Hormones & Optimization
THYROID OPTIMIZATION
Your thyroid controls metabolism, energy, mood, and body composition. Most standard testing misses dysfunction entirely. Here's what optimal actually looks like and why "normal" isn't good enough.
WHAT YOUR THYROID DOES
The thyroid is a butterfly-shaped gland at the base of your neck, and it functions as the master regulator of your metabolism. It produces two primary hormones: thyroxine (T4) and triiodothyronine (T3). T4 is the storage form — it circulates in large quantities but is biologically inactive. T3 is the active form — it's what your cells actually use. About 80% of T3 is produced by converting T4 in peripheral tissues (liver, gut, kidneys, muscles), not by the thyroid gland itself. This conversion step is where a huge amount of dysfunction hides.
Every cell in your body has thyroid hormone receptors. That's not hyperbole — it's physiology. T3 enters the cell nucleus and directly regulates gene transcription. This is why thyroid dysfunction affects virtually every system in the body and why the symptom list is so broad that it gets dismissed as "stress" or "aging."
Here's what thyroid hormones directly regulate:
Basal Metabolic Rate
T3 sets the pace at which every cell burns fuel. Low T3 means fewer calories burned at rest, lower body temperature, and a sluggish metabolism that makes fat loss feel impossible even in a calorie deficit.
Energy Production
Thyroid hormones regulate mitochondrial function and ATP production. When thyroid output is low, your cells produce less energy. The result is fatigue that sleep doesn't fix — because the problem isn't rest, it's cellular energy output.
Cognitive Function
T3 directly affects neurotransmitter synthesis, neural myelination, and cerebral blood flow. Brain fog, poor concentration, memory issues, and slowed processing speed are hallmark symptoms of low thyroid function.
Heart Rate & Cardiovascular Function
T3 regulates heart rate, cardiac output, and vascular resistance. Hypothyroidism is directly linked to elevated LDL cholesterol, increased arterial stiffness, and higher cardiovascular risk — even at subclinical levels.
Body Temperature Regulation
Cold hands, cold feet, always needing an extra layer — this is a classic sign of suboptimal thyroid function. T3 drives thermogenesis. Low T3 means low heat production.
Hair, Skin & Nail Health
Thyroid hormones regulate keratinocyte and fibroblast activity. Hair thinning (especially the outer third of the eyebrow), dry skin, and brittle nails are among the earliest visible signs of thyroid dysfunction.
Menstrual Regularity & Fertility
Thyroid hormones influence GnRH pulsatility, sex hormone-binding globulin (SHBG), and progesterone production. Hypothyroidism is a documented cause of irregular periods, anovulation, and recurrent miscarriage. The American Thyroid Association recommends screening in women struggling with fertility.
Cholesterol Metabolism & Bone Density
T3 upregulates LDL receptors in the liver, increasing cholesterol clearance. Hypothyroidism raises LDL and total cholesterol. Thyroid hormones also regulate bone turnover — both deficiency and excess affect bone mineral density, making proper dosing critical.
The takeaway: Your thyroid isn't just one system among many. It's the pacemaker for your entire metabolism. When it's off, everything downstream is off — energy, body composition, cognition, mood, cardiovascular health, and reproductive function. And because the symptoms overlap with so many other conditions, thyroid dysfunction is one of the most under-recognized problems in medicine.
WHY STANDARD TESTING MISSES THE PROBLEM
Most doctors test only TSH. Some add Free T4. That's it. This is the standard of care in conventional medicine, and it misses a staggering amount of thyroid dysfunction.
TSH (thyroid-stimulating hormone) is produced by the pituitary gland. When thyroid hormone levels drop, the pituitary releases more TSH to tell the thyroid to produce more. When thyroid levels are adequate, TSH drops. It's a feedback loop — and testing TSH alone tells you what the pituitary thinks about thyroid levels. It does not tell you how much active hormone is reaching your cells, whether you're converting T4 to T3 properly, whether reverse T3 is blocking your receptors, or whether your immune system is slowly destroying the gland.
Testing only TSH is like checking the thermostat reading but never checking whether the furnace is actually producing heat, whether the ducts are open, or whether someone left a window open. The thermostat might read "fine" while you're freezing.
TSH (Thyroid-Stimulating Hormone)
The pituitary's signal to the thyroid. Tells you whether the brain thinks it's getting enough thyroid hormone. Useful, but it's an indirect marker. TSH can be "normal" while Free T3 is low, Reverse T3 is high, or antibodies are elevated. It also fluctuates throughout the day (lowest in the afternoon, highest in the early morning) and is suppressed by stress, cortisol, and certain medications.
Free T4 (Free Thyroxine)
The unbound, available form of the storage hormone. Most T4 in your blood is bound to proteins (mainly thyroxine-binding globulin, or TBG) and is biologically inactive. Free T4 is what's available for conversion to T3. Important to measure, but T4 is not the active hormone — it has to be converted. A patient with adequate Free T4 but poor conversion will still be functionally hypothyroid.
Free T3 (Free Triiodothyronine)
The active hormone. This is what actually enters your cells, binds to nuclear receptors, and drives metabolic activity. Free T3 is arguably the single most important thyroid marker for how you actually feel and function — and it's the one most commonly left off standard panels. You can have a "normal" TSH and Free T4 while your Free T3 is at the bottom of the range, leaving you fatigued, foggy, and gaining weight.
Reverse T3 (rT3)
An inactive metabolite of T4 that competes with T3 for receptor binding. Under stress, caloric restriction, inflammation, or illness, the body preferentially converts T4 to Reverse T3 instead of active T3. This is a protective mechanism — it slows metabolism when the body perceives threat. But in chronic stress, overdieting, or systemic inflammation, Reverse T3 stays elevated and effectively blocks your cells from using the T3 you do produce. High Reverse T3 with "normal" TSH and Free T4 is one of the most common patterns we see in patients who feel terrible but are told their thyroid is fine.
TPO Antibodies (Thyroid Peroxidase Antibodies)
The primary marker for Hashimoto's thyroiditis — the autoimmune condition that is the most common cause of hypothyroidism in the developed world. Elevated TPO antibodies mean your immune system is attacking your thyroid gland. The damage is gradual. TSH may remain normal for years while the gland is slowly being destroyed. By the time TSH finally rises out of range, significant gland damage has already occurred. Early detection through antibody testing allows intervention before irreversible damage.
Thyroglobulin Antibodies (TgAb)
Another autoimmune marker. Some patients with Hashimoto's have elevated TgAb but normal TPO antibodies, so testing both increases diagnostic sensitivity. Thyroglobulin is a protein the thyroid uses to produce hormones — antibodies against it indicate immune-mediated gland destruction.
Why this matters: A TSH-only test gives you one data point out of six. It's the medical equivalent of checking one tire on a car and declaring the vehicle safe to drive. You can have a TSH of 2.0 (perfectly "normal") and still have low Free T3, elevated Reverse T3, and positive TPO antibodies — meaning you're functionally hypothyroid, your cells are blocked from using the T3 you do make, and your immune system is destroying the gland. A comprehensive panel catches all of this. A TSH-only test catches none of it.
NORMAL VS. OPTIMAL RANGES
Reference ranges on lab reports are derived from the statistical distribution of the testing population. That population includes the elderly, the obese, the chronically ill, and people with undiagnosed thyroid disease. The range represents where 95% of that population falls — not where people feel and function their best.
Optimal ranges are based on clinical outcomes — the ranges where patients consistently report the best energy, cognition, body composition, and mood. The gap between "normal" and "optimal" is where most thyroid dysfunction lives, undiagnosed and untreated.
| Marker | Standard "Normal" Range | Optimal Range |
|---|---|---|
| TSH | 0.4 – 4.5 mIU/L | 0.5 – 2.0 mIU/L |
| Free T4 | 0.8 – 1.8 ng/dL | 1.0 – 1.5 ng/dL |
| Free T3 | 2.0 – 4.4 pg/mL | 3.0 – 4.0 pg/mL |
| Reverse T3 | < 24 ng/dL | < 15 ng/dL |
| TPO Antibodies | < 35 IU/mL | < 10 IU/mL |
| Thyroglobulin Antibodies | < 40 IU/mL | < 10 IU/mL |
Look at TSH. The standard range goes up to 4.5 mIU/L. A patient with a TSH of 4.2 will be told "your thyroid is normal." But research published in the Journal of Clinical Endocrinology & Metabolism has shown that TSH levels above 2.5 are associated with increased risk of progression to overt hypothyroidism, and that patients with TSH in the 0.5-2.0 range report significantly better energy, mood, and cognitive function. The National Academy of Clinical Biochemistry has recommended narrowing the upper limit of the TSH reference range to 2.5 mIU/L — a recommendation that most labs and conventional practitioners still have not adopted.
The same pattern holds for Free T3. A value of 2.3 pg/mL is technically "in range" but sits at the bottom — a level where most patients experience fatigue, brain fog, and difficulty with body composition. Moving that same patient to 3.2-3.8 pg/mL often resolves symptoms entirely.
Reverse T3 is especially overlooked. A value of 20 ng/dL is "normal" by most lab ranges but indicates significant T3 receptor blockade. When the Reverse T3 to Free T3 ratio is too high, you have adequate thyroid hormone production that isn't getting into cells effectively. This is functional hypothyroidism that a standard panel will never detect.
The difference matters. "Normal" means you don't have a disease that requires emergency intervention. "Optimal" means your thyroid is actually performing at the level that supports how you want to feel and function. These are not the same standard, and most people are being held to the wrong one.
COMMON THYROID DYSFUNCTION PATTERNS
Thyroid dysfunction isn't one thing. It's a spectrum of patterns, each with a different root cause and requiring a different approach. Here are the most common patterns we identify and treat:
Overt Hypothyroidism
The classic pattern: TSH elevated above 4.5-10+ mIU/L, Free T4 and Free T3 below range. This is what standard medicine is built to catch. Symptoms are typically severe — significant fatigue, weight gain, cold intolerance, constipation, depression. Treatment with thyroid hormone replacement is straightforward and universally accepted. This is the easy one. The problem is the patterns below, which are far more common and far more frequently missed.
Subclinical Hypothyroidism
TSH elevated (typically 2.5-10 mIU/L) with Free T4 still in range. Conventional medicine debates whether this needs treatment. The data is clear: subclinical hypothyroidism is associated with increased cardiovascular risk (Rodondi et al., 2010, JAMA), progression to overt hypothyroidism (Vanderpump et al., 1995), impaired cognitive function, and symptoms that reduce quality of life. A meta-analysis by Razvi et al. (2008) in the Journal of Clinical Endocrinology & Metabolism showed that treatment of subclinical hypothyroidism improved lipid profiles, cardiac function, and symptom scores. Waiting for it to get worse is not a strategy.
Hashimoto's Thyroiditis (Autoimmune Thyroiditis)
The most common cause of hypothyroidism in iodine-sufficient countries. Elevated TPO and/or Thyroglobulin antibodies indicate the immune system is attacking and gradually destroying thyroid tissue. The insidious part: TSH and thyroid hormones can remain "normal" for years while the gland is under active autoimmune attack. By the time TSH rises out of range, 50-80% of functional thyroid tissue may already be destroyed. Early detection through antibody testing allows intervention with lifestyle, nutrition, and immune-modulating strategies before irreversible gland loss. Hashimoto's affects up to 5% of the population and is 5-8 times more common in women.
Poor T4-to-T3 Conversion
TSH and Free T4 are normal, but Free T3 is low. The thyroid is producing adequate T4, but the body isn't converting it to the active T3 form efficiently. Conversion depends on the enzyme 5'-deiodinase, which requires selenium, zinc, and iron as cofactors, and is impaired by chronic stress (elevated cortisol), inflammation, gut dysfunction, caloric restriction, and certain medications. This pattern is extremely common in patients under chronic stress or those who have been aggressively dieting. Standard treatment with levothyroxine (T4 only) won't fix this — you're adding more of the hormone the body can't convert. These patients often need direct T3 supplementation or combination therapy.
High Reverse T3
Reverse T3 is elevated, effectively blocking T3 receptors even when Free T3 is adequate. Common triggers: chronic physiological or psychological stress, caloric restriction or prolonged fasting, systemic inflammation, chronic illness, and iron deficiency. The body is diverting T4 to the inactive pathway instead of the active one. This is a protective mechanism — the body is downregulating metabolism because it perceives a threat. The fix requires addressing the root cause (stress, inflammation, nutritional deficiency) in addition to potential medication adjustments.
Thyroid + Sex Hormone Interactions
Thyroid function doesn't exist in isolation. Estrogen increases thyroxine-binding globulin (TBG), which binds more T4 and T3, reducing the amount of free (usable) hormone available. This is why women on oral estrogen (birth control pills, oral HRT) frequently develop thyroid symptoms — their total thyroid hormone may be adequate, but free hormone levels drop. Conversely, hypothyroidism increases SHBG and alters estrogen/progesterone ratios. Testosterone replacement can also affect thyroid-binding proteins. This is why hormone optimization requires looking at the entire endocrine system, not one axis at a time.
SYMPTOMS OF THYROID DYSFUNCTION
Thyroid symptoms are non-specific — meaning they overlap with dozens of other conditions. This is part of why thyroid dysfunction is so often dismissed. But when multiple symptoms from this list cluster together, thyroid should be high on the differential. These are the most common presentations of hypothyroidism and suboptimal thyroid function:
Fatigue & Low Energy
Persistent tiredness that doesn't resolve with sleep. The hallmark symptom. Driven by reduced mitochondrial ATP production.
Weight Gain
Unexplained weight gain or inability to lose weight despite diet and exercise. Reduced metabolic rate plus increased water retention.
Brain Fog
Poor concentration, memory issues, slowed processing speed. T3 directly regulates cerebral blood flow and neurotransmitter synthesis.
Cold Intolerance
Always cold, cold hands and feet, needing extra layers. T3 drives thermogenesis. Low T3 means low heat production.
Hair Thinning & Loss
Diffuse hair thinning, loss of the outer third of the eyebrow, brittle hair. Thyroid hormones regulate the hair growth cycle directly.
Dry Skin
Rough, dry, flaky skin — especially on the shins, elbows, and hands. Reduced keratinocyte turnover and decreased sebum production.
Constipation
Slowed gut motility is a direct consequence of reduced T3 activity on smooth muscle. Often dismissed as a dietary issue when thyroid is the root cause.
Depression & Mood Changes
Low mood, irritability, anxiety, or frank depression. T3 modulates serotonin receptor sensitivity. Thyroid dysfunction should be ruled out before starting antidepressants.
Elevated Cholesterol
High LDL and total cholesterol that doesn't respond to diet. T3 upregulates hepatic LDL receptors. Fix the thyroid and cholesterol often normalizes without statins.
Irregular Periods
Heavy, irregular, or absent menstrual cycles. Thyroid dysfunction disrupts the HPG axis, alters SHBG, and impairs progesterone production.
Muscle Weakness
Generalized weakness, slow recovery from exercise, muscle cramps. T3 regulates muscle protein synthesis and mitochondrial density in skeletal muscle.
Fluid Retention
Puffy face, swollen hands or ankles. Hypothyroidism causes accumulation of hyaluronic acid in tissues, drawing water in. This is myxedema — distinct from normal edema.
The pattern matters more than any single symptom. Fatigue alone could be a hundred things. Fatigue plus cold intolerance plus weight gain plus brain fog plus hair thinning — that clustering is thyroid until proven otherwise. And "proven otherwise" means a full panel, not just TSH.
HOW THYROID OPTIMIZATION WORKS AT MOONSHOT
Thyroid optimization at Moonshot isn't a standalone protocol. It's part of a comprehensive approach to endocrine and metabolic health. The thyroid doesn't exist in isolation — it's regulated by the hypothalamic-pituitary-thyroid (HPT) axis, influenced by cortisol (HPA axis), affected by sex hormones, and dependent on nutritional cofactors. We treat the system, not just the gland.
1. Comprehensive Testing
Full thyroid panel: TSH, Free T4, Free T3, Reverse T3, TPO antibodies, and Thyroglobulin antibodies. We also assess related markers: fasting insulin, inflammatory markers (hs-CRP, ferritin), iron studies (ferritin, serum iron, TIBC), vitamin D, selenium, zinc, and cortisol. These cofactors directly impact thyroid production, conversion, and receptor sensitivity. Without them, you're treating a symptom while the root cause persists.
2. Clinical Interpretation in Context
Numbers don't exist in a vacuum. A TSH of 1.5 in a 30-year-old with severe fatigue, weight gain, elevated TPO antibodies, and a Free T3 of 2.2 is not "fine." We interpret labs in the context of your symptoms, medical history, other hormone levels, body composition goals, and overall clinical picture. The question isn't "is this in range?" The question is "is this optimal for this patient?"
3. Treatment Options
Treatment is individualized based on the specific pattern of dysfunction. Options include: Levothyroxine (synthetic T4) — the standard first-line treatment; provides T4 that the body converts to T3. Works well for patients with intact conversion capacity. Liothyronine (synthetic T3) — direct T3 replacement, used when conversion is impaired or when patients don't respond adequately to T4 alone. Often added to levothyroxine as combination therapy. Desiccated thyroid (Armour Thyroid, NP Thyroid) — derived from porcine thyroid glands, contains both T4 and T3 in a physiologic ratio. Some patients prefer desiccated thyroid and report better symptom resolution compared to synthetic T4 alone. Nutritional optimization — correcting selenium, zinc, iron, iodine, and vitamin D deficiencies that impair thyroid function. Lifestyle modification — addressing chronic stress, sleep, gut health, and inflammatory triggers that suppress thyroid function.
4. Ongoing Monitoring
Thyroid optimization isn't "prescribe and forget." We recheck labs 6-8 weeks after initiation or dose changes (the time required for thyroid levels to reach steady state), then every 3-6 months once stable. Dosing is adjusted based on labs and symptoms — the goal is how you feel and function, not just where the numbers land. We also monitor for signs of over-replacement (resting heart rate, anxiety, bone density considerations) to ensure the dose stays in the therapeutic sweet spot.
Integration with hormone optimization: Thyroid function affects and is affected by testosterone, estrogen, progesterone, cortisol, and insulin. Optimizing thyroid in isolation while ignoring a cortisol problem, an estrogen dominance pattern, or insulin resistance is incomplete medicine. At Moonshot, thyroid is one component of a full endocrine assessment. We address the entire system because that's how the body actually works.
COMMON QUESTIONS
Why doesn't my doctor check more than just TSH?
Most standard panels only test TSH, and sometimes Free T4. This is driven by insurance guidelines and a conventional model that treats thyroid disease as binary: you either have it or you don't. But this approach misses subclinical dysfunction, T4-to-T3 conversion issues, elevated reverse T3, and thyroid antibodies (Hashimoto's). A TSH-only approach is like checking your car's oil light but never testing the oil quality, filter condition, or engine temperature. Moonshot tests the full thyroid panel — TSH, Free T4, Free T3, Reverse T3, TPO antibodies, and Thyroglobulin antibodies — because you can't optimize what you don't measure.
What's the difference between normal and optimal thyroid levels?
Normal reference ranges are derived from population averages — which include sick, sedentary, and metabolically unhealthy people. They tell you whether you have a diagnosable disease, not whether your thyroid is performing well. Optimal ranges are narrower and based on where patients report feeling and performing their best. For example, a TSH of 4.0 mIU/L falls within the "normal" reference range (0.4-4.5), but most patients feel significantly better with a TSH under 2.0. The same pattern holds for Free T3, Free T4, and Reverse T3. Normal keeps you out of the emergency room. Optimal is where you actually feel good.
Can thyroid problems cause weight gain?
Yes. Hypothyroidism — even subclinical hypothyroidism — slows your basal metabolic rate, increases water retention, and impairs your body's ability to mobilize and burn fat. Overt hypothyroidism can cause 10 to 30 pounds of weight gain, and even mild thyroid underperformance (TSH in the 3-5 range) can make fat loss significantly harder despite consistent diet and exercise. This is one of the most frustrating patterns we see: patients doing everything right but unable to lose weight because their thyroid is technically "normal" but functionally sluggish.
What does Moonshot's thyroid panel include?
Our full thyroid panel includes: TSH (thyroid-stimulating hormone), Free T4 (the inactive storage form), Free T3 (the active hormone your cells actually use), Reverse T3 (an inactive metabolite that blocks T3 receptors), TPO antibodies (thyroid peroxidase antibodies — the primary marker for Hashimoto's thyroiditis), and Thyroglobulin antibodies (another autoimmune marker). This gives us the complete picture: how much signal your brain is sending, how much hormone your thyroid is producing, how well you're converting it to the active form, whether it's being blocked, and whether your immune system is attacking the gland itself. A TSH-only test gives you one data point out of six.
Is thyroid medication safe long-term?
Yes. Thyroid hormone replacement — whether levothyroxine (synthetic T4), liothyronine (synthetic T3), or desiccated thyroid (Armour Thyroid, NP Thyroid) — is one of the most well-studied and commonly prescribed medication classes in medicine. It has been used safely for over 60 years. You are not adding a foreign substance to your body; you are replacing what your thyroid isn't producing enough of. The key is proper dosing and ongoing monitoring. Over-replacement can cause symptoms of hyperthyroidism (anxiety, rapid heart rate, bone loss), which is why regular lab work and clinical follow-up are essential. When dosed correctly and monitored properly, thyroid replacement is safe indefinitely.
References
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TIRED OF BEING TOLD YOUR THYROID IS "NORMAL"?
If you have the symptoms but keep getting told your labs are fine, you probably haven't had the right labs run. A full thyroid panel takes the guesswork out of it.
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