Thyroid Science 2(9):E1, 2007
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
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.
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
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
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. An occasional researcher
does mention that FNA may show lymphocytic thyroiditis.
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
Only half of these 87 patients had elevated antithyroid antibodies.
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
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.”
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
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
1. Wikland, B.: Personal written communication. Stockholm, Sweden, March
2. Wikland, B., Löwhagen, T., and Sandberg, P.O.: Fine-needle aspiration
cytology of the thyroid in chronic fatigue. The Lancet, 357(9260):
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.,
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.,
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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