MD & DO "Normal" serum TSH level

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cbrons

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Was going to PM him but I think this is a beneficial for anyone interested.

@Raryn - what is the normal serum TSH for young otherwise healthy people?

Based on reading UpToDate, Harrison's and a few endocrinology texts, I haven't found a definitive answer. However, I did recently read this from the ATA/AACE Guidelines:

https://www.aace.com/files/hypothyroidism_guidelines.pdf


The National Academy of Clinical Biochemists, however, indicated that 95% of individuals without evidence of thyroid disease have TSH concentrations below 2.5 mIU/L (85), and it has been suggested that the upper limit of the TSH reference range be lowered to 2.5 mIU/L (86). While many patients with TSH concentrations in this range do not develop hypothyroidism, those patients with AITD are much more likely to develop hypothyroidism, either subclinical or overt (87) (see Therapeutic endpoints in the treatment of hypothyroidism for further discussion).

In individuals without serologic evidence of AITD, TSH values above 3.0 mIU/L occur with increasing frequency with age, with elderly (>80 years of age) individuals having a 23.9% prevalence of TSH values between 2.5 and 4.5 mIU/L, and a 12% prevalence of TSH concentrations above 4.5 mIU/L (88). Thus, very mild TSH elevations in older individuals may not reflect subclinical ATA/AACE Guidelines for Hypothyroidism in Adults, Endocr Pract. 2012;18(No. 6) e13 thyroid dysfunction, but rather be a normal manifestation of aging. The caveat is that while the normal TSH reference range—particularly for some subpopulations—may need to be narrowed (85,86), the normal reference range may widen with increasing age (84).
^ So in an otherwise healthy 30 year old female or heck even 20 or 25 year old with a few vague symptoms that may or may not be related to PH, what do you do with a TSH of 4.0 mIU/L?

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Young person with normal ft4 and tsh between upper limit of normal to ~7 I believe you only treat if they are overtly symptomatic. For a borderline tsh with symptoms my guess is you just propose a risk benefit to the patient and see what they decide.

Personally I had a tsh of 4.3 or something and felt much better after starting thyroxine.
 
It's controversial.

The normal range for any lab test is determined as the 95% confidence interval for a sample of "young", "healthy" controls. Traditionally, that range for TSH has been ~0.5-5.0, though I've seen the ULN depending on the lab being anywhere from 4.5 to 6.0. The problem is that that 95% confidence interval is primarily grouped in the lower half of that range and determining "healthy" is difficult. If you rigorously screen your control population and exclude anyone with even a family hx of thyroid disease, you end up with a normal TSH range closer to 0.3-3.0, with that ULN being sometimes even as low as 2 or 2.5.

What to do with these intermediate TSH values (in the 2.5 to 5 or even 2.5 to 10 range) is something that if you ask three endocrinologists you'll get four opinions. Everyone is pretty certain that in pregnant women you should get the TSH < 2.5 in the first trimester and <3 thereafter (though the evidence on that is mixed as well), but for every other population it's really hard to say. Women of childbearing age I'll commonly start on LT4 to get them under 2.5. Anyone with clear symptoms is worth a trial of therapy as well, though clear symptoms is a nebulous thing to define (everyone is fatigued if you ask them often enough).

Other expert advised individuals to treat are those with a TSH above 10, those with a goiter, and those with positive antibodies. If you search for evidence supporting treatment in each of those cases, it's hard to get a clear answer. For a young person with these indications, I tend to err on the side of treatment.

The opposite problems happens with elderly individuals btw. The normal range is based on young people, but TSH tends to go up as you get older. So a TSH of 6 or 7 in an 85 year old might be perfectly normal, and it's even more controversial whether or not to treat them. Without clear symptoms, if a geriatric patient has a TSH <10, I typically avoid treating them.

Can also call on @rokshana for another opinion.
 
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It's controversial.

The normal range for any lab test is determined as the 95% confidence interval for a sample of "young", "healthy" controls. Traditionally, that range for TSH has been ~0.5-5.0, though I've seen the ULN depending on the lab being anywhere from 4.5 to 6.0. The problem is that that 95% confidence interval is primarily grouped in the lower half of that range and determining "healthy" is difficult. If you rigorously screen your control population and exclude anyone with even a family hx of thyroid disease, you end up with a normal TSH range closer to 0.3-3.0, with that ULN being sometimes even as low as 2 or 2.5.

What to do with these intermediate TSH values (in the 2.5 to 5 or even 2.5 to 10 range) is something that if you ask three endocrinologists you'll get four opinions. Everyone is pretty certain that in pregnant women you should get the TSH < 2.5 in the first trimester and <3 thereafter (though the evidence on that is mixed as well), but for every other population it's really hard to say. Women of childbearing age I'll commonly start on LT4 to get them under 2.5. Anyone with clear symptoms is worth a trial of therapy as well, though clear symptoms is a nebulous thing to define (everyone is fatigued if you ask them often enough).

Other expert advised individuals to treat are those with a TSH above 10, those with a goiter, and those with positive antibodies. If you search for evidence supporting treatment in each of those cases, it's hard to get a clear answer. For a young person with these indications, I tend to err on the side of treatment.

The opposite problems happens with elderly individuals btw. The normal range is based on young people, but TSH tends to go up as you get older. So a TSH of 6 or 7 in an 85 year old might be perfectly normal, and it's even more controversial whether or not to treat them. Without clear symptoms, if a geriatric patient has a TSH <10, I typically avoid treating them.

Can also call on @rokshana for another opinion.
Thanks, this was very helpful.
I also have a few other related questions:

1. Is it standard to send for TPO antibodies in every patient who is technically subclinical hypothyroidism? I see it mentioned that it often helps stratify those who will go on to develop overt hypothyroidism, but I don't see general cutoffs and recommendations on what to do with those numbers.
2. In elderly patients on Synthroid (I'm talking over 75), what is a generally reasonable TSH? E.g. is a TSH below 2 in this population considered overtreatment? I can't get a clear answer on this.
 
It's controversial.

The normal range for any lab test is determined as the 95% confidence interval for a sample of "young", "healthy" controls. Traditionally, that range for TSH has been ~0.5-5.0, though I've seen the ULN depending on the lab being anywhere from 4.5 to 6.0. The problem is that that 95% confidence interval is primarily grouped in the lower half of that range and determining "healthy" is difficult. If you rigorously screen your control population and exclude anyone with even a family hx of thyroid disease, you end up with a normal TSH range closer to 0.3-3.0, with that ULN being sometimes even as low as 2 or 2.5.

What to do with these intermediate TSH values (in the 2.5 to 5 or even 2.5 to 10 range) is something that if you ask three endocrinologists you'll get four opinions. Everyone is pretty certain that in pregnant women you should get the TSH < 2.5 in the first trimester and <3 thereafter (though the evidence on that is mixed as well), but for every other population it's really hard to say. Women of childbearing age I'll commonly start on LT4 to get them under 2.5. Anyone with clear symptoms is worth a trial of therapy as well, though clear symptoms is a nebulous thing to define (everyone is fatigued if you ask them often enough).

Other expert advised individuals to treat are those with a TSH above 10, those with a goiter, and those with positive antibodies. If you search for evidence supporting treatment in each of those cases, it's hard to get a clear answer. For a young person with these indications, I tend to err on the side of treatment.

The opposite problems happens with elderly individuals btw. The normal range is based on young people, but TSH tends to go up as you get older. So a TSH of 6 or 7 in an 85 year old might be perfectly normal, and it's even more controversial whether or not to treat them. Without clear symptoms, if a geriatric patient has a TSH <10, I typically avoid treating them.

Can also call on @rokshana for another opinion.

Overall, I agree...i do tend to let them know that normalizing the TSH may not necessarily improve the symptoms they are attributing to their thyroid since they may not really be related to the thyroid...some will say to even start treating younger people with TSH in the 7 and up range, but unclear if there is any benefit in doing so.

The current discussions at the ATA meetings and amongst thyroidologists is that the TSH drifts upward as we age and a TSH of 5-8 may indeed be the normal range for those older than 70 and treating to have a "normal" TSH may be over treatment and put them in a subclinical hyperthyroid state...which for these older pts can be more harmful.
 
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Thanks, this was very helpful.
I also have a few other related questions:

1. Is it standard to send for TPO antibodies in every patient who is technically subclinical hypothyroidism? I see it mentioned that it often helps stratify those who will go on to develop overt hypothyroidism, but I don't see general cutoffs and recommendations on what to do with those numbers.
2. In elderly patients on Synthroid (I'm talking over 75), what is a generally reasonable TSH? E.g. is a TSH below 2 in this population considered overtreatment? I can't get a clear answer on this.
1) Depends on who you ask. The risk of progression to overt hypothyroidism is proportional to antibody titer and TSH but never rises much above 50 or 60% even with a high antibody titer. If you're not sure whether you want to treat, get antibodies. But if they're 60 years old with a TSH of 4.6 (and the ULN at your lab being 4.5), I wouldn't get them.

2. I get them to somewhere in the normal range if I'm treating them, but I do my best to avoid treating them. And I certainly don't try to push them down to 1.0 or anything. Risk for afib and osteoporosis goes up if you do.

And yes, fully agree with @rokshana. I tell all my patients that they have to have realistic expectations. They won't ever feel like they were 22 years old again, and not all fatigue is a thyroid, testosterone, or adrenal issue. Lots of crazy people on the internet that try to convince them otherwise though, including too many doctors that treat patients with t3 until they become thyrotoxic and "feel good".
 
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Lots of crazy people on the internet that try to convince them otherwise though, including too many doctors that treat patients with t3 until they become thyrotoxic and "feel good".

I love those patients! "What do you mean, you're not going to treat my TSH of 2?? Didn't you know that normal thyroid levels are less than 1? I'm calling a lawyer!! And I suppose that you're not going to treat my adrenal fatigue either!"

Out of curiosity, what's your opinion on Armour Thyroid? I don't see any reason why it should work better than Synthroid, and the supply is not reliable, but what are your thoughts on it?
 
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I love those patients! "What do you mean, you're not going to treat my TSH of 2?? Didn't you know that normal thyroid levels are less than 1? I'm calling a lawyer!! And I suppose that you're not going to treat my adrenal fatigue either!"

Out of curiosity, what's your opinion on Armour Thyroid? I don't see any reason why it should work better than Synthroid, and the supply is not reliable, but what are your thoughts on it?
Ugh, I get so irritated with patients who insist on "natural" thyroid.

I've got one now who takes both armour and synthroid and orders her own labs. It's infuriating.
 
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I love those patients! "What do you mean, you're not going to treat my TSH of 2?? Didn't you know that normal thyroid levels are less than 1? I'm calling a lawyer!! And I suppose that you're not going to treat my adrenal fatigue either!"

Out of curiosity, what's your opinion on Armour Thyroid? I don't see any reason why it should work better than Synthroid, and the supply is not reliable, but what are your thoughts on it?

I don't prescribe it and tell people that are coming into the office on referral that if they are to be managed by me then they will have to switch to LT4 and if...IF they are one of the few that needs to be managed with dual therapy, then we can add in Cytomel to their LT4...have only had one pt that has really required dual therapy.
 
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I love those patients! "What do you mean, you're not going to treat my TSH of 2?? Didn't you know that normal thyroid levels are less than 1? I'm calling a lawyer!! And I suppose that you're not going to treat my adrenal fatigue either!"

Out of curiosity, what's your opinion on Armour Thyroid? I don't see any reason why it should work better than Synthroid, and the supply is not reliable, but what are your thoughts on it?
I don't start new patients on armour. If they're already on it, I humor them and will titrate it. If they demand to be titrated into the thyrotoxic range, I decline. These patients are typically then lost to followup for some reason.

If someone starts jabbering at me about "adrenal fatigue" or "estrogen dominance", I do a basic workup for real endocrine issues, then tell them they have no evidence based endocrinological etiology for their fatigue, give them a handout on chronic fatigue syndrome and send them back to PCP.
 
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