Fatigue Flashcards
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?
Depression
What are some important questions you should be asking when a patient presents with fatigue?
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
What is a typical physical exam of a patient with fatigue?
- 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
What is the differential diagnosis of fatigue?
- 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
What is the appropriate diagnostic studies for fatigue?
- 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
What are the DSM-V criteria used to make the diagnosis of depression?
- 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
What are some other diagnostic considerations with depressed patients?
- 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
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
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
What is the definition of a manic episode?
What are the common symptoms?
What is hypomania?
- 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
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
Bipolar disorder
Meets criteria for manic episode
What are the characteristics of normal grief/bereavement?
- 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
What are the characteristics of complicated grief/depression?
- 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
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
Initial loss of appetite w/ mild weight loss
Before you plan to administer pharmacotherapy to a diagnosed depressive patient, what else do you need to discuss & document in your note?
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
What are the risk factors for completed suicide?
*women try more, men succeed more*
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
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
Previous attempts is the biggest risk factor for suicide completion
What are some important factors to consider when selecting anti-depressants?
- 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
What are the SSRIs?
- Fluoxetine
- Sertraline
- Paroxetine
- Citalopram
- Escitalopram
- Fluvoxamine
SSRIs
- Mechanism
- Indications
- Side effects/toxicity
- 5-HT reuptake inhibitors
- Onset of action: 4-6 wks
- Indications
- Depression
- Anxiety disorders
- Bulimia
- Side effects
- Nausea/vomiting
- Sexual dysfunction
- Serotonin Syndrmoe
What is Serotonin Syndrome?
How is it treated?
What are the symptoms?
- 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
What should you consider when you have a fatigue patient w/o improvement?
- 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
What are the SNRIs?
- Venlafaxine
- Desvenlafaxine
- Duloxetine
- Milnacipran
- Sibutramine
SNRIs
- Mechanism
- Indications
- Side effects/toxicity
- Inhibit serotonin & NE reuptake
- Indications
- Depression
- Anxiety disorders
- Pain from diabetic peripheral neuropathy
- Fibromyalgia
- Obesity
- Side effects
- Elevated BP
- Nausea
What are the TCAs?
- Amitriptyline
- Nortriptyline
- Imipramine
- Desipramine
- Clomipramine
- Doxepin
- Amoxapine
TCAs
- Mechanism
- Indications
- Side effects/toxicity
- 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)
__________ is a tricyclic antidepressant that inhibits the reuptake of NE more strongly than 5-HT.
Nortriptyline
What are the MAOIs?
- Tranlcypromine
- Phenelzine
- Isocarboxazid
- Selegiline
MAOIs
- Mechanism
- Indications
- Side effects/toxicity
- 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
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
He was drinking merlot & eating parmesan
Eating tyramine rich foods would lead to hypertensive crisis, not serotonin syndrome
Buproprion
- Use
- Mechanism
- Side effects
- Approved for depression & smoking cessation
- Increases NE & DA by inhibiting reuptake
- Side effects
- Insomnia
- Headache
- Seizures
- No sexual side effects, unlike the serotonergic agents
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
Buproprion
carries the risk of seizures, especially in patients w/ eating disorders
Mirtazapine
- Mechanism
- Side effects
- α2-antagonist that increases release of NE & serotonin, 5-HT2 & 5-NT3 receptor antagonist
- Side effects
- Sedation
- Increased appetite
- Weight gain
- Dry mouth
Lithium
- Use
- Side effects
- Approved for bipolar mania
- Side effects
- Tremor
- Hypothyroidism
- Nephrogenic diabetes insipidus
- Teratogenic (Ebstein’s anomaly)
- Acne
- Leukocytosis
- Narrow therapeutic window
Buspirone
- Mechanism
- Use
- Side effects
- Serotonin receptor agonist
- RDA approved for generalized anxiety disorder
- Side effects
- Dizziness
- Drowsiness
- Headache
- Nausea
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?
-
Adrenal Insufficiency
- ACTH stimulation test
-
Hypothyroidism
- TSH
-
Hypercalcemia
- Comprehensive metabolic panel
Your patient has hypercalcemia, hypophosphatemia, hypercalciuria & elevated PTH.
What is the diagnosis?
What are the treatments?
Primary Hyperparathyroidism
- Do nothing
- Remove parathyroid tumor (surgery)
- Cinacalcet (Sensipar)
What are the actions of PTH in the body?
*First Aid*
- 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
Fill in the blanks:
GI Ca2+ absorption = _____%
____% in duodenum & jejunum
Energy-dependent, cell-mediated process regulated by ___________.
Passive diffusional _________ pathway.
GI Ca2+ absorption = 20-70%
90% in duodenum & jejunum
Energy-dependent, cell-mediated process regulated by 1,25(OH)2D.
Passive diffusional paracellular pathway.
How does the calcium receptor on PTH-secreting cells operate?
- Increased serum Ca2+ normally decreases PTH
- Elevated PTH in this patient means there is something wrong with the gland itself
PTH controls Ca2+ balance directly & indirectly through _______.
1,25(OH)2D
What are the signs & symptoms of hypercalcemia?
- 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
What is the diagnostic evaluation of hypercalcemia?
- 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
What are the differential diagnoses for Hypercalcemia?
-
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
What is the epidemiology of primary hyperparathyroidism?
- 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
What are the Primary Hyperparathyroidism Familial Syndromes?
- MEN1
- MEN2
- Familial Hyperparathyroidism
- Familial Hyperparathyroidism & jaw tumors
What is the pneumonic for primary hyperparathyroidism?
*First Aid*
“stones, bones, groans & psychiatric overtones”
- Hypercalcemia
- Hypercalciuria (renal stones)
- Weakness & constipation (groans)
- Osteitis fibrosa cystica (bones)
- Depression (overtones)
What are the indications for surgery in Primary Hyperparathyroidism?
- Symptomatic hypercalcemia
- Calcium 1 mg/dl above upper limit of nl
- Nephrolithiasis
- Osteoporosis/Fragility fractures
- Renal insufficiency
- Age <50 yrs
- Patient preference
Why can patients w/ primary hyperparathyroidism have hypercalciuria if PTH increases calcium reabsorption?
Why can they have hypophosphatemia?
Transport max for Ca2+ is saturated
PTH inhibits phosphate absorption in the proximal tubule
What are the possible ways to do parathyroidectomy?
- Conventional neck exploration
- Minimally invasive parathyroidectomy
Describe a minimally invasive parathyroidectomy
- 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
What is the medical management for hyperparathyroidism?
- Optimize hydration
- Avoid calcium sparing diuretics
- Normal calcium intake
- Optimize vitamin D status
- Potential use of a calcimimetic
- Calcium sensing receptor agonist
- Cinacalcet (Sensipar)
What are the mechanisms of hypercalcemia of malignancy?
- PTH related protein (PTHrP)
- Osteolytic bone metastases
- Unregulated 1,25-dihydroxy-vitamin D production
- Osteoclast activating factors
- Ectopic PTH (rare)
What is PTH related protein?
Where is it found?
Why is it important?
- 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)
What are the characteristics of MEN 1? (Wermer syndrome)
*First Aid*
-
3 P’s
- Parathyroid tumors
- Pituitary tumors (prolactin or GH)
- Pancreatic endocrine tumors (Zollinger-Ellison syndrome, insulinomas, VIPomas, glucagonomas)
- Presentation: kidney stones & stomach ulcers
What are the characteristics of MEN 2A? (Sipple Syndrome)
*First Aid*
-
2 P’s
- Pheochromocytoma
- Parathyroid hyperplasia
- Medullary thyroid carcinoma (secretes calcitonin)
- ret gene mutation
What are the characteristics of MEN 2B?
*First Aid*
- 1 P = Pheochromocytoma
- Medullary thyroid carcinoma (secretes calcitonin)
- Oral/intestinal ganglioneuromatosis (mucosal neuromas)
- Associated w/ marfanoid habitus
- ret gene mutation
