Endocrine Flashcards
What is acute adrenal insufficiency (adrenal crisis)?
Etiology: adrenal hemorrhage or infarction; acute illness/injury/surgery in pt w/ chronic adrenal insufficiency or long-term glucocorticoid use
RF: underlying primary adrenal insufficiency (Addison disease) or suppression of HPA axis due to chronic glucocorticoid use
Presentation: hypotension/shock; nausea, vomiting, abdominal pain; weakness, fever
Tx: hydrocortisone or dexamethasone; high flow IVF
What is primary hyperparathyroidism?
Etiology: parathyroid adenoma (most common), hyperplasia, carcinoma, increased in MEN1 and 2A
Presentation: asymptomatic (most common); mild, nonspecific symptoms (eg fatigue, constipation), abdominal pain, renal stones, bone pain, neuropsychiatric symptoms
Dx: hypercalcemia, hypophosphatemia, elevated or inappropriately normal PTH, elevated 24h urinary ca excretion
Indications for parathyroidectomy: age <50yo, symptomatic hypercalcemia; complications - osteoporosis (T score < -2.5, fragility fracture), nephrolithiasis/calcinosis, CKD (GFR <60);
elevated risk of complications - calcium >/= 1mg/dl above normal, urinary ca excretion >400mg/day
What is thyroid storm/hyperthyroidism?
Precipitating factors: thyroid or non-thyroid surgery, acute illness (eg trauma, infection), childbirth; acute iodine load (eg iodine contrast)
Presentation: fever as high as 40-41.1C (104-106F); tachycardia, hypertension, CHF, cardiac arrhythmias (eg atrial fibrillation); agitation, delirium, seizure, coma; goiter, lid lag, tremor, warm and moist skin; nausea, vomiting, diarrhea, jaundice
Tx: beta blocker (eg propranolol) to decrease adrenergic manifestations; PTU (to block new hormone synthesis) followed by iodine solution (SSKI) (to block release; given 1h later to prevent excess I incorporation into TH); glucocorticoids (eg hydrocortisone) to decrease peripheral T4 to T3 conversion and improve vasomotor stability; identify trigger and treat, supportive care
What is hypocalcemia?
After confirmation, next step is to check PTH level to distinguish between low PTH-assoc. conditions (eg parathyroid surgery, polylglandular autoimmune) and elevated PTH-assoc. conditions (eg vit D deficiency, chronic kidney disease).
Causes: neck sugery (parathyroidectomy), pancreatitis, sepsis, tumor lysis syndrome, acute alkalosis, chelation: blood (citrate binds ionized ca) transfusion, EDTA, foscarnet
Presentation: muscle cramps, Chvostek and Trousseau signs, paresthesias (tingling and numbness), hyperreflexia/tetany, seizures; QT interval prolongation
Pts w/ impaired hepatic function are at increased risk due to decreased clearance of citrate by the liver.
Lactate, foscarnet, and EDTA can chelate calcium in the blood
Tx: IV calcium gluconate/chloride
What is papillary thyroid cancer?
Most common thyroid epithelial malignancy
Characterized by slow spread into local tissues and regional lymph nodes
Pathology: large cells w/ ground glass cytoplasm; pale nuclei w/ inclusion bodies and central grooving; and grainy, lamellated calcification known as psammoma bodies
Tx: surgical resection; postoperative adjuvant therapies for pts at increased risk of recurrence include radioiodine ablation and suppressive doses of thyroid hormone
What is follicular thyroid cancer?
Second most common thyroid epithelial malignancy
Peak incidence of 40-60yo
Presentation: firm thyroid nodule
Thyroid scintigraphy usually shows a nonmetabolically active “cold” nodule
Dx: surgically excised nodule - invasion of tumor capsule and/or blood vessels; invasion pattern accounts for tendency of FTC to metastasize via hematogenous spread and to distant tissues (eg bone, lung)
What is thyroid lymphoma?
Uncommon, though high incidence in pts w/ pre-existing chronic lymphocytic (Hashimoto) thyroiditis (ie chronic hypothyroidism, positive antithyroid peroxidase antibody)
Presentation: rapidly enlarging, firm goiter assoc. w/ compressive symptoms (eg dysphagia, hoarseness); systemic B sxs (fever, night sweats, wt loss); retrosternal extension (prominent venous distension, facial redness=Pemberton sign)
What is Riedel thyroiditis?
Progressive fibrosis of thyroid gland and surrounding tissues
Resulting fibrotic mass may resemble malignancy, but sxs are chronic and slowly progressive rather than acute
What is constitutional growth delay?
Characterized by delayed growth spurt, delayed puberty, and delayed bone age.
What is glucose 6 phosphatase deficiency (type 1 glycogen storage disease/von Gierke disease)?
Caused by deficient glucose 6 phosphatase in liver, kidney, intestinal mucosa which results in impaired conversion of glycogen to glucose, leading to glycogen accumulation in affected organs
Presentation: 3-4mo, hypoglycemia (seizures), lactic acidosis (due to buildup in liver); DOLL LIKE FACE, thin extremities, short stature, LARGE LIVER
No spleen and heart involvement
Labs: hyperuricemia, hyperlipidemia
What is euthyroid sick syndrome?
AKA “low T3 syndrome”; any pt w/ acute, severe illness
Labs: decreased total and free T3 levels, normal TSH and T4
What is subclinical hypothyroidism?
Elevated TSH
Normal T4, T3 (until late stages)
What is chronic lymphocytic (Hashimoto) thyroiditis?
Form of hypothyroidism; subclincal hypothyroidism may convert to overt hypothyroidism
Presentation: symmetrically enlarged non-tender thyroid
Labs: antithyroid peroxidase and anti-thyroglobulin antibodies
High titers of anti-tpo assoc. w/ increased risk of miscarriage
Tx: levothyroxine
Estrogen and TH.
Oral E decreases clearance of thyroxine-binding globulin, leading to elevated TBG levels.
Pt w/ nl thyroid fxn can readily increase thyroxine production to saturate increased number of TBG binding sites.
Hypothyroid pts are dependent on exogenous thyroid replacement and cannot compensate resulting in decreased free thyroxine and increased TSH. So, higher dosing of levothyroxine may be required.
Radioactive iodine uptake (RAIU) scintigraphy
Increased in cases of hormone overproduction (graves)
Low/undetectable in cases of release of preformed hormone (painless thyroiditis)
Water deprivation test.
Urine osm >600 suggest primary polydipsia due to intact ADH and ability to concentrate urine in absence of water intake.
Less than 600 = diabetes insipidous
Desmopression distinguishes between central and nephrogenic DI.
Central DI: >50% increase in urine osmolality w/ desmopressin; Tx: intranasal desmopressin
Nephrogenic DI: minimal change in urine osmolality w/ desmopression
Thyrotoxicosis.
Causes increased sensitivity to catecholamines due to increased expression of beta-1 adrenergic receptors as well as changes in proteins controlling post beta-1 adrenergic receptor activity.
It DOES NOT stimulate catecholamine production.
What is metabolic syndrome?
At least 3/5 are met: BP >130/80 Fasting glucose >100-110 Abdominal obesity (M: waist circum >40in; W: >35in) Triglycerides >150 HDL (M: <40, W: <50)
Diabetic neuropathy.
Small fiber injury: predominance of positive sxs (eg pain, paresthesias, allodynia)
Large fiber injury: predominance of negative sxs (numbness, loss of proprioception and vibration sense, diminished ankle reflexes)
Hypercalcemia.
Nephrolitihiasis, osteoporosis, nausea, constipation, neuropsychiatric symptoms (confusion, stupor, coma); (“stones, bones, abdominal moans, psychic groans”)
Tx: severe - calcitonin (inhibits osteoclast-mediated bone resorption, quickly reduces serum Ca concentrations and can be admnistered w/ saline)
Bisphosphonates also inhibit bone resorption and provide a sustained reduction in ca levels. however their effect is delayed usually occuring over 2-4d and they are typically given after initial administeration of saline and calcitonin
What is painless (silent) thyroiditis?
Variant of chronic lymphocytic (Hashimoto) thyroiditis
Presentation: self-limited hyperthyroid phase, then hypothyroid phase
Low uptake on RAIU scan
Labs: thyroid peroxidase autoantibodies
Tx: beta blocker for hyperthyroid symptoms
What is methimazole?
Decreases TH production
Used in thyrotoxicosis
What is radioactive iodine?
Causes radiation-induced destruction of thyroid follicular cells
Leads to clincial and biochemical resolution of hyperthyroidism over the subsequent 6-18 weeks
Can lead to permanent hypothyroidism w/in months in >90% of pts (Graves)
In contrast, when used to treat toxic nodular goiter and toxic adenoma, the radioisotope is taken up only by the autonomous thyroid tissue, and the function of the remaining normal tissue is usually adequate to prevent permanent hypothyroidism
Used in thyrotoxicosis
What is Gauchers disease?
Most common lysosomal storage disease Due to GLUCOcerebrosidase deficiency resulting in accumulation of glucocerebrosidase in lipid-laden MACROPHAGES of different tissues - BM: anemia + thrombocytopenia Splenomegaly > hepatomegaly Bone: bone pain FFT, delayed puberty Tx: enzyme replacement
Primary hyperparathyroidism and HTN.
Primary hyperparathyroidism can cause HTN, arrhythmias, ventricular hypertrophy, and vascular and valvular calcification.
Hypothyroidism and metabolic abnormalities.
Causes-
Hyperlidemia: due to decreased LDL surface receptors and/or decreased LDL receptor activity
Hypertriglyceridemia: due to decreased lipoprotein lipase activity
Hyponatremia: due to decreased free water clearance
Asx elevation of creatinine and serum transaminases
Glucose control in DM.
Pts who have an elevated HbA1c despite good control of fasting glucose may have POSTPRANDIAL hyperglycemia.
Combined regimen including a long-acting basal insulin (to control baseline/fasting glucose) and a rapid-acting mealtime insulin (to control postprandial glucose) may be needed to provide optimal control.
Hyperthyroid drugs.
Antithyroid drugs (methimazole, PTU) are used in pts w/ mild disease who are likely to have a permanent remission. Also used in preparation for treatment w/ radioactive iodine in pts w/ significant hyperthyroidism or who are at increased risk of complications.
What is acute thyrotoxic myopathy?
Presentation: severe distal or proximal muscle weakness; muscle atrophy
DTR are frequently normal
Tx: treatment of hyperthyroidism usually improves the myopathy
Genitalia in classic congenital adrenal hyperplasia.
Newborn girls: ambiguous genitalia, ranging from clitoromegaly appears as underdeveloped phallus w/ a displaced urethral meatus; nonpalpable gonads as ovaries are intraabdominal and testes are not present
Labioscrotal folds may be partially or completely fused
Interal organs are female, no testes
Newborn boys: normal or sometimes hypervirilized genitalia w/ palpable testes
What is 5 alpha reductase deficiency?
Causes defective conversion of testosterone to dihydrotesterone
Classically presents in genotypically male newborns (46XY) w/ female or undervirilized external genitalia.
Testosterone level is normal.
What is androgen insensitivity syndrome?
Due to a defect in the androgen receptor
Presents in a genotypically male newborn (46XY) w/ undervirilized ambiguous or female external genitalia
What is glucagonoma?
Necrolytic migratory erythema (indurated plaques w/ scaling + central clearing on face, groin, + extremities) + diarrhea, wt loss, and anemia.
Dx: glucagon >500
Imaging: CT scan or MRI to localize tumor and evaluate for mets
Tissue transglutaminase IgA antibodies
Seen in dermatitis herpetiformis, typically assoc. w/ celiac disease
Skin manifestations: grouped, intensely pruritic papules and vesicles on the extensor surfaces of the elbows, knees, back, and butt.
DKA
Worsening hyperglycemia and metabolic acidosis can manifest as abdominal pain, altered mentation, and hyperventilation.
Dx: based on clinical presentation and beside capillary blood glucose
Tx: aggressive IV hydration and insulin
Primary aldosteronism (Conn’s syndrome)
HTN, metabolic alkalosis, hypokalemia, mild hypernatremia
Tx: aldosterone antagonists (spironolactone, eplerenone)
Subacute (de quervain’s) thyroiditis.
Hypothyroid
Tx: beta blockers to control thyrotoxic sxs and NSAIDs for pain relief
Whatis suppurative thyroiditis?
Infectious.
Rare condition causing high-grade fever and pain at thyroid gland.
Gland may be palpably enlarged due to abscess formation.
However, pts are usually euthyroid as involvment of the thyroid gland is focal.
Fetal hyperglycemia
Fetus cannot produce insulin during the 1st trimester and therefore cannot protect itself from hyperglycemia.
Neonatal hypoglycemia
After delivery, fetal insulin production takes time to decrease whereas maternal glucose exposure ends as soon as the umbilical cord is clamped.
This often results in a period of neonatal hypoglycemia until insulin levels normalize.
Hypoglycemia is the most common complication among infants of DM mothers.
Pheochromocytoma
Can be precipitated by increases in abdominal pressures (tuor palpation, positional changes), surgical procedures, anesthetic agents
Non-selective beta blockers can cause a state of unopposed alpha adrenergic stimulaton leading to vasoconstriction and paradoxical HTN.
Therefore, alpha adrenergic blockers (phenoxybenzamine) should be administered prior to beta blockers.
Precocious puberty
Onsest of secondary sex characteristics (eg pubic/axillary hair, cystic acne, accelerated growth) in girls age <8 and boys age <9)
Central precocious puberty: results from early activation of the hypothalamic pituitary gonadal axis; pulsatile GnRH secretion stimulates elevated FSH and LH levels
Peripheral precocious puberty: LOW FSH and LH; caused by gonadal or adrenal release of excess sex hormones; basal levels of FSH and LH are low due to neg fb and remain low following GnRH agonist stimulation
MRI of the brain to evaluate for hypothalamic or pituitary tumor.
If idiopathic central PP, GnRH therapy, it desensitizes the pituitary and suppresses FSH and LH secretion to slow pubertal progression, prevent premature epiphyseal plate fusion, and maximize height potential.
Central adrenal insufficiency
Pts w/ cushingoid appearance are more likely to have a suppressed HPA axis.
Following glucocorticoid discontinuation, normal HPA axis function may not fully return for up to 6-12 months.
Hypothyroid myopathy
Myalgias, proximal muscle weakness, elevated serum CK
Features of hypothyroidism (fatigue, delayed reflexes)
Dx: TSH, T4 levels
Refeeding syndrome
Carb ingestion whether enteral or IV, causes pancreatic insulin secretion and cellular uptake of P, K, and Mg. P is the primary deficient electrolyte as it is required for energy (ATP).
Deficiencies in P and Mg potentiate cardiac arrhythmias in a heart already atrophic from prolonged malnutrition.
Therefore, aggressive initiation of nutrition w/o adequate electrolye repletion can quickly precipitate cardiopulmonaory failure.
Aldosterone + cortisol are high during starvation but less so during refedding. They do not directly mpact P or Mg uptake.
What is milk alkali syndrome?
Caused by excessive intake of calcium and absorbable alkali (eg ca carbonate preparation used in pts w/ osteoporosis); resulting hypercalcemia causes renal vasoconstriction and decreased glomerular blood flow; inhibition of NKCl transporter and impaired ADH acitivity lead to loss of Na and free water.
It can be seen in pts taking calcium bicarbonate for osteoporosis.
Clinical finding: symptomatic hypercalcemia, AKI, metabolic akalosis.
Thiazides are assoc. w/ MILD hypercalcemia. Not event to get to symptomatic hypercalcemia.
What is hypercalcemia of immobilzation?
Insidious, Due to increased osteoclastic bone resorption
Onset usuallly around 4w after immbolizaitoins, althought pts w/ chronic renal insufficiency may develop hypercalcemia in as little as 3d
RF: pre-existig high rate of bone turnover (younger pts, Paget disease)
Suppressed PTH
Tx: bisphosphonates inhibit osteoclastic bone resorption and are effective in tx
Albumin + Calcium
40% of Ca bound to albumin
Hypoalbuminemia: lowers the total Ca level so measured ca levels are corrected upward based on extent of hypoalbuminemia
Hyperalbuminemia: assoc. w/ increase in total ca
In either case, total ionized fraction is unaffected + pt will not have ca-related sxs directly related to the change in albumin levels
Hyperthyroidism + Calcium
Untreated hyperthyroid pt are at increasd risk for rapid bone loss from increased osteoclastic activity in the bone cells. Leading to osteoporosis and increased risk of fracture.
Pts can also develop hypercalcemia and hypercalciuria due to increased bone turnover.
Untreated hyperthyroid pts are also at risk for cardiac tachyarrhythmias, including a fib.
What is congenital hypothyroidism?
Infants initially appear normal at birth, but gradually develop apathy, weakness, hypotonia, large tongue, sluggish movement, abdominal bloating, and an umbilical hernia.
For this reason, screening newborns for hypothyroidism, along with phenylketonuria and galactosemia, is standardly performed in all states.
Diabetic nephropathy
Target HbA1c <7%
Intensive BP control is assoc. w/ reduced progressive of DN.
Ideal BP <130/80
ACE-i and ARBs are preferred antihypertensive drugs
These agents lower systemic BP and reduce intraglomerular pressure, which may be renoprotective
What is thyroglobulin?
Produced only by thyroid tissue (either normally functioning or malignant).
Serum thyroglobulin measurements are used as a tumor marker once the normally functioning thyroid tissue is removed. Rising levels indicated recurrence of differentiated thyroid cancer.
Levothyroxine suppresses TSH release (neg FB). B/c TSH stimulates thyroid tissue growth, levo supplementation to suppress TSH (i.e., by causing a mildly hyperthytroid state) may help prevent thyroid cancer recurrence.
Vitamin D deficiency
Pts w/ osteomalacia due to vit. D deficiency have low or low-normal serum ca, low serum P, increased serum PTH, low plasma 25OHvit D levels, and elevated ALP.
Unlike in osteoporosis, most pts complain of bone pain and muscle weakness.
XR: decreased bone density w/ thinning of cortex and pseudofractures (Looser zones).
Prolactinoma + TSH
TSH may be NORMAL or low; depends on compressive effect on thyrotroph cells.
What is familial hypocalciuric hypercalcemia?
Caused by a mutation in the calcium sensing receptor.
Benign disorder characterized by asymptomatic hypercalcemia, elevated or inappropriately normal PTH levels and low urinary calcium excretion.
It can be differentiated from primary hyperparathyroidism, which has increased urinary ca excretion, by the urine calcium/creatinine clearance ratio.
Congenital hypothyroidism
Assoc. w/ neurodevelopmental injury if not recognized and treated early.
Decreased activity, hoarse cry, and jaundice are commonly assoc. w/ congenital hypothyroidism, but majority of infants are asx.
Thyroid dysgenesis is the most common cause of congenital hypothyroidism worldwide.
Hyperthyroidism + RAIU
In hypertyroidism, increased RAIU suggests denovo thyroid hormone synthesis, whereas decreased RAIU suggests release of preformed hormone (eg thyroiditis) or exogenous hormone intake.
Thyrotoxicosis due to exogenous TH is characterized by low serum thyroglobulin levels.
Wt loss supplements contain TH derived from porcine or other animal sources.
DKA
Best markers indicating resolution of DKA are serum anion gap and beta-hydroxybutyrate levels
The serum AG estimates the unmeasured anion concentration in the blood and returns to normal w/ disappearance of ketoacid anions.
BH is not measured by the nitroprusside test so it needs to be measured directly with serum assay of BH.
Nonclassical congenital adrenal hyperplasia
Occurs secondary to 21 hydroxylase deficiency
Increase in 17OH progesterone
Sufficient mineralocorticoids and glucocorticoids
Increase in testosterone
Causes gonadotropin-independent precocious puberty; pts can have premature secondary sex characteristics (pubic hair, cystic acne), accelerated growth and bone age, and low/normal LH
Evaluation of adrenal insufficiency?
Should include 8AM serum cortisol and plasma ACTH
In addition, an ACTH stimulaton test (cosyntropin test) can identify pt w/ primary adrenal insufficiency (and most pts w/ central adrenal insufficiency) and should be performed in the initial evaluation.
Urinary cortisol levels are decreased, but sensitivity is too low for use in initial diagnosis
Dexamethasone suppression test.
Dexamethasone suppresses release of ACTH from the pituitary, which subsequently reduces adrenal cortisol production.
The dexamethasone suppression test is used to evaluate hypercortisolism not primary adrenal insufficiency.
What is cushing syndrome?
Wt gain, psych sxs, hirsutism, HTN, hyperglycemia
Initial step in eval of Cushing syndrome is to confirm hypercortisolism w/ a 24h urine free cortisol, late night salivary cortisal assay, and/or low dose dexamethasone test
If hypercortisolism is confirmed, ACTH levels are measured to differentiate ACTH-dependent (Cushign disease - pituitary) from ACTH-independent (eg small cell lung cancer, primary adrenal disease) causes
Hyperaldosteronism
Ratio of plasma aldosterone to plasma renin is useful for primary evaluation.
Euthryroid state: elevated T4, normal TSH
TH is normally bound to TBG, transthyretin, and albumin
Only free TH is biologically active
Changes in binding protein levels can affect the total circulating pool of TH, but if the axis is intact, free hormone levels are unchanged.
Estrogen (pregnancy, OCP, HRT) increases the level of T4 binding globulin by decreasing its metabolism and increasing synthesis in the liver. As additional TBG binds more TH, TH production increases to maintain euthyroid state.
This effect is seen in pregnancy and in pts on OCP or menopausal estrogen replacement.
Total TH levels are elevated, but pts w/ normal hypothalamic pituitary thyroid function maintain a euthyroid state and normal free T4 and TSH level.
Hirsutism
Rapid onset hirsutism (<1y) w/ virilizaiton (eg temporal balding, excessive muscular development, enlarged clitoris) suggests very high androgen levels due to an androgen-secreting neoplasm of the ovaries or adrenal glands
Ovaries naturally secrete: T, androstenedione, and dehydroepiandrosterone (DHEA)
Adrenals: T, androstenedione, DHEA, and DHEAS
Therefore, women w/ androgen-producing tumor should be evaluated w/ serum T and DHEAS levels
Ovarian source - elevated T and normal DHEAS (more common)
Adrenal source - elevated DHEAS (less common)
DHEAS and DHEA have negligible intrinsic androgenic action but are converted to adrostenedione and subsequently to testosterone in peripheral tissues.
Type II DM + CVD
Metform is recommended 1st line med for most pts w/ type 2 DM.
Options for add-on tx in pts w/ established cardiovascular disease:
-GLP1 agonists: decreased cardiovas events, induce signficant wt loss
-SGLT2 ihibitors: assoc. w/ decreased BP, decreased risk for HF and cardiovasc events, minor wt loss
Insulin and sulfonylureas
Not shown to reduce risk of cardiovascular events
Thiazolidinediones
Assoc. w/ possible wt gain.
Cause fluid retention, which can lead to symptomatic HF in pts w/ underlying heart disease
DPP4 inhitibors
Less effective than GLP1 agonists
Have minimal effect on wt
Not assoc. w/ a decreased risk of cardiovasc events
PTH-related protein
From malignant tumor cells, causes hypercalcemia
Hypoparathyroidism
Treatment of chronic hypoparathyroidism is w/ calcium and vit D, but calcium and phosphorus must be closely monitored.
A calcium phosphorus product (serum ca x serum p) >55 increases the risk of soft tissue calcification.
Calcification in the basal ganglia can cause extrapyramidal manifestations.
Hypothyroidism + carpal tunnel syndrome
CTS is common in pts w/ hypothyroidism and is frequently bilateral.
Hypothyroidism causes soft tissue thickening and mucinous infiltration, which can lead to compression of the median nerve w/in the carpal tunnel.
Tx: levothyroxine
CTS + renal disease
Pts w/ ESRD on hemodialysis frequently develop CTS due to accumulaton of dialysis-related amyloid.
When CTS occurs, it is more common in the arm used for vascular access (eg access graft, arteriovenous fistula) suggesting a contribution of vascular steal or venous HTN.
ESRD can also lead to pathologic calcification w/ deposition of calcium phosphate, which can compress the nerve.
