UW Endo Flashcards
What is the next best step after serum calcium levels are found to be low in a pt. ?
-Confirm with a repeat test, and *correct/adjust if serum albumin is low, OR measure ionized calcium.
*Sr. Ca2+ decreases by 0.8 mg/dL for ever 1gm/L drop in sr. albumin levels; hence,
corrected calcium= measured total calcium + [0.8 x (4 g/dL -measured sr. albumin in g/dL)].
What is the next best approach after low serum calcium levels are confirmed by repeat testing as well as corrected for low serum albumin?
-Check Sr. Mg2+ (n: 1.5-2 mg/dL): replace if low
-Evaluate medication history (?loop diuretics)
-Check for h/o recent blood transfusion? (high citrate, volume).
*Check PTH levels if all of the above are normal.
Normal serum Ca2+ level is ____,
Normal sr. phosphorus (i) level is ______.
Normal sr. Mg2+ level is ______.
Normal serum albumin level is ______.
Normal range of
-sr. Mg2+ : 1.5-2 mg/dL
-sr. phosphorus (i): 3.0-4.5 mg/dL.
-sr. Ca2+ : 8.4-10.2 mg/dL.
Serum albumin: 3.5-5.5 g/dL.
How does HypoMg2+ (commonly seen in alcoholics) drive hypoCa2+?
By
-inducing resistance to PTH, as well as
-decreasing the secretion of PTH.
*normally/abnormally HypoPTH is a/w elevated phosphorus levels; however, in hypoMg2+ induced hypoPTH, sr. phosphate levels are normal or low possibly d/t IC phosphorus depletion. .
What is the cause of HypoMg2+ in alcoholics?
multifactorial etiology
-urinary loss of Mg2+
-malnutrition
-acute pancreatitis
-diarrhea
PTH levels return to normal rapidly after Mg2+ is replaced in pts. with hypoMg+ induced hypocalcemia but ____ takes longer to improve because _____ takes time to normalize.
hypocalcemia may persist because PTH resistance induced by hypoMg2+ takes longer to normalize.
Hypocalcemia d/t extracellular deposition of Ca2+ may occur in _____ conditions.
hyperphosphatemia,
osteoblastic bone metastasis,
acute pancreatitis.
In addition to hypoMg2+ and consequent hypocalcemia, ____ e- disturbance may also coexist in alcoholics.
hypophosphatemia.
The best initial t/t for acromegaly d/t a somatotroph adenoma is _____.
trans-sphenoidal resection of the tumor.
Medical therapy with ______ or ______ is instituted in which cases of acromegaly?
somatostatin analogues (Octeotride), or
GHRB (Pegvisomant);
indicated in pts. with residual or unresectable tumors.
What is the next best test in pts. suspected of GH hyper-secretion with equivocal IGF-1 results (best initial test)?
Oral Glucose suppression test.
*load of glucose must suppress GH levels; in hyper-secreting tumors, no suppression will occur.
Circulating levels of PTH and calcium are _____ (? elevated, low, normal) in osteoporosis.
normal
PTH-dependent hypercalcemia (a/w increased or high-normal PTH) is seen in _____ conditions.
-primary hyperPTH: PTH gland adenoma (~80%), hyperplasia (~15%), parathyroid cancer.
-FHH
-Lithium
PTH-independent hypercalcemia (low PTH) is seen in _____ conditions.
-Elevated PTHrP (malignancy)
-Vit D toxicity (measure 25-H Vit D)
-Vit A toxicity
-drug-induced (thiazides)
-granulomatous d (*Sarcoidosis)
-milk-alkali syndrome
-Thyrotoxicosis
-Immobilization.
*measure 1, 25-DH Vit. D (extra-renal conversion of 25-H vit D to 1, 25-DH vit. D).
Cirrhosis leads to hypogonadism by which mechanisms?
-primary gonadal injury
-hypothalamic-pituitary dysfunction
-High estrogen state c/by increased conversion from androgens.
Cirrhosis is a high ____ state d/t increased conversion from androgens, leading to s/s such as telangiectasias, palmar erythema, testicular atrophy and bilateral/unilateral gynecomastia (men).
estrogen state (estradiol)
In cirrhosis, total T4 and total T3 levels are _____ (? low, high) d/t ________, and free T3, T4 and TSH levels are ____ (? low, high, normal).
total T3 & T4 level is low d/t decreased hepatic synthesis of THBP (TH binding proteins such as TBG, transthyretin, albumin, lipoproteins).
free T3 , free T4 and TSH levels are normal indicating a euthyroid state.
True/False? All pts. with adrenal insufficiency p/w features of hypogonadism.
False;
only women with AI p/w hypogonadism (loss of libido, decreased pubic hair) d/t decreased adrenal production of androgens.
Men with AI do not p/w hypogonadism in AI because androgens are primarily produced in testes in men.
*Men p/w s/s of hypogonadism (testicular atrophy) plus gynecomastia in high estrogen states such as hepatic cirrhosis.
The first best step in evaluation of a thyroid nodule is ____.
serum TSH and thyroid USG.
_____ sonographic features in a thyroid nodule carry a much higher risk of malignancy as compared to features such as _____.
solid (hypoechoic), micro-calcifications, irregular margins, internal vascularity in a thyroid nodule carry a much higher risk of malignancy as compared to cystic or spongiform features in a nodule.
Thyroid nodules of ____ size with high-risk features, and all non-cystic nodules of _____ size must undergo FNAC examination.
> 1cm with high risk features (micro-calcifications, irregular margins, internal vascularity +/- normal/high TSH), and
> 2cm all non-cystic nodules +/- normal/high TSH.
*normal/high TSH may suggest a hypo-functioning (COLD) nodule.
A pt. with a thyroid nodule and low TSH (hyperthyroid) must undergo ____, for evaluation of a potential malignancy.
radionuclide thyroid scan (e.g. Radioactive iodine scintigraphy).
Nodule with increased iodine uptake–> HOT nodule (low r/o malignancy).
Nodule with decreased iodine uptake–> COLD nodule (high r/o malignancy).
____ is a useful tumor marker in suspected medullary thyroid cancers, and ______ is post-thyroidectomy tumor marker for papillary and follicular thyroid cancers.
Calcitonin for suspected medullary Thyroid ca;
serum thyroglobulin for post-surgical follow-up for papillary and follicular thyroid ca.
In hypercalcemia d/t malignancy, serum calcium levels are very high, usually more than ____ mg/dL.
usually > 14 mg/dL.
*normal sr. Ca2+ level is 8.4 - 10.2 mg/dL (narrow range and rigid control in plasma).
In hypothyroidism, increased total cholesterol and LDL levels are due to ______, and increased triglyceride levels are due to ________.
increased total cholesterol and LDL levels d/t
-decreased expression and activity of LDL receptor
Increased triglyceride levels are d/t
-decreased activity of LPL
Pts. with newly diagnosed hypercholesterolemia must undergo ___ tested to screen for underlying ____.
serum TSH to screen for underlying hypothyroidism.
If not tested prior, serum ___ must be tested before initiation of statin therapy because underlying untreated ____ will increase the r/o statin-associated myopathy.
serum TSH; underlying hypothyroidism.
*Statins also increase hypothyroidism associated myopathy.
exogenous androgen use is a/w dyslipidemias such as increase in ____ and ____ , decreased ____ but normal ___.
increase in TC and LDL , and decreased HDL, but normal triglycerides (TGs).
Hypothyroidism increases the r/o coronary atherosclerosis by causing ___.
dyslipidemia.
Euthyroid sick syndrome (ESS) aka _____ or _____, is characterized by _____ in setting of _____.
ESS is aka Non-thyroidal illness syndrome (NTI) or Low T3 syndrome.
-characterized by alterations in TFTs in setting of a non-thyroidal illness and no prior h/o endocrine/thyroid illness.
Most prominent alterations include
-low T3
-T4 & TSH may initially be normal but as illness increases in severity, all decrease.
Increase in rT3 (non-functional)
See attached Image for details.
Image courtesy: Medscape
Thyroid function tests must be interpreted with caution in acutely ill patients d/t ____.
the possibility of ESS in acutely ill pts.
Thyroid function must be reassessed after recovery from the acute illness, and t/t initiated only of thyroid abnormality persists.
In an acutely ill pt. what are the possible factors responsible for decrease in peripheral deiodination of T4 ?
-high endogenous cortisol levels
-inflammatory cytokines (TNF)
-starvation (to decrease T3 mediated catabolism?)
-medications such as glucocorticoids, amiodarone.
Hospitalized/ICU pts. may have low total T4 levels (but normal free T4) d/t ______.
decrease in levels of hormone/other binding proteins such as TBG, transthyretin, albumin.
Thyroid hormones undergo enterohepatic circulation and are reabsorbed in _____; hence, excessive fecal loss of thyroid hormones can occur in _____.
reabsorbed in ileum and jejunum;
hence, excessive fecal loss of thyroid hormones can occur in small intestine diseases such as Crohn disease and celiac disease.
Carcinoids are slow growing neuroendocrine tumors most commonly originating in _____.
distal small intestine, proximal colon, and lungs;
*metastasis to liver most commonly occurs from from GI carcinoid.
Deficiency of vitamin ____ can occur in carcinoid syndrome, as tumor cells use ____ to synthesize _____ .
Vit. B3 (Niacin); as carcinoid tumor cells use *tryptophan to synthesize serotonin; tryptophan is normally used in synthesis of Vit B3.
B3 deficiency aka PELLAGRA is manifested by 3 D’s:
diarrhea (also occurs independently in carcinoid syn.), dermatitis, and dementia.
What are some common skin manifestations in carcinoid syndrome?
Flushing (d/t vasoactive peptides),
telangiectasias,
cyanosis (bronchospasm induced).
What is the most common secondary cause of hyper-prolactinemia?
pregnancy.
A pt. p/w h/o a painful/pruritic papules on extremities, groin and/or face that coalesce to form plaques with scaling and central clearing along with h/o diarrhea, weight loss, abdominal pain and hyperglycemia/diabetes. What is the most likely disorder?
Glucagonoma, a pancreatic NE tumor that causes excessive production of catalytic hormone glucagon.
____ skin manifestation is the presenting feature in about 70% cases of Glucagonoma.
Necrolytic migratory erythema (NME) (see Image) is characterized by initial painful/pruritic ring-shaped red rash that blisters, erodes and crusts leaving a brown mark.
-may affect any site but most often affects the genital and anal region, the buttocks, groin and lower legs.
-The rash fluctuates in severity.
Image: DermNet NZ @Dermnetnz.org
Serum glucagon levels are markedly elevated in glucagonoma to about _____, as compared to other conditions that raise glucagon such as hypoglycemia, Cushing syndrome, and pancreatitis where mild elevations in glucagon levels are noted.
> 500 pg/dL
Milk-alkali syndrome is characterized by ____, ____ and ___.
hypercalcemia, renal insufficiency, and metabolic alkalosis.
What is the percentage of occurrence of each of the 3 Ps in autosomal dominant MEN1 syndrome?
Pituitary adenomas: in 10-20% cases
Parathyroid (Primary HyperPTH): > 90% cases
Pancreatic/GIT NE tumors: in 60-70% cases
Rapid onset hirsutism (< 1 yr duration) in a female accompanied by s/o virilization (temporal balding, excessive muscular development, and/or enlargement of clitoris) is suggestive of very high androgen levels (> 3 x normal), most likely d/t _______ .
androgen secreting tumor of the ovaries or adrenals.
List the androgens produced by the ovaries.
testosterone,
androstenedione,
dehydro-epi-andro-sterone (DHEA).
List the androgens produced by the adrenals.
testosterone,
androstenedione,
dehydroepiandrosterone (DHEA), and
dehydroepiandrosterone sulfate (DHEAS).
Elevated testosterone levels with normal DHEAS levels in a women under evaluation for hirsutism and virilization suggests ___ source of hyper-androgenism.
ovarian source
*Ovarian > > adrenal, hyperandrosteronism.
Elevated testosterone and DHEAS levels in a women under evaluation for hirsutism and virilization suggests ___ source of hyper-androgenism.
adrenal source of hyperandrogenism.
What are the common causes of hyperandrogenism and their differentiating features?
- PCOS (↑ LH—> ↑ testosterone —> ↑ estrogen)
- Non-classic CAH (↑ 17-hydroxyprogesterone level)
- Ovarian/adrenal tumors: old age, rapidly progressing; ↑↑↑ androgen levels.
- Hyper-PRL: amenorrhea, galactorrhea; ↑ PRL
- Cushing syndrome: non-suppressible dexa suppression test; ↑ 24 hr. ur free cortisol levels
- Acromegaly: ↑ IGF-1
What is the difference between classic and non-classic CAH, d/t 21-alpha hydroxylase (21 OHD) deficiency?
Classic CAH: d/t 98-100% 21 OHD deficiency
-At Birth, p/w ambiguous genitalia in female infants
-precocious puberty in male children.
Non-classic CAH: d/t PARTIAL 21OHD deficiency.
-p/w slowly progressing hyperandrogenism starting in adolescence-early adulthood.
For diagnosis, check 17-hydroxyprogesterone (17OHP) or ACTH stimulation test. See Image: myendoconsult.com.
Which anti-diabetic agents have a cardioprotective and weight loss profile?
GLP-1 Receptor Agonists (Exenatide, Liraglutide), and
SGLT-2 inhibitors (Canagliflozin, Empagliflozin).
MN: The GLP tides!
MN: SGLT gliflozins!
Which anti-diabetic agents have a low risk of hypoglycemia?
GLP-1 Receptor Agonists (Exenatide, Liraglutide), and
SGLT-2 inhibitors (Canagliflozin, Empagliflozin).
What is the MOA of GLP-1 Receptor agonists (exenatide, liraglutide)?
-Suppress Glucagon, and
-increase glucose dependent insulin release from the pancreas (hence, low r/o hypoglycemia).
-suppress appetite by delaying gastric emptying, and thus promote weight loss.
What is the MOA of SGLT-2 inhibitors (Canagliflozin, Empagliflozin)?
-Inhibit SGLT2 pump in renal PCTs–> Increasing glucose and Na+ excretion –> weight loss and mild diuresis.
*reduce HF-associated mortality, and
*reduce progression of diabetic nephropathy.
What is the MOA of dipeptidyl-peptidase 4 (DPP-4) inhibitors “gliptins”?
Inhibit DPP-4 –> inhibit GLP-1 degradation thus acting like GLP-1 receptor agonists but do not provide weight loss or cardio-protective benefits.
Which anti-diabetic agents are a/w weight gain and high risk of hypoglycemia?
Insulin,
sulfonylureas, and
Thiazolidinediones (“-glitazones”).
High estrogens levels increase TBG levels by _____ and _____.
by inhibiting TBG catabolism, and increasing TBG synthesis in the liver.
THINK: estrogens favor pregnancy, and pregnancy demands increase in THs; so estrogens facilitate increase in TBG so that more THs are available, raising total T4 (but free T4 and TSH remain normal).
Increased TBG levels are seen in which conditions/states?
-high estrogen states: pregnancy, OCPs, HRT,
-Estrogenic medications: tamoxifen
-Liver: Acute hepatitis, cirrhosis
-Hypothyroidism
Decreased TBG levels are seen in which conditions/states?
-High androgenic states: androgenic hormones
-Glucocorticoids/hypercortisolism
-Hypoproteinemia: nephrotic syndrome, starvation
-LIVER: chronic liver disease.
Displacement of thyroid hormones from binding proteins will initially _____ (? increase, decrease) free T4 levels, which will lead to decreased TH production d/t ____, ultimately leading to ____ total T4.
Displacement of thyroid hormones from binding proteins will initially increase free T4 levels, which will lead to decreased TH production d/t negative feedback to the hypothalamus/ant. pituitary ultimately leading to low total T4 (and normal free T3/T3 levels).
Which medications can displace T4 from its binding proteins in plasma?
salicylates,
Loop diuretic: furosemide,
heparin.
Preservation of morning erections in a man with decreased libido and failure to maintain erections during sexual intercourse most likely suggests _____ cause of erectile dysfunction.
psychogenic cause of ED.
A pt. with normal BMI p/w diabetes, joint pains, hypogonadism, and hepatomegaly, most likely has _____.
Hereditary hemochromatosis (HH)
How is hypogonadism induced in hereditary hemochromatosis?
d/t iron deposition in pituitary –>decrease in gonadotropins–> testicular atrophy and ↓ testosterone.
A 59 yr old female pt. on t/t for osteoporosis p/w AKI, hypercalcemia and metabolic alkalosis. What is the most likely disorder?
Milk-alkali syndrome;
d/t ingestion of calcium carbonate antacids to relieve heartburn caused by Alendronate t/t for osteoporosis.
What is the mechanism of AKI in milk-alkali syndrome?
Hypercalcemia leads to
-renal vasoconstriction–> ↓ GFR
-Ca2+-R activation in thick Al-LOH–> ↓ Na-K-2Cl cotransporter–> loss of Na+ & free water.
-Impaired activity of ADH–> loss of Na+ & free water.
All of the above–> hypovolemia–> AKI, and
–> increased reabsorption of HCO3 –> met. alkalosis.
What are some risk factors a/w development of milk-alkali syndrome?
-pre-existing CKD and concurrent use of thiazides, ACEIs, NSAIDS.
What are some additional lab findings in milk-alkali syndrome?
-suppressed PTH (d/t hypercalcemia)
-HypoPO4 (d/t intestinal binding by CaCO3)
-HypoMg2+ (d/t decreased renal reabsorption).
Difficulty combing hair or seating in and out of chair are signs of _______.
proximal muscle weakness.
Proximal muscle weakness can be seen in which conditions/disease states?
-Drugs: Glucocorticoid use
-Autoimmune diseases: Polymyositis/Dermatomyositis
-Endocrine: Hypo-/Hyperthyroidism, Cushing disease
-Neuromuscular: Myasthenia gravis, Lambert-eaton syndrome.
DTR are usually _____ (? increased, decreased, normal) in hyperthyroidism.
Increased (hyperreflexia) or frequently normal.
Peripheral motor neuropathy typically p/w _______ (? proximal, distal) muscle weakness and _____ (? increased, decreased, normal) DTRs with associated sensory symptoms.
distal muscle weakness and decreased DTR’s.
Hypoglycemia associated autonomic failure can be described as_____.
Reduced awareness of hypoglycemia and thus progressively worsening episodes of hypoglycemia d/t blunting of autonomic response in diabetics caused by recurrent and/or severe hypoglycemia.
In pts. with hypoglycemia associated autonomic failure, hypoglycemia awareness can be restored by _______.
by STRICTLY avoiding hypoglycemia.
In diabetics, intensive glycemic control to a target HbA1c of less than _____, and BP less than ______ mmHg is associated with reduced progression to DKD.
HbA1c < 7%, and BP < 130/80 mmHg
Which clinical tests are used for screening/evaluation for diabetic kidney disease (DKD)?
-Serum creatinine: s/o advanced DKD.
-*Urine spot albumin: creatinine ratio (uACR), or
24-hr urine protein.
-Urinalysis/microscopy: to rule out other causes.
*See image
** 24 hr. urine protein of 30-300 mg indicates albuminuria; 24 hr. urine protein of > 300 mg indicates severely increased albuminuria
Which drugs are a/w reduced progression to DKD?
-ACEIs/ARB’s (for strict BP control in diabetics).
-SGLT2 Inhibitors (most effective at GFR ≥ 30 mL/min/1.73 m2)
*SGLT2 inhibitors include “flozin’s” such as Dapagliflozin, Empagliflozin etc.
Normal serum osmolality is _____, and normal urine osmolality is ______.
normal serum osmolality: 275-290 mOsm/kg of H2O.
urine osmolality: 50-1200 mOsm/kg of H2O.
*Ur. osmolality < 300 mOsm/kg of H2O is considered low.
What is the difference between constitutional growth delay and Familial short stature?
See Image
How does plasma pH affect calcium homestasis?
In acidosis (low pH d/t ↑↑↑ H+ OR ↓↓↓ HCO3-, in ECS), MORE H+ are bound to albumin–> more Ca2+ in its active unionized form–> hypercalcemic state.
In alkalosis (high pH d/t ↓↓↓ H+ OR ↑↑↑ HCO3), LESS H+ are bound to albumin–> more Ca2+ can bind to albumin–> ↓ active unionized form–> hypocalcemic state (eg. can be seen in a severely tachypneic pt. who develops respiratory alkalosis freeing H+ binding sites on albumin which causes ionized ca2+ to quickly bind with albumin–> hypocalcemia.
SEE IMAGE for clarification: Reference: UWorld
