Thyroid Dysfunction and Depression: Why "Normal" Labs Might Be Missing Your Real Problem

If you've had blood work done showing your thyroid is "fine," but you're still struggling with depression, you're not alone. In fact, this a very common scenario we see in practice.

Here's the problem: most doctors only check TSH (thyroid-stimulating hormone), and sometimes Free T4. But this only tells part of the story. It's like checking your car's fuel gauge but ignoring the engine temperature, oil pressure, and battery voltage. You might be within "normal range" on TSH while your actual thyroid function is significantly compromised—and your depression is directly caused by that thyroid dysfunction.

You can have TSH and Free T4 ‘within range’ and still have:

• Low‑normal thyroid hormone levels linked with higher depression risk,

• Untreated subclinical hypothyroidism,

•  Autoimmune thyroiditis (Hashimoto’s) that was never checked for, or

•  Issues converting T4 to the active hormone T3.

 None of these show up clearly if only TSH and Free T4 are measured and read as simply ‘normal’.

This happens constantly in midlife women, and it's one of the most straightforward physiological drivers of depression to fix once it's properly identified.

 

Why Thyroid Directly Affects Mood

Your thyroid gland produces hormones (T4 and T3) that regulate your metabolism, body temperature, heart rate, and critically, neurotransmitter production in your brain.

Here's how thyroid hormones affect depression:

Brain Energy Production

Thyroid hormones increase the rate at which your brain cells produce ATP (energy). A sluggish thyroid = a brain running on low energy = difficulty producing adequate serotonin, dopamine, and other mood-regulating neurotransmitters.

Serotonin Sensitivity

Thyroid hormones increase the sensitivity of serotonin receptors in your brain. When thyroid hormone is low, your brain becomes less responsive to serotonin—even if you have adequate serotonin. This is why some women stay depressed even on SSRIs (serotonin reuptake inhibitors) until their thyroid is optimized.

Dopamine Production

T3 (the active form of thyroid hormone) is necessary for dopamine synthesis. Low T3 means low dopamine, which manifests as:

• Lack of motivation and drive

• Difficulty initiating tasks

• Loss of pleasure (anhedonia)

• Depression

Brain-Derived Neurotrophic Factor (BDNF)

Thyroid hormones increase BDNF, which is essential for neuroplasticity—your brain's ability to form new connections and heal. Low BDNF is associated with depression and anxiety.

Temperature Regulation & Inflammation

Thyroid hormones regulate body temperature. Low thyroid function often comes with cold intolerance, but more importantly, thyroid dysfunction is associated with increased neuroinflammation—a primary driver of depression.

 Two Ways Thyroid Dysregulation Causes Depression

 1. Low Thyroid Function (Hypothyroidism)

Symptoms include:

• Persistent low mood and depression

• Fatigue despite adequate sleep

• Brain fog and difficulty concentrating

• Weight gain or difficulty losing weight

• Cold hands and feet

• Hair loss

• Slow metabolism

• Constipation

• Dry skin

• Sluggish, slow speech

When thyroid is low, your entire brain slows down. Depression is nearly inevitable.

 2. High Thyroid Function (Hyperthyroidism)

Symptoms include:

• Anxiety and racing thoughts

• Irritability and mood swings

• Insomnia despite feeling exhausted

• Weight loss despite adequate eating

• Heart palpitations

• Excessive sweating

• Tremors or shakiness

• Difficulty tolerating heat

When thyroid is high, your brain is essentially over-stimulated. This creates anxiety, but prolonged elevation leads to burnout and depression as your nervous system becomes exhausted from constant overstimulation.

Both extremes create depression, just through different mechanisms.

Why Midlife Women Are Particularly Vulnerable

Three factors converge in midlife to create thyroid dysfunction:

1. Autoimmune Thyroiditis (Hashimoto's) Peaks in Midlife Women

Hashimoto's is an autoimmune condition where your immune system attacks your thyroid gland, gradually destroying thyroid tissue and reducing hormone production. It's the most common cause of hypothyroidism in iodine-sufficient countries, and it peaks in women aged 40-60.

Contributing factors in midlife:

• Accumulated stress and cortisol dysregulation

• Gut dysbiosis and intestinal permeability

• Nutrient deficiencies (selenium, zinc, iron, B12)

• Oestrogen shifts during perimenopause

2. Nutrient Deficiencies That Worsen with Age

Thyroid hormone production requires:

• Iodine (raw material for thyroid hormone)

• Selenium (enzyme needed to convert T4 to active T3)

• Zinc (supports thyroid receptors and immune regulation)

• Iron (needed for thyroid peroxidase enzyme)

• B12 and folate (support methylation, which is needed for hormone clearance)

Many midlife women are deficient in several of these nutrients, either from restricted eating patterns, gut dysfunction, or simply increased nutritional demands.

3. Oestrogen Dysregulation During Perimenopause

Oestrogen affects thyroid binding proteins and thyroid hormone clearance. As oestrogen fluctuates during perimenopause, thyroid function can become increasingly unstable. Read more in our blog 'Progesterone & Oestrogen Imbalance: The Hormonal Depression Trap in Midlife Women'

 The TSH Problem: Why "Normal" Isn't Adequate

Here's what happens: Your doctor checks TSH (thyroid-stimulating hormone). Your TSH comes back in the "normal range" (typically 0.4–4.0 mIU/L). Your doctor says your thyroid is fine. But you're still depressed, tired, and foggy.

Here's the problem with "normal": Reference ranges are designed to catch overt disease—they're based on statistical averages of everyone tested at that lab, including people who already have undiagnosed thyroid dysfunction. More than 95% of truly healthy people have a TSH below 2.5 mIU/L, and research shows that TSH levels above 2.5 mIU/L are strongly associated with depression, even when conventional testing says you're "fine".

In functional medicine, we look at optimal ranges, not just "normal" ones. For TSH, that means 0.5–2.5 mIU/L (and ideally closer to 1.0–2.0). We're not asking "Is this person sick enough to diagnose?"; we're asking "Is this person's thyroid functioning well enough to support their mental health, energy, and quality of life?" Those are two very different questions—and they require different thresholds.

When we assess thyroid function for mood and energy, we also test Free T3, Free T4, Reverse T3, and thyroid antibodies (TPO, Tg)—not just TSH. This gives us the full picture of how your thyroid is actually working, not just whether your pituitary is sending signals.

What they missed: TSH can be normal while your actual thyroid hormones (T4 and T3) are inadequate.

Think of TSH as your pituitary's "order form" for thyroid hormone. TSH rises when the pituitary senses you need more thyroid hormone. TSH falls when it senses you have enough.

But here's the catch:

• A woman with a TSH of 2.5 might feel fantastic

• Another woman with a TSH of 2.5 might feel severely depressed

The difference? Their actual T4 and T3 levels weren't tested

Additionally:

• High TSH with "normal range" T4 = your thyroid is struggling but hasn't failed yet (subclinical hypothyroidism). You feel terrible, but TSH-only testing misses it.

• Low-normal T3 = even if TSH and T4 look okay, insufficient active hormone reaches your brain (T3 is the active form; T4 must be converted)

• Thyroid antibodies (TPO, thyroglobulin) = you're autoimmune attacking your thyroid, but antibody-only testing misses this

Most depression-prone midlife women have one of these patterns, not just "high TSH."

What a Complete Thyroid Panel Looks Like

To properly assess thyroid function, you need:

Minimum panel:

1. TSH - pituitary signalling

2. Free T4 - circulating thyroid hormone (not bound to proteins)

3. Free T3 - active thyroid hormone at the cellular level

Complete panel (recommended):

1. TSH

2. Free T4

3. Free T3

4. Reverse T3 - an inactive form; if high, indicates poor T4-to-T3 conversion

5. TPO antibodies - autoimmune attack on thyroid peroxidase

6. Thyroglobulin antibodies - autoimmune attack on thyroglobulin protein

If you've been told your thyroid is "fine" but only TSH was checked, you need a complete panel. We regualry run full thyroid panels at urban Wellness, incuding checking for iron, B12, folate and vitamon D status all in one test.

Reverse T3: The Overlooked Culprit

Here's one more important piece: Reverse T3 (rT3).

Your body produces both T3 (active) and Reverse T3 (inactive) from T4. When you're under chronic stress, malnourished, or dealing with inflammation, your body preferentially produces more Reverse T3.

High Reverse T3 creates a depressed state because:

• Your T3 levels might look "normal," but a lot of it is the inactive form

• Your brain isn't getting adequate active thyroid hormone despite "normal" results

• You feel depressed, sluggish, and unmotivated

This is extremely common in midlife women dealing with stress, poor nutrition, or inflammation—and it's almost never tested unless a functional practitioner specifically orders it.

Important Note on Antidepressants

Many women with thyroid-driven depression are prescribed SSRIs without their thyroid being properly assessed. Here's the issue:

SSRIs don't work well when thyroid is insufficient because your brain doesn't have the basic metabolic machinery (T3) to produce serotonin adequately. You can take all the serotonin you want, but without adequate T3, your brain can't synthesize more.

The result: women stay depressed despite SSRIs, get their doses increased, try multiple SSRIs, but never get better—because the root cause (thyroid dysfunction) was never addressed.

If you're on an SSRI and depressed, thyroid assessment should be step one, not a last resort.

If this sounds familiar—you've been on antidepressants but still don't feel like yourself—it's time to look deeper. Learn how we help midlife women identify and address the physiological root causes of depression

Depression & Antidepressant Support

The Bottom Line

Thyroid dysfunction is one of the most correctable causes of depression in midlife women. Yet it's consistently overlooked because doctors don't order complete thyroid panels.

If you've never had your Free T3, Free T4, and thyroid antibodies tested—or if you were told your "thyroid is fine" based only on TSH—that's your first actionable step. Get a complete panel.

Your depression may not be a serotonin problem. It may be a thyroid problem. And thyroid problems are eminently fixable.

Next: In our next blog, we explore cortisol dysregulation, and how chronic stress rewires your brain toward depression.

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Reference Research:

- American Journal of Clinical Nutrition - thyroid hormones and brain function

- Journal of Thyroid Research - thyroid dysfunction and depression prevalence

- Functional Medicine Research Foundation - complete thyroid assessment protocols

- Mayo Clinic - thyroid hormone and neurotransmitter interactions

- NCBI/PMC - T3 supplementation and antidepressant response