Best Doctors Experts Dr. Martin Samuels, Dr. Harris McIlwain and Dr. Michael Morse discuss their own mistakes in diagnosing patients presenting with fatigue. The panel will discuss pitfalls when diagnosing symptoms of fatigue and offer tips for identifying conditions related to fatigue such as: Symptoms of hypercalcemia: - polyuria, polydipsia, anorexia, nausea, constipation, include weakness, confusion, coma Causes of hypercalcemia: - primary hyperparathyroidism and malignancy (bone metastases, humeral hypercalcemia of malignancy, myeloma) are the most common; - others: thyrotoxicosis, hypervitaminosis D, Milk alkali syndrome, adrenal insufficiency, thiazides, immobilization, sarcoidosis Chronic Fatigue: - Chronic fatigue – over 6 months - 60% or more medical or psychiatric - Psychiatric illness—major depression, anxiety/panic disorder, somatization disorder - 5% Clarified by lab studies

1. Best Doctors
Physician Webinars
Case Studies in Diagnostic Errors:
Our Errors in Diagnosing Fatigue

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Our Errors in Diagnosing Fatigue
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3. Disclosure Information
Our Errors in Diagnosing Fatigue
The panelists on today’s webinar have the following financial relationships to disclose:
• Dr. Harris McIlwain has the following relationships to disclose:
– Speakers’ Bureau: Takada, Warner Chilcott
• Dr. Michael Morse has the following relationships to disclose:
– Grant/Research Support: BMS, Novartis, Precision Biologics
– Speakers’ Bureau: Genentech, Novartis, Onyx, Bayer, Amgen, Prometheus
– Advisory Committee: Genentech, Amgen, Sanofi
• Dr. Martin A. Samuels has no relevant financial relationships to disclose
• None of the Best Doctors staff who assisted in preparing the content of this webinar
have relevant financial relationships to disclose
• No reference will be made to off label use and/or investigational use of
pharmaceuticals/devices in this webinar

4. Harris McIlwain, MD
Internal Medicine, Rheumatology, Geriatric Medicine
McIlwain Medical Group
Michael Morse
Department of Medicine, Medical Oncology Division
Specializing in Gastrointestinal Oncology
Duke University School of Medicine
Martin Samuels, MD, MSc, FAAN, MACP, FRCP
Chairman, Department of Neurology, Brigham and Women’s Hospital
Professor of Neurology, Harvard Medical School
Moderator and Panel

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6. Harris McIlwain, MD
Internal Medicine, Rheumatology, Geriatric Medicine
McIlwain Medical Group
Michael Morse
Department of Medicine, Medical Oncology Division
Specializing in Gastrointestinal Oncology
Duke University School of Medicine
Martin Samuels, MD, MSc, FAAN, MACP, FRCP
Chairman, Department of Neurology, Brigham and Women’s Hospital
Professor of Neurology, Harvard Medical School
Moderator and Panel

7. Dr. Martin Samuels
Fatigue
• 79 y/o woman with 5 months of progressive fatigue.
• Difficulty climbing stairs and rising from chair 5
months ago.
• Difficulty combing her hair and began using walker 1
month ago.
• Problem progressed to point where walking was very
difficult; admitted to the hospital

8. History
• hypertension, hyperlipidemia, stroke in 1995 without residual
symptoms, stable angina and diastolic dysfunction, osteoarthritis
s/p R shoulder and hip arthroplasty.
• During current illness noted bilateral leg swelling, worsened chronic
hip pain, 20lb weight gain, and easy bruising; newly diagnosed with
diabetes shortly after admission to hospital.
• No fevers, night sweats, shortness of breath, chest
pain, rash, alopecia, constipation/diarrhea, cold/heat
intolerance, numbness, incontinence, dysphagia, diplopia, or
dysarthria.
• Medications:
furosemide, KCl, lisinopril, atenolol, imdur, norvasc, celexa, insulin.
• SH: No smoking, drugs, or alcohol.
• FH: Father died of MI at age 53.

9. Physical Exam
• Vital signs: normal
• General: obese, facial edema, 2+ pitting edema in distal arms and
legs, multiple ecchymoses on arms
• MS: poor attention and delayed recall.
• CN: no bulbar weakness.
• Motor: normal tone; decreased deltoid bulk bilaterally. Moderate
proximal weakness upper and lower extremities; full distal power.
No fasciculations. Decreased direct muscle excitability
• Reflexes: slightly diminished and slow in upper extremities, normal
at knees, absent at ankles, no Babinski signs
• Sensation: decreased pinprick in feet.
• Coordination: normal in upper extremities.
• Gait: needs assistance to stand and can only take a few steps.

10. Labs
• Labs: 143 | 105 | 29 /
------------------ 174
3.5 | 34 | 1.0
• AST 35, ALT 92, Alk Phos 72, TBili 0.9, albumin 2.1
• CK 29
• ESR 9
• MRI Spine unremarkable
• EMG/NCS normal

11. Diagnosis?

12. Hypothyroidism

13. TSH = 1.5 (normal)

14. More History
On re-examination, found that patient had
started waxing her upper lip several months
ago for the first time. She had a plethoric
and swollen face. Her IV sites refused to
heal.

15. More Testing
• 8AM cortisol = 71 (nl 8-25)
• dexamethasone suppression test (1mg dex at
11PM)  subsequent 8am cortisol 71
• 24 hr urine free cortisol 1459 (nl range 4-50)

16. More Test Results…
• ACTH 120 (nl 5-27)
• MRI Brain: slightly delayed enhancement in
two small areas of pituitary gland

17. Cushing Disease Take-aways
Basophilic adenoma of the pituitary
Treatment is transphenoidal hypophysectomy
Can imitate hypothyroidism
Diabetes and poor wound healing
are clues to the correct diagnosis

18. Dr. Michael Morse
Fatigue due to iron deficiency anemia
due to an undiagnosed colon cancer
• 46 yo woman complained of 6 mo of “tiredness” by the end of
her workday;
• mild dyspnea climbing stairs she attributed to obesity
• Reported history of restless legs
• Exam was unremarkable; Chewing ice chips.
• Labs: normal TSH, Hgb 11.8 MCV 78
• Initially thought to have fatigue from her obesity and anemia
from menses
• 6 months later diagnosed with colon cancer of the cecum
when she became more anemia and GI work-up performed.

19. Take away points:
• Colon cancer symptoms: crampy abdominal pain, change in
stool habits, blood in stool are not always present with early
tumors or cecal tumors.
• Iron deficiency anemia can be a presenting sign of colon
cancer
• Signs of iron deficiency include fatigue, pica (especially
pagophasia = the pathologic consumption of ice), and
secondary restless leg syndrome

20. Worsening Fatigue in a patient with chronic
hepatitis C/cirrhosis due to an undiagnosed (due
to lack of screening) hepatocellular carcinoma
• 67 yo man with hypertension, diabetes mellitus, CAD, and
cirrhosis with a prior diagnosis of Hepatitis C when he was
noted to have elevated LFTs on a physical exam
• Had tried interferon but was noncompliant
• Presented with worsening fatigue, increased abdominal
distension, peripheral edema
• Labs: anemia, elevated transaminases and bilirubin
• Initially observed
• Diagnosed with HCC on CT scan after presenting 3 months
later with worsening abdominal pain.

21. Take away points
• Fatigue is present in 50-100% of hepatitis C infected
individuals
• AASLD recommends screening for HCC in: Cirrhosis (any
etiology) or HBV+: older, family history, cirrhosis; Surveillance
for HCC should be performed with ultrasonography (level II);
Screening should occur every 6-12 months

22. Fatigue due to hypercalcemia in a patient with a
gastric cancer with bone metastases and
humoral hypercalcemia of malignancy.
• 68 yo woman originally from China; in generally good health
but was brought to clinic by her son for
lethargy, tiredness, and back pain after working in her garden
all day.
• Labs: TSH normal; Hgb 11.0; normal LFTs
• No initial diagnosis made
• Diagnosed with hypercalcemia and eventually to gastric
cancer when she returned with confusion.

23. Take away points:
• Symptoms of hypercalcemia:
– polyuria, polydipsia, anorexia, nausea, constipation, includ
e weakness, confusion, coma
• Causes of hypercalcemia:
– primary hyperparathyroidism and malignancy (bone
metastases, humeral hypercalcemia of
malignancy, myeloma) are the most common;
– others: thyrotoxicosis, hypervitaminosis D, Milk alkali
syndrome, adrenal
insufficiency, thiazides, immobilization, sarcoidosis

24. Dr. Harris McIlwain
Fatigue and Pain
• 42 year old female
• 1 year history of fatigue, exhaustion, difficult
to keep up with children as a teacher
• Extreme fatigue, difficulty
concentration, decreased short term memory

25. • Pain and stiffness in feet, then legs and whole
body over past year
• Muscle weakness arms and legs, muscle
fatigue with use
• Pain in shoulders, hips, neck, back

27. • No inflammation in joints on exam
• Tender trigger points present
• Multiple negative lab studies, consultants

28. • Negative nerve conduction
studies, electromyography
• No improvement with
corticosteroids, antidepressants, IVIG

29. Fatigue History
• Felt as generalized weakness (hard to get
started)
• Felt as easy fatigability (difficulty with
endurance)
• Felt as mental fatigue (lower concentration
and short term memory)

30. • Chronic fatigue – over 6 months
• 60% or more medical or psychiatric
• Psychiatric illness—major depression,
anxiety/panic disorder, somatization
disorder
• 5% Clarified by lab studies

31. • Medications:
sleep
1st generation antihistamines
narcotic analgesics
muscle relaxants
antidepressants

32. Chronic Fatigue
• Fibromyalgia
• Chronic Fatigue Syndrome
Specific CDC criteria
• Idiopathic Chronic Fatigue
Without specific CDC criteria

33. Chronic Fatigue Treatment
• Physician Relationship
• Cognitive Behavioral Therapy
• Gradual increase exercise
• Antidepressants

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