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Improved thyroid function in oncological
patients with Hashimoto Thyroiditis treated
with Immunomodulators

Francesco Matozza MD*, Guillermo H. Artero Ph **, Guillermo E. Artero
MD***, Monica Rodriguez Laborda MD****



Introduction
Hashimoto's thyroiditis is chronic autoimmune inflammation of the thyroid with
lymphocytic infiltration
The destruction of the thyroid gland occurs through the action of CD8 positive killer
T cells. CD4 positive helper T cells and B cells are also identified in the thyroid
glands of patients with Hashimoto thyroiditis
Hashimoto's thyroiditis is the most common cause of primary of hypothyroidism
The disease is 7 times more frequent in women.
The incidence of Hashimoto thyroiditis worldwide is estimated to be 0.3-1.5 cases
per 1000 of population per year
 Incidence increases with age and in patients with chromosomal disorders,
including Turner's, Down, and Klinefelter's syndromes. A family history of thyroid
disorders is common.

An increased incidence of cancer is seen in people with an autoimmune disease.
The treatment of Hashimoto thyroiditis consists of replacing thyroid hormone with
levothyroxine, when the patients have become hypothyroid.
Purpose.
The aim of the study was to evaluate the improvement in thyroid function as well as
quality of life in oncological patients with Hashimoto Thyroiditis treated with
Immunomodulators
.
Material
We retrospectively review in a multicentric study, 161 patients with Hashimoto
thyroiditis, and different types of tumors (breast, kidney, ovarian, uterus, colorectal,
thyroid, lung, pancreas, larynx, stomach, bladder, prostate, etc).
Age range 40 to 70 years old.




98 patients were treated with (chemotherapy or radiotherapy) + levothyroxine and
Immunomodulators during 6 month.
This Immunomodulators compound contains: Astragalus Ext., Zinc, Mg and
Selenium.”
63 patients treated only with oncological treatment (chemotherapy or radiotherapy)
+ levothyroxine as a control group.


Method
Thyroid function: T3.T4. TSH, TPO and TG antibodies were measured before,
during and after six month treatment with Immunomodulators treatment.
Immunomodulators was administered orally sublingual at a dose of 4ml / day
In the control group the thyroid function was evaluated every four month



Result


87 patients (78.5 %) treated with Immunomodulators showed increase T3, T4, and
diminution of TSH, TPO and TG after 2 month of treatment.
These patients required less levothyroxine than there were taken before.
8 patients (8.16%) did not show changes in their thyroid function.
3 patients (3.06%) withdrew the treatment
We also observed a better quality of life in these patients. (Increase WBC, RBC).
Less fatigue, dry skin, depression, Cold Intolerance,
In the control group the thyroid function as well as the antibodies did not show any
changes.
 




      Laboratory results in
      Hashimoto thyroiditis
             Subclinic   Clinic
                ↑          ↑
TSH
                ↓         ↓↓
FT4
                          ↓↓
FT3             N
               ↑↑         ↑↑
TPO
               ↑↑         ↑↑
TG

                ↑         ↑↑
Colesterol
Hashimoto treated with
               immunomodulators
                          Hashimoto                    AFTER
                                                  IMMUNOMODULATOR

                    Subclinic        Clinic        Subclinic     Clinic
                                          ↑                          ↓
      TSH                N                               N
                                       ↓↓                            ↑↑
      FT4                N                               N

                                       ↓↓                            ↑↑
      FT3                N                               N

                         ↑↑            ↑↑                ↓↓          ↓↓
      TPO

                        ↑↑            ↑↑
      TG
                                                         ↓↓          ↓↓



Clinical implication




Evolution of hashimoto thyroiditis
1-Hahimoto disease --------------------Hashimoto thyroiditis ( HT)
2-Hashimoto disease-------------------- other autoimmune disease LES, AR, Psoriasis,
3-Hashimoto disease ------------------- ovarian cyst, breast dysplasia, uterus fibroma
4-Hashimoto disease ---------------- malignant tumors (breast, ovarian, lung, prostate,
                                          Colorectal,)


Immunomodulators improves thyroid function in patients with Hashimoto thyroiditis
No side effect were seen in this patients
IM treatment is safe and well tolerated
In cancer patients with Hahimoto thyroiditis IM also improve, RBC, WBC, platelets and the
disease free survival period.


Keywords: hashimoto thyroiditis-Immunomodulators-cancer-thyroid function
Francesco Matozza Is Oncologist at Rawson Hospital in Buenos Aires,
Guillermo E. Artero is Physician at Tornu Hospital in Buenos Aires
Guillermo H Artero is Pharmacist in Pharmaceutical Industry in Buenos Aires, Argentina
Monica Rodriguez Laborda is psychoimmunoendocrinologist in Buenos Aires

Contact
F.Matozza M:D.      frankmatozza@libero.it
G.H.Artero Ph       arteroguillermo@fibertel.com.ar

References

1-Block KI, Mead MN. 

Immune system effects of echinacea, ginseng, and astragalus: a review.
Integr Cancer Ther. 2003 Sep;2(3):247-67. Review.

PMID: 15035888 [PubMed - indexed for MEDLINE]


2--Zagrodzki P, Ratajczak R.

Selenium Supplementation in Autoimmune Thyroiditis Female Patient-Effects on Thyroid
and Ovarian Functions (Case Study).
Biol Trace Elem Res. 2008 Aug 6. [Epub ahead of print]
PMID: 18679588 [PubMed - as supplied by publisher]
3-Duntas LH.

Environmental factors and autoimmune thyroiditis.
Nat Clin Pract Endocrinol Metab. 2008 Aug;4(8):454-60. Epub 2008 Jul 8. Review.
PMID: 18607401 [PubMed - indexed for MEDLINE]
4-Erdal M, Sahin M, Hasimi A, Uckaya G, Kutlu M, Saglam K.

Trace element levels in hashimoto thyroiditis patients with subclinical hypothyroidism.
Biol Trace Elem Res. 2008 Summer;123(1-3):1-7. Epub 2008 Mar 6.
PMID: 18322655 [PubMed - indexed for MEDLINE]
5-Mazokopakis EE, Papadakis JA, Papadomanolaki MG, Batistakis AG, Giannakopoulos
TG, Protopapadakis EE, Ganotakis ES.

Effects of 12 months treatment with L-selenomethionine on serum anti-TPO Levels in
Patients with Hashimoto's thyroiditis.
Thyroid. 2007 Jul;17(7):609-12.
PMID: 17696828 [PubMed - indexed for MEDLINE]
6-Mazokopakis EE, Chatzipavlidou V.

Hashimoto's thyroiditis and the role of selenium. Current concepts.

Hell J Nucl Med. 2007 Jan-Apr;10(1):6-8. Review.
PMID: 17450242 [PubMed - indexed for MEDLINE]


7--Kaprara A, Krassas GE.

[Selenium and thyroidal function; the role of immunoassays]
Hell J Nucl Med. 2006 Sep-Dec;9(3):195-203. Review. Greek, Modern.
PMID: 17160166 [PubMed - indexed for MEDLINE]
8--Caturegli P, Kimura H, Rocchi R, Rose NR.
autoimmune thyroid diseases.
Curr Opin Rheumatol. 2007 Jan;19(1):44-8. Review.
PMID: 17143095 [PubMed - indexed for MEDLINE]
9--Zagrodzki P, Nicol F, Arthur JR, Słowiaczek M.

Selenoproteins in human thyroid tissues.
Biofactors. 2001;14(1-4):223-7.
PMID: 11583018 [PubMed - indexed for MEDLINE]
10-Erdal M, Sahin M, Hasimi A, Uckaya G, Kutlu M, Saglam K.

Trace element levels in hashimoto thyroiditis patients with subclinical hypothyroidism.
Biol Trace Elem Res. 2008 Summer;123(1-3):1-7. Epub 2008 Mar 6.
PMID: 18322655 [PubMed - indexed for MEDLINE]
11-Autoimmune thyroid disease: new models of cell death in autoimmunity.
G Stassi, R De Maria - Nat Rev Immunol, 2002 - ncbi.nlm.nih.gov
Autoimmunity to thyroid antigens leads to two distinct pathogenic processes with
opposing clinical outcomes: hypothyroidism in Hashimoto's thyroiditis and
hyperthyroidism in Graves' disease. The high frequency of these diseases ...
12-Control of target cell survival in thyroid autoimmunity by T helper cytokines via
regulation of …
G Stassi, D Di Liberto, M Todaro, A Zeuner, L … - Nature Immunology, 2000 -
nature.com
Article. Nature Immunology 1, 483 - 488 (2000) doi:10.1038/82725 Control
of target cell survival in thyroid autoimmunity by T helper cytokines
via regulation of apoptotic proteins. Giorgio Stassi ...

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Immunomodulators in patients with hasimoto thyroiditis and cancer

  • 1. Improved thyroid function in oncological patients with Hashimoto Thyroiditis treated with Immunomodulators Francesco Matozza MD*, Guillermo H. Artero Ph **, Guillermo E. Artero MD***, Monica Rodriguez Laborda MD**** Introduction Hashimoto's thyroiditis is chronic autoimmune inflammation of the thyroid with lymphocytic infiltration The destruction of the thyroid gland occurs through the action of CD8 positive killer T cells. CD4 positive helper T cells and B cells are also identified in the thyroid glands of patients with Hashimoto thyroiditis Hashimoto's thyroiditis is the most common cause of primary of hypothyroidism The disease is 7 times more frequent in women. The incidence of Hashimoto thyroiditis worldwide is estimated to be 0.3-1.5 cases per 1000 of population per year Incidence increases with age and in patients with chromosomal disorders, including Turner's, Down, and Klinefelter's syndromes. A family history of thyroid disorders is common. An increased incidence of cancer is seen in people with an autoimmune disease. The treatment of Hashimoto thyroiditis consists of replacing thyroid hormone with levothyroxine, when the patients have become hypothyroid.
  • 2. Purpose. The aim of the study was to evaluate the improvement in thyroid function as well as quality of life in oncological patients with Hashimoto Thyroiditis treated with Immunomodulators . Material We retrospectively review in a multicentric study, 161 patients with Hashimoto thyroiditis, and different types of tumors (breast, kidney, ovarian, uterus, colorectal, thyroid, lung, pancreas, larynx, stomach, bladder, prostate, etc). Age range 40 to 70 years old. 98 patients were treated with (chemotherapy or radiotherapy) + levothyroxine and Immunomodulators during 6 month.
  • 3. This Immunomodulators compound contains: Astragalus Ext., Zinc, Mg and Selenium.” 63 patients treated only with oncological treatment (chemotherapy or radiotherapy) + levothyroxine as a control group. Method Thyroid function: T3.T4. TSH, TPO and TG antibodies were measured before, during and after six month treatment with Immunomodulators treatment. Immunomodulators was administered orally sublingual at a dose of 4ml / day In the control group the thyroid function was evaluated every four month Result 87 patients (78.5 %) treated with Immunomodulators showed increase T3, T4, and diminution of TSH, TPO and TG after 2 month of treatment. These patients required less levothyroxine than there were taken before. 8 patients (8.16%) did not show changes in their thyroid function. 3 patients (3.06%) withdrew the treatment We also observed a better quality of life in these patients. (Increase WBC, RBC). Less fatigue, dry skin, depression, Cold Intolerance, In the control group the thyroid function as well as the antibodies did not show any changes.
  • 4.   Laboratory results in Hashimoto thyroiditis Subclinic Clinic ↑ ↑ TSH ↓ ↓↓ FT4 ↓↓ FT3 N ↑↑ ↑↑ TPO ↑↑ ↑↑ TG ↑ ↑↑ Colesterol
  • 5. Hashimoto treated with immunomodulators Hashimoto AFTER IMMUNOMODULATOR Subclinic Clinic Subclinic Clinic ↑ ↓ TSH N N ↓↓ ↑↑ FT4 N N ↓↓ ↑↑ FT3 N N ↑↑ ↑↑ ↓↓ ↓↓ TPO ↑↑ ↑↑ TG ↓↓ ↓↓ Clinical implication Evolution of hashimoto thyroiditis 1-Hahimoto disease --------------------Hashimoto thyroiditis ( HT) 2-Hashimoto disease-------------------- other autoimmune disease LES, AR, Psoriasis, 3-Hashimoto disease ------------------- ovarian cyst, breast dysplasia, uterus fibroma 4-Hashimoto disease ---------------- malignant tumors (breast, ovarian, lung, prostate, Colorectal,) Immunomodulators improves thyroid function in patients with Hashimoto thyroiditis No side effect were seen in this patients IM treatment is safe and well tolerated
  • 6. In cancer patients with Hahimoto thyroiditis IM also improve, RBC, WBC, platelets and the disease free survival period. Keywords: hashimoto thyroiditis-Immunomodulators-cancer-thyroid function Francesco Matozza Is Oncologist at Rawson Hospital in Buenos Aires, Guillermo E. Artero is Physician at Tornu Hospital in Buenos Aires Guillermo H Artero is Pharmacist in Pharmaceutical Industry in Buenos Aires, Argentina Monica Rodriguez Laborda is psychoimmunoendocrinologist in Buenos Aires Contact F.Matozza M:D. frankmatozza@libero.it G.H.Artero Ph arteroguillermo@fibertel.com.ar References 1-Block KI, Mead MN.  Immune system effects of echinacea, ginseng, and astragalus: a review. Integr Cancer Ther. 2003 Sep;2(3):247-67. Review. PMID: 15035888 [PubMed - indexed for MEDLINE] 2--Zagrodzki P, Ratajczak R. Selenium Supplementation in Autoimmune Thyroiditis Female Patient-Effects on Thyroid and Ovarian Functions (Case Study). Biol Trace Elem Res. 2008 Aug 6. [Epub ahead of print] PMID: 18679588 [PubMed - as supplied by publisher] 3-Duntas LH. Environmental factors and autoimmune thyroiditis. Nat Clin Pract Endocrinol Metab. 2008 Aug;4(8):454-60. Epub 2008 Jul 8. Review. PMID: 18607401 [PubMed - indexed for MEDLINE] 4-Erdal M, Sahin M, Hasimi A, Uckaya G, Kutlu M, Saglam K. Trace element levels in hashimoto thyroiditis patients with subclinical hypothyroidism. Biol Trace Elem Res. 2008 Summer;123(1-3):1-7. Epub 2008 Mar 6. PMID: 18322655 [PubMed - indexed for MEDLINE] 5-Mazokopakis EE, Papadakis JA, Papadomanolaki MG, Batistakis AG, Giannakopoulos TG, Protopapadakis EE, Ganotakis ES. Effects of 12 months treatment with L-selenomethionine on serum anti-TPO Levels in Patients with Hashimoto's thyroiditis.
  • 7. Thyroid. 2007 Jul;17(7):609-12. PMID: 17696828 [PubMed - indexed for MEDLINE] 6-Mazokopakis EE, Chatzipavlidou V. Hashimoto's thyroiditis and the role of selenium. Current concepts. Hell J Nucl Med. 2007 Jan-Apr;10(1):6-8. Review. PMID: 17450242 [PubMed - indexed for MEDLINE] 7--Kaprara A, Krassas GE. [Selenium and thyroidal function; the role of immunoassays] Hell J Nucl Med. 2006 Sep-Dec;9(3):195-203. Review. Greek, Modern. PMID: 17160166 [PubMed - indexed for MEDLINE] 8--Caturegli P, Kimura H, Rocchi R, Rose NR. autoimmune thyroid diseases. Curr Opin Rheumatol. 2007 Jan;19(1):44-8. Review. PMID: 17143095 [PubMed - indexed for MEDLINE] 9--Zagrodzki P, Nicol F, Arthur JR, Słowiaczek M. Selenoproteins in human thyroid tissues. Biofactors. 2001;14(1-4):223-7. PMID: 11583018 [PubMed - indexed for MEDLINE] 10-Erdal M, Sahin M, Hasimi A, Uckaya G, Kutlu M, Saglam K. Trace element levels in hashimoto thyroiditis patients with subclinical hypothyroidism. Biol Trace Elem Res. 2008 Summer;123(1-3):1-7. Epub 2008 Mar 6. PMID: 18322655 [PubMed - indexed for MEDLINE] 11-Autoimmune thyroid disease: new models of cell death in autoimmunity. G Stassi, R De Maria - Nat Rev Immunol, 2002 - ncbi.nlm.nih.gov Autoimmunity to thyroid antigens leads to two distinct pathogenic processes with opposing clinical outcomes: hypothyroidism in Hashimoto's thyroiditis and hyperthyroidism in Graves' disease. The high frequency of these diseases ...
  • 8. 12-Control of target cell survival in thyroid autoimmunity by T helper cytokines via regulation of … G Stassi, D Di Liberto, M Todaro, A Zeuner, L … - Nature Immunology, 2000 - nature.com Article. Nature Immunology 1, 483 - 488 (2000) doi:10.1038/82725 Control of target cell survival in thyroid autoimmunity by T helper cytokines via regulation of apoptotic proteins. Giorgio Stassi ...