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Thyroid Science 2(9):E1, 2007

“Subchemical Hypothyroidism”:
Autoimmune Thyroid Disease that Eludes
Detection by Standard Laboratory Tests

Dr. John C. Lowe

I recently received a letter from a physician, Dr. Bo Wikland, who practices in Stockholm, Sweden.[1] I was happy to receive his letter. The reason is two fold: First, in it, he introduced me to a phenomenon I wasn’t aware of before. Second, the phenomenon makes me realize that within the field of clinical thyroidology, we’re in more of a diagnostic muddle than I imagined.

Current wisdom in the U.S. is that we should diagnose failure of the thyroid gland under two conditions. First is when the TSH is high (with or without a low free T3 or free T4 level). The second condition is when the patient has high antithyroid antibodies. (I know, of course, that many doctors tell patients that high antibodies aren’t a problem, but the opinion of these doctors is remarkable only for noting how oblivious of thyroid science some doctors are.)

If only the TSH is high, the clinician usually gives the diagnosis of primary hypothyroidism not caused by autoimmune thyroiditis. If the antithyroid antibodies are high, the diagnosis is typically autoimmune thyroiditis without hypothyroidism. And if both the TSH and antibodies are high, the clinician usually gives a diagnosis of hypothyroidism due to autoimmune thyroiditis.

The letter from Dr. Wikland, however, shows that only the last diagnosis is likely to be right, and the two others may be wrong. He and his colleagues have found that a patient’s TSH may be within or outside its reference range. Regardless, if the antithyroid antibody levels are within their reference ranges, the patient may still have autoimmune thyroiditis and hypothyroidism.

Dr. Wikland included with his letter two short articles he and his coauthors wrote for the medical journal The Lancet.
[2][3] What they wrote is extremely important for identifying patients suffering from hypothyroidism from autoimmune thyroiditis  despite “normal” antithyroid antibody levels.

He wrote that in Stockholm, he and his colleagues have a tradition of including fine-needle aspiration (FNA) of the thyroid gland when a patient’s symptoms and signs raise suspicion of thyroid imbalance. (He noted, incidentally, that they also include conventional thyroid function lab tests.) “Often,” he wrote, “a finding of unequivocal lymphocytic (autoimmune) thyroiditis is the only evidence of active thyroid affection.”

FNA is commonly used today, but virtually always to examine samples of thyroid nodules aspirated through the needles. The purpose is usually to classify the nodules according to the absence or presence and degree of malignancy.
[4][5][6][7] Generally, papers on the diagnosis of autoimmune thyroiditis don’t include mention of FNA; they deal mainly with blood levels of thyroid antibodies, although they may say that the antibodies arise from lymphocytes that have infiltrated the thyroid gland.[8] An occasional researcher does mention that FNA may show lymphocytic thyroiditis.[9]

Dr. Wikland and his colleagues, however, provide us with information on the use of FNA for identifying a special class of hypothyroid patients: those who otherwise would not be identified by abnormal levels of the TSH or antithyroid antibodies. They performed FNA on 219 patients who complained of chronic fatigue. Among these patients, the aspirations showed that 87 patients (40%) had definite lymphocytic (autoimmune) thyroiditis.
[2] Only half of these 87 patients had elevated antithyroid antibodies.[3]

The TSH levels of the patients with thyroiditis were scattered between 3 and 5 mU/L. (In 2002 and 2003, the upper end of the reference range was lowered in the U.S. to 2.5 to 3.0 mU/L, but most U.S. doctors don’t seem to be aware of this. In many other countries, clinicians still consider 5 mU/L or higher the upper limit.) The researchers wrote that patients responded favorably to thyroid hormone therapy no matter what their initial TSH levels were.

I can’t improve on the conclusions of Dr. Wikland and his coauthors: “Our interpretation of these findings is that fine-needle aspiration cytology of the thyroid has a higher diagnostic sensitivity than antibody assay in showing thyroid autoimmune activity; and that, compared with biochemical assessment alone, a higher proportion of patients with clinical hypothyroidism is identified.”
[3] (Italics mine.)

Dr. Wikland and his coauthors end by proposing a new diagnostic category: “To describe the group of patients with clinical hypothyroidism not meeting conventional biochemical criteria, but showing definite evidence of thyroid autoimmunity, we propose the term ‘subchemical hypothyroidism.’”

I heartily agree with Dr. Wikland and his colleagues. FNA has served patients well by showing whether or not thyroid nodules are malignant, and if so, to what degree. However, the use of this procedure can be extended to patients who seem hypothyroid, have physiological evidence of hypothyroidism (such as low temperatures and resting metabolic rates), but have “normal” TSH and antithyroid antibody levels. Extending the procedure to these patients will, in my judgment, confirm a suspicion many of them hold: that they indeed have thyroid disease and are hypothyroid. In these cases, the test would also show the patients’ clinicians that the blood tests they depended on in the past (the TSH and anti-thyroid antibodies) simply failed to show the underlying thyroid disorder.

I believe Dr. Wikland’s research is commendable. I believe that all clinicians who care for thyroid patients should heed his research findings.


1. Wikland, B.: Personal written communication. Stockholm, Sweden, March 6, 2007.

2. Wikland, B., Löwhagen, T., and Sandberg, P.O.: Fine-needle aspiration cytology of the thyroid in chronic fatigue. The Lancet, 357(9260): 956-957, 2001.

3. Wikland, B., Sandberg, P.O., Wallinder, H.: Subchemical hypothyroidism. The Lancet, 361(9365): 1305, 2003.

4. Tabaqchali, M.A., Hanson, J.M., Johnson, S.J., et al.: Thyroid aspiration cytology in Newcastle: a six year cytology/histology correlation study. Ann. R. Coll. Surg. Engl., 82(3):149-155, 2000.

5. Morgan, J.L., Serpell, J.W., and Cheng, M.S.: Fine-needle aspiration cytology of thyroid nodules: how useful is it? ANZ J. Surg., 73(7):480-483, 2003.

6. Egorycheva, E.K., Troshina, E.A., Abdulkhabirova, F.M., et al.: Diagnostics and treatment of the functional autonomy of the thyroid gland. Klin. Med. (Mosk), 84(9):14-21, 2006.

7. Cheung, Y.S., Poon, C.M., Mak, S.M., et al.: Fine-needle aspiration cytology of thyroid nodules--how well are we doing? Hong Kong Med. J., 13(1):12-15, 2007.

8. Trbojevic, B. and Djurica, S.: Diagnosis of autoimmune thyroid disease. Srp. Arh. Celok. Lek., 133 Suppl 1:25-33, 2005.

9. Clerc, J.: Thyroid nodule. Rev Prat., 55(2):137-148, 2005.

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