Long-Term Outcome of Interferon-α-Induced Thyroid Autoimmunity and Prognostic Influence of Thyroid Autoantibody Pattern at the End of Treatment
Thyroid autoimmunity and dysfunction have been widely reported as side effects of interferon-α (IFN-α) treatment, but the literature lacks data regarding the long-term course of these complications, clinical observation being limited to 6–12 months off therapy. Our study is the first that has aimed...
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| Veröffentlicht in: | The journal of clinical endocrinology and metabolism 2001-05, Vol.86 (5), p.1925-1929 |
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| creator | Carella, Carlo Mazziotti, Gherardo Morisco, Filomena Manganella, Giovanni Rotondi, Mario Tuccillo, Concetta Sorvillo, Francesca Caporaso, Nicola Amato, Giovanni |
| description | Thyroid autoimmunity and dysfunction have been widely reported as side
effects of interferon-α (IFN-α) treatment, but the literature lacks
data regarding the long-term course of these complications, clinical
observation being limited to 6–12 months off therapy. Our
study is the first that has aimed to evaluate the natural history of
IFN-related thyroid autoimmunity during a 6.2-yr follow-up after the
IFN-α withdrawal as well as to investigate the potential role of the
autoantibody pattern at the end of treatment to predict the long-term
outcome.
Our study group included 114 patients (79 males, 35 females), mean age
48 yr (range 23–67 yr) with no preexisting thyroid disease, undergoing
a 12-month treatment with recombinant IFN-α for C virus-related
chronic active hepatitis. Thyroid autoimmunity (serum TgAb and TPOAb)
and function (serum FT4, FT3, TSH) were
retrospectively evaluated at the end of IFN therapy, 6 months after IFN
withdrawal and after a median period of 6.2 yr (range 5.5–8.4 yr).
At the end of treatment, 78 patients were negative for thyroid
autoantibodies (Abs−) and all but one of them remained so for the
following evaluations. The remaining 36 patients had thyroid
autoantibodies (Abs+) at the end of treatment, and they subsequently
showed a heterogeneous behavior: 16 patients remained Abs+ for the
whole length of the study (persistent thyroiditis); 10 patients became
Abs− 6 months off therapy but were again Abs+ 6.2 yr later
(remitting/relapsing thyroiditis); 10 patients reverted to autoantibody
negativity at different observation times (transient thyroiditis).
The absence of thyroid autoantibodies at the end of treatment was a
protective factor for the successive development of thyroiditis (odds
ratio: 0.02, confidence interval (CI) 95%: 0–0.1). On the contrary,
the positivity for TgAb and/or TPOAb at high titers at the end of IFN
treatment was significantly related to the highest risk of having
chronic thyroiditis (odds ratio: 17.3, CI 95%: 3.2–91.7 for TgAb
levels > 50 degree percentile; odds ratio: 7.3, CI 95%:
1.5–35.2 for TPOAb levels > 50 degree percentile).
None of the patients showed overt thyroid dysfunction throughout the
study, whereas a subclinical hypothyroidism was found in 12 patients.
In all 12 cases, the functional abnormality was accompanied by the
presence of thyroid autoantibodies. Eight of these 12 patients belonged
to the group with persistent thyroiditis (P <
0.05).
The absence of thyroid autoantibodies at the end of t |
| doi_str_mv | 10.1210/jcem.86.5.7459 |
| format | Article |
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effects of interferon-α (IFN-α) treatment, but the literature lacks
data regarding the long-term course of these complications, clinical
observation being limited to 6–12 months off therapy. Our
study is the first that has aimed to evaluate the natural history of
IFN-related thyroid autoimmunity during a 6.2-yr follow-up after the
IFN-α withdrawal as well as to investigate the potential role of the
autoantibody pattern at the end of treatment to predict the long-term
outcome.
Our study group included 114 patients (79 males, 35 females), mean age
48 yr (range 23–67 yr) with no preexisting thyroid disease, undergoing
a 12-month treatment with recombinant IFN-α for C virus-related
chronic active hepatitis. Thyroid autoimmunity (serum TgAb and TPOAb)
and function (serum FT4, FT3, TSH) were
retrospectively evaluated at the end of IFN therapy, 6 months after IFN
withdrawal and after a median period of 6.2 yr (range 5.5–8.4 yr).
At the end of treatment, 78 patients were negative for thyroid
autoantibodies (Abs−) and all but one of them remained so for the
following evaluations. The remaining 36 patients had thyroid
autoantibodies (Abs+) at the end of treatment, and they subsequently
showed a heterogeneous behavior: 16 patients remained Abs+ for the
whole length of the study (persistent thyroiditis); 10 patients became
Abs− 6 months off therapy but were again Abs+ 6.2 yr later
(remitting/relapsing thyroiditis); 10 patients reverted to autoantibody
negativity at different observation times (transient thyroiditis).
The absence of thyroid autoantibodies at the end of treatment was a
protective factor for the successive development of thyroiditis (odds
ratio: 0.02, confidence interval (CI) 95%: 0–0.1). On the contrary,
the positivity for TgAb and/or TPOAb at high titers at the end of IFN
treatment was significantly related to the highest risk of having
chronic thyroiditis (odds ratio: 17.3, CI 95%: 3.2–91.7 for TgAb
levels > 50 degree percentile; odds ratio: 7.3, CI 95%:
1.5–35.2 for TPOAb levels > 50 degree percentile).
None of the patients showed overt thyroid dysfunction throughout the
study, whereas a subclinical hypothyroidism was found in 12 patients.
In all 12 cases, the functional abnormality was accompanied by the
presence of thyroid autoantibodies. Eight of these 12 patients belonged
to the group with persistent thyroiditis (P <
0.05).
The absence of thyroid autoantibodies at the end of treatment was a
protective factor for the successive development of thyroid dysfunction
(odds ratio: 0.06, CI 95%: 0.01–0.56). On the contrary, the
positivity for both TgAb and TPOAb at the end of IFN therapy was
significantly correlated with the highest risk of having subclinical
hypothyroidism 6.2 yr. later (odds ratio: 38.7; CI 95%:
6.2–242).
Our study demonstrates that in patients undergoing an IFN-α therapy
for chronic hepatitis C and with no evidence of preexisting thyroid
disease: 1) the negativity for thyroid autoantibodies after IFN
treatment is a protective factor for the developing thyroid
autoimmunity and/or dysfunction in following years; 2) the
IFN-α-related thyroid autoimmunity is not a complete reversible
phenomenon because some patients can develop chronic thyroiditis; 3)
high autoantibody levels at the end of IFN therapy are related to the
risk of having chronic thyroid autoimmunity; and 4) the coexistence of
TgAb and TPOAb at the end of treatment is a predictive factor for the
presence of thyroid dysfunction, even if subclinical, many years after
IFN withdrawal.</description><identifier>ISSN: 0021-972X</identifier><identifier>EISSN: 1945-7197</identifier><identifier>DOI: 10.1210/jcem.86.5.7459</identifier><identifier>PMID: 11344186</identifier><identifier>CODEN: JCEMAZ</identifier><language>eng</language><publisher>Bethesda, MD: Endocrine Society</publisher><subject>Adult ; Aged ; Autoantibodies - biosynthesis ; Autoimmunity - drug effects ; Biological and medical sciences ; Drug toxicity and drugs side effects treatment ; Female ; Humans ; Interferon-alpha - adverse effects ; Male ; Medical sciences ; Middle Aged ; Miscellaneous (drug allergy, mutagens, teratogens...) ; Pharmacology. Drug treatments ; Prognosis ; Thyroid Gland - drug effects ; Thyroid Gland - immunology</subject><ispartof>The journal of clinical endocrinology and metabolism, 2001-05, Vol.86 (5), p.1925-1929</ispartof><rights>2001 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2529-e5f00f33880b1b5cd50e4bfa6553ae8a568721615391119f44475e257a0b95983</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=988877$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11344186$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Carella, Carlo</creatorcontrib><creatorcontrib>Mazziotti, Gherardo</creatorcontrib><creatorcontrib>Morisco, Filomena</creatorcontrib><creatorcontrib>Manganella, Giovanni</creatorcontrib><creatorcontrib>Rotondi, Mario</creatorcontrib><creatorcontrib>Tuccillo, Concetta</creatorcontrib><creatorcontrib>Sorvillo, Francesca</creatorcontrib><creatorcontrib>Caporaso, Nicola</creatorcontrib><creatorcontrib>Amato, Giovanni</creatorcontrib><title>Long-Term Outcome of Interferon-α-Induced Thyroid Autoimmunity and Prognostic Influence of Thyroid Autoantibody Pattern at the End of Treatment</title><title>The journal of clinical endocrinology and metabolism</title><addtitle>J Clin Endocrinol Metab</addtitle><description>Thyroid autoimmunity and dysfunction have been widely reported as side
effects of interferon-α (IFN-α) treatment, but the literature lacks
data regarding the long-term course of these complications, clinical
observation being limited to 6–12 months off therapy. Our
study is the first that has aimed to evaluate the natural history of
IFN-related thyroid autoimmunity during a 6.2-yr follow-up after the
IFN-α withdrawal as well as to investigate the potential role of the
autoantibody pattern at the end of treatment to predict the long-term
outcome.
Our study group included 114 patients (79 males, 35 females), mean age
48 yr (range 23–67 yr) with no preexisting thyroid disease, undergoing
a 12-month treatment with recombinant IFN-α for C virus-related
chronic active hepatitis. Thyroid autoimmunity (serum TgAb and TPOAb)
and function (serum FT4, FT3, TSH) were
retrospectively evaluated at the end of IFN therapy, 6 months after IFN
withdrawal and after a median period of 6.2 yr (range 5.5–8.4 yr).
At the end of treatment, 78 patients were negative for thyroid
autoantibodies (Abs−) and all but one of them remained so for the
following evaluations. The remaining 36 patients had thyroid
autoantibodies (Abs+) at the end of treatment, and they subsequently
showed a heterogeneous behavior: 16 patients remained Abs+ for the
whole length of the study (persistent thyroiditis); 10 patients became
Abs− 6 months off therapy but were again Abs+ 6.2 yr later
(remitting/relapsing thyroiditis); 10 patients reverted to autoantibody
negativity at different observation times (transient thyroiditis).
The absence of thyroid autoantibodies at the end of treatment was a
protective factor for the successive development of thyroiditis (odds
ratio: 0.02, confidence interval (CI) 95%: 0–0.1). On the contrary,
the positivity for TgAb and/or TPOAb at high titers at the end of IFN
treatment was significantly related to the highest risk of having
chronic thyroiditis (odds ratio: 17.3, CI 95%: 3.2–91.7 for TgAb
levels > 50 degree percentile; odds ratio: 7.3, CI 95%:
1.5–35.2 for TPOAb levels > 50 degree percentile).
None of the patients showed overt thyroid dysfunction throughout the
study, whereas a subclinical hypothyroidism was found in 12 patients.
In all 12 cases, the functional abnormality was accompanied by the
presence of thyroid autoantibodies. Eight of these 12 patients belonged
to the group with persistent thyroiditis (P <
0.05).
The absence of thyroid autoantibodies at the end of treatment was a
protective factor for the successive development of thyroid dysfunction
(odds ratio: 0.06, CI 95%: 0.01–0.56). On the contrary, the
positivity for both TgAb and TPOAb at the end of IFN therapy was
significantly correlated with the highest risk of having subclinical
hypothyroidism 6.2 yr. later (odds ratio: 38.7; CI 95%:
6.2–242).
Our study demonstrates that in patients undergoing an IFN-α therapy
for chronic hepatitis C and with no evidence of preexisting thyroid
disease: 1) the negativity for thyroid autoantibodies after IFN
treatment is a protective factor for the developing thyroid
autoimmunity and/or dysfunction in following years; 2) the
IFN-α-related thyroid autoimmunity is not a complete reversible
phenomenon because some patients can develop chronic thyroiditis; 3)
high autoantibody levels at the end of IFN therapy are related to the
risk of having chronic thyroid autoimmunity; and 4) the coexistence of
TgAb and TPOAb at the end of treatment is a predictive factor for the
presence of thyroid dysfunction, even if subclinical, many years after
IFN withdrawal.</description><subject>Adult</subject><subject>Aged</subject><subject>Autoantibodies - biosynthesis</subject><subject>Autoimmunity - drug effects</subject><subject>Biological and medical sciences</subject><subject>Drug toxicity and drugs side effects treatment</subject><subject>Female</subject><subject>Humans</subject><subject>Interferon-alpha - adverse effects</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Miscellaneous (drug allergy, mutagens, teratogens...)</subject><subject>Pharmacology. Drug treatments</subject><subject>Prognosis</subject><subject>Thyroid Gland - drug effects</subject><subject>Thyroid Gland - immunology</subject><issn>0021-972X</issn><issn>1945-7197</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10UFu1DAYBWALgehQ2LJElpDYJdiJHdvLqiplpJHaxSCxsxznd5tRbA-2s5hb9CpchDM1w4yADStvvvcs_Q-h95TUtKHk886Cr2VX81owrl6gFVWMV4Iq8RKtCGlopUTz_QK9yXlHCGWMt6_RBaUtY1R2K_S0ieGh2kLy-G4uNnrA0eF1KJAcpBiqXz-rdRhmCwPePh5SHAd8NZc4ej-HsRywCQO-T_EhxFxGuyTdNEOwv2v-DZhQxj4OB3xvylIesCm4PAK-WfJHmsAUD6G8Ra-cmTK8O7-X6NuXm-3112pzd7u-vtpUtuGNqoA7QlzbSkl62nM7cAKsd6bjvDUgDe-kaGhHeasopcoxxgSHhgtDesWVbC_Rp1PvPsUfM-Si_ZgtTJMJEOesBZGMCkoWWJ-gTTHnBE7v0-hNOmhK9HEDfdxAy05zfdxgCXw4N8-9h-EvPx99AR_PwGRrJpdMsGP-45SUUohF8ZOCMESbxgD7BDnrXZxTWC7zv--fAe89o3E</recordid><startdate>200105</startdate><enddate>200105</enddate><creator>Carella, Carlo</creator><creator>Mazziotti, Gherardo</creator><creator>Morisco, Filomena</creator><creator>Manganella, Giovanni</creator><creator>Rotondi, Mario</creator><creator>Tuccillo, Concetta</creator><creator>Sorvillo, Francesca</creator><creator>Caporaso, Nicola</creator><creator>Amato, Giovanni</creator><general>Endocrine Society</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>200105</creationdate><title>Long-Term Outcome of Interferon-α-Induced Thyroid Autoimmunity and Prognostic Influence of Thyroid Autoantibody Pattern at the End of Treatment</title><author>Carella, Carlo ; Mazziotti, Gherardo ; Morisco, Filomena ; Manganella, Giovanni ; Rotondi, Mario ; Tuccillo, Concetta ; Sorvillo, Francesca ; Caporaso, Nicola ; Amato, Giovanni</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2529-e5f00f33880b1b5cd50e4bfa6553ae8a568721615391119f44475e257a0b95983</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Autoantibodies - biosynthesis</topic><topic>Autoimmunity - drug effects</topic><topic>Biological and medical sciences</topic><topic>Drug toxicity and drugs side effects treatment</topic><topic>Female</topic><topic>Humans</topic><topic>Interferon-alpha - adverse effects</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Miscellaneous (drug allergy, mutagens, teratogens...)</topic><topic>Pharmacology. Drug treatments</topic><topic>Prognosis</topic><topic>Thyroid Gland - drug effects</topic><topic>Thyroid Gland - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Carella, Carlo</creatorcontrib><creatorcontrib>Mazziotti, Gherardo</creatorcontrib><creatorcontrib>Morisco, Filomena</creatorcontrib><creatorcontrib>Manganella, Giovanni</creatorcontrib><creatorcontrib>Rotondi, Mario</creatorcontrib><creatorcontrib>Tuccillo, Concetta</creatorcontrib><creatorcontrib>Sorvillo, Francesca</creatorcontrib><creatorcontrib>Caporaso, Nicola</creatorcontrib><creatorcontrib>Amato, Giovanni</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The journal of clinical endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Carella, Carlo</au><au>Mazziotti, Gherardo</au><au>Morisco, Filomena</au><au>Manganella, Giovanni</au><au>Rotondi, Mario</au><au>Tuccillo, Concetta</au><au>Sorvillo, Francesca</au><au>Caporaso, Nicola</au><au>Amato, Giovanni</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Long-Term Outcome of Interferon-α-Induced Thyroid Autoimmunity and Prognostic Influence of Thyroid Autoantibody Pattern at the End of Treatment</atitle><jtitle>The journal of clinical endocrinology and metabolism</jtitle><addtitle>J Clin Endocrinol Metab</addtitle><date>2001-05</date><risdate>2001</risdate><volume>86</volume><issue>5</issue><spage>1925</spage><epage>1929</epage><pages>1925-1929</pages><issn>0021-972X</issn><eissn>1945-7197</eissn><coden>JCEMAZ</coden><abstract>Thyroid autoimmunity and dysfunction have been widely reported as side
effects of interferon-α (IFN-α) treatment, but the literature lacks
data regarding the long-term course of these complications, clinical
observation being limited to 6–12 months off therapy. Our
study is the first that has aimed to evaluate the natural history of
IFN-related thyroid autoimmunity during a 6.2-yr follow-up after the
IFN-α withdrawal as well as to investigate the potential role of the
autoantibody pattern at the end of treatment to predict the long-term
outcome.
Our study group included 114 patients (79 males, 35 females), mean age
48 yr (range 23–67 yr) with no preexisting thyroid disease, undergoing
a 12-month treatment with recombinant IFN-α for C virus-related
chronic active hepatitis. Thyroid autoimmunity (serum TgAb and TPOAb)
and function (serum FT4, FT3, TSH) were
retrospectively evaluated at the end of IFN therapy, 6 months after IFN
withdrawal and after a median period of 6.2 yr (range 5.5–8.4 yr).
At the end of treatment, 78 patients were negative for thyroid
autoantibodies (Abs−) and all but one of them remained so for the
following evaluations. The remaining 36 patients had thyroid
autoantibodies (Abs+) at the end of treatment, and they subsequently
showed a heterogeneous behavior: 16 patients remained Abs+ for the
whole length of the study (persistent thyroiditis); 10 patients became
Abs− 6 months off therapy but were again Abs+ 6.2 yr later
(remitting/relapsing thyroiditis); 10 patients reverted to autoantibody
negativity at different observation times (transient thyroiditis).
The absence of thyroid autoantibodies at the end of treatment was a
protective factor for the successive development of thyroiditis (odds
ratio: 0.02, confidence interval (CI) 95%: 0–0.1). On the contrary,
the positivity for TgAb and/or TPOAb at high titers at the end of IFN
treatment was significantly related to the highest risk of having
chronic thyroiditis (odds ratio: 17.3, CI 95%: 3.2–91.7 for TgAb
levels > 50 degree percentile; odds ratio: 7.3, CI 95%:
1.5–35.2 for TPOAb levels > 50 degree percentile).
None of the patients showed overt thyroid dysfunction throughout the
study, whereas a subclinical hypothyroidism was found in 12 patients.
In all 12 cases, the functional abnormality was accompanied by the
presence of thyroid autoantibodies. Eight of these 12 patients belonged
to the group with persistent thyroiditis (P <
0.05).
The absence of thyroid autoantibodies at the end of treatment was a
protective factor for the successive development of thyroid dysfunction
(odds ratio: 0.06, CI 95%: 0.01–0.56). On the contrary, the
positivity for both TgAb and TPOAb at the end of IFN therapy was
significantly correlated with the highest risk of having subclinical
hypothyroidism 6.2 yr. later (odds ratio: 38.7; CI 95%:
6.2–242).
Our study demonstrates that in patients undergoing an IFN-α therapy
for chronic hepatitis C and with no evidence of preexisting thyroid
disease: 1) the negativity for thyroid autoantibodies after IFN
treatment is a protective factor for the developing thyroid
autoimmunity and/or dysfunction in following years; 2) the
IFN-α-related thyroid autoimmunity is not a complete reversible
phenomenon because some patients can develop chronic thyroiditis; 3)
high autoantibody levels at the end of IFN therapy are related to the
risk of having chronic thyroid autoimmunity; and 4) the coexistence of
TgAb and TPOAb at the end of treatment is a predictive factor for the
presence of thyroid dysfunction, even if subclinical, many years after
IFN withdrawal.</abstract><cop>Bethesda, MD</cop><pub>Endocrine Society</pub><pmid>11344186</pmid><doi>10.1210/jcem.86.5.7459</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-972X |
| ispartof | The journal of clinical endocrinology and metabolism, 2001-05, Vol.86 (5), p.1925-1929 |
| issn | 0021-972X 1945-7197 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_70841710 |
| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Adult Aged Autoantibodies - biosynthesis Autoimmunity - drug effects Biological and medical sciences Drug toxicity and drugs side effects treatment Female Humans Interferon-alpha - adverse effects Male Medical sciences Middle Aged Miscellaneous (drug allergy, mutagens, teratogens...) Pharmacology. Drug treatments Prognosis Thyroid Gland - drug effects Thyroid Gland - immunology |
| title | Long-Term Outcome of Interferon-α-Induced Thyroid Autoimmunity and Prognostic Influence of Thyroid Autoantibody Pattern at the End of Treatment |
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