Hashimoto’s Thyroiditis with Normal TSH, When to Treat ?
A 15 year old high school student came into the office with her mother with the the diagnosis of Hashimotos thyroid disease with normal TSH. Her thyroid antibodies, anti-thyroglobulin (anti-Glob) and anti-thyroperoxidase (TPO) antibody levels were 425 IU/mL and 350 IU/mL, and the thyroid gland was moderately enlarged (Goiter).?Additional laboratory testing showed low vitamin D3 and B12 levels.
Above left image: Hashimotos Thyroiditis Histology Showing Lymphocytic infiltration?(black arrows) in thyroid gland courtesy of?wikimedia commons
This young lady had been to a number of endocrinologists who?declined to treat her with thyroid hormone medication (Levothyroxine), claiming treatment was not necessary.?The doctors preferred to wait until thyroid function declines, as determined by elevated TSH which indicates hypothyroidism.
In spite of the normal TSH, the 15 year old was symptomatic with menstrual irregularities, mood disorders, weight gain, acne.?In addition she consumed junk food and carbonated sodas on a regular basis.
It is quite true that endocrinologists will NOT TREAT the “Euthyroid Hashimotos patient” (normal TSH). In my opinion, this is an error. In my office, we make a point of offering treatment with thyroid hormone medication to all Euthyroid Hashimoto’s patients, those with TSH in the normal range. This is a practice supported by the medical literature.(1-6)
Over the years of treating Hashimotos patients, we have seen anti-thyroid antibody levels decline in most patients under treatment with TSH suppressive doses of thyroid hormone. We use NDT, natural desiccated thyroid, rather than the T4 only levothyroxine, commonly used by endocrinologists and primary care physicians.
In addition to TSH suppressive doses of thyroid medication, our treatment protocol also includes:
Conclusion:?Another Error in Endocrinology is the refusal to treat Euthyroid?Hashimotos patients with thyroid medication (NDT or Levothyroxine). Such treatment?is supported by massive evidence in the medical literature, and is even more beneficial when combined with Selenium, D3, B12 and a Gluten Free Diet.
Articles with Related Interest
Jeffrey Dach MD
7450 Griffin Road, Suite 190
Davie, Fl 33314
954-792-4663
Links and References
euthyroid Hashimoto’s thyroiditis
treatment needs to be started as soon as Hashimoto’s disease is diagnosed.
1) Korzeniowska, Katarzyna, et al. “L-thyroxine stabilizes autoimmune inflammatory process in euthyroid nongoitrous children with Hashimoto’s thyroiditis and type 1 diabetes mellitus.” Journal of Clinical Research in Pediatric Endocrinology 5.4 (2013): 240.
Conclusions:?The data demonstrate that treatment with L-T4 in euthyroid pediatric patients with T1DM and AIT stabilizes autoimmune inflammation in the thyroid gland and is to be recommended as soon as the diagnosis is established.
To sum up, our findings also indicate that the treatment of patients with autoimmune polyglandular syndrome type 3a who are euthyroid or subclinically hypothyroid is to be recommended.?This treatment needs to be started as soon as Hashimoto’s disease is diagnosed.
Animal models of spontaneous Hashimoto’s autoimmune thyroiditis (HT) show that prophylactic treatment with levothyroxine (LT4) can reduce incidence and degree of lymphocytic infiltration in HT.
2) Padberg, S., et al. “One-year prophylactic treatment of euthyroid Hashimoto’s thyroiditis patients with levothyroxine: is there a benefit?.” Thyroid: official journal of the American Thyroid Association 11.3 (2001): 249-255.
Studies in animal models of spontaneous Hashimoto’s autoimmune thyroiditis (HT) show that prophylactic treatment with levothyroxine (LT4) can reduce incidence and degree of lymphocytic infiltration in HT.?The aim of the present study was to clarify whether there is a benefit of prophylactic treatment with LT4 in patients with euthyroid HT with respect to the progression of the autoimmune process.
Twenty-one patients with euthyroid HT?were checked for thyroid function (thyrotropin [TSH], free triiodothyronine [FT3], free thyroxine [FT4]), thyroid volume, antibodies (thyroglobulin [Tg-Ab], thyroid peroxidase [TPO-Ab]), and lymphocyte subsets. Peripheral (PBL) and thyroid-derived lymphocytes (TL) were analyzed by triple color flow cytometry. One-half of the patients with euthyroid HT were treated with LT4 for 1 year (n = 10). The other half (n = 11) were never treated with LT4. TL were obtained by fine-needle aspiration biopsy (FNAB). Thirteen healthy subjects (C) without medical history of thyroid disease served as controls concerning PBL, and patients with nontoxic nodular goiter (NG; n = 10) served as controls concerning TL. Thyroid-derived T-helper cells were found more frequently in euthyroid patients with HT compared to patients with NG (p < 0.01).
After 1 year of therapy with LT4, TPO-Abs and B lymphocytes decreased significantly only in the treated group of euthyroid patients with HT (p < 0.05).?In contrast, TPO-Abs levels did not change or even increased in untreated euthyroid patients with HT. Thyroid volume did not differ before and after therapy.?Prophylactic treatment of euthyroid patients with HT reduced both serological and cellular markers of autoimmune thyroiditis. Therefore, prophylactic LT4 treatment might be useful to stop the progression or even manifestation of the disease.?However, the long-term clinical benefit of prophylactic LT4 therapy in euthyroid patients with HT is yet to be established.
Antibody levels decline in most patients on Levothyroxine
3) Schmidt, Matthias, et al. “Long-term follow-up of antithyroid peroxidase antibodies in patients with chronic autoimmune thyroiditis (Hashimoto’s thyroiditis) treated with levothyroxine.” Thyroid: official journal of the American Thyroid Association 18.7 (2008): 755-760.
Background:?A number of studies show that the serum levels of antithyroid peroxidase antibodies (TPO-Ab) in patients with Hashimoto’s thyroiditis decline during levothyroxine treatment,?but do not provide quantitative data or report the fraction of patients in whom test for TPO-Ab became negative (“normalization percentage”). The objective of the present study was to provide this information.
Methods: This was a retrospective study of TPO-Ab concentrations in?36 women and 2 men?(mean age 51 +/- 16 years; range 19-81 years) with Hashimoto’s thyroiditis as defined by the following criteria: elevated plasma TPO-Ab and typical hypoechogenicity of the thyroid in high-resolution sonography at first presentation or during follow-up and?low pertechnetate uptake in thyroid scintigraphy. When first studied 17 women and 1 man were not yet taking levothyroxine. The remaining 20 patients were receiving levothyroxine. At initial examination 18 patients had serum thyroid-stimulating hormone (TSH) concentrations above normal. Results of up to eight (mean = 5.8) measurements obtained over a mean period of 50 months while patients were receiving levothyroxine were analyzed. In addition, serum TSH, free triiodothyronine (fT3), and free thyroxine (fT4) were measured, and ultrasound of the neck was performed at each follow-up examination.
Results:?In terms of TPO-Ab levels, 35 of 38 patients (92%) had a decrease, 2 patients had undulating levels, and 1 patient had an inverse hyperbolic increase in her TPO-Ab levels.?In the 35 patients in whom there were decreasing TPO-Ab values, the mean of the first value was 4779 IU/mL with an SD of 4099 IU/mL.?The mean decrease after 3 months was 8%, and after 1 year it was 45%. Five years after the first value, TPO-Ab levels were 1456 +/- 1219 IU/mL, a decrease of 70%.?TPO-Ab levels became negative, < 100 IU/mL, in only six patients, a normalization percentage of 16%. There were no correlations between changes in thyroid volume and changes in TPO-Ab.
Conclusion:?Serum TPO-Ab levels decline in most patients with Hashimoto’s thyroiditis who are taking levothyroxine, but after a mean of 50 months,?TPO-Ab became negative in only a minority of patients.
4) Aksoy, Duygu Yazgan, et al. “Effects of prophylactic thyroid hormone replacement in euthyroid Hashimoto’s thyroiditis.” Endocrine journal 52.3 (2005): 337-343.
Hashimoto’s thyroiditis is the most frequent autoimmune thyroid disease.?L-thyroxine therapy can reduce the incidence and alleviate the symptoms of this disease.?The aim of this study was to evaluate the effects of?prophylactic L-thyroxine treatment?on clinical and laboratory findings of patients who were euthyroid at the time of diagnosis.?Thirty-three patients who had diagnosis of euthyroid Hashimoto’s thyroiditis?were randomized to two groups, one group received prophylactic L-thyroxine treatment and the other was followed-up without treatment. Initial thyroid function tests, autoantibodies, ultrasonography, fine needle aspiration biopsy and peripheral blood lymphocyte subsets were similar in the two study groups.?After 15 months of L-thyroxine treatment, there was a significant increase in free T4 and a significant decrease in TSH and anti-thyroglobulin antibody anti-thyroid peroxidase antibody levels.?CD8+ cell counts increased in both groups, CD4/CD8 levels decreased significantly because of the increase in CD8+ cell count levels. Though there was no change in cytological findings,?ultrasonography showed a decrease in thyroid volume in L-thyroxine receiving patients whereas an increase was detected in patients who were followed without treatment. In conclusion, prophylactic thyroid hormone therapy can be used in patients with Hashimoto’s thyroiditis even if they are euthyroid.
Benefits of Combination Levo and Selenium in Euthyroid Hashimotos pts
5) Krysiak, Robert, and Boguslaw Okopien. “The effect of levothyroxine and selenomethionine on lymphocyte and monocyte cytokine release in women with Hashimoto’s thyroiditis.” The Journal of Clinical Endocrinology & Metabolism 96.7 (2011): 2206-2215.
Design, setting, participants, and intervention:?We conducted a randomized clinical trial involving a group of?170 ambulatory euthyroid women?with recently diagnosed and previously?untreated Hashimoto’s thyroiditis?and 41 matched healthy subjects. Participants were randomized in a double-blind fashion to receive a?6-month treatment with levothyroxine, selenomethionine, levothyroxine plus selenomethionine, or placebo.?One hundred sixty-five patients completed the study.
Main outcome measures:?Monocyte and lymphocyte release of proinflammatory cytokines and plasma levels of C-reactive protein (CRP) were assessed.
Results:?Compared with the control subjects, monocytes and lymphocytes of?Hashimoto’s thyroiditis patients released greater amounts of all cytokines studied.?Levothyroxine reduced monocyte release of TNF-α, IL-1β, IL-6, and monocyte chemoattractant protein-1, whereas selenomethionine inhibited lymphocyte release of IL-2, interferon-γ, and TNF-α, which was accompanied by a reduction in plasma CRP levels. The decrease in cytokine release and in plasma CRP levels was strongest when both drugs were given together.
Conclusions:?Despite affecting different types of inflammatory cells, levothyroxine and selenomethionine exhibit a similar systemic antiinflammatory effect in euthyroid females with Hashimoto’s thyroiditis.?This action, which correlates with a reduction in thyroid peroxidase antibody titers, may be associated with clinical benefits in the prevention and management of Hashimoto’s thyroiditis, particularly in subjects receiving both agents.
Better IVF outcome in Euthyroid Hashimotos patients when treated with combination LEVO plus anti-inflammatories (ASA and prednisone)
6) Revelli, Alberto, et al. “A retrospective study on IVF outcome in euthyroid patients with anti-thyroid antibodies: effects of levothyroxine, acetyl-salicylic acid and prednisolone adjuvant treatments.” Reproductive Biology and Endocrinology 7.1 (2009): 1-6.
The prevalence of ATA among euthyroid, infertile patients was 10.5%, similar to the one reported in euthyroid women between 18 and 45 years. ATA+ patients who did not receive any adjuvant treatment showed significantly poorer ovarian responsiveness to stimulation and IVF results than controls.?ATA+ patients receiving LT responded better to ovarian stimulation, but had IVF results as poor as untreated ATA+ women.
Patients receiving LT+ASA+P had significantly higher pregnancy and implantation rates than untreated ATA+ patients (PR/ET 25.6% and IR 17.7% vs. PR/ET 7.5% and IR 4.7%, respectively), and overall IVF results comparable to patients without ATA (PR/ET 32.8% and IR 19%).
Conclusion
These observations suggest that euthyroid ATA+ patients undergoing IVF could have better outcome if given LT+ASA+P as adjuvant treatment.?This hypothesis must be verified in further randomized, prospective studies.
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7) D?rr, Helmuth G., et al. “Levothyroxine treatment of euthyroid children with autoimmune Hashimoto thyroiditis: results of a multicenter, randomized, controlled trial.”?Hormone research in paediatrics?84.4 (2015): 266-274.
Background: Levothyroxine (L-T4) treatment of euthyroid children with Hashimoto thyroiditis (HT) is a controversial issue. Patients and Methods: We conducted a prospective, randomized, controlled clinical trial. Out of 79 identified euthyroid patients, 59 started the study; 25 patients (21 female, 4 male; age: 11.8 ± 2.3 years) received L-T4 at a mean dose of 1.6 μg/kg (SD, 0.8) daily, and 34 (27 female, 7 male; age: 12.6 ± 1.2 years) were not treated.
Patients developing subclinical hypothyroidism during follow-up (n = 13) were treated with L-T4 and removed from the observation group.
As the main outcome measures, thyroid gland volume (determined by ultrasound) as well as serum levels of TSH, free T4, and antibodies against thyroid peroxidase and thyroglobulin were assessed every 6 months for 36 months. Results: At the start, the mean thyroid volume (standard deviation score, SDS) was 2.5 in the treatment group and 1.6 in the observation group.?There was a constant decline in mean thyroid volume (SDS) from 2.13 (month 12) to 1.12 (month 30) in the treated group,?with a delta thyroid volume of -1.01 SDS. In the observation group, the mean delta thyroid volume increased to +0.27 SDS. The change of the delta thyroid volume was statistically significantly different between both groups during the 12- and 30-month time points (p < 0.05).?L-T4 had no effect on thyroid function and serum thyroid antibodies.?Conclusions: L-T4 treatment can decrease the thyroid volume in euthyroid children with HT, but the effect is limited to a definite time period.
Selenium Reduces Antibody Levels
8) Wichman, Johanna, et al. “Selenium supplementation significantly reduces thyroid autoantibody levels in patients with chronic autoimmune thyroiditis: a systematic review and meta-analysis.” Thyroid 26.12 (2016): 1681-1692.
9) Onal, Hasan, et al. “Effects of selenium supplementation in the early stage of autoimmune thyroiditis in childhood: an open-label pilot study.”?Journal of Pediatric Endocrinology and Metabolism 25.7-8 (2012): 639-644.
Results:?Serum TPOAb, TgAb, and thyroid echogenicity were unchanged with Se supplementation. A prominent decrease in thyroid volume was noteworthy; 35% of patients showed a thyroid volume regression rate of > or = 30%.
10) Yu, L., et al. “Levothyroxine monotherapy versus levothyroxine and selenium combination therapy in chronic lymphocytic thyroiditis.”?Journal of endocrinological investigation?40.11 (2017): 1243-1250.
11) Pirola, Ilenia, et al. “Selenium supplementation could restore euthyroidism in subclinical hypothyroid patients with autoimmune thyroiditis.”?Endokrynologia Polska?67.6 (2016): 567-571.
12) Fan, Yaofu, et al. “Selenium supplementation for autoimmune thyroiditis: a systematic review and meta-analysis.”?International journal of endocrinology?2014 (2014).
Vitamin D3 Benefits for Hashimotos
13) Piekarska, Ma?gorzata, et al. “The correlation between vitamin D and autoimmune thyroid function–short review.”?Journal of Education, Health and Sport?11.9 (2021): 401-408.
14) Vieira, Inês Henriques, Dírcea Rodrigues, and Isabel Paiva. “Vitamin D and Autoimmune Thyroid Disease—Cause, Consequence, or a Vicious Cycle?.”?Nutrients?12.9 (2020): 2791.
15) Koehler, Viktoria F., Natalie Filmann, and W. Alexander Mann. “Vitamin D status and thyroid autoantibodies in autoimmune thyroiditis.”?Hormone and Metabolic Research?51.12 (2019): 792-797.
16) Mazokopakis, Elias E., et al. “Is vitamin D related to pathogenesis and treatment of Hashimoto’s thyroiditis.” Hell J Nucl Med 18.3 (2015): 222-7.
Results: There was a signicant negative correlation only between serum 25(OH)D levels and anti-TPO levels among all 218 HT patients. Also, antiTPO levels were signicantly higher in 186/218 vitamin D decient HT patients compared to 32/218 HT patients with no vitamin D deciency (364±181IU/mL versus 115.8±37.1IU/mL, P<0.0001). Supplementation of CF in 186 vitamin D decient HT patients caused a signicant decrease (20.3%) in serum anti-TPO levels. Although at the end of the 4 months period of the study body mass index (BMI), serum anti-TG and TSH
levels decreased by 2.2%, 5.3% and 4% respectively,?these dierences were not signicant. No changes in the sonographic ndings were observed. Conclusions: The majority (85.3%) of the Greek Caucasian patients with HT studied who lived and worked in Crete had low serum 25(OH)D levels inversely correlated
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with serum anti-TPO thyroid antibodies. After 4 months of CF supplementation in the 186 HT patients with vitamin D deciency, a signicant decrease (20.3%) of serum anti-TPO levels was found. These findings suggest that vitamin D deciency may be related to pathogenesis of HT and that its supplementation could contribute to the treatment of patients with HT.
17) Chahardoli, Reza, et al. “Can supplementation with vitamin D modify thyroid autoantibodies (Anti-TPO Ab, Anti-Tg Ab) and thyroid profile (T3, T4, TSH) in Hashimoto’s thyroiditis? A double blind, Randomized clinical trial.” Hormone and Metabolic Research 51.05 (2019): 296-301.
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18) Krysiak, Robert, Witold Szkróbka, and Bogus?aw Okopień. “The effect of vitamin D on thyroid autoimmunity in levothyroxine-treated women with Hashimoto’s thyroiditis and normal vitamin D status.” Experimental and Clinical Endocrinology & Diabetes 125.04 (2017): 229-233.
Results: There were no significant differences in baseline values between
both study groups. 25-hydroxyvitamin D levels inversely correlated
with titers of thyroid antibodies. No changes in hypothalamic-pituitary-
thyroid axis activity and thyroid antibody titers were observed
in vitamin-na?ve patients. Vitamin D increased serum levels of 25-hydroxyvitamin
D, as well as reduced titers of thyroid antibodies. This
effect was more pronounced for thyroid peroxidase than for thyroglobulin
antibodies and correlated with their baseline titers.
Conclusions: Vitamin D preparations may reduce thyroid autoimmunity
in levothyroxine-treated women with Hashimoto’s thyroiditis and
normal vitamin D status.
19) Koehler, Viktoria F., Natalie Filmann, and W. Alexander Mann. “Vitamin D status and thyroid autoantibodies in autoimmune thyroiditis.” Hormone and Metabolic Research 51.12 (2019): 792-797.
20) Fang, Fang, et al. “Vitamin D deficiency is associated with thyroid autoimmunity: results from an epidemiological survey in Tianjin, China.”?Endocrine?73.2 (2021): 447-454.
21) Mazokopakis, Elias E., et al. “Is vitamin D related to pathogenesis and treatment of Hashimoto’s thyroiditis.” Hell J Nucl Med 18.3 (2015): 222-7.
Conclusion:?The majority (85.3%)?of the Greek Caucasian patients with HT studied who lived and worked in Crete had?low serum 25(OH)D levels inversely correlated with serum anti-TPO thyroid antibodies.?After 4 months of CF supplementation in the 186 HT patients with vitamin D deficiency, a significant decrease (20.3%) of serum anti-TPO levels was found.?These findings suggest that vitamin D deficiency may be related to pathogenesis of HT and that its supplementation could contribute to the treatment of patients with HT.
D3 and B12 deficiency in Hashimotos
22) Akta?, Hanife ?erife. “Vitamin B12 and vitamin D levels in patients with autoimmune hypothyroidism and their correlation with anti-thyroid peroxidase antibodies.”?Medical Principles and Practice?29.4 (2020): 364-370.
Iodine, Selenium, Vitamin D3 Gluten
23) Liontiris, Michael I., and Elias E. Mazokopakis. “A concise review of Hashimoto thyroiditis (HT) and the importance of iodine, selenium, vitamin D and gluten on the autoimmunity and dietary management of HT patients. Points that need more investigation.” Hell J Nucl Med 20.1 (2017): 51-56.
24) Ihnatowicz, Paulina, et al. “The importance of nutritional factors and dietary management of Hashimoto’s thyroiditis.”?Annals of agricultural and environmental medicine?27.2 (2020).
Gluten
25) Pob?ocki, Jakub, et al. “Whether a Gluten-Free Diet Should Be Recommended in Chronic Autoimmune Thyroiditis or Not?—A 12-Month Follow-Up.”?Journal of Clinical Medicine?10.15 (2021): 3240.
During the 12-month follow-up between the CG and the GFDG, no differences
were found in anti-TPO and anti-TG antibodies, fT3 or fT4 levels, except a significant reduction in TSH levels in the GFDG. Additionally, performed analysis between individual appointments presented no significant differences in changes in the median concentrations of anti-TPO, anti-TG or fT3,?but confirmed a significant decrease in TSH and showed accessory an increase in fT4 after 12 months?in?GFDG. Statistical analyses performed separately for both groups indicated a constant reduction of anti-TG concentrations in the GFDG. I
26) Krysiak, Robert, Witold Szkróbka, and Bogus?aw Okopień. “The effect of gluten-free diet on thyroid autoimmunity in drug-na?ve women with Hashimoto’s thyroiditis: a pilot study.”?Experimental and Clinical Endocrinology & Diabetes?127.07 (2019): 417-422.
27) Wojtas, Natalia, Lidia Wadolowska, and El?bieta Bandurska-Stankiewicz. “Evaluation of qualitative dietary protocol (diet4hashi) application in dietary counseling in hashimoto thyroiditis: study protocol of a randomized controlled trial.”?International journal of environmental research and public health?16.23 (2019): 4841.
28) Agardh, Daniel, et al. “Reduction of tissue transglutaminase autoantibody levels by gluten-free diet is associated with changes in subsets of peripheral blood lymphocytes in children with newly diagnosed coeliac disease.”?Clinical & Experimental Immunology?144.1 (2006): 67-75.
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29) Talebi, Sepide, et al. “Trace element status and hypothyroidism: a systematic review and meta-analysis.”?Biological trace element research?197.1 (2020): 1-14.
LDN
30) Kim, Yoon Hang John. “Case Report: Reversing Hypothyroidism with Low Dose Naltrexone (LDN).”?Multiple sclerosis?3: 4.
31) McDermott, Michael T. “Low-dose naltrexone treatment of Hashimoto’s thyroiditis.”?Management of Patients with Pseudo-Endocrine Disorders. Springer, Cham, 2019. 317-326.
32) Neuman, Daniel L., and Andrea L. Chadwick. “Utilization of Low-Dose Naltrexone for Burning Mouth Syndrome: A Case Report.”?A&A Practice?15.5 (2021): e01475.
BY Dana Trentini?HypoThyroid MOM
Doctors refuse to treat Hashimoto’s when TSH is normal.
Another major problem is that many traditional doctors refuse to treat patients who test positive for thyroid antibodies, even when they suffer debilitating symptoms, all because their TSH level is “normal”. Unfortunately TSH rules above all else in mainstream medicine when it comes to hypothyroidism. You may have Hashimoto’s disease with elevated thyroid antibodies, yet all because the destruction of your thyroid gland has not YET destroyed enough of your gland yet to trigger an abnormal TSH reading, you are refused treatment and forced to cope with your symptoms.?End Quote
34) ?zen, Samim, et al. “Clinical course of Hashimoto’s thyroiditis and effects of levothyroxine therapy on the clinical course of the disease in children and adolescents.” Journal of clinical research in pediatric endocrinology 3.4 (2011): 192.
Levothyroxine therapy may have beneficial effects on the clinical course of the disease and on antibody titers.
Jeffrey Dach MD
7450 Griffin Road, Suite 190
Davie, Fl 33314
954-792-4663
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1 年I found this to be super interesting. I have for years had my TSH and Free T3 checked based on my symptoms of chronic fatigue, weight gain, menstrual irregularities, etc. to which have all been normal. I recently also had my TPO AB checked and my level was 14 IU/ml. While the reference range for many is <35, I recently read that optimal value for this test is actually <2. I additionally had low Vitamin D and B12 levels. Could my levels be indicative of Hasimoto’s and warrant treatment?