropathy:
*FIRST SIGN: microalbuminuria:Cr ratio test = most sensitive
ACE-inhibitor if microalbuminuria even with normal BP
Progresses to: GBM thickening, nodular glomerulosclerosis (kimmelstein) or diffuse hyalinization
Retinopathy: Annual dilated eye exam
Graves’ disease path, presentation, dx, tx*
Autoimmune thyroid-stimulating immunoglobulin (TSI) antibodies stimulate TSH receptor increasing T3/T4 levels
Anxiety
Palpitations
Increased bowel frequency
Proximal muscle weakness if left untreated*
—-
Exopthalmos 2/2 retroorbital tissue expansion*
Thyroid bruit
Pretibial myxedema (red tibias)
Tachycardia, tremor, hyperactive reflexes
+TSI (thyroid stimulating immunoglobulin) antibodies
Low TSH
Elevated T3/T4
+CK for muscle weakness
Radioactive iodine uptake: diffuse uptake
Propranolol: palpitations
Iodine ablation: PREFERRED treatment; however, causes transient T3/4 increase with subsequent hypothyroid, teratogenicity, worsens opthalmopathy*
Alternatives: Surgery, methimazole or propylthiouracil
==> levothyroxine (oral T4) replacement (because hypothyroid is common s/e)
Toxic adenoma / multinodular goiter path, sequelae, presentation, dx*, tx
Autonomous thyroid nodules secreting T3/T4 ==> elevated osteoclast activity, arrhythmias, but very low cancer risk*
Anxiety, palpitations, bowel frequency
*Proximal muscle weakness if left untreated
Tachycardia, tremor, hyperactive reflexes
Focal thyroid nodules
[No exopthalmos, bruit, myxedema]
Low TSH
Isolated nodular radioactive iodine uptake sites unlike diffuse uptake of Graves
*Propranolol
Methimazole or propylthiouracil
Iodine ablation or surgery if severe ==> levothyroxine replacement
Thyroiditis path, presentation, dx*, tx
Transient inflammation 2/2 post-partum, amiodarone, radiation, postviral, subacute states ==> transient T3/T4 uptake
Often with hypothyroid phase following
Anxiety palpitations, bowel frequency
Tachycardia, tremor, hyperactive reflexes
TENDER thyroid (only painful form…unless subacute)
[No exopthalmos, bruit, myxedma]
Low TSH
LOW radioactive iodine uptake*
Propranolol
Methimazole or propylthiouracil
Iodine ablation or surgery if severe ==> levothyroxine replacement
Thyroid storm path, presentation, tx
Life-threatening thyroid storm
Fever
Delirium
Atrial fibrillation
Propranolol
Steroids
ICU
Hypothyroid path, presentation, dx, tx
Usually 2/2 Hashimoto’s autoimmune thyroid destruction
Cold intolerance Weight gain Depression Bradycardia Symmetric proximal muscle weakness (mimicking -myositis)
Hashimoto’s: anti-thyroglobulin, anti-microsomal (TPO) antibodies
High TSH, low T4 (free)
+CK for muscle weakness
Hyperlipidemia, hyponatremia, liver enzymes elevation
Levothyroxine
Thyroid cancer types w/ commonality, diagnostic path features, presentation, general diagnostic workup for thyroid nodule, tx
75% papillary ==> follicular Hurthle cells; pupil orphan annie nuclei, ground glass appearance, psammoma inclusions, non-encapsulated ==> benign
15% follicular: also follicular Hurthle cell tumors ==> unencapsulated with rapid hematogenous spread to brain, lung, bone
5% medullary: *calcitonin C-cells, consider MEN 2A/B ==> relatively benign
5% anaplastic: rapidly metastatic & fatal
Hyperthyroid symptoms
Local symptoms: dysphagia, hoarsness
Nodule palpated ==> TSH & ultrasound FIRST
If high TSH, hypoechoic/calcified/vascular ultrasound, cancer history, or symptoms (compressive) ==> FNA
If low TSH without above features ==> radioactive iodine scintigraphy uptake ==> if “hot”, unlikely to be malignant, treat hyperthyroidism; if “cold”, likely malignant ==> fine needle aspiration w/ biopsy
If malignant, thyroidectomy
Osteoporosis path, presentation, risk factors, dx, tx
Low bone mass
Kyphosis
Bone breaks
Smoking, corticosteroids, estrogen depletion, age etc.
DEXA: Bone mineral density > 2.5 SDs from PEAK (30y/o) bone mass
Weight bearing exercise
Vitamin D & calcium
Bisphosphonates (alendronate, zolendronic acid) ==> prevent resorption
Estrogen receptor modifiers (raloxifene)
RANK-L antibody (denosumab)
Hyperparathyroidism path, presentation, dx, tx
Primary: parathyroid nodule (5% malignant) hypersecretes PTH ==> hypercalcemia + hypophosphatemia
[Secondary: physiologic PTH increase 2/2 renal insufficiency or calcium/vitamin D deficiency ==> low-normal calcium + HYPERphosphatemia]
Tertiary: PTH hyperactivity 2/2 dialysis
STONES: calcium nephrolithiasis
BONES: myalgia, arthralgia, fractures
GROANS: abdominal pain, n/v, pancreatitis
MOANS: depression, anxiety, fatigue
Ultrasound + technicium sestamibi scan to localize adenoma
Normal saline fluids
Calcitonin
IV bisphosphonate (zolendronate etc.)
Parathyroidectomy
Secondary: oral phosphate binder (aluminum hydroxide)
Tertiary: cinacalcet calcimimetic lowers PTH
Familial hypocalciuiric hypercalcemia (FHH) path, presentation, dx, ddx, tx
Autosomal dominant disorder of calcium sensing @ kidneys & parathyroid ==> hypercalcemia + low urinary calcium excretion
Hypercalcemia Normal-high PTH Calcium:Cr ratio < 0.1 24 hr urinary calcium < 100mg Asymptomatic
Primary hyperparathyroidism often presents asymptomatically but the urinary/renal tests above distinguish the two ==> parathyroidectomy for non-familial
No tx
If PTH is low but calcium is high, suspect:
PTHrP ==> hypercalcemia of malignancy, usually breast or lung
Cushing’s path w/ ddx, presentation, dx*, tx
Elevated cortisol (adrenal) 2/2
- iatrogenic corticosteroids
- pituitary adenoma hypersecretion of ACTH (Cushing “disease”)
- adrenal hyperplasia
- ectopic ACTH 2/2 neoplasia ==> carcinoid syndrome, medullary thyroid cancer, small cell lung cancer
Obesity, hirsuitism, striae, muscle wasting
HTN, DM2, depression
Cushing’s disease: headache & cranial nerve deficits 2/2 tumor growth
———
All: elevated 24 hour urinary cortisol & salivary cortisol
ACTH-dependent (pituitary, ectopic) ==> elevated ACTH levels ==> only pituitary Cushing’s shows lowered AM cortisol 2/2 high dose dexamethasone suppression (thus, if remains high, its ectopic) ==> pituitary MRI
Surgical resection
Spironolactone suppresses adrenals
Acromegaly path, presentation, complications, dx, tx
Excess pituitary GH release 2/2 adenoma ==> elevated IGF-1 causes growth
Enlarged “coarse” features features
Bilateral hemianopsia
Diabetes 2/2 persistent hyperglycemia
CHF #1 cause of death
Elevated liver insulin-like growth factor (IGF-1) 2/2 excess GH
Glucose suppression test: glucose administration fails to lower GH levels
*Baseline growth hormone is not diagnostic
MRI: sellar lesion
Octreotide: suppresses GH release
Pegvisomant: GH receptor antagonist
Transphenoidal resection
Hyperprolactinemia path* w/ ddx*, presentation, dx, tx
Hyperprolactinemia 2/2 pituitary tumor (lactotroph tumor…most common pituitary tumor*), dopamine antagonists (haloperidol, antipsychotics, tricyclics, antiemetics), renal failure, cirrhosis
Suppression of GnRH ==> suppression of FSH/LH ==> galactorrhea, amenorrhea, infertility
Hemianopsia
RULE OUT PREGNANCY
Serum prolactin > 200
Pituitary tumor: causes other features of pituitary dysfunction, including low LH/FSH/testosterone, low TSH (prolactin is high bc dopamine receptor impaired by tumor)
MRI: sellar lesion
Dopamine agonists: gabergoline, bromocriptine
If refractory to medical, surgery
SIADH path, presentation, dx, tx*
Excess ADH 2/2 head injury, drugs (antipsychotics, antidepressants), pulmonary (sarcoid, COPD), paraneoplastic (small cell lung carcinoma*) ==> excess H20 reabsorption
Perhaps lethargy, confusion, weakness
Hyponatremia
Low serum osmolality 100
High urine Na > 25
FLUID RESTRICTION + salt tablets
…unless Na < 120 or severely symptomatic ==> hypertonic saline!
Pheochromocytoma path, syndrome associations, presentation, dx, tx**
Chromaffin tumor in kidney or ectopic ==> secretes catecholamines
MEN 2a/b
Neurofibromatosis
Von-hippel lindau
Paroxysmal (sudden) tachycardia, sweating, hypertension, headache, anxiety
Urine VMA, metanephrines & catecholamines
CT to localize
Surgical resection
- alpha-blockade ==> then beta-blockade ==> unopposed alpha activity causes severe hypertension
- or labetalol, both alpha and beta blocker
Hyperaldosteronism path w/ ddx, presentation, dx workup**, tx
Primary: excessive zona glomerulosa production of aldosterone 2/2 hyperplasia or adenoma (Conn’s syndrome)
Secondary: fibromuscular dysplasia or renal artery stenosis
Hypertension (especially young people!!!)
+/- Headache, weakness, cramps
Hypokalemia, worsened by thiazides! Hypernatremia Metabolic alkalosis ----- PRIMARY: Low renin Plasma aldosterone:renin > 20!! ==> adrenal suppression test with Na+ ==> imaging or renal vein sampling to differentiate hyperplasia from adenoma SECONDARY: Aldosterone:renin CT to find FMD or RAS
If bilateral hyperplasia: spironolactone/eplerenone (aldosterone receptor antagonists)
If unilateral adenoma: surgical resection
Congenital adrenal hyperplasia path/types, presentation, dx, tx
Impaired cortisol synthesis ==> overproduction of precursors & compensatory ACTH elevation ==> excessive androgens
95% autosomal recessive 21-hydroxylase deficiency
5% 11- and 17-hydroxylase deficiencies
Females: ambiguous genitalia @ birth
Males: salt-losing @ birth or precocious puberty without salt-losing
Hyponatremia
Hyperkalemia
Metabolic acidosis
Elevated 17-hydroxyprogesterone
Cortisol administration to decrease ACTH
Fluid resuscitation
Salt repletion
Hashimoto’s thyroiditis path, presentation, risks, dx, tx
Autoimmune inflammation / destruction of thyroid gland
May initially be hyperthyroid, progressing to hypo- or euthyroid
Non-tender, rubbery thyroid without nodularity
Thyroid lymphoma ==> rapidly expanding, compressive thyroid
Elevated TSH, low T4
Anti-TPO (thyroid peroxidase or microsomal) or thyroglobulin antibodies
Sheehan’s syndrome path, presentation, dx*
Post-partum pituitary ischemic necrosis 2/2 bleeding
Post-partum failure to lactate
Post-partum hypothyroidism
Clinical
Osteomalacia path, presentation, dx*
Defective osteoid matrix mineralization 2/2 inadequate calcium/phosphorous deposition
Etiologies:
-vitamin D deficiency (rickets in children; malabsorption or kidney or liver disease in adults) prevents uptake of calcium and phosphorous, thus increasing PTH which further degrades bone calcium and increases urinary phos excretion
-kidney disease
-liver disease
-RTA
Usually 2/2 dietary malabsorptive issue ==> diarrhea, malabsorptive condition
PAIN
Fatigue
*LOW-NORMAL calcium
*LOW phosphate
*Elevated PTH
Elevated Alk-P
XR: cortical thinning & vertebral body concavity
Paraneoplastic PTHrP path, presentation, dx
2/2 squamous, lung, breast, renal, bladder, etc. ==> tumor cells produce PTHrP
*More common than hypercalcemia 2/2 lytic lesions
Hypercalcemia effects: fatigue, confusion, CONSTIPATION, polyuria, n/v
Hypercalcemia
*Low-normal PTH
Hypophospatemia
Metabolic syndrome path*, dx**
Peripheral insulin resistance prior to development of beta cell dysfunction of DM2
3 of 5 criteria: Waist > 40 (men), 35 (women) BP > 130 Fasting glucose > 110 HDL < 45 TGL > 150
Vitamin D toxicity path, presentation*
Excess vitamin D ==> excess calcium & phos absorption
Hypercalcemia symptoms: constipation, abdominal pain, polyuria, polydipsia
Panhypopituitary path, presentation, dx
2/2 pituitary tumor
HEADACHE in history!
Secondary hypoaldosteronism: EOSINOPHILIA, hypotension, weight loss
Hypothyroidism: cold intolerance, fatigue, weight
Secondary hypogonadism: amenorrhea, decreased libido
Struma ovarii path, presentation, dx
Monodermal teratoma comprised of thyroid tissue…often in ovary but not necessarily
Hyperthyroid?
Leydig tumor path, presentation, dx, tx
Sex cord stromal tumor ==> overproduction of testosterone and estrogen
Any age
Gynecomastia
Testicular nodule
High testosterone & estradiol
Suppression of LH and FSH
Choriocarcinoma, teratoma, seminoma, yolk sac etc.
Find out
Iatrogenic cushing’s path, dx
Glucocorticoids suppress hypothalamic CRH [even after cessation] ==> suppresses ANTERIOR pituitary ACTH ==> decreased cortisol & androgen (fasciculata & reticularis, respectively) without affecting aldosterone (glomerulosa) ==> no cortisol to suppress posterior pituitary ADH ==> hyponatremia
Low ACTH
Low cortisol
Hyponatremia
Normal aldosterone
Prolactinoma path, presentation, dx, tx*
Pituitary adenoma secreting prolactin ==> inhibits GnRH & stimulates milk
HEADACHES / visual change
Gynecomastia
Small balls
Low testosterone & low FSH/LH
High prolactin ==> MRI to confirm tumor
Initially, NO MATTER THE SIZE: dopamine agonist (cabergoline, bromocriptine)
If refractory ==> surgery
Adrenal layers & hormones
Pituitary divisions & hormones w/ functions
Hypothalamus hormones w/ functions
Cortex = GFR…deeper you go the sweeter it gets
Glomerulosa: aldosterone (salt)
Fasciculata: cortisol (sugar)
Reticulata: androgens (sex)
Medulla = chromaffin cells ==> epinephrine, NE
Posterior: ADH, oxytocin Anterior: FLATPiG FH LH ACTH TSH Prolactin ==> stimulates milk; inhibits GnRH (ovulation/speratogenesis) GH
TRH ==> TSH, prolactin Dopamine ==| prolactin Somatostatin ==| GH, TSH GnRH ==> LH, FSH ...others but less important
Hypoparathyroidism path, presentation, dx
True: Autoimmune, post-surgical, DiGeorge ==> low PTH
Pseudo: lacking PTH sensor
Secondary: renal failure
Tingling/numbness
Trousseau’s / Chvostek
Long QT
Hypocalcemia
Hyperphosphatemia
MUST REVIEW THIS…you suck at it
And memorize lab values
Male pubertal gynecomastia path, presentation, dx, tx
Transient estrogen increase
Uni- or bilateral subareolar masses, sometimes tender
No tx until persistent for 2+ years
Sick euthyroid syndrome path, presentation, dx, tx
Any acute, severe illness can trigger fall in thyroid function
History of severe, acute illness
Incidental finding of low T3 with low-normal T4 & TSH
No tx
Thyroid nodule vs thyroid cancer path*, commonality
Nodule: colloid ==> far more common
Cancer: see above
Factitious thyrotoxicosis path, presentation, dx*
Exogenous thyroid hormone (weight loss / psych patients)
Anxiety, palpitation, sweating
No propoptosis
Low TSH
Low T3/T4
Low serum thyroglobulin
Diffusely low radioactive iodine uptake
Simple gluconeogenesis pathway*
Alanine in protein/fat ==> pyruvate ==> glucose
Female virilization ddx w/ path, dx*
Think ovarian or renal neoplasm secreting testosterone and/or DHEA
Ovarian: testosterone
DHEA: kidney
Insulinoma path, presentation, ddx, dx, tx
Pancreatic beta-cell tumor hypersecreting insulin
Hypoglycemia sx
Surreptitious insulin ==> no C-peptide
Sulfonylurea ==> in history
Insulin w/ elevated C-peptide & proinsulin levels
Resection
Diabetes screening recommendations*
All adults >45 if no risk factors
Screen earlier if suspicious
TSH secreting pituitary adenoma presentation, dx
ALWAYS headache or visual disturbance in question stem!
Hyperthyroid sx
High TSH 2/2 TSH secreting tumor
High T3/T4
Nipple discharge workup with path*
Unilateral ==> mammogram and/or ultrasound
Bilateral
==> bloody / serous ==> mammogram or ultrasound
==> milky, green etc. ==> evaluate for lump
+ lump ==> mammogram or ultrasound
- lump ==> prolactin, TSH, pregnancy test
