05. Unintentional Weight Loss

Michael Thomashow, M.D.

Alka Kanaya, M.D.

BOTTOM LINE

✔ Unintentional weight loss is concerning for undiagnosed medical or psychiatric illness and is associated with increased mortality.

✔ Broad ddx includes malignancy, infection, endocrine, GI, neuro/psych.

✔ Do a thorough history & physical exam before step-wise diagnostic work-up.

Background

  • Involuntary clinically important weight loss >5% of body weight over 6-12 months
  • Excludes weight loss from treatment (e.g. weight loss from chemotherapy) or known illness
  • Concerning for underlying medical or psychiatric illness and can be associated with increased mortality

Differential diagnosis

  1. Malignancy:
    • Account for 15-37% of etiologies
    • GI, lung, lymphoma, prostate and renal cancer are particularly associated with weight loss
    • Cachexia (muscle mass loss) of cancer is a hypercatabolic state 2/2 cytokine activation and tumor-derived substances
    • Associated with pain, abdominal distention, nausea, early satiety, anorexia
  2. Infection:
    • HIV, TB, chronic HCV
    • Consider chronic fungal infection (e.g. aspergillus, cocci), chronic bacterial infection (e.g. endocarditis), lung abscess, chronic parasitic infections causing diarrhea and nutritional deficiencies
  3. Advanced Chronic Disease:
    • CHF (50% of NYHA III/IV lose lean body mass), chronic lung disease (aka pulmonary cachexia; prevalence 30-70%), advanced kidney disease (anorexia 2/2 uremia), ESLD
    • For CHF, CKD, ESLD patients, fluid retention can mask loss of lean body mass
  4. Endocrinopathy:
    • Uncontrolled type I diabetes (consider undiagnosed type I in a young, lean patient with increased appetite)
    • Hyperthyroidism (associated with increased appetite)
    • Chronic primary adrenal insufficiency  
    • Hypercalcemia from malignancy or hyperparathyroidism can lead to weight loss via abdominal pain and constipation
  5. Gastrointestinal:
    • Malabsorption (celiac, IBD), vascular (chronic mesenteric ischemia), obstruction (chronic constipation, obstructive tumor), dehydration (vomiting or diarrhea), dysmotility, ulceration
    • Associated symptoms: abdominal pain, dyspepsia, vomiting, early satiety, dysphagia, odynophagia, diarrhea, steatorrhea, chronic GI bleeding
  6. Neuro/Psychiatric/Toxin:
    • Neuro: Complications of dementia, stroke, neuromuscular disease
    • Psych: Depression, eating disorders, mania, psychotic delusions/paranoia
    • Toxins: prescribed meds (e.g. metformin, levothyroxine, digoxin, certain antidepressants and anticonvulsants) vs. unprescribed meds (OTC/herbal medications such as phen-fen) vs. illicit drugs (tobacco, heavy EtOH, amphetamines, cocaine)
  7. Rheumatologic:
    • RA, GCA

Evaluation

  1. History: Document weight loss and pattern of weight loss. ROS aimed at ddx: ask about age-appropriate cancer screening, other constitutional symptoms, family history of malignancy, exposures to HIV/TB/hepatitis or other infections, endocrine sx, GI sx, psychiatric ROS, eating d/o, Rx, OTC meds, illicit substances.
    • Consider Nine Ds for geriatric patient history: dentition, dysphagia, diarrhea, dysgeusia, depression, dementia, disease, dysfunction, drugs 
  2. Physical:
  • General: Check for flat affect, pressured speech, masked facies
  • HEENT: Check for cheilosis, glossitis, thrush, dentition, LAD, thyroid nodules
  • CV: Check for tachycardia, murmurs, adventitious lung sounds
  • Pulm: Check for cough, evidence of obstructive lung disease
  • GI: Check for abdominal distention, tenderness, masses, hepatosplenomegaly, rectal for FOBT & prostate
  • Neuro: Check for any focal neuro deficits, cognitive impairment
  • Derm: Check for rashes or skin changes
  1. Labs/Tests: (Can perform targeted diagnostics if history/exam are reveleaing)
  • Labs: CBC w/ diff & smear, CHEM 10, HbA1C, LFTs, HIV, TSH, PPD/Quantiferon, FOBT, ESR/CRP, and HCV
  • Studies: CXR, age-appropriate malignancy-screening
  • Consider CT Chest/Abdomen/Pelvis only if aforementioned tests are negative but clinical suspicion for malignancy is very high

BOTTOM LINE

✔ Consider sending CBC w/ diff & smear, CMP, HIV, TSH, PPD, CXR, age-appropriate malignancy screening.

✔ If first pass tests are negative but high suspicion for malignancy remains, then consider CT Chest/Abdomen/Pelvis.

Treatment

  • Treatment hinges on identifying the cause of unintentional weight loss!
  • Once cause is established, consider nutrition consult
  • Avoid starting medicines like mirtazapine or megestrol acetate until underlying cause is established
  • Watchful waiting: if no cause is identified after initial evaluation ok to wait 1-6 months and discuss diet, psychosocial causes and revisit ROS/exam above for new manifestations of underlying occult illness
     

Evans AT, Gupta R. Approach to the patient with unintentional weight loss. UpToDate. Sep 7, 2017.

Jatoi A, Loprinzi CL. Pathogenesis, clinical features, and assessment of cancer cachexia. UpToDate. Oct 10, 2017.

Gaddey HL, Holdder K. Unintentional weight loss in older adults. Am Fam Physician. 2014;89(9):718-722.