Lab Work for Fatigue and Weight Gain: What to Check First

Fatigue plus weight gain is one of the most frustrating symptom combos because it can be caused by multiple systems at once, thyroid signaling, insulin resistance, iron status, inflammation, sleep disruption, and sex hormones. And in many clinics, you still get a basic TSH and a “normal labs” shrug.

The fix is not “test everything forever.” It is starting with high-yield lab work that rules in (or rules out) the most common, most actionable patterns, then adding targeted follow-ups based on what you find.

If you want to run comprehensive labs quickly, Vitals Vault lets you order 100 to 160+ biomarkers with no doctor referral needed, draw at 2,000+ Quest/Labcorp locations, and typically see results in 24 to 48 hours with clinician-reviewed insights.

Quick safety note (when not to “just do labs”)

Lab work is educational and can guide next steps, but it is not a substitute for urgent care.

Seek urgent evaluation if you have chest pain, shortness of breath, fainting, new confusion, black or bloody stools, rapid unintentional weight loss, pregnancy complications, or severe weakness. If you have symptoms of severe depression or suicidal thoughts, seek immediate help.

What to check first for fatigue and weight gain (the “first-pass” labs)

If you only do one round of lab work to start, prioritize tests that cover:

• Blood counts and iron handling (oxygen delivery)
• Thyroid signaling (metabolic “set point”)
• Glucose and insulin dynamics (energy access and fat storage)
• Inflammation (chronic fatigue amplifier)
• Liver, kidney, electrolytes (metabolism, detox, hydration, medication handling)
• Key nutrients and hormones (common, correctable contributors)

Here is a practical “check first” set that maps well to real-world fatigue and weight gain.

To learn what each marker does and how it is interpreted in systems, you can browse the Vitals Vault biomarker library (for example, ApoB, hs-CRP, and ferritin) on the full biomarkers hub.

The 3 biggest “misses” in standard fatigue labs

Many people get a TSH, a glucose, and maybe a CBC, then get told everything looks fine. Three high-yield adds often change the story.

1) Fasting insulin (and HOMA-IR)

A normal fasting glucose does not rule out early insulin resistance. Fasting insulin helps you see whether your body is working overtime to keep glucose “normal.” Pairing fasting glucose with fasting insulin allows a simple insulin resistance estimate (HOMA-IR).

• Why it matters: insulin resistance is strongly linked to weight gain around the midsection, brain fog, post-meal sleepiness, and harder-than-expected fat loss.
• External reference: The American Diabetes Association explains how HbA1c and glucose relate to diabetes and prediabetes, but insulin adds earlier signal for many people.

2) Ferritin (not just hemoglobin)

Hemoglobin can be normal while iron stores are low. Ferritin is your storage marker, and it is one of the most common “quiet” findings in fatigued people, especially with heavy menstrual bleeding, endurance training, frequent blood donation, vegetarian diets, or GI issues.

• Important nuance: ferritin can also rise with inflammation, so interpret it with hs-CRP.

3) hs-CRP (low-grade inflammation)

When you feel tired “in your bones,” inflammation is often part of the picture. hs-CRP is a simple, widely used marker for chronic low-grade inflammation (it is also used in cardiometabolic risk conversations).

• If hs-CRP is elevated, the next move is usually to look for the pattern stack: insulin resistance, liver stress, sleep apnea, periodontal disease, smoking, overtraining, alcohol load, autoimmune activity, or a recent infection.

Thyroid lab work: what to order beyond “just TSH”

TSH is a useful starting point, but fatigue and weight gain cases often require more context.

A practical thyroid lab work set includes:

• TSH
• Free T4
• Free T3 (often helpful when symptoms are strong but TSH is borderline)
• Thyroid antibodies (TPOAb, TgAb) when autoimmune thyroid disease is a possibility

If you want a reputable explainer on thyroid function tests, the American Thyroid Association has a clear overview.

Metabolic lab work: the “energy access” panel

Fatigue with weight gain is frequently a metabolic mismatch: calories may be plentiful, but cells are not accessing energy efficiently.

The most useful starter cluster is:

• Fasting glucose
• HbA1c
• Fasting insulin
• HOMA-IR (calculated)
• Triglycerides and HDL-C (often move early in insulin resistance)
• ApoB (risk signal that can track with metabolic health)

If fasting insulin is high and triglycerides are elevated, that is a classic “start here” signal for nutrition, strength training, sleep, and alcohol strategy adjustments (and clinician follow-up when indicated).

Liver, kidney, and electrolytes: fatigue can be a “chemistry” issue

A CMP is not glamorous, but it is high ROI. Fatigue can show up when hydration is off, electrolytes drift, kidney filtration is impaired, or the liver is under strain.

Markers worth paying attention to include:

• Creatinine and eGFR (kidney filtration context)
• ALT, AST, ALP, GGT (liver stress patterning)
• Albumin and total protein (nutrition, inflammation, liver synthesis)
• Sodium, chloride, CO2 (bicarbonate) (fluid balance and acid-base context)

Vitals Vault has deep dives on many of these, for example eGFR, GGT, albumin, sodium, and chloride.

When to add hormone lab work (and what to measure)

Hormones are not always the first thing to test, but if fatigue and weight gain come with low libido, mood changes, menstrual disruption, poor recovery, hot flashes, hair changes, or sleep fragmentation, hormone testing becomes much more relevant.

For men (common fatigue and weight gain add-ons)

• Total testosterone and free testosterone (interpret with SHBG)
• SHBG
• Estradiol (sensitive, ideally LC-MS/MS when available)
• LH and FSH (signal to pituitary vs testicular patterning)
• DHEA-S
• Morning cortisol (contextual, not a standalone diagnosis)

Relevant reading from Vitals Vault includes FSH, estradiol, DHEA-S, and cortisol.

For women (common add-ons depend on cycle stage)

Women’s hormone interpretation depends heavily on cycle timing, contraception, perimenopause status, and symptoms. Discuss timing with a clinician when possible, but common labs include:

• TSH and Free T4 (thyroid remains a top contributor)
• Fasting insulin and HbA1c (metabolic)
• Ferritin and iron studies
• Estradiol and progesterone (timed)
• LH and FSH (especially in perimenopause evaluation)

A simple “if this, then that” follow-up table

This is not medical advice, but it is a useful way to think about what your first-pass lab work is trying to answer.

How to prep so your lab work is actually comparable

Fatigue and weight gain workups fail when the data is noisy. To improve signal:

• Test in the morning, ideally at the same time for retests.
• Use an 8 to 12 hour fast if you are checking insulin, triglycerides, or glucose patterns.
• Hydrate normally, avoid “over-hydrating” right before the draw.
• Avoid unusually hard training and alcohol for 24 to 48 hours before, if possible.
• Bring a list of meds and supplements. Biotin can interfere with some thyroid immunoassays.

If you want a deeper prep checklist, see Vitals Vault’s guide on blood sample basics.

“My doctor won’t order these tests.” What are your options?

This is a common pain point, especially for fasting insulin, ApoB, Lp(a), and deeper hormone panels.

With Vitals Vault, you can:

• Order comprehensive lab work with no doctor referral needed
• Draw at Quest or Labcorp locations nationwide
• Get results typically in 24 to 48 hours
• Receive clinician-reviewed insights focused on actionable next steps

Explore the full marker catalog on /biomarkers, or go straight to ordering at /checkout.

Vitals Vault vs Function Health, InsideTracker, Superpower, and Mito Health

If you are comparing platforms, fatigue and weight gain is exactly where biomarker depth and clinician context matter. Many “wellness” reports look polished but do not cover enough markers to explain symptoms.

Bottom line: Vitals Vault is positioned as the comprehensive, affordable alternative, with more biomarkers at 50 to 70% lower cost than some popular competitors, no waitlist, and dedicated clinician access included.

For deeper head-to-head reads, see Vitals Vault’s comparisons like Function Health vs Vitals Vault and Vitals Vault vs InsideTracker.

Frequently Asked Questions

What lab work should I get for fatigue and weight gain? Start with CBC, iron studies (ferritin, serum iron, % saturation), thyroid labs (TSH and Free T4), fasting glucose, HbA1c, fasting insulin (plus HOMA-IR), hs-CRP, and a CMP. Add hormone testing if symptoms suggest it.

What is the most important blood test for unexplained fatigue? There is rarely one. The highest-yield “first-pass” combo is CBC plus iron studies, thyroid labs, and metabolic labs (fasting insulin with glucose and HbA1c). Patterns across multiple markers are usually more informative than a single test.

Can insulin resistance cause fatigue and weight gain even if my glucose is normal? Yes. Many people compensate for years with higher insulin while fasting glucose remains normal. Checking fasting insulin and calculating HOMA-IR can reveal early insulin resistance that glucose alone may miss.

Can low ferritin cause fatigue even with normal hemoglobin? It can be associated with fatigue in some people, especially when iron stores are low but anemia has not developed. Ferritin should be interpreted with symptoms and context (including hs-CRP, since inflammation can raise ferritin).

Which thyroid labs should I check first for weight gain and fatigue? TSH and Free T4 are the usual starting point. If symptoms are significant or results are borderline, Free T3 and thyroid antibodies (TPOAb, TgAb) can add helpful context.

How can I get lab work without a doctor referral? With Vitals Vault, you can order labs directly, with no doctor referral needed, then complete your draw at a Quest or Labcorp location and receive clinician-reviewed insights.

How fast will I get results? Vitals Vault typically delivers results in 24 to 48 hours after the lab processes your draw (timing can vary by test and lab logistics).

Get answers faster with comprehensive lab work

If you are tired of being told your labs are “fine,” you are not alone. The problem is often that the lab set is too shallow to explain the symptom pattern.

Start with a comprehensive panel and clinician-reviewed insights so you can stop guessing.

• Explore what Vitals Vault tests: Browse biomarkers
• Order your panel now: Go to checkout