When patients tell us their primary care doctor said their hormones were “all fine,” we ask one question: which markers did they actually run? The answer is almost always the same. TSH, total testosterone if the patient is male, and maybe estradiol if the patient is female. That panel has been the standard for decades, and it screens for overt disease reasonably well. What it does not do is explain why a 47-year-old executive with a normal TSH still needs three coffees by noon, or why a 52-year-old lawyer with normal total testosterone has lost his edge in the gym.
Three markers carry most of that explanatory weight. They are SHBG, reverse T3, and DHEA-S. Each one is well-validated, available at LabCorp and Quest, and rarely included in standard panels. The reasons have more to do with insurance reimbursement and primary care workflow than with clinical value.
Why Standard Hormone Panels Look So Thin
A typical 15-minute primary care appointment is not designed for hormone optimization. It is designed for disease screening. The panels that get ordered reflect that purpose. TSH catches hypothyroidism. Total testosterone catches frank hypogonadism. A basic metabolic panel catches diabetes and kidney issues. These are screening tests, and they have specific cutoffs that flag established disease, not subclinical dysfunction.
Insurance reimbursement reinforces the pattern. Tests that fall outside common screening guidelines often require prior authorization or get billed to the patient. A primary care office running 30 patients a day cannot afford the administrative load of justifying advanced hormone panels for symptoms that do not yet meet diagnostic criteria. So the panels stay narrow.
The result is a long stretch of years where patients feel measurably worse than they used to but cannot get a meaningful workup. They are stuck between “still in range” and “not yet diseased.” The three markers below sit exactly in that gap.
SHBG: The Variable That Distorts Every Other Reading
Sex hormone binding globulin (SHBG) is a protein produced by the liver. Its job is to bind to testosterone, estradiol, and DHT and carry them through the bloodstream. Hormones bound to SHBG are biologically inactive. Only the unbound (free) fraction can enter cells and do work.
This matters because total testosterone, the number on most lab panels, includes both bound and free hormone. If SHBG is high, total testosterone can look normal while free testosterone is low, and the patient feels every bit of that deficit. If SHBG is low, total testosterone can look low while free testosterone is actually adequate.
SHBG itself is influenced by a long list of other variables. Insulin resistance pushes it down. Estrogen excess pushes it up. Thyroid status moves it. Liver function changes it. Chronic alcohol use lowers it. Oral contraceptives raise it dramatically.
For a male patient, the practical consequence is that a total testosterone of 450 ng/dL means very different things depending on whether SHBG is 20 or 70. For a female patient in perimenopause, SHBG often rises sharply, which can leave free testosterone functionally lower than the total reading suggests. Either way, you cannot interpret testosterone without knowing SHBG. Most standard panels skip it.
Reverse T3: The Thyroid Detour No One Mentions
The thyroid produces mostly T4 (thyroxine), which is largely a storage form. T4 has to convert into T3 (triiodothyronine) to become biologically active. That conversion happens in the liver, the gut, and at the cellular level, and it is regulated by enzymes called deiodinases.
Under stress, illness, calorie restriction, or chronic inflammation, the body can shunt T4 into a different metabolite called reverse T3. Reverse T3 looks structurally similar to active T3 but does not activate the receptor. It actually competes with T3 at the receptor site. So elevated reverse T3 functions as a brake on thyroid activity even when TSH and free T4 look fine.
This is the mechanism behind what some practitioners call functional hypothyroidism. The brain is sending a normal signal (normal TSH), the thyroid is producing T4 (normal free T4), but the active hormone never reaches tissues in adequate amounts. The patient is hypothyroid at the cellular level despite normal screening labs.
The American Thyroid Association takes a conservative position on routine reverse T3 testing, partly because the ratio is hard to interpret in isolation and partly because TSH-only screening is cheaper and reasonably effective for catching primary disease. That conservatism is defensible from a population health standpoint. It is less useful for the individual patient who feels hypothyroid and tests “normal.” For more on why the thyroid axis can fail at the conversion step, see why TSH alone misses functional hypothyroidism.
DHEA-S: The Adrenal Reserve Marker
DHEA (dehydroepiandrosterone) is produced by the adrenal glands and serves as a precursor to both testosterone and estrogen. DHEA-S is the sulfated form, which is more stable in blood and easier to measure. Levels peak in the mid-20s and decline steadily through life.
For patients over 40, DHEA-S tends to track loosely with energy, libido, cognitive sharpness, immune resilience, and exercise recovery. It is not a perfect marker, and the research on supplementing DHEA is mixed for many endpoints. But the level itself is a useful window into adrenal reserve and into the precursor pool the body draws on to make sex hormones.
Patients who present with persistent fatigue, low libido, and brain fog despite normal testosterone or estrogen often have low DHEA-S. The adrenal contribution to circulating sex hormones is small in younger adults, but it becomes more important in midlife and beyond, especially after menopause when the ovary stops producing estrogen and the adrenal pathway becomes a primary source.
DHEA-S is inexpensive to test and almost never ordered as part of a standard panel. It is one of the simpler additions a primary care physician could make if the workflow allowed for it.
How These Three Markers Talk to Each Other
These tests are even more useful in combination than in isolation.
SHBG and free testosterone are inseparable. You cannot calculate free testosterone accurately without SHBG (or measure it directly with equilibrium dialysis, which most labs skip). A man with a total testosterone of 500 and an SHBG of 65 has functionally lower free testosterone than a man with a total of 400 and an SHBG of 25.
Reverse T3 and free T3 form a ratio that is more diagnostic than either alone. When the ratio is skewed (high rT3, low or low-normal free T3), it points to a conversion problem driven by stress, inflammation, nutrient deficiency, or calorie restriction. The fix is rarely thyroid medication. The fix is usually addressing the upstream driver.
DHEA-S provides context for the cortisol picture. When DHEA-S is low and cortisol patterns are dysregulated (which requires its own testing), the HPA axis is not coping well. This often shows up clinically as the high-functioning professional who is running on fumes but still hitting deadlines. The labs explain why coffee stopped working.
Add insulin resistance into the picture (often missed because fasting insulin is not on standard panels), and the same patient suddenly has a unified explanation. Insulin resistance pushes SHBG down, which raises free estrogen relative to free testosterone in men and contributes to PCOS-pattern symptoms in women. It also impairs T4 to T3 conversion, which raises reverse T3. The whole system is connected. For a deeper look at how insulin and hormone status link together, our team has written more on the topic on the main hormone optimization page.
What an Optimization-Focused Workup Includes
At Towsen Clinic, the initial hormone panel goes well beyond TSH and total testosterone. A typical first visit pulls:
For thyroid: TSH, free T4, free T3, reverse T3, TPO antibodies, and thyroglobulin antibodies. The antibody markers catch Hashimoto’s even when TSH still looks acceptable.
For sex hormones in men: total testosterone, free testosterone (calculated and ideally measured), SHBG, estradiol (sensitive assay), DHT, prolactin, LH, FSH, and DHEA-S.
For sex hormones in women: estradiol, progesterone (timed appropriately to cycle if still cycling), total testosterone, free testosterone, SHBG, DHEA-S, LH, FSH, and prolactin. For women in perimenopause, the panel often gets repeated across two or three months to capture the swings, since a single snapshot can mislead. We cover the timeline question in more detail under perimenopause and menopause care.
For metabolic context: fasting glucose, fasting insulin, HOMA-IR, HbA1c, full lipid panel, and inflammatory markers like hs-CRP. These are not strictly “hormone” tests, but the hormone picture cannot be read accurately without them.
This is more bloodwork than a standard physical, but it is also the difference between treating a patient and screening a patient. The point is not to find more things to medicate. The point is to find the actual root of the symptoms and address it precisely.
If your last set of labs came back “normal” and you still feel something is off, the missing markers may be the reason. Schedule a hormone consultation and we will start with a workup that actually looks at the variables that matter.
