Worrisome involuntary weight loss (losing weight without trying) is defined as losing >5% of normal body weight within 6 months. Of course, losing it sooner is even worse. Obese patients who lose weight always make us worry, since they’d never been successful before. If they can’t describe in depth how they’ve managed, we start to look for possible causes (i.e. diseases).
Depending on how much weight has been lost in how short a time, & whether the patient is aware of it or not, the first step may simply be to weigh them again. For example, a 150 lb. persons happens to weigh 143 lb. when seen 4 months later.
- That’s about 5%, but we don’t know if it was lost over 4 months or in just a few weeks.
- If the patient knows it’s recent, they need a work-up.
- If they’re unaware, we see them back in 2-3 weeks to see how quickly they may be losing it (or if they’ve begun to regain it).
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. We consider the following:
Causes of Involuntary Weight Loss
• Infection (acute/chronic; internal abscesses)
• Diabetes (uncontrolled)
• Depression / Psychosis
|• Hepatitis (acute)|
• Peptic Ulcer (stomach ulcer)
• Nausea / Vomiting (from various causes)
• Adrenal Insufficiency (very rare)
Urgency of work-up depends on how fast they’re losing weight. We determine if there are any standout clues, or simply weight loss without clear explanation. “Key Clues” are those uncovered by a basic History & Physical Examination. Any such findings guide the subsequent testing.
Key Clues From the Medical History
1. Diarrhea – Acute weight loss will be due to fluids, chronic weight loss to malnutrition. However, the diarrhea must be significant. A couple of loose stools a day won’t be enough. If the diarrhea is impressive, we seek its causes. See topics Acute Diarrhea and Chronic Diarrhea.
2. Nausea / Vomiting (N/V) – In contrast to diarrhea, these symptoms don’t have to be excessive to cause weight loss. There are many possible causes; if nausea / vomiting are occurring daily for weeks or months and causing weight loss, something bad is happening.
We obtain basic laboratory tests (see topic Nausea / Vomiting). If all are normal, we bet on something happening in the stomach — maybe just treat for an Ulcer, or refer to a Gastroenterologist for upper endoscopy to tell for sure if there’s one, and rule out Stomach Cancer.
Next step would be an abdominal CT scan. We certainly don’t do this for N/V in general, but for that which causes continued weight loss.
3. Cough – If cough is prominent, a Chest X-ray (CXR) should make the diagnosis for most lung diseases. If the CXR is normal, the cough may be an unrelated red herring. [Google “red herring” if you don’t understand the term]. Lung Cancer can cause cough with weight loss, but probably not a cancer that’s too small to see on CXR.
If the cough is accompanied by shortness of breath, especially recent shortness of breath that’s worse with exertion (like going up stairs or hills), then whatever is causing it could account for the weight loss. A patient with chronic shortness of breath and normal CXR should have pulmonary function tests (see topic Chronic Shortness of Breath).
3a. Smoker – If a patient with weight loss has smoked a pack-a-day for over 20 years (or 1/2 pack for over 40, etc.), they should have a CXR and also a Chest CT scan. We also need to do a good exam of the mouth, feeling for lumps under the tongue for Oral / Tongue Cancer
4. Hoarseness – They need a referral to an Ear-Nose-and-Throat specialist (ENT; Otolaryngology) to look down the trachea by laryngoscopy to rule out Cancer of the Larynx (“voice box”).
5. Swallowing Problem – Defined as, “feels like something gets stuck as I swallow.” We refer to a Gastroenterologist for endoscopy to rule out Esophageal Cancer. (If the swallowing problem occurs only with liquids, not solids, it has to do with mouth & tongue coordination, which is usually a neurological condition, like after a stroke, etc. Those patients get referred to a Speech Pathologist for swallowing tests).
6. Fever / Sweats – There’s a difference between just feeling feverish, & actually having a temperature over 100.6° F (38.0° C). If there is an actual proven fever for over 1 week, the patient needs all the tests described below, including CT scans if no diagnosis (to seek Cancers, or Internal Abscesses). May need to be admitted to a hospital for antibiotic treatment during extensive testing.
For patients who just “feel feverish,” we follow the general diagnostic approach to weight loss outlined below. By definition, “night sweats” are truly drenching (like if you wring your pajamas / sheets, then sweat actually drips out).
7. Lump or Mole that’s Enlarging – This is ominous, because the fact that there’s weight loss implies a Skin Cancer that has metastasized. Ideally the patient would have sought care sooner. A biopsy will make the diagnosis.
8. Blood From Any Body Orifice (opening) – We follow the orifice by ordering tests:
- Coughing up blood: Chest X-ray and likely Chest CT scan for Lung Cancer, Lung Infections (TB, etc.)
- Vomiting blood: Refer to Gastroenterologist for Endoscopy for Ulcers, or Stomach Cancer
- Blood in stool (not just specks on toilet paper: Refer to Gastroenterologist for Colonoscopy for Colon Cancer
- Blood in Urine: Abdominal CT scan by “renal protocol” (a.k.a. “CT-Urogram”) for Kidney Cancer; then refer to Urologist for Cystoscopy (looking into the bladder for Bladder Cancer)
- Vaginal Bleeding: Pelvic Ultrasound or CT scan for Ovarian / Endometrial Cancer; will likely need endometrial biopsy for Endometrial Cancer. See topic Vaginal Bleeding.
- Black Tarry Stools (“Melena”): Refer to Gastroenterologist for both Endoscopy (Stomach Cancer; Ulcer) & Colonoscopy (Colon Cancer) [Note: iron pills and Pepto-Bismol® both turn stools black]
- Blood from ear or nose: Needs an exam, but unlikely there’d be anything causing weight loss
9. Pain (as a significant symptom, not just occasional) – We explore the area:
9a. Chest Pain + Wt. Loss: Chest X-ray, looking for a Lung Cancer.
- We’d also examine the Ribs. If there’s very localized tenderness tapping on one specific rib, or a spot hurts when we “punch” on the same rib from farther away, we order a Rib X-ray [different from a “chest” x-ray]. May even order a “bone scan,” all to rule out Bone Metastasis from a Cancer somewhere else.
9b. Upper Abdominal Pain + Wt. Loss – We’d suspect an Ulcer, and try treatment with a high-dose antacid proton-pump inhibitor (PPI).
- If no relief in 1 week, we’d refer to a Gastroenterologist for endoscopy to confirm the Ulcer, or find Stomach Cancer)
- May also need Abdominal CT-scan to rule-out other Cancers: Pancreas / Liver / Gallbladder
- If the pain eases up with PPI but weight loss continues, we also refer for endoscopy, since PPIs can mask the pain of Stomach Cancer.
9c. Lower Abdominal Pain + Wt. Loss – We refer to Gastroenterology for colonoscopy to rule-out Colon Cancer
- Would also order an Abdominal-Pelvic CT scan, for Ovarian Cancer & others
9d. Pelvic Pain + Wt. Loss – We begin with a pelvic exam (women) & prostate exam (men)
- We obtain an Abdominal-Pelvic CT scan too, no matter what we find or don’t find on pelvic exam, mainly for Ovarian Cancer.
- A woman may need to see Gynecology for laparoscopy (rule-out Ovarian Cancer)
- A man needs a blood test prostate-specific antigen (PSA) for Prostate Cancer. Even if normal, with weight loss + pelvic pain, he should see a Urologist (for special prostate ultrasound / prostate MRI). [note that a screening PSA for asymptomatic men isn’t universally recommended, but here we’re talking about diagnosing men with weight loss].
9e. [ Headache ] – Brain tumors don’t cause weight loss, so we don’t order an MRI. Headache can easily be an effect of whatever happens to be the underlying disease.
10. Medications – I’ve read about how some over-the-counter and prescription drugs can cause weight loss — you’d think their manufacturers would reap a fortune if that was commonly the case. The effect is either a rare one, and/or an early side effect that wears off. Still, if a patient had just begun a new medication, we’d look it up to see if there might be a connection.
11. Drugs – Cocaine & methamphetamines are notorious for causing weight loss, usually just among daily users. Heavy alcohol use can cause weight loss by depriving a person of real nutrients, & also by dehydration.
12. Psychiatric Disease – This might be the cause of involuntary weight loss in up to 40% of patients [much higher in institutions].
- Depression leads the list
- Acute Mania and Psychosis (delusions) are other causes.
- Anorexia Nervosa certainly causes weight loss, but those patients desire it & don’t seek medical care (their families might).
- Even if we suspect weight loss is due to psychiatric disease, we still have to do a basic work-up for physical causes. Click for a Sad Story of prematurely attributing physical symptoms to psychiatric illness.
Key Clues On Physical Examination
1. Lymph Node Enlargement (Lymphadenopathy; “swollen glands”) – Depends on the type:
1a. One single Lymph Node that’s newly swollen — if it’s warm and tender, there’s an infection in it or near-by. But if it feels rock-hard, doesn’t hurt, or can’t be wiggled, it could be cancer (Lymphoma)
- We’d start with an easy biopsy by simply sticking a needle in to aspirate (fine needle aspiration, called “FNA”).
- However, if the report says “no cancer,” in the face of weight loss, we still wouldn’t be sure. So we’d refer to a surgeon to remove it (excisional biopsy).
- A non-tender swollen lymph node in the axilla (armpit) suggests Breast Cancer, requiring a mammogram, and also a biopsy
- We examine the area / organs that might drain into the node. For example, if suspicious nodes are under the jaw, we’d look and feel inside the mouth for Oral or Tongue Cancer
- A lymph node just above the collarbone on the right suggests Lung / Breast Cancer. We’d get a Chest X-ray and chest CT scan, do a breast exam and order a Mammogram
- A lymph node just above the collarbone on the left suggests cancer anywhere down below. This is the most ominous lymph node in the body, because an asymmetric duct drains into the left. We’d get CT scans of the chest, abdomen, and pelvis for Cancer of any organ there; also a mammogram.
1b. Generalized Lymphadenopathy — lymph nodes felt in several places (not just front of the neck):
- We’d start with an HIV test for HIV
- Mononucleosis is possible, but shouldn’t cause ongoing long-term weight loss
- We’d biopsy the biggest and most accessible node for Chronic Leukemia, Lymphoma / Unusual Infections
- Generalized lymphadenopathy plus weight loss would lead us to order a chest. abdominal, and pelvic CT scans, looking for more nodes suggesting Cancer / Unusual Infections
2. Enlarged Liver and/or Spleen – Lots of possible causes, in particular various Cancers. We’d order CT scans of the abdomen and pelvis.
3. Jaundice (eyes turn yellow, maybe even the skin) – If there’s chronic weight loss, jaundice is ominous. It suggests either liver metastases from cancer somewhere, or a Cancer of the Liver / Gallbladder / Pancreas.
- We’d certainly explore less serious causes (like Hepatitis), and order various blood tests. But if they don’t give a clear diagnosis, we’d get a CT scan of the abdomen and pelvis.
- If the CT is negative, we’d refer to a Gastroenterologist, who’d perform special endoscopic tests (like “ERCP” and/or endoscopic ultrasound) for Gallbladder / Pancreatic Cancer.
4. Lumps (Masses) – Depends where they are
- If superficial and “suspicious” (hard, can’t be wiggled), we obtain a biopsy
- Thyroid: We can biopsy easily, for Thyroid Cancer, but if negative, it needs a biopsy by ultrasound to first identify and then aim for the most suspicious part
- Breast: We order “diagnostic mammogram,” which includes ultrasound & biopsy when needed, for Breast Cancer
- Testicle: We order an ultrasound, refer to Urology if suspicious for Testicular Cancer
- Abdomen (internal mass): We order an Abdominal CT scan to see if it’s Cancer
- Rectum: We refer to a Gastroenterologist or Proctologist to biopsy for Rectal Cancer
- Ovary or Uterus: We order a Pelvic CT scan for Ovarian / Uterine Cancer, and refer to Gynecology
- Prostate: We order a blood test for prostate-specific antigen (PSA) & refer to Urology for likely biopsy for Prostate Cancer
5. Suspicious Skin Lesion – Biopsy for Skin Cancer. “Suspicious” means getting larger, also the following “A-B-C-D”:
- A = Asymmetrical shape
- B = Borders (irregular edge)
- C = Color changes (various colors in the lesion)
- D = Diameter (over 1 cm., about the size of an eraser on a pencil)
HOWEVER, for most patients losing weight the medical history and physical examination usually wind up being completely normal. No clues, just weight loss. So we proceed to order various…
Basic Laboratory Tests (see links for explanation)
- Complete Blood Count (CBC)
- Erythrocyte Sedimentation Rate (ESR, Sed Rate) / C-Reactive Protein (CRP)
- Thyroid Stimulating Hormone (TSH)
- Comprehensive Metabolic Panel (CMP; around 20 blood tests)
- Lactose Dehydrogenase (LD; LDH)
- HIV Test
- Prostate Specific Antigen (PSA) in man >50 (if African-American >40)
- Serum Protein Electrophoresis / Urine Protein Electrophoresis
- Chest X-Ray (this isn’t a lab test)
The above tests are helpful in the following ways:
- Anemia (microcytic = small Red Blood Cells): Suggests low iron due to blood loss; additional tests confirm the loss. Where from? We refer to a Gastroenterologist for endoscopy (rule-out Ulcer; Stomach Cancer) and colonoscopy (rule out Colon Cancer)
- Anemia (normocytic = normal Red Blood Cells): This justifies an extensive search for underlying Infection or Cancer. This kind of anemia is called Anemia of Chronic Disease.
- Anemia (macrocytic = large Red Blood Cells): May suggest Alcoholism, Liver Disease, Vitamin B12 Deficiency, or Blood Cancers (Leukemias, others)
- Elevated White Blood Cell count: We’d seek an underlying Infection or Blood Cancer
- Low Platelets: It’s the earliest finding in liver Cirrhosis; also common in HIV (test if not yet done)
- Elevated Eosinophil count (over 1,500): A type of white blood cell that, in a patient with weight loss, might suggest rare Blood Cancer — we’d refer to a Hematologist
** ESR / CRP: If ESR is very elevated (close to 100), it justifies an extensive search for an underlying Infection or Cancer. Crohn’s Disease would be another possibility. But we wouldn’t do a big work-up if the ESR is only slightly high.
** Comprehensive Metabolic Panel: Various abnormalities possible:
- Glucose (sugar): If very high, Diabetes is likely cause of weight loss
- Liver Function Tests elevated: Could be Acute Hepatitis, or Metastases from Cancer elsewhere in the body
- Albumin low: We’d suspect Cancer somewhere, or Cirrhosis
- Calcium elevated: We’d order a blood test for “PTH-related peptide” (PTH-rp), which is produced by various cancers and elevates calcium. However, calcium will be falsely high if the Albumin is also high (there’s an easy calculation to tell; never let anyone say the calcium is high without also checking an albumin)
- Creatinine elevated: Diagnoses Kidney Failure, maybe due to Multiple Myeloma (a blood cancer)
- Globulin elevated: Occurs with chronic infections (like HIV) and also with Multiple Myeloma. The latter is diagnosed initially by ordering a Serum & Urine Protein Electrophoresis (SPEP & UPEP)
** LDH elevated — Suggests either lung disease, or various cancers. If the chest x-ray is normal, the high LDH may justify a more extensive search for cancer.
** HIV Test— Weight loss can be a pre-AIDS symptom of advancing disease. Anyone with weight loss and even the least likelihood of HIV infection who hasn’t been tested in the last 2 years should be.
** Prostate Specific Antigen — For Prostate Cancer. Screening PSAs are controversial, but here we’re talking about diagnosis. Any man over 50 y.o., or African-American man over 40, with weight loss should have a PSA.
** Serum Protein Electrophoresis / Urine Protein Electrophoresis — mainly used to screen for Multiple Myeloma and other rarer blood cancers. Might not be ordered among initial tests, unless weight loss was more extreme
** Urinalysis — Blood in urine then requires CT scan (by “renal protocol”) for Kidney Cancer. If negative, we refer to Urologist for cystoscopy (look in the bladder) for Bladder Cancer
** Chest X-Ray — A simple test which can identify many Lung Cancers, virtually all non-viral Lung Infections, large lymph nodes due to Lymphomas or Sarcoidosis, and possible clues to Interstitial Lung Disease. Weight loss with a normal chest x-ray virtually eliminates a pulmonary cause, though heavy smokers should also get a CT scan for Lung Cancer.
Everything’s Normal (but still Losing Weight)
1. If there’s any suggestion of Upper Abdominal Pain, or Nausea / Vomiting, we may refer to a Gastroenterologist for Endoscopy, or give a treatment trial for Stomach Ulcer (high-dose PPI – see Antacid Medicines).
- At follow-up, we lower it to normal dose if it helped, since we’d have a likely diagnosis.
- But beware; PPI’s can relieve the pain of Stomach Cancer. We’d change soon to an “H-2 Blocker”, which also cure ulcers but won’t help cancer pain (see Antacid Medications)
- If pain returns, or weight doesn’t improve rapidly, we refer to Gastroenterologist for endoscopy to rule-out Stomach Cancer.
2. If no symptoms to suggest a possible ulcer, and all our history, exam, & tests are normal, we explore Psychiatric Disorders, especially Depression. If we identify a condition, treat. And if not…
3. Everything normal & no psychiatric disease — if weight has still declined during the 2-3 weeks it took to do the above tests, we continue with a bigger work-up:
- Abdominal and Pelvic CT scans (for various Cancers)
- Refer for colonoscopy (for Colon Cancer) if the patient is over 45 and hasn’t had one recently; otherwise, it’d be a long shot.
- Same with mammograms for women, to rule out Breast Cancer
- Adrenal Insufficiency (very rare) can cause weight loss, but we’d likely notice a new change in skin color like a suntan (JFK had this), or at least find a drop in blood pressure between lying down & then abrupt standing up (if so, we’d refer to an Endocrinologist)
Fortunately, for patients with Weight Loss, the vast majority of diagnoses will be identified through a decent History and Physical Exam, plus basic lab tests.
See also Weight Loss for the clinician’s condensed thought-process when face-to-face with a patient.