Dr. John C. Lowe
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Structural Pathology in the
Muscles of Subclinical Hypothyroid Patients:
Another Call for Early Treatment
Dr. John C. Lowe
June 8, 2009
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study report we published
in Thyroid Science this past week is well worth announcing.
It stirs a hope in us—that the report will motivate more clinicians to
provide subclinical hypothyroid patients with early thyroid hormone
treatment. Early treatment is likely to relieve the patients’ suffering,
enable them to maintain normal function, and reduce their overall costs
for health care services. In addition, early treatment will—if
assertively engaged in—halt incipient functional and structural
abnormalities, or reverse the frank pathology that has already
developed, such as the muscle abnormalities reported by the authors of
the report we published this week.
Four of the researchers and authors of the report (Drs. Michael Dunn,
Arthur Cosmas, Linda Lamont, and Thomas Manfredi) are from the
Department of Kinesiology, University of Rhode Island. The fourth (Dr.
James Hennessey) is from the Division of Endocrinology, Rhode Island
Hospital, Brown University School of Medicine.
To qualify a patient to enter
their study, Dunn et al.
used the conventional criteria for the diagnosis of subclinical
hypothyroidism, the mildest form of hypothyroidism. The criteria
included an above-range TSH level and an in-range free T4 level.
Their study shows that among subclinical hypothyroid patients, muscle
symptoms may be underlain by objectively verifiable structural muscle
abnormalities. The study is the first to document with light and
electron microscopy, pathological structural changes in the skeletal
muscles of subclinical hypothyroid patients. The researchers note that
their findings indicate a progression of such changes from subclinical
to overt hypothyroidism.
The structural muscle pathology that Dunn et al. report is consistent
with other researchers’ reports of other muscle-related abnormalities in
subclinical hypothyroid patients. (To read the specific findings of Dunn
et al., detailed on pages 4 through 6 of their paper,[1,pp.4-6]
must be compelling to clinicians who are committed to the well-being of
their patients.) Hekimsoy and Oktem,
for example, reported elevated creatine kinase levels in subclinical
patients. The patients’ levels were not significantly elevated. Overall,
however, the TSH and creatine kinase levels were positively correlated;
that is, the higher the TSH levels, the higher the creatine kinase
levels. Conversely, creatine kinase levels and free T3 and free T4
levels were inversely correlated; higher creatine kinase levels were
associated with lower free T3 and free T4 levels.
Monzani et al. reported that during exercise, the average blood lactate
level of subclinical hypothyroid patients was significantly higher than
in controls “from the third exercise step onward.”
The researchers wrote that the patients’ mean increase of blood lactate
during exercise was positively related to the duration of their
subclinical hypothyroidism. “We conclude,” they wrote, “that muscle
energy metabolism is impaired in [subclinical hypothyroidism] in rough
proportion to the known duration of the disease.” This finding has an
important practical implication: among subclinical hypothyroid patients,
the energy-related biochemical abnormality of elevated blood lactate may
progressively worsen when patients fail to undergo early therapy hormone
As Dunn et al. point out,
the muscle pathology they found is among a range of possible adverse
health consequences when hypothyroid patients go untreated. They note
that some of the adverse effects (“coronary heart disease, osteoporosis,
atrial fibrillation, cognitive impairment, and depression”) are among
the nation’s most common causes of illness, death, and diminished
quality of daily life among older adults.[1,p.1]
But older adults aren’t the only people adversely affected by untreated
hypothyroidism. In more than two decades of working clinically with
hypothyroid patients, I’ve regularly seen subclinical hypothyroid
patients—ranging in age from the teens through the fifties—in an
unfortunate circumstance: their clinicians cavalierly denied them
thyroid hormone therapy, preferring to wait until the patients’
subclinical condition progressed to an overt and, in some cases,
The delayed treatment was, to me, patently unjustified. The patients had
multiple classic hypothyroid symptoms. These included different
combinations of fatigue, depression, cognitive dysfunction, cold
intolerance, constipation, dry skin, hair loss, depression, cognitive
dysfunction, exercise intolerance, chronic muscle pain and tension. The
patients also had test results consistent with hypothyroidism, such as
high cholesterol and LDL levels despite wholesome diets and regular
exercise. Many patients had high thyroid peroxidase and thyroglobulin
antibodies. The first of these subclinical hypothyroid patients I worked
with suffered from treatment-resistant myofascial pain syndromes. The
patients had failed to get more than palliation, even with high-quality
Most of my patients—perhaps because they were younger than the more
commonly afflicted older adults—responded quickly, often dramatically,
to thyroid hormone therapy; they had either complete or nearly-complete
recovery from their symptoms and signs. On the other hand, I observed
that in general, when clinicians had allowed their patients’
hypothyroidism to progress from subclinical to overt, the patients’
health problems had become compounded and complicated. As a result, more
time and greater effort were needed for them to recover their health.
Observing the results of delayed treatment were troubling to witness and
worse for the patients. Hence, I’m especially appreciative of the report
of the muscle pathology found by Dunn et al. in that it may lead to
earlier treatment for many subclinical hypothyroid patients.
The muscle pathology that Dunn et al. report add to other types of
muscle abnormalities that researchers have previously reported.
Together, the different research groups’ findings make clear to us
ominous possibilities for subclinical hypothyroid patients whose
clinicians deny them early treatment. If treatment is delayed, some of
the patients are highly likely to undergo more advanced muscle pathology
with associated worsening of their muscle symptoms and signs. It’s
highly likely that early treatment will prevent the proliferation of
muscle pathology, reverse incipient muscle abnormalities, and relieve
the patients’ suffering from muscle tension, cramps, energy-deficiency
contractures, and treatment-resistant myofascial pain.
Early treatment for subclinical hypothyroidism will prevent clinicians
from diagnosing some patients as having “fibromyalgia.” Nowadays this
diagnosis leads to FDA-approved “fibromyalgia” drug therapies (Cymbalta
and Lyrica) that are inappropriate, unnecessary, and “effective” only in
the most liberal sense of the term. We regularly hear complaints of
adverse effects from patients who have undergone treatment with the
drugs. The muscle abnormalities Dunn et al. report are similar to those
of patients with a diagnosis of fibromyalgia.[4,5,6,7,8]
The muscle abnormalities among fibromyalgia patients, along with other
similarities to hypothyroidism, led Eisinger et al. in France[7,8]
and me in the U.S., separately but almost simultaneously in the early
to conclude that fibromyalgia is a metabolic disorder; in most respects,
it is virtually identical to hypothyroidism. The hypothyroid-like muscle
abnormalities of fibromyalgia patients were among the research findings
that led my colleagues and me to conclude that the main underlying
mechanism of fibromyalgia is inadequate thyroid hormone regulation.[9,10]
The findings of Dunn et al. add carbon to our already-steel hard
conclusion about the etiology of fibromyalgia.[9,10]
When Monzani et al. reported high lactate levels in subclinical
hypothyroid patients, they concluded, “Early [thyroid hormone] therapy
may be useful not only to provide specific treatment for such metabolic
changes, but also to avoid progression to frank hypothyroidism.” This
humane proposal—early thyroid hormone treatment—is echoed by Dunn et al.[1,pp.7-8]
For emphasis, I’ll quote their conclusion:
“Establishing consistent morphological markers of subclinical
hypothyroidism prior to disease progression could justify an earlier,
more efficacious treatment with thyroid hormone. This treatment strategy
may diminish morbidity by preventing disease progression from
subclinical to overt hypothyroidism. Earlier initiation of this therapy
may ultimately translate into an improvement in patients’ lifestyle.”[1,pp.7-8]
At Thyroid Science, we earnestly concur with
Dunn et al.
1. Dunn, M.E., Hennessey, J.V., Cosmas, A.C., Lamont, L.S., and Manfredi,
T.G.: Clinical Case Report: Ultrastructural Evidence of Skeletal Muscle
Mitochondrial Dysfunction in Patients With Subclinical Hypothyroidism.
Thyroid Science, 4(6):CLS1-8, 2009.
2. Hekimsoy, Z. And Oktem, I.K.: Serum creatine kinase levels in overt
and subclinical hypothyroidism. Endocr. Res., 2005;31(3):171-175, 2005.
Monzani, F.,Caraccio, N., Siciliano, G., et al.: Clinical and biochemical features of muscle dysfunction in subclinical hypothyroidism.
J. Clin. Endocrinol.
Metab., 82(10):3315-3318, 1997.
4. Kalyan-Raman, U.P., Kalyan-Raman, K., Yunus, M.B. and Masi, A.T.:
Muscle pathology in primary fibromyalgia syndrome: a light microscopic,
histological and ultrastructural study. J. Rheumatol., 11:808-813, 1984.
Awad, E.A.: Pathological changes in fibromyalgia. First International
Symposium on Myofascial Pain and Fibromyalgia. Minneapolis, Minnesota,
May 9, 1989.
6. Awad, E.A.: Histopathological changes in fibrositis. In Advances in
Pain Research and Therapy, Vol.17. Edited by J.R. Fricton and E.A. Awad,
New York, Raven Press, Ltd., 1990, pp.249-258.
7. Eisinger, J., Plantamura, A., and Ayavou, T.: Glycolysis
abnormalities in fibromyalgia. J. Am. Coll. Nutr., 13:144-148, 1994.
8. Eisinger, J., Clairet, D., Zakarian, H., and Ayavou, T.: ATP
érythrocytaire et apparel locomoteur: action de la calcitonine. Lyon Méditerranée Med., 26:326-328, 1990.
9. Lowe, J.C.:
The Metabolic Treatment of Fibromyalgia. Boulder,
McDowell Publishing Co., 2000.
10. Lowe, J.C. and Yellin, J.: Inadequate Thyroid Hormone Regulation as
the Main Mechanism of Fibromyalgia: A Review of the Evidence. Thyroid
Science, 3(6):R1-14, 2008.
11. Lowe, J.C.: Improvement in euthyroid fibromyalgia patients treated
with T3 (tri-iodothyronine). J. Myofasc. Ther., 1(2):16-29, 1994.
12. Lowe, J.C.: T3-induced recovery from fibromyalgia by a hypothyroid
patient resistant to T4 and desiccated thyroid. J. Myofasc. Ther.,
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