Clinically significant involuntary weight loss is defined as losing >5% of normal body weight within 6 months. Of course, losing the equivalent within 1 month is even worse. Sometimes weight loss is the chief complaint; sometimes you notice the difference from past values.
Note that we’re discussing involuntary weight loss. If the patient was unaware of the change, it’s important to clarify “involuntary” in terms of intent, not merely desire. Obese patients who lose weight always make me worry, since they’d never been successful before. I’d expect them to describe in depth how they’ve managed; otherwise, I work up the decrease.
Depending on how much has been lost in how short a time, & whether the patient is aware of it or not, the first step may simply be a repeat. For example, a 150 lb. persons happens to weigh 143 lb. when seen 4 months later. That’s just about 5%, but we don’t know if it was lost over 4 months or a few weeks. If the patient knows it’s recent, work it up. If they’re unaware, see them back in 2-3 weeks & you’ll have an idea of the trajectory.
From now on, let’s say the weight loss is clearly involuntary. We’ll also assume we can’t attribute it to any major illness we already know about. Our differential will be:
Differential Diagnosis of Involuntary Weight Loss
Urgency of work-up depends on how fast they’re losing. We divide the differential into weight loss with standout clues, and that with unclear explanation. “Key Clues” are those uncovered by a basic History & Physical, focusing on the following Signs and Symptoms (though we always proceed via symptoms & then signs). Let any positives guide the subsequent testing.
Key Clues By History
1. Diarrhea – Acute weight loss will be due to fluids, chronic weight loss to malnutrition. However, be sure that the diarrhea is significant. A couple of loose stools a day won’t be enough. If the diarrhea impresses you, seek its intestinal etiologies. See our postings Acute Diarrhea and Chronic Diarrhea.
2. Nausea / Vomiting – In contrast to diarrhea, these symptoms don’t have to be excessive to cause weight loss. The overall differential for acute nausea & vomiting is broad; if it’s occurring daily for weeks / months & causing weight loss, something bad is happening.
Obtain a CBC, Chemistry Panel, UA, TSH, Lipase, and ESR. While waiting for results, bet on the stomach. Give a high-dose PPI (e.g omeprazole 40 mg B.I.D.) for one or two weeks. See the patient back for results, & repeat the weight.
If labs are all normal, the patient feels a lot better, and weight loss has ceased — Great! Reduce the dose to a standard peptic-ulcer regimen.
But if N/V persist, weight loss continues, & labs are unrevealing – send to G-I for upper endoscopy. Next step would be an abdominal CT. We certainly don’t do this for for N/V in general, but for that which causes continued weight loss.
3. Cough – If cough is prominent, a chest x-ray should make the diagnosis. If the CXR is normal, I’m not sure how far I’d pursue that clue. Lung cancers too small to see on CXR probably don’t cause chronic coughing. If you get a history compatible with Allergic Rhinitis (runny nose, sneezing), the cough may be an incidental red herring [allergic rhinitis shouldn’t cause weight loss] [Google “red herring” if you need to].
If the cough is accompanied by shortness of breath or dyspnea on exertion, then its underlying cause could account for the weight. For chronic SOB with normal CXR, consider ordering PFTs (see posting Chronic SOB-2).
3a. Smoker – If the history confirms >20-30 pack/years, smoking + weight loss warrants an CXR and also a Chest-CT.
- Also be sure to do a good oral exam; don a glove and palpate the tongue’s underside well for nodules.
4. Hoarseness – Send to ENT to r/o Laryngeal Cancer
5. Dysphagia – Defined as, “feels like something gets stuck as I swallow.” Send to G-I for endoscopy to r/o Esophageal Cancer. If liquids “get stuck” & solids don’t, it’s psychological; organic dysphagia always begins with swallowing solids. Dysphagia with liquids only, right at the onset of swallowing, occurs due to neurologic conditions interfering with oropharyngeal mechanisms (& shouldn’t cause weight loss).
6. Fever / Sweats – Fever may be objective or subjective. Weight loss accompanied by objective fever for >2 wks. deserves an admission. If you choose to pursue an out-patient work-up, look up “Fever of Unknown Origin” in a text or full-fledged on-line equivalent like Up-To-Date or eMedicine. [this Blog doesn’t pretend to be a textbook]
For patients without objective fevers who feel feverish, follow the general diagnostics for weight loss that we outline below. You might include the extra testing for infections that we’ll mention, especially if they also complain of “night sweats.” Even if a patient sweats at night, don’t call them “night sweats” unless they’re truly drenching (i.e. if they wring their pajamas / sheets, drops emerge).
7. History of an enlarging Lump or skin Lesion – You’d think this would generate a chief complaint in and of itself, but denial can weigh heavily. So it’s always important to ask about this. A positive, if suspicious on exam, gets biopsied.
8. Blood From Any Orifice – Follow the orifice:
- Hemoptysis: Get a CXR and Chest CT
- Hematemesis: Send for upper G-I Endoscopy (EGD)
- Hematochezia: Send for Colonoscopy
- Hematuria: Get a Renal-Protocol Abdominal CT (CT-Urogram)
- Vaginal Bleeding (no “H” word): Pelvic CT and Endometrial Biopsy
- Melena: Needs both EGD and Colonoscopy
Blood from an ear: just look in the ear. If you see a lesion, or grossly abnormal TM, send to ENT, though I doubt it’ll have anything to do with the weight loss. Same with epistaxis: brief unilateral nosebleeds with or without anterior bleeding points are benign; more serious bleeding goes to ENT for its own sake. (I think I’ve covered all the orifices [or maybe, orificia]).
9. Pain (as a significant symptom, not just occasional) – Explore the locale:
- Pleuritic Chest Pain + Wt. Loss warrants not only CXR & maybe chest CT, but also a rib exam. If you find focal tenderness to percussion, or tenderness to punch-percussion or compression of the rib at a distant site, get rib films & maybe a bone scan [r/o bony met].
- Upper Abdominal Pain + Wt. Loss – Therapeutic trial of high-dose PPI. If no relief in 1 week, send to G-I for endoscopy; may also need a pancreatic-protocol CT. If the pain abates but weight loss continues, send to G-I, since PPIs can mask the pain of gastric cancer.
- Lower Abdominal Pain + Wt. Loss – Send to G-I for colonoscopy; may also warrant an abdominal + pelvic CT
- Pelvic Pain + Wt. Loss – Start with a pelvic bimanual, but obtain an abdominal + pelvic CT no matter what you don’t palpate.
- Headache – Brain tumors don’t cause weight loss, so don’t order a head MRI. Headache can easily be an effect of whatever happens to be the underlying etiology.
10. Medications – I’ve read about how some OTC and Prescription drugs can cause weight loss; you’d think their manufacturers would reap a fortune if that was commonly the case. However, the decrease is either an unusual idiosyncratic effect, and/or an early side effect that’s not sustained. Still, if any med correlates temporally, look it up.
11. Drugs – Stimulant abuse is notorious for causing weight loss. It usually occurs among daily users. Heavy alcohol use can cause weight loss by nutritional deprivation as well as dehydration.
12. Psychiatric Disease – This might be the cause of involuntary weight loss in up to 40% of patients in the community [much higher in institutions]. Depression leads the list, though acute mania and psychotic delusions are other entities. Anorexia Nervosa doesn’t concern us; those patients don’t complain of weight loss, but rather seek it.
Though anorexia is a common symptom of Depression, the latter is a diagnosis of exclusion; you still have to do a basic work-up. Click for a Sad Story of prematurely attributing physical symptoms to psychiatric illness.
Key Clues On Physical Exam
1. Lymphadenopathy – Depends on the type:
- Single node that’s hard or fixed: Start with a fine needle aspiration (FNA). If no malignancy identified (either lymphoma or a metastasis), don’t believe it. Send to surgery for excisional biopsy.
- Generalized: Suggests a systemic condition. Ignore anterior cervical and submandibular nodes (unless there’s an oral lesion). Posterior cervical, occipital, & especially epitrochlear nodes suggest HIV.
By the way — What’s the most ominous lymph node in the body?
2. Hepatosplenomegaly – Lots of possibilities. You’ll need an abdominal-pelvic CT (with contrast).
3. Jaundice – Ominous. Suggests either liver mets, or a primary biliary tract / pancreatic neoplasm. Certainly explore other etiologies; obtain LFTs and serologies for hepatitis, plus a CBC for hemolysis. But if they’re unrevealing, get an abdominal-pelvic CT with “pancreatic protocol”.
If negative, either order an MRCP (non-invasive), or send to GI for the endoscopic version (ERCP). [MRCP = “Magnetic Resonance Cholangio-Pancreatography”; ERCP = “Endoscopic Retrograde CP”].
4. Masses (abdominal or pelvic) – CT is the obvious first step.
4a. Breast Mass – Diagnostic mammogram & biopsy of whatever sort.
4b. Prostate Nodule – Obtain a PSA, but send to Urology anyway, for biopsy.
5. Suspicious Skin Lesion – Biopsy. When dermatologists evaluate patients with multiple nevi or perhaps family history of melanoma (or actually, sometimes for anything [!]), they have the patient sit stark naked and eyeball every square centimeter while a nurse records findings. That’s not my practice in primary care; I settle for the torso, and maybe the legs below mid-thigh. After all, an early melanoma doesn’t cause weight loss.
That’s it for today. Next posting we’ll discuss the work-up for involuntary weight loss without any clinical clues to guide us.