Why do I still have symptoms when my hormone levels are normal?
A blood test counts how much of a hormone is in your blood. It cannot tell you whether your cells responded to it. A hormone is a message, and a receptor is what receives it. When receptors respond less, you can have a normal number and a body that behaves as if the hormone is running low. This is well established for insulin and for cortisol. It is the reason I read the number and the person together, whether that person is a woman of 46, a man of 55 or someone in their twenties.
Hormones ask. Receptors decide.
A hormone is a chemical messenger. A gland releases it, the blood carries it, and it reaches almost every cell you have. Most of those cells ignore it. Only a cell with the matching receptor can respond.
A receptor is a protein that sits on the surface of a cell or inside it. The hormone fits it the way a key fits a lock. Once the key turns, the cell does something. It takes in sugar, or burns fuel, or builds bone, or calms an immune response.
Your cells are in charge of their own receptors. They can make more of them or fewer of them. They can also turn the signal up or down after the hormone has arrived. So the same amount of hormone can produce a strong effect in one person and a weak effect in another. The lab report shows the amount. It is silent on the effect.
Insulin is the clearest example
Insulin tells muscle, liver and fat cells to take sugar out of the blood. In insulin resistance those cells respond less. The pancreas makes more insulin to get the same job done, and for a long time that works. Blood sugar stays in range while insulin runs high.
This is why a fasting glucose can look fine for years in someone whose body is already working hard to keep it there. I see it in women in perimenopause whose waist changed and whose diet did not. I see it in men in their fifties with rising triglycerides. I see it in women in their twenties with PCOS. The number that would show it, fasting insulin, is often never ordered. I wrote about that in Issue 012.
Cortisol can stop being heard too
Cortisol has many jobs. One of them is to tell the immune system when to stand down. In a well known study from Carnegie Mellon, people who had been under long lasting stress had immune cells that responded less to cortisol. When the researchers exposed volunteers to a cold virus, those people were more likely to get sick.
Their cortisol was still being made. The cells had stopped listening to it. That is a research finding and there is no clinic test for it. I include it because it explains something clients tell me all the time. They went through 2 hard years, their cortisol test came back normal, and they catch everything their kids bring home. More on that pattern in Issue 019.
What turns receptors down
The research on insulin gives the clearest list.
A hormone that stays high for a long time is the first cause. Cells that are flooded with insulin all day respond by paying less attention to it. The pancreas answers with more insulin, and the loop feeds itself.
Short sleep is the second. In one study of healthy adults, a single night of 4 hours of sleep lowered insulin sensitivity by roughly a fifth the next day.
Sitting most of the day matters, and so does losing muscle. Muscle is where most of your blood sugar goes after a meal. Less muscle means fewer places for it to go. Fat stored deep in the belly, around the organs, also makes cells less responsive to insulin.
Some medications do this as a side effect. Steroid medications such as prednisone are the common example. Never stop a prescribed medication on your own. Ask the prescriber what they are watching for.
Then there is what you inherited. Family history is biology. If a parent had type 2 diabetes, your cells may respond less to insulin from a younger age, and that is worth knowing at 25 instead of 55.
What turns them back up
Movement comes first because it works through 2 routes. A working muscle pulls sugar out of the blood without needing insulin at all. Then, after the session, your cells stay more sensitive to insulin for a day or longer. That effect fades, which is why regular movement matters more than one hard workout a week.
Strength training adds muscle, and muscle is storage space for sugar. I wrote about how to start when you are already tired in Issue 021.
If you take insulin or a diabetes medication that can cause low blood sugar, talk to your prescriber before you change how much you move. Your dose may need to change with it.
Sleep is the third lever, and the study above shows how fast it acts in both directions. The fourth is the load on your nervous system. I cannot promise that lowering stress will change a lab value. I can tell you the research on cortisol points that way, and that my clients sleep, eat and move differently once their system stands down.
A lab measures what was sent. Your body shows you what was received.
Thyroid, estrogen and testosterone: what is known and what is guessed
I want to be careful here, because the receptor idea gets stretched online.
Thyroid hormone has to get inside the cell and bind to receptors there. A true inherited resistance to thyroid hormone exists, and it is rare, about one person in 40,000. The claim that most tired people with normal thyroid labs have a hidden receptor problem goes further than the evidence. The more common story is that only TSH was tested, which I covered in Issue 011, or that the cause sits somewhere else, such as iron, sleep or blood sugar.
Estrogen receptors sit in the brain, bone, blood vessels and bladder, in men as well as women. In perimenopause the estrogen level itself swings from week to week, so one blood draw tells you very little. If hot flashes are the problem, hormone therapy is the most effective treatment for them. That is a conversation for a menopause trained doctor.
Testosterone works the same way in principle. Two men with the same level can feel very different, and inherited differences in the receptor are one studied reason. There is no routine test for that. What the Endocrine Society guideline asks for is symptoms plus a low level on 2 separate morning tests.
What I ask people to get
I do not order tests or diagnose. I tell clients what to ask their doctor for, and why.
I ask for fasting insulin drawn with fasting glucose, from the same morning sample. Together they let a doctor estimate how hard the pancreas is working. Either one alone hides the picture.
I ask for an A1c and a lipid panel. High triglycerides with low HDL is a pattern that often travels with insulin resistance, and most people already have those results sitting in a folder.
I ask people to measure their waist with a tape and write it down with the date. It is free and it tracks the kind of fat that affects insulin most.
If the only thyroid test on file is TSH, I ask for a fuller panel. For a man with low drive, low mood and low energy, I ask about a morning testosterone, repeated once if it comes back low.
Last, I ask for 2 weeks of real sleep notes. Bedtime, wake time, and how many nights fell under 6 hours. It often explains more than the panel does.
When to push harder with your doctor
Go back the same week if you have strong thirst, frequent urination, blurred vision or weight loss you cannot explain. Those can be signs of high blood sugar.
Ask directly about insulin if you notice dark, velvety patches of skin on the neck or in the armpits, or a cluster of skin tags there.
Ask for a PCOS workup if you are a younger woman with irregular periods plus acne or new hair growth on the face. Ask for a workup if your periods stopped before 40.
Men should raise a loss of morning erections, low libido or new breast tissue. Those deserve testing, and a shrug is the wrong answer.
Easy bruising, purple stretch marks, a rounder face and weak thigh muscles together can point to too much cortisol. That needs a medical evaluation.
If your fatigue is getting worse and every result is called normal, ask one question. What has not been tested yet?
FAQ
Can you test hormone receptors?
There is no routine clinic test for how sensitive your receptors are. Doctors infer it from pairs of results, such as insulin read next to glucose. Receptor testing does exist in cancer care, where a tumor is checked for estrogen receptors, and that is a different purpose.
Can I have insulin resistance with normal blood sugar?
Yes. In the early years the pancreas makes extra insulin and that keeps glucose in range. Blood sugar rises later, when the pancreas can no longer keep up. A fasting insulin drawn with a fasting glucose can show the earlier stage.
Is thyroid hormone resistance real?
It is real and it is rare. It is an inherited condition that affects about one person in 40,000. If you have thyroid symptoms and a normal TSH, the first step is a fuller thyroid panel and a look at other causes such as low iron.
How fast can insulin sensitivity improve?
One session of exercise improves it for a day or longer. One short night of sleep lowers it the next day. Lasting change comes from weeks and months of regular movement, enough sleep and more muscle.
Does this apply to men and younger people?
Yes. Receptors work the same way in every body. Insulin resistance can begin in the twenties, and men in midlife often have it for years before a glucose test flags.
In good health,
Yvette Rose
Sources
- NIDDK. Insulin resistance and prediabetes.
- Cohen S et al. Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk. PNAS, 2012.
- Donga E et al. A single night of partial sleep deprivation induces insulin resistance in multiple metabolic pathways in healthy subjects. J Clin Endocrinol Metab, 2010.
- Colberg SR et al. Physical activity/exercise and diabetes: a position statement of the American Diabetes Association. Diabetes Care, 2016.
- Bhasin S et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab, 2018.
This is general wellness education and not medical advice, diagnosis or treatment. Talk to a qualified professional, especially if you are pregnant, nursing, taking medication or managing a condition.