Weight Loss

Can’t Lose Weight? 5 Medical Reasons to Rule Out

The Pin Health Staff Writer

January 21, 2026 11 min read

Diet and exercise not working? Before blaming yourself, rule out these 5 medical conditions that make weight loss nearly impossible — and can be detected with blood tests.

You’re eating less, You’re moving more, You’re doing everything “right” — but the scale won’t budge. Before you blame your willpower or try yet another diet, consider this: sometimes the problem isn’t effort. It’s biology.

Several medical conditions can make weight loss extraordinarily difficult — or nearly impossible — regardless of how disciplined you are. These conditions often go undiagnosed for years because their symptoms are subtle, develop gradually, or get dismissed as “normal” stress, aging, or lifestyle factors.

The frustrating reality is that many people spend years fighting their bodies, cycling through diets, feeling like failures — when the real issue is an underlying metabolic or hormonal problem that no amount of calorie restriction will fix.

The good news? These conditions can be detected through blood testing. And once identified, they can often be treated — finally allowing your body to respond to the healthy changes you’re already making.

Here are five medical reasons your weight loss efforts might be stalling, and what testing can reveal.

1. Hypothyroidism: When Your Metabolism Slows to a Crawl

Your thyroid gland — a small butterfly-shaped organ in your neck — controls your metabolic rate. It determines how efficiently your body burns calories, regulates body temperature, and influences energy levels. When your thyroid is underactive (hypothyroidism), everything slows down.

Hypothyroidism is remarkably common, affecting roughly 5% of the population — and the majority of cases are undiagnosed. Women are 5-8 times more likely to be affected than men, and risk increases with age.

Why it makes weight loss difficult:

• Your basal metabolic rate drops — you burn fewer calories at rest
• Your body becomes more efficient at storing fat
• Fatigue makes exercise feel impossible
• Fluid retention adds to the number on the scale

Other signs to watch for:

• Fatigue that doesn’t improve with sleep
• Feeling cold when others are comfortable
• Dry skin and brittle hair
• Constipation
• Brain fog and difficulty concentrating
• Depression

What testing reveals:

TSH (thyroid-stimulating hormone) is the primary screening test. When the thyroid is underactive, TSH rises as your body tries to stimulate more hormone production. Free T4 and Free T3 show the actual thyroid hormone levels. TPO antibodies can reveal Hashimoto’s thyroiditis, the autoimmune condition responsible for most hypothyroidism cases.

The tricky part: you can have “subclinical” hypothyroidism — where TSH is elevated but still within the lab’s reference range — and still experience symptoms including weight loss resistance. This is where comprehensive testing and tracking trends over time becomes valuable.

2. Insulin Resistance: When Your Body Can’t Use Its Own Fuel

Insulin is the hormone that allows glucose to enter your cells for energy. When you’re insulin resistant, your cells don’t respond properly to insulin. Your pancreas compensates by producing more and more insulin — and this excess insulin has a powerful effect: it promotes fat storage and blocks fat burning.

Insulin resistance is the precursor to prediabetes and type 2 diabetes. It’s estimated that over 40% of adults have some degree of insulin resistance — most without knowing it.

Why it makes weight loss difficult:

• High insulin levels signal your body to store fat, especially around the abdomen
• Your body struggles to access stored fat for energy
• Blood sugar swings cause intense hunger and cravings
• Energy crashes make consistent exercise challenging

Other signs to watch for:

• Weight concentrated around the midsection
• Intense cravings for carbohydrates and sugar
• Energy crashes, especially after meals
• Difficulty going long periods without eating
• Darkened skin patches (acanthosis nigricans), often on neck or armpits
• Skin tags

What testing reveals:

Fasting insulin is the key marker — and it’s often not included in standard checkups. You can have completely normal blood sugar while your insulin is elevated, meaning your pancreas is working overtime to maintain that normal glucose. Fasting glucose and HbA1c show the downstream effects, but insulin often rises years before glucose does.

Triglycerides and HDL cholesterol also provide clues — insulin resistance typically shows elevated triglycerides and lower HDL.

3. PCOS: The Hormonal Condition Affecting 1 in 10 Women

Polycystic ovary syndrome (PCOS) is one of the most common hormonal disorders in women of reproductive age, affecting roughly 10% — yet up to 70% of affected women remain undiagnosed.

PCOS is closely linked to insulin resistance (most women with PCOS have it), but also involves elevated androgens (male hormones) that further complicate metabolism and weight regulation.

Why it makes weight loss difficult:

• Insulin resistance (see above) is present in most cases
• Elevated androgens promote abdominal fat storage
• Hormonal imbalances affect appetite regulation
• Inflammation is often elevated
• The condition itself worsens with weight gain, creating a vicious cycle

Other signs to watch for:

• Irregular or absent periods
• Excess facial or body hair (hirsutism)
• Acne, especially along the jawline
• Thinning hair on the scalp
• Difficulty getting pregnant

What testing reveals:

PCOS diagnosis involves multiple markers: testosterone and free testosterone (often elevated), LH and FSH ratio, DHEA-S, and insulin/glucose markers. SHBG (sex hormone-binding globulin) is often low in PCOS, which increases the amount of active testosterone.

4. Cortisol Dysregulation: When Stress Hormones Work Against You

Cortisol is your body’s primary stress hormone. In short bursts, it’s helpful — it gives you energy to handle challenges. But when cortisol is chronically elevated (from ongoing stress, poor sleep, or conditions like Cushing’s syndrome), it wreaks havoc on your metabolism.

Why it makes weight loss difficult:

• Cortisol promotes fat storage, particularly visceral fat around the organs
• It increases appetite, especially for high-calorie “comfort” foods
• It breaks down muscle tissue (and muscle burns more calories than fat)
• It impairs sleep, which further disrupts metabolism
• It worsens insulin resistance

Other signs to watch for:

• Weight gain concentrated in the face, neck, and abdomen (while arms and legs may stay thin)
• Difficulty sleeping or unrefreshing sleep
• Anxiety or feeling “wired but tired”
• Easy bruising
• Muscle weakness
• High blood pressure

What testing reveals:

Cortisol testing is nuanced because levels naturally fluctuate throughout the day — highest in the morning, lowest at night. A single measurement has limitations. Multiple measurements, salivary cortisol testing, or 24-hour urine cortisol can provide a fuller picture. For suspected Cushing’s syndrome, specific suppression tests are needed.

It’s worth noting that severe cortisol excess (Cushing’s syndrome) is rare. More common is chronic stress-related cortisol elevation, which is harder to quantify but still impacts weight.

5. Low Testosterone: Not Just a Male Problem

While testosterone is often considered a “male” hormone, it plays important metabolic roles in everyone. In men, low testosterone (hypogonadism) becomes increasingly common with age — affecting roughly 40% of men over 45. But women also need adequate testosterone for metabolic health.

Why it makes weight loss difficult:

• Testosterone helps build and maintain muscle mass — and muscle is metabolically active tissue
• Low testosterone is associated with increased fat mass, especially visceral fat
• It reduces energy and motivation for physical activity
• Low testosterone often coexists with insulin resistance

Other signs to watch for (in men):

• Decreased energy and motivation
• Reduced muscle mass and strength
• Increased body fat
• Low libido
• Erectile dysfunction
• Mood changes, including depression
• Brain fog

What testing reveals:

Total testosterone and free testosterone are the key markers. SHBG affects how much testosterone is actually available to tissues. In men, LH and FSH help determine whether low testosterone is due to a testicular problem or a signaling issue from the pituitary.

Bonus: Other Factors Worth Investigating

Beyond these five major conditions, other factors can contribute to weight loss resistance:

Sleep apnea: Obstructive sleep apnea disrupts sleep quality and is strongly linked to weight gain, insulin resistance, and difficulty losing weight. It’s vastly underdiagnosed.

Nutrient deficiencies: Low vitamin D, iron, or B12 can cause fatigue that sabotages your ability to stay active, and some research links deficiencies to metabolic dysfunction.

Chronic inflammation: Elevated inflammatory markers like hs-CRP are associated with obesity and metabolic dysfunction. Whether inflammation causes weight gain or results from it is complex, but addressing it often helps.

Medications: Certain medications — including some antidepressants, antipsychotics, beta-blockers, corticosteroids, and insulin — can promote weight gain. Never stop medications without consulting your doctor, but it’s worth discussing alternatives if weight is a concern.

The “I’ve Tried Everything” Trap

If you’ve been struggling with weight loss, you’ve probably heard (or told yourself) some version of these statements:

• “You just need to try harder.”
• “It’s simple: eat less, move more.”
• “You must be eating more than you think.”

These messages are not only unhelpful — they can be harmful. When an underlying medical condition is sabotaging your efforts, no amount of willpower will overcome it. And the shame and frustration of “failing” at diet after diet takes a real psychological toll.

This isn’t about making excuses. It’s about recognizing that your body is a complex system. Hormones, metabolism, and weight regulation involve dozens of interconnected factors. When something is off, the standard advice stops working.

Getting tested isn’t giving up — it’s getting smart.

What to Do Next

If you’ve been struggling with unexplained weight loss resistance, consider these steps:

1. Get comprehensive blood work. A basic metabolic panel isn’t enough. You want a complete picture: thyroid markers (TSH, Free T4, Free T3, antibodies), metabolic markers (fasting glucose, HbA1c, fasting insulin), lipids, and relevant hormones based on your situation.

2. Track trends over time. A single measurement is a snapshot. Patterns over months or years tell you much more about what’s happening in your body and whether interventions are working.

3. Look beyond “normal.” Lab reference ranges are based on population averages — not optimal health. A result at the edge of “normal” might still be a clue worth investigating.

4. Address root causes. If testing reveals an issue, work with your healthcare provider on treatment. Whether that’s thyroid medication, addressing insulin resistance through lifestyle changes or medication, or managing another condition — treating the underlying cause often allows weight loss to finally happen.

5. Be patient with yourself. If you’ve been fighting your biology for years, it takes time to recalibrate. Once underlying issues are addressed, your body can finally respond to your efforts — but healing isn’t instant.

The Bottom Line

Weight loss isn’t always as simple as calories in, calories out. Multiple medical conditions can stack the deck against you — and these conditions are common, often undiagnosed, and treatable.

If you’ve been doing everything right without results, don’t blame yourself. Get tested. The answer might be in your blood work.

You deserve to know what’s happening in your body. And you deserve a fair fight.

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Key Takeaways

• Hypothyroidism slows metabolism and affects roughly 5% of adults, with most cases undiagnosed
• Insulin resistance promotes fat storage and blocks fat burning — affecting over 40% of adults
• PCOS affects 1 in 10 women and combines insulin resistance with hormonal imbalances
• Cortisol dysregulation from chronic stress promotes abdominal fat storage
• Low testosterone reduces muscle mass and metabolic rate
• Blood testing can identify these conditions — often years before they’re diagnosed through symptoms alone
• Once identified, these conditions can be treated — finally allowing your body to respond to diet and exercise