Endo Flashcards
1
Q
Type of inheritance in familial hyper cholesterolemia?
A
Autosomal co-dominance with high penetrance.
2
Q
What is the defect in familial vs polygenic hyper cholesterolemia?
A
Familial: Defect in LDL receptor on cell membrane.
Polygenic: Defect in cholesterol metabolism.
3
Q
Labs in familial vs polygenic hypercholestrolemia?
A
Both show high TC + LDL
4
Q
Clinical presentation in familial vs polygenic hyper cholesterolemia?
A
Familial:
Lipid deposits => tendinous xanthomatosis + xanthelasmata + arcus cornealis
Polygenic:
Asymptomatic
5
Q
Risk of CAD in familial hypercholestrolemia. (Heteo vs homo)
A
Heterozygotes: 50% risk of MI in men by age 30
Homozygotes: CAD and vascular disease early in childhood
6
Q
Rx of familial (hetero/homo) vs polygenic hypercholestrolemia.
A
Hetero Familial: HMG-coA reductase inhibitors + niacin / ezetimibe / bile acid sequestrant
Homo familia: portocaval shunt or LDH apheresis + niacin / atorvastatin
Polygenic: HMG-CoA reductase inhibitors, ezetimibe, niacin or bile acid sequestrant
7
Q
Causes of 2ry hypercholestrolemia?
A
Endo: hypothyroidism Renal: nephrotic syndrome Hepatic: PBC Immune: monoclonal gammopathy Diet: anorexia nervosa Drugs: cyclosporin + carbamazepine + anabolic steroids.
8
Q
What are the syndromes of 1ry hyper-Triglyceridemia?
A
- Familial lipoprotein lipase deficiency
2. Familial hyper-triglyceridemia
9
Q
Pathophysiology of familial lipoprotein lipase deficiency vs familial hyper-triglyceridemia?
A
Familial lipoprotein lipase: deficiency or lipoprotein lipase or its co-factor.
Familial hyper-TG: increased hepatic VLDL production or decreased VLDL clearance.
10
Q
Lab findings in familial lipoprotein lipase vs familial hyper-TG?
A
Familial lipoprotein lipase: high TG, VLDL, chylomicrons.
Familial hyper-TG: high TG + VLDL
11
Q
Sx of familial lipoprotein lipase vs hyper-TG?
A
1.Familial lipoprotein lipase: Hepatosplenomegaly + splenic infarcts => anemia, granulocytopenia, thrombocytopenia. Pancreatitis Lipemia retinalis Eruptive xanthomata
- Familial hyper-TG:
Premature CAD
Syndrome of obesity, high TG, high insulin, high urea.
12
Q
Treatment of familial lipoprotein lipase vs familial hyper-TG?
A
- Familial lipoprotein lipase:
Fat intake
13
Q
When is hyper-triglyceridemia associated with pancreatitis?
A
When Serum TG > 1000 mg/dL
14
Q
Drugs cause 2ry hyper-Triglyceridemia?
A
Alcohol Steroids Estrogen OCP Hydrochlorothiazide Retinoic acid Anti-retrovials Atypical antipsychotics
15
Q
Side effects of atypical antipsychotics?
A
Dyslipidemia
HTN
Hyperglycemia
Metabolic syndrome
16
Q
Types of combined hyperlipidemia?
A
Both 1ry.
- Familial combined hyperlipidemia
- Dysbetalipoproteinemia
17
Q
Path physiology of familial combined hyperlipidemia vs Dysbetalipoproteinemia?
A
- Familial combined:
Excess hepatic synthesis of ApoB - Dysbetalipoproteinemia: abnormal ApoE
18
Q
Labs in familial combined hyperlipidemia vs Dysbetalipoproteinemia?
A
- Familial combined: high TC, TG, VLDL, LDL
2. Dysbetalipoproteinemia: high TC, TG, VLDL, IDL
19
Q
Sx of familial combined hyperlipidemia vs Dysbetalipoproteinemia?
A
- Familial combined:
CAD
Xanthelasma - Dysbetalipoproteinemia:
Tuberous, eruptive, palmar xanthomata
Impaired glucose tolerance
CAD + PAD.
20
Q
Rx of familial combined hyperlipidemia vs Dysbetalipoproteinemia?
A
Both: Weight reduction Low fat, carbs intake + stop EtOH HMG-CoA reductase inhibitors Niacin, fibrates
21
Q
Types of dyslipidemias?
A
Hyper cholesterolemia
Hyper triglyceridemia
22
Q
When to screen to dyslipidemias?
A
- Healthy men at 40 women after menopause.
- Children with FHx
- At any age if patient has:
- DM
- HTN
- Smoker
- Obese
- Sx of hyperlipidemia (xanthomata, arcus cornealis)
- FHx of premature CAD
- Atherosclerosis
- Rheumatoid arthritis / SLE / psoriasis
- HIV on HAART
- CKD (GFR
23
Q
What’s the effect of high LDL on CAD risk?
A
Each 40mg/dL (1 mmol/L) reduction in LDL = 20% relative risk reduction in CAD.
24
Q
Labs for statin F/U?
A
- Liver profile: before Rx and after initiation.
- Lipid profile: after stabilization check annually.
- CK at baseline + if patient complains of myalgia.
NB: D/C statins if CK>10x upper limit.
25
Define Diabetes Mellitus.
Inappropriate hyperglycemia 2ry to insulin deficiency and/or reduction in its biological effectiveness.
26
Types of primary hypertricholestrolemia?
Familia and polygenic
26
Age of indent in T1DM + T2DM?
T1DM less than 30
| T2DM more than 40
27
Psychophysiology of T1DM vs T2DM?
1. T1DM:
Autoimmune
Genetic, immune, environmental factors => B-cell destruction via infiltration with lymphocytes.
80% cells destroyed before Sx
2. T2DM:
- multi factorial
Impaired insulin secretion, peripheral insulin resistance and excess hepatic glucose production.
NB: resistance 2ry to receptor abnormalities.
28
Genetics in T1DM vs T2DM
1. T1DM:
Associated w/ HLA-DR3 + DR4 + DQ
2. T2DM:
No HLA association
29
What acute complications occur in diabetes?
Diabetic ketoacidosis DKA
| Hyperosmolar hyperglycemic state HHS
30
Path physiology of DKA vs HHS
1. DKA:
Lack of insulin => high stress hormones (glucagon, cortisol, catecholamines, GH).
Stress hormones => cont hepatic glucose > hyperglycemia > osmotic diuresis > dehydration + electrolyte imbalance (low Na | high K)
FFA metabolism to make glucose => ketoacids > metabolic acidosis.
Sever hyperglycemia + ketone = glucosuria + ketonuria.
2. HHS
After stress => High stress hormones
Stress hormones => high hepatic glucose production > hyperglycemia > osmotic diuresis > dehydration.
Bcz insulin is present => no need for lipolysis => no ketones.
31
Explain decreased LOC / coma in DKA + HHS
Volume contraction => renal insufficiency > hyperglycemia + high osmolality > fluid shift from neurons to ECF > coma.
32
Sx of DKA vs HHS
```
1. DKA:
Polyuria, polydipsia, polyphagia + fatigue + N/V
Abdominal pain
Dehydration
Low LOC / Coma
Fruity smelling breath
Kussmaul's respiration
```
```
2. HHS:
Polyuria, polydipsia, weakness
Dehydration
Low LOC / coma
Kussmaul's respiration
Hx low fluid intake + ingestion of glucose containing food.
```
33
Labs of DKA vs HHS?
| Serum, ABG, urine
```
1. DKA:
Serum =>
- hyperglycemia >200
- pseudohyponatremia
- high K
- low HCO3
- high BUN + Cr
- low PO4
- High osmolality
```
ABG =>
Metabolic acidosis with high AG
+/- respiratory alkalosis or metabolic alkalosis (sever vomiting)
Urine =>
Glucosuria + ketonuria
```
2. HHS:
Serum =>
- hyperglycemia > 200
- hypo or hyper natermia.
- high osmolality
```
ABG =>
Normal unless the stressor causes acidosis eg: lactic acidosis in MI.
Urine =>
Glycosuria
34
Rx of DKA vs HHS?
1. DKA:
- ABC + monitor acidosis with ABG
- Rehydration:
• 1st 2 hr > NS at 1L/h
• Then 0.45 NaCl at 300-400 ml/hr
• If glucose ~250 => start D5W
- Insulin:
• maintain on 0.1 U/kg/h regular insulin
• DO NOT use with low K.
• Check glucose hourly.
- K replacement:
• develops 2ry to insulin
• in K hold insulin + K 40 meq/L
• if K 3.5 - 5 => KCL 20-40 meq/L IV
NB: use HCO3 if PH 7.1
```
2. HHS:
ABC
- Rehydration:
• NS 1L/hr for 1 hour.
• Then check Na:
high/normal Na > 0.45 NaCl at 4-14 ml/kg/hr
Low Na > cont NS at 4-14 ml/kg/hr
• If glucose ~250 => switch to D5W
```
- Insulin
• Loading dose = 0.1 U/kg bolus
• Infusion regular insulin at 0.1 U/kg/hr
• check glucose hourly
- K replacement
• K
35
Causes of ketoniema?
DKA
Alcohol ketosis
Starvation
36
Complications of DM (macro + micro)
1. Macrovasculr:
• CAD:
3-5x higher risk of MI
• stroke:
2.5x higher risk.
• PAD:
Intermittent claudication, intestinal angina, foot ulcers.
30x higher risk of foot gangrene + 15x higher risk of amputations
2. Micro vascular:
• Retinopathy:
T1DM => 25% affected at 5yr + 100% at 20 yrs
T2DM => 25% affected at Dx + 60% at 20 yrs
• Nephropathy:
T1DM => 20-40% after 5-10 yr
T2DM => 4-20%
• Neuropathy
50% of T1DM + T2DM at 10yrs
Sensory + motor + autonomic
37
What's C-peptide? How does it distinguish endogenous vs exogenous insulin?
1. It's peptide released when pro-insulin cleaved into insulin
2. High C-peptide = endogenous
Low C-peptide = exogenous
38
Causes of hypoglycemia?
1. Fasting:
- hyperinsluinism:
Exogenous insulin
Sulfonylurea or meglitinide reaction
Pentamidine
Autoimmune hypoglycemia
Insulinoma
```
- Non-hyperinsluinism:
Hepatic dysfunction
Renal failure
High cortisol
Alcohol
Non-pancreatic tumor
```
```
2. Post-prandial:
GI tract
Occult DM
Fructose intolerance
Galactosemia
Newborn of DM mom
```
39
What's a pituitary adenoma?
Benign slow growing tumor of pituitary gland
39
Sx of hypoglycemia? (Whippel's Triad).
1. Glucose ranges less 45-40 (2.2-2.5)
2. Neuroglycopenic Sx
3. Rapid relief after glucose
40
Classification of pituitary adenoma?
Microadenoma 1cm
Functional = secretory
Non-functional = not secretory
41
Sx of pituitary adenoma?
1. Mass effects
Headache
Bitemporal
42
Investigation of pituitary adenoma?
Hormones tests (PRL, TSH, 8AM cortisol, FSH/LH, IGF-1, fasting glucose)
MRI w/o contrast (image of choice)
Visual field test
43
Causes of hypopituitarism? (8 I's)
8 I's:
- Invasive:
Tumor, craniopharyngioma, cysts (Rathke's | dermoid | arachnoid)
- Infarction:
• Sheehan
• apoplexy
- Inflammatory:
Sarcoidosis, histiocytosis, hemochromatosis
- Infectious:
TB, syphilis, toxo
- immune: autoimmune destruction
- iatrogenic
- Injury
- Idiopathic
44
Investigation for hypopituitarism?
Triple bolus test
45
Sx of hyperthyroidism?
THYROIDISM:
```
Tremor
HR up
Yawning (fatigue)
Restlessness
Oligomenorrhea/amenorrhea
Intolerance to heat
Diarrhea
Irritability
Sweating
Muscle waiting / weight loss.
```
46
DDx of thyrotoxicosis?
1. Hyperthyroidism:
- Graves Dz
- Toxic nodular goiter
- Toxic nodule
2. Thyroiditis:
- subacute, Silent, post-partum
3. Extra-thyroidal hormone:
- Endogenous: ovarian teratoma, met follicular carcinoma
- Exogenous: drugs
4. Excessive Thyroid production:
- pituitary thyrotophoma
- pituitary T4 receptor resistance
- high hCG (pregnancy)
47
Define Graves Disease?
Autoimmune disorder with antibodies to TSH receptor leading to hyper thyroidism
48
Genetics of Graves' disease?
Associated with HLA-B8 + DR3
49
What's the most common cause of thyrotoxicosis?
Graves' disease
50
Pathophysiology of Graves Disease?
- autoimmune defect in T- suppressor cells
| B lymphocytes > TSI > stimulate gland.
51
What triggers Graves' disease?
Postpartum state
Viral or bacterial infection
Drug: iodine or lithium
Glucocorticoids withdrawal.
52
Sx of Graves' disease?
```
Sx of thyrotoxicosis
Diffuse goiter + bruit
Ophthalmology
Dermopathy
Acropachy
```
53
What ophthalmopathy seen in Graves' disease by order? (NO SPECS)
- No signs
- Only: Lid lag + lid retraction
- Soft tissue: puffiness, conjunctival injection, chemosis
- Proptosis/exophthalmos
- Extra ocular (diplopia)
- Corneal abrasion (cuz can't close eyes)
- Sight loss.
54
What causes ophthalmopathy and dermopathy in Graves' disease?
Deposition of glycosaminoglycan
55
Rx of Graves' disease
1. Anti-thyroid drugs = thionamides.
PTU or Methimazole
Cont until remission (at 6 mo)
NB: MMI better than PTU cuz longer action.
2. Thyroid ablation if PTU/MMI fail.
3. Sx treatment via B-blockers
4. Thyroidectomy for large thyroid.
Risk of vocal cord palsy.
56
Mechanism of action of PTU + methimazole?
Inhibit peroxidase-catalyzed reactions => no iodide organification => no iodotyrosine coupling.
PTU also stops peripheral deiodination of T4 to T3.
57
Side effects of PTU + Methimazole?
Hepatitis
Agranulocytosis
Fever / arthralgia
Rash
MMI is teratogenic in 1st trimester
58
Natural Hx of subacute thyroiditis?
Initial thyrotoxic state > hypothyroidism > euthyroidism.
59
Pathophysiology of subacute thyroiditis?
Acute inflammation by giant cells + lymphocytes => disruption of thyroid follicles => release of stored hormones.
60
Subtypes of subacute thyroiditis?
1. Painful (De quervian's)
| 2. Painless (silent)
61
Causes of subtypes of subacute thyroiditis?
1. Painful:
• viral or URTI
• granulomatous thyroiditis
2. Painless
• post-partum
• autoimmune
• lymphocytic.
62
Sx of painful subacute thyroiditis?
- thyroid, ear, jaw, occipital pain.
| - fever + malaise in granulomatous
63
When dose post-parting thyroiditis occur?
2-3 mo after delivery
64
Rx of subacute thyroiditis?
1. Painful:
• High dose NSAIDs
• Prednisone for sever pain, fever, malaise.
- iodinated contrast agents (ipodate | iopanic acid)
- BB for Sx hyperthyroid
- thyroxin if hypothyroid
65
What is the prognosis in subacute thyroiditis thyroiditis?
Full recovery, permanent hypothyroid in 10%.
66
Rx of toxic nodular goiter?
1. Surgical removal
2. PTU or MMI
3. Radioactive ablation
67
Define thyroid storm
Acute exacerbation of all symptoms of thyrotoxicosis in a life-threatening state.
68
Patio physiology of thyroid storm
Excessive stimulation of thyroid hormones in hyperthyroid patient due to stress (infection, trauma, surgery)
69
Signs of thyroid storm?
```
Hyperthyroidism
Extreme hyperthermia
Tachycardia + CHF
Vomiting + diarrhea
Vascular collapse + shock
Delirium + coma
```
70
Rx of thyroid storm?
PTU is drug of choice
- give iodide 1hr after PTU
- DXS 2-4 mg IV q6hr for 48hr.
71
What is the most common cause of primary hypothyroidism?
North America: Hashimoto's
| World: low iodine
72
What are forms of Hashimoto's thyroiditis? (2)
1. Goitrous
| 2. Atrophic
73
Pathophysiology of Hashimoto's?
Defect in T suppressors => cell medicated destruction of thyroid follicles via b lymphocyte antibodies.
Ab against => thyroglobulin, thyroid peroxidase, TSH receptor
74
Association with Hashimoto's?
Down's syndrome
Turner's
Cytotoxic T lymphocyte associated protein 4 (CTLA-4)
75
What is sick euthyroid syndrome?
Changes in circulating thyroid hormones in patients with serious illness not due to intrinsic thyroid or pituitary disease
76
What is pheochromocytoma?
It is a catecholamine secreting tumor derived from chromaffin cells of the sympathetic system in adrenal medulla.
77
What is the classic triad of pheochromocytoma? (PHE)
Palpitation, headache, episodic sweating.
78
What are the associations with pheochromocytoma?
1. Multiple endocrine neoplasia II (Men IIA + IIB)
2. Von Hippel-Lindau
3. Paraganglioma
4. Neurofibromatosis-1
79
Sx A pheochromocytoma?
1. HTN or orthodontic hypotension
2. Classic triad palpitation, sweating, headache.
3. Others: tremor, anxiety, N/V, blurred vision
80
Labs in pheochromocytoma
1. Urine catecholamines:
High free catecholamines and Metanephrines.
2. CT abdomen (if -ve => total body)
81
Rx of pheochromocytoma?
Surgical removal is curative.
82
Preoperative preparation of pheochromocytoma?
1. Alpha blockers for BP control
2 Beta blockers for HR control
3. Metyrosine + phenoxybenzamine.
4. Volume restoration.
5. Re-screen urine 1-3 mo post-op
83
Causes of primary secondary and tertiary Hyperparathyroidism?
1. Primary:
Parathyroid adenoma
Lithium
Carcinoma
2. Secondary:
Partial PTH resistance (renal failure + osteomalacia).
3. Tertiary:
Irreversible clonal outgrowth of parathyroid gland.
84
Most common cause of hypercalcemia (healthy bs hospitalized)?
- Healthy = Primary Hyperparathyroidism.
| - Hospitalized = Cancer.
85
Rx of primary Hyperparathyroidism?
Surgery is curative only if symptomatic
86
When is surgery recommended for Asymptomatic 1ry Hyperparathyroidism?
if has 1 ore more of the following:
* Ca is 1.0 mg/dL above upper limit
* Cr clearance
87
Ca levels in hypercalcemia (corrected + ionized).
Corrected > 10.5 mg/dL (2.6 mmol/L)
Ionized > 5.4 mg/dL (1.35 mmol/L)
88
How to correct Ca?
Measured Ca + 0.02 (40-albumin)
NB: for every decrease in albumin by 10, increase of Ca by 0.2
89
Symptoms of hypercalcemia?
Bones stones groans and psychic overtones
GI: N/V, constipation
Renal: polyuria, stones, failure.
MSK: weakness, bone pains, gout/pseudo gout
Psych: anxiety, depression
Neuro: hypotonia, hyporeflexia, myopathy
CVS: HTN, arrhythmia, short QT
90
Rx of acute hypercalcemia?
1. Increase urinary excretion:
• volume expansion = NS 500 cc/hr.
• loop diuretics (only if hypervolemic
• Calcitonin
2. Diminish bone resorption:
• Bisphosphonate (Rx of choice)
3. Decrease GI absorption:
• Corticosteroid:
Most useful in vitD toxicity, granulomatous disease.
4. Dialysis
Sever malignancy-associated hypercalcemia
91
Causes of low PO4?
| GI, Randal, MSK
1. GI:
Antacid
Alcohol
Malabsorption
```
2. Renal:
Hyperparathyroidism
Rickets
Fanconi
Multiple myeloma
Recovery of metabolic acidosis
```
3. MSK:
Hungary bone syndrome
92
Normal level of PO4?
2.4 - 4.1 mg/dL (0.85-1.45 mmol/L)
93
Normal Mg levels?
1.7 - 2.1 mg/dL (0.7 -0.85 mmol/L)
94
Sx of low Mg?
```
Chvostek + Trousseau
Torsades de pointes
ECG: wide QRS, long PR, T-wave
Seizure
Paralysis.
```
