Fatigue Flashcards

1
Q

B.D. is a 50 YO male who has been feeling tired for the past 2-3 mo. The onset of tiredness is gradual. He can’t fall asleep at night b/c he is “thinking about stuff”. No matter how much he sleeps, he doesn’t feel energetic in the morning. He has stopped working out because of the lack of motivation and focal weakness & dyspnea. His mother committed suicide when he was 2 YO. Aside from obesity & trace ankle edema, he has a normal physical exam.

What are you thinking?

A

Depression

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2
Q

What are some important questions you should be asking when a patient presents with fatigue?

A

What does low energy mean to patient?

  • Obtain a sleep history to determine if the patient is excessively sleepy during the day
  • Inquire about weakness/loss of physical strength
  • Explore of the patient has decreased exercise tolerance due to dyspnea on exertion
  • Ask about mood symptoms
  • Review medication list
  • Review chronic medical conditions in the PMH that can cause fatigue
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3
Q

What is a typical physical exam of a patient with fatigue?

A
  • Pallor, tachypnea
  • BMI, neck circumference
  • Jaundice
  • Edema seen in CHF, CKD & liver disease
  • Pulmonary rales, displaced PMI, S3, JVD
  • Coarse hair, “hung up” reflexes, weight gain
  • Rash, synovitis of joints
  • Fever, lymphadenopathy, heart murmur
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4
Q

What is the differential diagnosis of fatigue?

A
  • Psychiatric: depression/anxiety, substance abuse
  • Sleep disorder: OSA, insomnia
  • Endocrine: thyroid, DM, adrenal insufficiency
  • Medication: side effects
  • Heme/Onc: anemia, cancer
  • Infections: HIV, endocarditis, TB, Lyme
  • Chronic Systemic Diseases: heart, lung, kidney, liver, neuro, rheum
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5
Q

What is the appropriate diagnostic studies for fatigue?

A
  • CBC
  • Sleep Study
  • BMP
  • LFTs
  • TSH & free T4
  • Cortisol
  • Echocardiogram
  • Age appropriate cancer screening
    • Colonoscopy, mammogram
  • HgA1c
  • Pulmonary function tests
  • Rheumatoid factor, ANA, ESR, CRP
  • CXR
  • Cortisol
  • HIV
  • Urine Drug Screen
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6
Q

What are the DSM-V criteria used to make the diagnosis of depression?

A
  • At least 5/9 symptoms, including depressed mood or anhedonia, lasting 2 weeks
  • SIG E CAPS
    • Sleep disturbance
    • Interest loss
    • Guilt or worthlessness
    • Energy loss or fatigue
    • Concentration problems
    • Appetite or weight change
    • Psychomotor agitation or retardation
    • Suicidal ideation
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7
Q

What are some other diagnostic considerations with depressed patients?

A
  • Persistent depressive disorder (dysthmia)
    • Chronic (2+ yrs) low grade (<5/9) depression
  • Seasonal affective disorder
    • Reduced daylight in temperate regions
  • Substance induced depression
    • Alcoholic
  • General medical condition
    • Pancreatic cancer
  • Bipolar disorder
    • Ask about past manic episodes
  • Normal grief/bereavement needs to be distinguished from depression
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8
Q

A 31 YO presents c/o depression. Which of the following rules out the possibility of the patient having major depressive disorder?

  • She has recently gained weight
  • Her sleep pattern has changed so that she wakes up in the morning before her alarm rings
  • She reports being depressed since her miscarriage 2 yrs ago
  • She was hospitalized for mania 10 yrs ago
  • She reports feeling like a worthless person
A

She was hospitalized for mania 10 yrs ago

If a patient only has 1 manic episode, no matter how many major depressive episodes, she is bipolar

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9
Q

What is the definition of a manic episode?

What are the common symptoms?

What is hypomania?

A
  • Distinct period of elevated, expansive or irritable mood & abnormally increased energy or activity lasting 1 wk
  • Symptoms
    • Distractibility
    • Irresponsible/hedonistic
    • Grandiose
    • Racing thoughts
    • Psychomotor agitation
    • Decreased neep for sleep
    • Pressured speech
  • Hypomanic lasts 4 days, not impaired in functioning or psychotic, not hospitalized
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10
Q

Upon completing the USMLE Step I a rising M3 runs out of the testing center shouting “I’m the smartest man in the world”. His roommate reports that for 2 wks he has stopped sleeping, been quite irritable & talks incessantly. He is brought in for evaluation after attempting to use his student loan money to buy a lamborghini. Which of the following is the most likely diagnosis?

  • Amphetamine intoxication
  • Bipolar disorder
  • Hyperthyroidism
  • Schizophrenia
A

Bipolar disorder

Meets criteria for manic episode

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11
Q

What are the characteristics of normal grief/bereavement?

A
  • Minor weight loss
  • Minor sleep disturbance
  • Mild guilty feelings
  • Illusions, thinking saw loved on in a crowd of people
  • Attempts to return to work & social activities
  • Crying/expressing sadness
  • Symptoms improved in a couple months, resolved at one year
  • Anti-depressants not indicated
  • Shock & denial if unexpected
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12
Q

What are the characteristics of complicated grief/depression?

A
  • Significant weight loss
  • Significant sleep disturbance
  • Intense feelings of guilt/worthlessness
  • Hallucinations or delusions of having contact w/ deceased person
  • Resumes few if any work or social activities
  • Contemplates or attempts suicide
  • Disabling symptoms for months, symptoms persisting after 1 year
  • Anti-depressants should be used
  • Failure to adjust to loss w/ changes in personality
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13
Q

Your 75 YO male patient just lost his wife of 52 yrs to cancer. If he experiences normal bereavement/uncomplicated grief which of the following responses would be normal?

  • Initial loss of appetite w/ mild weight loss
  • Feelings of worthlessness
  • Threatening suicide
  • Intense disabling grief for the next 2 yrs
  • Feelings of hopelessness
A

Initial loss of appetite w/ mild weight loss

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14
Q

Before you plan to administer pharmacotherapy to a diagnosed depressive patient, what else do you need to discuss & document in your note?

A

Documentation of Suicide Risk Assessment

  • Worst clinical outcome: suicide
  • Difficult to predict
  • Asking about suicidal ideation will not increase a patient’s risk or “give them the idea”
  • Failure to assess & document suicide risk assessment represents a significant malpractice risk
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15
Q

What are the risk factors for completed suicide?

*women try more, men succeed more*

A

SAD PERSONS

  • Sex male (Caucasian at higher risk)
  • Age teenagers or elderly
  • Depression
  • Previous suicide attempts in patient or FaHx
  • Ethanol or other drug use/addiction or impulsivity
  • Rational thinking absent, command hallucinations
  • Sickness, chronic medical condition or pain, 3+ meds
  • Organized plan w/ means (ex: has a gun)
  • No spouse (divorced, widowed)
  • Social supporting lacking, no children, church or job
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16
Q

Which statement encapsulates the highest risk factor for suicide completion?

  • His wife just left him on account of his drinking
  • He is an atheist w/ a gun
  • He is a 60 YO male police officer
  • He is feeling hopeless about his prostate cancer
  • He still walks w/ a limp after jumping off a bridge last year & you can see noose marks on his neck from his attempted hanging last week
A

Previous attempts is the biggest risk factor for suicide completion

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17
Q

What are some important factors to consider when selecting anti-depressants?

A
  • Cost/insurance formulary
  • Ease of administration/dosing frequency
  • Side effect profile
  • Potential drug interactions
  • Co-morbid medical conditions
  • Other approved drug indications that may apply to your patient
  • Toxicity in overdose in suicidal patients
  • Drugs used by family members
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18
Q

What are the SSRIs?

A
  • Fluoxetine
  • Sertraline
  • Paroxetine
  • Citalopram
  • Escitalopram
  • Fluvoxamine
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19
Q

SSRIs

  • Mechanism
  • Indications
  • Side effects/toxicity
A
  • 5-HT reuptake inhibitors
  • Onset of action: 4-6 wks
  • Indications
    • Depression
    • Anxiety disorders
    • Bulimia
  • Side effects
    • Nausea/vomiting
    • Sexual dysfunction
    • Serotonin Syndrmoe
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20
Q

What is Serotonin Syndrome?

How is it treated?

What are the symptoms?

A
  • Symptoms
    • High fever
    • Autonomic instability
    • Seizures
    • Confusion
    • Myoclonus
    • Flushing
  • Treated with cyproheptadine
  • May result from combining SSRI with:
    • MAOI, TCA, SNRI, meperidine, tramadol, St. John’s Wort
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21
Q

What should you consider when you have a fatigue patient w/o improvement?

A
  • Reconsider your differential diagnosis
  • Use an objective measure to evaluate for improvement
    • PHQ-9 Patient health questionnaire
    • Hamilton Rating Scale for Depression
  • Search the medical literature for a randomized trial to guide your treatment
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22
Q

What are the SNRIs?

A
  • Venlafaxine
  • Desvenlafaxine
  • Duloxetine
  • Milnacipran
  • Sibutramine
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23
Q

SNRIs

  • Mechanism
  • Indications
  • Side effects/toxicity
A
  • Inhibit serotonin & NE reuptake
  • Indications
    • Depression
    • Anxiety disorders
    • Pain from diabetic peripheral neuropathy
    • Fibromyalgia
    • Obesity
  • Side effects
    • Elevated BP
    • Nausea
24
Q

What are the TCAs?

A
  • Amitriptyline
  • Nortriptyline
  • Imipramine
  • Desipramine
  • Clomipramine
  • Doxepin
  • Amoxapine
25
Q

TCAs

  • Mechanism
  • Indications
  • Side effects/toxicity
A
  • Block the reuptake of NE & SE
  • Indications
    • Depression
    • OCD
    • Nocturnal enuresis
  • Side effects
    • Sedation
    • Orthostasis
    • Tachycardia
    • Urinary retention
    • Dry mouth
    • Risk of seizures
    • Coma
    • Cardiac arrhythmia
    • Death (overdose)
26
Q

__________ is a tricyclic antidepressant that inhibits the reuptake of NE more strongly than 5-HT.

A

Nortriptyline

27
Q

What are the MAOIs?

A
  • Tranlcypromine
  • Phenelzine
  • Isocarboxazid
  • Selegiline
28
Q

MAOIs

  • Mechanism
  • Indications
  • Side effects/toxicity
A
  • Increases the levels of amine NTs (NE, 5-HT, DA) by impairing degradation
  • Indications
    • Atypical depression
    • Anxiety
  • Side effects
    • Hypertensive crisis w/ tyramine ingestion & serotonin syndrome
    • Orthostasis
    • Weight gain
29
Q

A 40 YO male c/o persistent depression w/ weight gain & hypersomnia. You prescribe tranylcypromine. A few days later he is in the ER with fever, tachycardia, myoclonus & confusion. BP 130/60. Which of the following does NOT explain his presentation?

  • He had recently been taking fluoxetine
  • He received meperidine during a colonoscopy
  • He was drinking merlot & eating parmesan
  • He took tramadol & cyclobenzaprine after throwing out his back moving a sofa
  • He uses amitriptyline for diabetic neuropathy
A

He was drinking merlot & eating parmesan

Eating tyramine rich foods would lead to hypertensive crisis, not serotonin syndrome

30
Q

Buproprion

  • Use
  • Mechanism
  • Side effects
A
  • Approved for depression & smoking cessation
  • Increases NE & DA by inhibiting reuptake
  • Side effects
    • Insomnia
    • Headache
    • Seizures
  • No sexual side effects, unlike the serotonergic agents
31
Q

A 13 YO female is brought into the ER with a seizure. On exam her BMI is 15, she has lanugo & is bradycardic. She states she has been taking a friend’s anti-depressant for 1 wk to treat her low mood. Which drug has the girl most likely been taking?

  • Buproprion
  • Amitriptyline
  • Mirtazapine
  • Selegiline
  • Fluoxetine
A

Buproprion

carries the risk of seizures, especially in patients w/ eating disorders

32
Q

Mirtazapine

  • Mechanism
  • Side effects
A
  • α2-antagonist that increases release of NE & serotonin, 5-HT2 & 5-NT3 receptor antagonist
  • Side effects
    • Sedation
    • Increased appetite
    • Weight gain
    • Dry mouth
33
Q

Lithium

  • Use
  • Side effects
A
  • Approved for bipolar mania
  • Side effects
    • Tremor
    • Hypothyroidism
    • Nephrogenic diabetes insipidus
    • Teratogenic (Ebstein’s anomaly)
    • Acne
    • Leukocytosis
  • Narrow therapeutic window
34
Q

Buspirone

  • Mechanism
  • Use
  • Side effects
A
  • Serotonin receptor agonist
  • RDA approved for generalized anxiety disorder
  • Side effects
    • Dizziness
    • Drowsiness
    • Headache
    • Nausea
35
Q

A 48 YO woman comes to your office complaining of fatigue & tiredness. No obvious abnormalities on physical exam. BP normal, BMI not increased, menopause at 45, normal fasting blood glucose.

What are the top 3 endocrine diagnoses?

How would you test for them?

A
  • Adrenal Insufficiency
    • ACTH stimulation test
  • Hypothyroidism
    • TSH
  • Hypercalcemia
    • Comprehensive metabolic panel
36
Q

Your patient has hypercalcemia, hypophosphatemia, hypercalciuria & elevated PTH.

What is the diagnosis?

What are the treatments?

A

Primary Hyperparathyroidism

  • Do nothing
  • Remove parathyroid tumor (surgery)
  • Cinacalcet (Sensipar)
37
Q

What are the actions of PTH in the body?

*First Aid*

A
  • Increases bone resorption of Ca2+ & PO43-
  • Increases kidney resorption of Ca2+ in distal convoluted tubule
  • Decreases reabsorption of PO43- in proximal convoluted tubule
  • Increases 1,25-(OH)2D3 (calcitriol) production by stimulating kidney 1α-hydroxylase
38
Q

Fill in the blanks:

GI Ca2+ absorption = _____%

____% in duodenum & jejunum

Energy-dependent, cell-mediated process regulated by ___________.

Passive diffusional _________ pathway.

A

GI Ca2+ absorption = 20-70%

90% in duodenum & jejunum

Energy-dependent, cell-mediated process regulated by 1,25(OH)2D.

Passive diffusional paracellular pathway.

39
Q

How does the calcium receptor on PTH-secreting cells operate?

A
  • Increased serum Ca2+ normally decreases PTH
  • Elevated PTH in this patient means there is something wrong with the gland itself
40
Q

PTH controls Ca2+ balance directly & indirectly through _______.

A

1,25(OH)2D

41
Q

What are the signs & symptoms of hypercalcemia?

A
  • None
  • General
    • Fatigue & weakness
  • GI
    • Constipation
    • Nausea & vomiting
    • Abdominal pain (ulcers)
  • Bone
    • Osteoporosis
  • Renal
    • Polyuria & polydipsia
    • Renal stones
  • Neuro/cognitive
    • Impaired memory, confusion, depression
    • Drowsiness
    • Coma
42
Q

What is the diagnostic evaluation of hypercalcemia?

A
  • Patient history & review of old labs
  • Serum calcium
  • Albumin
  • Phosphorus
  • PTH
    • If low –> PTHrP
  • 24 hr urine calcium & creatinine
  • Abdominal X-ray
  • Bone mineral density study
43
Q

What are the differential diagnoses for Hypercalcemia?

A
  • PTH dependent (high or inappropriately not suppressed)
    • Primary hyperparathyroidism
    • Familial hypocalciuric hypercalcemia
    • Parathyroid carcinoma (very rare)
  • PTH independent (low)
    • Malignancy
    • Granulomatous disease
    • Vitamin D toxicity
44
Q

What is the epidemiology of primary hyperparathyroidism?

A
  • Common
    • 1/1,000 post-menopausal women
  • F:M = 2:1
  • 80-85% adenomas
  • 5-12% 2 or more adenomas
  • 8-15% hyperplasia
  • <1% carcinomas
45
Q

What are the Primary Hyperparathyroidism Familial Syndromes?

A
  • MEN1
  • MEN2
  • Familial Hyperparathyroidism
  • Familial Hyperparathyroidism & jaw tumors
46
Q

What is the pneumonic for primary hyperparathyroidism?

*First Aid*

A

“stones, bones, groans & psychiatric overtones”

  • Hypercalcemia
  • Hypercalciuria (renal stones)
  • Weakness & constipation (groans)
  • Osteitis fibrosa cystica (bones)
  • Depression (overtones)
47
Q

What are the indications for surgery in Primary Hyperparathyroidism?

A
  • Symptomatic hypercalcemia
  • Calcium 1 mg/dl above upper limit of nl
  • Nephrolithiasis
  • Osteoporosis/Fragility fractures
  • Renal insufficiency
  • Age <50 yrs
  • Patient preference
48
Q

Why can patients w/ primary hyperparathyroidism have hypercalciuria if PTH increases calcium reabsorption?

Why can they have hypophosphatemia?

A

Transport max for Ca2+ is saturated

PTH inhibits phosphate absorption in the proximal tubule

49
Q

What are the possible ways to do parathyroidectomy?

A
  • Conventional neck exploration
  • Minimally invasive parathyroidectomy
50
Q

Describe a minimally invasive parathyroidectomy

A
  • Small incision
  • Local anesthesia
  • Must have preoperative localization
    • Ultrasound
    • 99m-technetium sestamibi
    • CT scan
  • Intraoperative parathyroid hormone monitoring
    • Need to see 50% decrease in PTH after removal of suspected adenoma
51
Q

What is the medical management for hyperparathyroidism?

A
  • Optimize hydration
  • Avoid calcium sparing diuretics
  • Normal calcium intake
  • Optimize vitamin D status
  • Potential use of a calcimimetic
    • Calcium sensing receptor agonist
    • Cinacalcet (Sensipar)
52
Q

What are the mechanisms of hypercalcemia of malignancy?

A
  • PTH related protein (PTHrP)
  • Osteolytic bone metastases
  • Unregulated 1,25-dihydroxy-vitamin D production
  • Osteoclast activating factors
  • Ectopic PTH (rare)
53
Q

What is PTH related protein?

Where is it found?

Why is it important?

A
  • N-terminal homology w/ PTH
  • Not measured by PTH assays
  • Found in normal tissues
  • May be important in fetal development
  • Chr 12 (PTH on 11)
54
Q

What are the characteristics of MEN 1? (Wermer syndrome)

*First Aid*

A
  • 3 P’s
    • Parathyroid tumors
    • Pituitary tumors (prolactin or GH)
    • Pancreatic endocrine tumors (Zollinger-Ellison syndrome, insulinomas, VIPomas, glucagonomas)
  • Presentation: kidney stones & stomach ulcers
55
Q

What are the characteristics of MEN 2A? (Sipple Syndrome)

*First Aid*

A
  • 2 P’s
    • Pheochromocytoma
    • Parathyroid hyperplasia
  • Medullary thyroid carcinoma (secretes calcitonin)
  • ret gene mutation
56
Q

What are the characteristics of MEN 2B?

*First Aid*

A
  • 1 P = Pheochromocytoma
  • Medullary thyroid carcinoma (secretes calcitonin)
  • Oral/intestinal ganglioneuromatosis (mucosal neuromas)
  • Associated w/ marfanoid habitus
  • ret gene mutation