Postpartum thyroiditis differential diagnosis: Difference between revisions

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__NOTOC__
__NOTOC__
{{Postpartum thyroiditis}}
[[Image:Home_logo1.png|right|250px|link=https://www.wikidoc.org/index.php/Postpartum_thyroiditis]]
{{CMG}} {{AE}} {{MMF}}
{{CMG}} {{AE}} {{MMF}}{{SKA}}


==Overview==
==Overview==
[[Postpartum thyroiditis]] must be differentiated from other causes of [[thyroiditis]], such as [[De Quervain's thyroiditis]], [[Hashimoto's thyroiditis]], [[Riedel's thyroiditis]], and suppurative thyroiditis. Postpartum thyroiditis must be differentiated from other causes of [[thyroiditis]], such as [[De Quervain's thyroiditis]], [[Riedel's thyroiditis]], and suppurative thyroiditis. Postpartum thyroiditis must also be differentiated from other diseases which cause [[hypothyroidism]]. As Postpartum thyroiditis may cause transient thyrotoxic symptoms, the diseases causing [[thyrotoxicosis]] must also be considered in the differential diagnosis.
[[Postpartum thyroiditis]] must be differentiated from other causes of [[thyroiditis]], such as [[De Quervain's thyroiditis]], [[Hashimoto's thyroiditis]], [[Riedel's thyroiditis]], and suppurative thyroiditis. Postpartum thyroiditis must also be differentiated from other diseases which cause [[hypothyroidism]]. As postpartum thyroiditis may cause transient thyrotoxic symptoms, the diseases causing [[thyrotoxicosis]] must also be considered in the differential diagnosis.


==Differentiating Postpartum Thyroiditis from other Diseases==
==Differentiating Postpartum Thyroiditis from other Diseases==
===Differentiating postpartum thyroiditis from other causes of thyroiditis===
===Differentiating postpartum thyroiditis from other causes of thyroiditis===
*Postpartum thyroiditis must be differentiated from other causes of [[thyroiditis]], such as [[De Quervain's thyroiditis]], [[Hashimoto's thyroiditis]], [[Riedel's thyroiditis]], and suppurative thyroiditis.<ref name="urlThyroiditis — NEJM">{{cite web |url=http://www.nejm.org/doi/full/10.1056/NEJMra021194 |title=Thyroiditis — NEJM |format= |work= |accessdate=}}</ref>
*Postpartum thyroiditis must be differentiated from other causes of [[thyroiditis]], such as [[De Quervain's thyroiditis]], [[Hashimoto's thyroiditis]], [[Riedel's thyroiditis]], and suppurative thyroiditis.<ref name="urlThyroiditis — NEJM">{{cite web |url=http://www.nejm.org/doi/full/10.1056/NEJMra021194 |title=Thyroiditis — NEJM |format= |work= |accessdate=}}</ref><ref name="pmid28781832">{{cite journal| author=Akuzawa N, Yokota T, Suzuki T, Kurabayashi M| title=Acute suppurative thyroiditis caused by Streptococcus agalactiae infection: a case report. | journal=Clin Case Rep | year= 2017 | volume= 5 | issue= 8 | pages= 1238-1242 | pmid=28781832 | doi=10.1002/ccr3.1048 | pmc=5538065 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28781832  }}</ref><ref name="pmid287818323">{{cite journal| author=Akuzawa N, Yokota T, Suzuki T, Kurabayashi M| title=Acute suppurative thyroiditis caused by Streptococcus agalactiae infection: a case report. | journal=Clin Case Rep | year= 2017 | volume= 5 | issue= 8 | pages= 1238-1242 | pmid=28781832 | doi=10.1002/ccr3.1048 | pmc=5538065 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28781832  }}</ref>
{| align="center"
{| align="center"
|-
|-
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! style="background:#4479BA; color: #FFFFFF;" | Conditions
! style="background:#4479BA; color: #FFFFFF;" | Conditions
! style="background:#4479BA; color: #FFFFFF;" |Causes
! style="background:#4479BA; color: #FFFFFF;" |Causes
! style="background:#4479BA; color: #FFFFFF;" |Age at onset
! style="background:#4479BA; color: #FFFFFF;" |Age of onset (years)
! style="background:#4479BA; color: #FFFFFF;" |Pathological findings
! style="background:#4479BA; color: #FFFFFF;" |Pathological findings
! style="background:#4479BA; color: #FFFFFF;" |Diagnostic approach     
! style="background:#4479BA; color: #FFFFFF;" |Diagnostic approach     
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| align="center" style="background:#DCDCDC;" |[[Hashimoto's thyroiditis]]
| align="center" style="background:#DCDCDC;" |[[Hashimoto's thyroiditis]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*Autoimmune
*[[Autoimmune]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*All ages, peak at 30-50
*All ages, peak at 30-50
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*Lymphocytic infiltration
*Lymphocytic infiltration
*Germinal centers
*Germinal centers
*Fibrosis (in some variants)
*[[Fibrosis]] (in some variants)
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*[[Thyroid function tests|Increased TSH]] (hypothyroidism)
*[[Thyroid function tests|Increased TSH]] ([[hypothyroidism]])
*[[Thyroid peroxidase|TPO antibodies]] present in high titer
*[[Thyroid peroxidase|TPO antibodies]] present in high titer
*[[I-123 thyroid imaging|I-123]] uptake usually decreased
*[[I-123 thyroid imaging|I-123]] uptake usually decreased
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*20-60
*20-60
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*Giant cells
*[[Giant cells]]
*Granulomas
*[[Granulomas]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*[[Thyroid function tests|Increased TSH]] (hypothyroidism) and/or
*[[Thyroid function tests|Increased TSH]] ([[hypothyroidism]]) and/or
* [[Thyroid function tests|Decreased TSH]] (Thyrotoxicosis)
* [[Thyroid function tests|Decreased TSH]] ([[thyrotoxicosis]])
*[[Thyroid peroxidase|TPO antibodies]] absent or very low titer
*[[Thyroid peroxidase|TPO antibodies]] absent or very low titer
*[[I-123 thyroid imaging|I-123]] uptake decreased
*[[I-123 thyroid imaging|I-123]] uptake decreased
Line 51: Line 51:
| align="center" style="background:#DCDCDC;" |[[Silent thyroiditis]]
| align="center" style="background:#DCDCDC;" |[[Silent thyroiditis]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*Autoimmune
*[[Autoimmune]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*All ages, peak at 30-40
*All ages, peak at 30-40
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*Lymphoid follicles
*Lymphoid follicles
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*[[Thyroid function tests|Increased TSH]] (hypothyroidism) and/or
*[[Thyroid function tests|Increased TSH]] ([[hypothyroidism]]) and/or
* [[Thyroid function tests|Decreased TSH]] (transient hypothyroidism)
* [[Thyroid function tests|Decreased TSH]] (transient [[hypothyroidism]])
*[[Thyroid peroxidase|TPO antibodies]] present in high titer
*[[Thyroid peroxidase|TPO antibodies]] present in high titer
*[[I-123 thyroid imaging|I-123]] uptake usually decreased
*[[I-123 thyroid imaging|I-123]] uptake usually decreased
Line 65: Line 65:
| align="center" style="background:#DCDCDC;" |[[Postpartum thyroiditis]]
| align="center" style="background:#DCDCDC;" |[[Postpartum thyroiditis]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*Autoimmune
*[[Autoimmune]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*Childbearing age
*Childbearing age
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*Lymphocytic infiltration
*Lymphocytic infiltration
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*[[Thyroid function tests|Increased TSH]] (hypothyroidism) and/or
*[[Thyroid function tests|Increased TSH]] ([[hypothyroidism]]) and/or
* [[Thyroid function tests|Decreased TSH]] (transient hypothyroidism)
* [[Thyroid function tests|Decreased TSH]] (transient [[hypothyroidism]])
*[[Thyroid peroxidase|TPO antibodies]] present in high titer
*[[Thyroid peroxidase|TPO antibodies]] present in high titer
*[[I-123 thyroid imaging|I-123]] uptake usually decreased
*[[I-123 thyroid imaging|I-123]] uptake usually decreased
Line 82: Line 82:
*30-60
*30-60
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*Dense fibrosis
*Dense [[fibrosis]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*[[Thyroid function tests|Normal TSH]] (euthyroidism)
*[[Thyroid function tests|Normal TSH]] (euthyroidism)
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| align="center" style="background:#DCDCDC;" |[[Suppurative thyroiditis]]
| align="center" style="background:#DCDCDC;" |[[Suppurative thyroiditis]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*Infection
*[[Infection]]
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*Children, 20-40
*Children, 20-40
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*Abscess formation
*[[Abscess]] formation
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
| style="padding: 5px 5px; background: #F5F5F5;" align="left" |
*[[Thyroid function tests|Normal TSH]] (euthyroidism)
*[[Thyroid function tests|Normal TSH]] (euthyroidism)
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|-
|-
| rowspan="3" style="background:#DCDCDC;" |[[Primary hypothyroidism]]
| rowspan="3" style="background:#DCDCDC;" |[[Primary hypothyroidism]]
| align="center" style="background:#DCDCDC;" |[[Hashimoto's thyroiditis|Autoimmune]] ([[Hashimoto's thyroiditis]])
| align="center" style="background:#DCDCDC;" |[[Hashimoto's thyroiditis|Autoimmune]]  
([[Hashimoto's thyroiditis]])
| align="center" style="padding: 5px 5px; background: #F5F5F5;" | -
| align="center" style="padding: 5px 5px; background: #F5F5F5;" | -
| align="center" style="padding: 5px 5px; background: #F5F5F5;" | -
| align="center" style="padding: 5px 5px; background: #F5F5F5;" | -
Line 146: Line 147:
*[[Riedel's thyroiditis]] usually presents with hard and fixed thyroid mass.
*[[Riedel's thyroiditis]] usually presents with hard and fixed thyroid mass.
|-
|-
| align="center" style="background:#DCDCDC;" |[[Infectious thyroiditis]]
| align="center" style="background:#DCDCDC;" |Infectious thyroiditis
| align="center" style="padding: 5px 5px; background: #F5F5F5;" | +
| align="center" style="padding: 5px 5px; background: #F5F5F5;" | +
| align="center" style="padding: 5px 5px; background: #F5F5F5;" | +
| align="center" style="padding: 5px 5px; background: #F5F5F5;" | +
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| align="center" style="background:#DCDCDC;" |Trauma induced
| align="center" style="background:#DCDCDC;" |Trauma induced
|-
|-
| align="center" style="background:#DCDCDC;" |Radioiodine induced
| align="center" style="background:#DCDCDC;" |[[Radioiodine]] induced
|-
|-
| align="center" style="background:#DCDCDC;" |Thyroidectomy
| align="center" style="background:#DCDCDC;" |[[Thyroidectomy]]
|-
|-
| align="center" style="background:#DCDCDC;" |Subclinical hypothyroidism
| align="center" style="background:#DCDCDC;" |Subclinical hypothyroidism
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|-
|-
|}
|}
<br style="clear:left" />''(†)T3RU; Triiodothyronine Resin uptake. (^)TPOAb; [[Thyroid peroxidase]] antibodies. (*)[[TSH]] may be decreased transiently in the [[thyrotoxicosis]]. (**)TPOAb may be present in drug-induced [[Hypothyroidism|hypo]]/[[hyperthyroidism]] such as [[Interferon-alpha]], [[Interleukin 2|interleukin-2]], and [[lithium]].''
<br style="clear:left" />''(†)T3RU; Triiodothyronine Resin uptake. (^)TPOAb; [[Thyroid peroxidase]] antibodies. (*)[[TSH]] may be decreased transiently in the [[thyrotoxicosis]]. (**)TPOAb may be present in drug-induced [[Hypothyroidism|hypothyroidism]] or [[hyperthyroidism]] such as [[Interferon-alpha]], [[Interleukin 2|interleukin-2]], and [[lithium]].''


===Differentiating postpartum thyroiditis from other causes of thyrotoxicosis===
===Differentiating postpartum thyroiditis from other causes of thyrotoxicosis===
*Postpartum thyroiditis can initially present with thyrotoxicosis which must be differentiated from other causes of thyrotoxicosis.<ref name="pmid16734054">{{cite journal |vauthors=Bindra A, Braunstein GD |title=Thyroiditis |journal=Am Fam Physician |volume=73 |issue=10 |pages=1769–76 |year=2006 |pmid=16734054 |doi= |url=}}</ref><ref name="pmid19949140">{{cite journal |vauthors=McDermott MT |title=In the clinic. Hypothyroidism |journal=Ann. Intern. Med. |volume=151 |issue=11 |pages=ITC61 |year=2009 |pmid=19949140 |doi=10.7326/0003-4819-151-11-200912010-01006 |url=}}</ref><ref name="urlThyroiditis — NEJM">{{cite web |url=http://www.nejm.org/doi/full/10.1056/NEJMra021194 |title=Thyroiditis — NEJM |format= |work= |accessdate=}}</ref><ref name="pmid18177256">{{cite journal |vauthors=Aoki Y, Belin RM, Clickner R, Jeffries R, Phillips L, Mahaffey KR |title=Serum TSH and total T4 in the United States population and their association with participant characteristics: National Health and Nutrition Examination Survey (NHANES 1999-2002) |journal=Thyroid |volume=17 |issue=12 |pages=1211–23 |year=2007 |pmid=18177256 |doi=10.1089/thy.2006.0235 |url=}}</ref><ref name="pmid18415684">{{cite journal |vauthors=Lania A, Persani L, Beck-Peccoz P |title=Central hypothyroidism |journal=Pituitary |volume=11 |issue=2 |pages=181–6 |year=2008 |pmid=18415684 |doi=10.1007/s11102-008-0122-6 |url=}}</ref><ref name="pmid25905413">{{cite journal |vauthors=De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, Stockigt J |title=Clinical Strategies in the Testing of Thyroid Function |journal= |volume= |issue= |pages= |year= |pmid=25905413 |doi= |url=}}</ref><ref name="urlClinical Finding and Thyroid Function in Women with Struma Ovarii">{{cite web |url=https://www.hindawi.com/archive/2013/717584/ |title=Clinical Finding and Thyroid Function in Women with Struma Ovarii |format= |work= |accessdate=}}</ref><ref name="pmid25146390">{{cite journal |vauthors=Vaidya B, Pearce SH |title=Diagnosis and management of thyrotoxicosis |journal=BMJ |volume=349 |issue= |pages=g5128 |year=2014 |pmid=25146390 |doi= |url=}}</ref><ref name="urlThink thyrotoxicosis factitia - measure thyroglobulin | The BMJ">{{cite web |url=http://www.bmj.com/content/349/bmj.g5128/rr/763450 |title=Think thyrotoxicosis factitia - measure thyroglobulin &#124; The BMJ |format= |work= |accessdate=}}</ref>
*Postpartum thyroiditis can initially present with [[thyrotoxicosis]] which must be differentiated from other causes of [[thyrotoxicosis]].<ref name="pmid16734054">{{cite journal |vauthors=Bindra A, Braunstein GD |title=Thyroiditis |journal=Am Fam Physician |volume=73 |issue=10 |pages=1769–76 |year=2006 |pmid=16734054 |doi= |url=}}</ref><ref name="pmid19949140">{{cite journal |vauthors=McDermott MT |title=In the clinic. Hypothyroidism |journal=Ann. Intern. Med. |volume=151 |issue=11 |pages=ITC61 |year=2009 |pmid=19949140 |doi=10.7326/0003-4819-151-11-200912010-01006 |url=}}</ref><ref name="urlThyroiditis — NEJM">{{cite web |url=http://www.nejm.org/doi/full/10.1056/NEJMra021194 |title=Thyroiditis — NEJM |format= |work= |accessdate=}}</ref><ref name="pmid18177256">{{cite journal |vauthors=Aoki Y, Belin RM, Clickner R, Jeffries R, Phillips L, Mahaffey KR |title=Serum TSH and total T4 in the United States population and their association with participant characteristics: National Health and Nutrition Examination Survey (NHANES 1999-2002) |journal=Thyroid |volume=17 |issue=12 |pages=1211–23 |year=2007 |pmid=18177256 |doi=10.1089/thy.2006.0235 |url=}}</ref><ref name="pmid18415684">{{cite journal |vauthors=Lania A, Persani L, Beck-Peccoz P |title=Central hypothyroidism |journal=Pituitary |volume=11 |issue=2 |pages=181–6 |year=2008 |pmid=18415684 |doi=10.1007/s11102-008-0122-6 |url=}}</ref><ref name="pmid25905413">{{cite journal |vauthors=De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, Stockigt J |title=Clinical Strategies in the Testing of Thyroid Function |journal= |volume= |issue= |pages= |year= |pmid=25905413 |doi= |url=}}</ref><ref name="urlClinical Finding and Thyroid Function in Women with Struma Ovarii">{{cite web |url=https://www.hindawi.com/archive/2013/717584/ |title=Clinical Finding and Thyroid Function in Women with Struma Ovarii |format= |work= |accessdate=}}</ref><ref name="pmid25146390">{{cite journal |vauthors=Vaidya B, Pearce SH |title=Diagnosis and management of thyrotoxicosis |journal=BMJ |volume=349 |issue= |pages=g5128 |year=2014 |pmid=25146390 |doi= |url=}}</ref><ref name="urlThink thyrotoxicosis factitia - measure thyroglobulin | The BMJ">{{cite web |url=http://www.bmj.com/content/349/bmj.g5128/rr/763450 |title=Think thyrotoxicosis factitia - measure thyroglobulin &#124; The BMJ |format= |work= |accessdate=}}</ref>
{| class="wikitable" align="center" style="border: 0px; margin: 3px;"
{| class="wikitable" align="center" style="border: 0px; margin: 3px;"
! colspan="2" rowspan="2" align="center" style="background: #4479BA; color: #FFFFFF; " |Disease
! colspan="2" rowspan="2" align="center" style="background: #4479BA; color: #FFFFFF; " |Disease
Line 250: Line 251:
! align="center" style="background: #4479BA; color: #FFFFFF; " |<small> Pain  
! align="center" style="background: #4479BA; color: #FFFFFF; " |<small> Pain  
! align="center" style="background: #4479BA; color: #FFFFFF; " |<small> TSH  
! align="center" style="background: #4479BA; color: #FFFFFF; " |<small> TSH  
! align="center" style="background: #4479BA; color: #FFFFFF; " |<small> Free T4  
! align="center" style="background: #4479BA; color: #FFFFFF; " |<small>Free T4  
! align="center" style="background: #4479BA; color: #FFFFFF; " |<small> T3  
! align="center" style="background: #4479BA; color: #FFFFFF; " |<small> T3  
! align="center" style="background: #4479BA; color: #FFFFFF; " |<small> T3RU<small>†
! align="center" style="background: #4479BA; color: #FFFFFF; " |<small> T3RU<small>†
! align="center" style="background: #4479BA; color: #FFFFFF; " |<small> Thyroglobin  
! align="center" style="background: #4479BA; color: #FFFFFF; " |<small>Thyroglobin  
! align="center" style="background: #4479BA; color: #FFFFFF; " |<small> TRH  
! align="center" style="background: #4479BA; color: #FFFFFF; " |<small> TRH  
! align="center" style="background: #4479BA; color: #FFFFFF; " |<small> TSH Receptor Antibody
! align="center" style="background: #4479BA; color: #FFFFFF; " |<small> TSH Receptor Antibody
Line 328: Line 329:
| align="center" style="padding: 5px 5px; background: #F5F5F5;" |Absent
| align="center" style="padding: 5px 5px; background: #F5F5F5;" |Absent
| align="left" style="padding: 5px 5px; background: #F5F5F5;" |
| align="left" style="padding: 5px 5px; background: #F5F5F5;" |
* Patient may have opthalmopathy and dermopathy
* Opthalmopathy and [[dermopathy]] may be present
|-
|-
| align="center" style="background:#DCDCDC;" |[[Toxic thyroid nodule]]
| align="center" style="background:#DCDCDC;" |[[Toxic thyroid nodule]]
Line 357: Line 358:
| align="center" style="padding: 5px 5px; background: #F5F5F5;" |Absent
| align="center" style="padding: 5px 5px; background: #F5F5F5;" |Absent
| align="left" style="padding: 5px 5px; background: #F5F5F5;" |
| align="left" style="padding: 5px 5px; background: #F5F5F5;" |
*Inappropriately normal or increased TSH
*Inappropriately normal or increased [[TSH]]
|-
|-
| rowspan="1" style="background:#DCDCDC;" |[[Tertiary hyperthyroidism]]  
| rowspan="1" style="background:#DCDCDC;" |[[Tertiary hyperthyroidism]]  
Line 372: Line 373:
| align="center" style="padding: 5px 5px; background: #F5F5F5;" |Absent
| align="center" style="padding: 5px 5px; background: #F5F5F5;" |Absent
| align="left" style="padding: 5px 5px; background: #F5F5F5;" |
| align="left" style="padding: 5px 5px; background: #F5F5F5;" |
*Inappropriately normal or increased TSH
*Inappropriately normal or increased [[TSH]]
|-
|-
| rowspan="2" style="background:#DCDCDC;" |Drug induced
| rowspan="2" style="background:#DCDCDC;" |Drug induced
Line 387: Line 388:
| align="center" style="padding: 5px 5px; background: #F5F5F5;" |Absent
| align="center" style="padding: 5px 5px; background: #F5F5F5;" |Absent
| align="left" style="padding: 5px 5px; background: #F5F5F5;" |
| align="left" style="padding: 5px 5px; background: #F5F5F5;" |
*High urinary iodine
*High urinary [[iodine]]
|-
|-
| align="center" style="background:#DCDCDC;" |[[Amiodarone|Amiodarone type 2]]
| align="center" style="background:#DCDCDC;" |[[Amiodarone|Amiodarone type 2]]
Line 401: Line 402:
| align="center" style="padding: 5px 5px; background: #F5F5F5;" |Absent
| align="center" style="padding: 5px 5px; background: #F5F5F5;" |Absent
| align="left" style="padding: 5px 5px; background: #F5F5F5;" |
| align="left" style="padding: 5px 5px; background: #F5F5F5;" |
*High urinary iodine
*High urinary [[iodine]]
|-
|-
| rowspan="3" style="background:#DCDCDC;" |Others
| rowspan="3" style="background:#DCDCDC;" |Others
Line 416: Line 417:
| align="center" style="padding: 5px 5px; background: #F5F5F5;" |Absent
| align="center" style="padding: 5px 5px; background: #F5F5F5;" |Absent
| align="left" style="padding: 5px 5px; background: #F5F5F5;" |
| align="left" style="padding: 5px 5px; background: #F5F5F5;" |
*Decreased thyroglobulin
*Decreased [[thyroglobulin]]
|-
|-
| align="center" style="background:#DCDCDC;" |[[Trophoblastic disease]]
| align="center" style="background:#DCDCDC;" |[[Trophoblastic disease]]
Line 449: Line 450:
<small>''(†)T3RU; Triiodothyronine Resin uptake. (^)TPOAb; [[Thyroid peroxidase]] antibodies.''</small>
<small>''(†)T3RU; Triiodothyronine Resin uptake. (^)TPOAb; [[Thyroid peroxidase]] antibodies.''</small>


===Differentiating various diseases on the basis of type of thyroid dysfunction===
{| class="wikitable"
{| class="wikitable"
!
! rowspan="2" |Stages
!
! rowspan="2" |Peek
! colspan="4" |
presenting
!
purpural
!
month
!
! rowspan="2" |Disease
!
! colspan="4" |Symptoms and Signs
!
! colspan="7" |Labs
!
! rowspan="2" |Mechanisum
!
!
|-
|-
!
!
!Fatiuge
!Fatiuge
!Neck swelling  
!Neck
!Low mood
swelling  
!Low  
mood
!Irritability
!Irritability
!
!TSH
!
!FT4
!
!TPO ab
!
!ESR
!
!RAI
!
 
!
U
!
!Thyroid U/S
!Microscopic
 
Picture
|-
|-
!Persistent hyperthyroidism
!Persistent
![[Grave's disease]]
hyperthyroidism
!Present
|4-6
!Small painful mass
|[[Grave's disease]]
!Present
| +
!Present early
|Small
!
painful
!
 
!
mass
!
| +
!
| +
!
Early
!
|↓
!
|↑↑
|Neg
|↑
|↑
|Diffusely
enlarged
 
hypervascular
 
heterogeneous
 
echotexture
 
|hyperplastic
 
follicles due to
 
eosinophilic
 
cytoplasm
 
scalloping
|TSHR
 
activating
 
antibodies
|-
|-
! rowspan="5" |Transient hyperthyroidism
! rowspan="5" |Transient
![[Silent thyroiditis]]
hyperthyroidism
!Present
| rowspan="5" |2-4
!Small painless goiter
|[[Silent thyroiditis]]
!Present late
| +
!Present early
|Small
!
painless  
!
 
!
goiter
!
| +
!
Late
!
| +
!
Early
!
|NL
 
or ↓
|↑↑
|50%
|NL
|↓
|Markedly
decreased
 
vascularity
 
variable
 
heterogeneous
 
texture
 
|Lymphocytic
 
infiltration & follicles
 
|CD4
 
T-cell
 
activation
 
mutation
|-
|-
![[Postpartum thyroiditis]]
|[[Postpartum thyroiditis]]
!Present
| +
!Small painless goiter
|Small
!Present late
painless goiter
!Present early
| +
!
Late
!
| +
!
Early
!
|NL
!
 
!
or ↓
!
|↑↑
!
|>80% 
|↑
|↓
|Hypoechoic
diffusely
 
enlarged
 
with
 
normal
 
or decreased
 
vascularity
|Lymphocytic
 
infiltration & follicles
|Reg
 
T-cell
 
gain in
 
function
 
mutation
|-
|-
![[De Quervain's thyroiditis|Subacute (de Quervain's) thyroiditis]]
|[[De Quervain's thyroiditis|Subacute (de Quervain's)]]
!Present
[[De Quervain's thyroiditis|granulomatous thyroiditis]]
!Small painful mass
| +
!Present late
|Small
!Present early
painful  
!
 
!
mass
!
| +
!
late
!
| +
!
early
!
|nl
!
 
or ↓
|↑↑
|neg
|↑
|↓
|Diffusely
enlarged &
 
normal or
 
decreased
 
 vascularity
|Giant cells
 
granulomas
 
|Systemic
 
viral
 
infections
|-
|-
![[Factitious thyrotoxicosis]]
|[[Factitious thyrotoxicosis|Factitious]]
!Present
[[Factitious thyrotoxicosis|thyrotoxicosis]]
!Normal
| +
!Absent
|Nl
!Present early
|Neg
!
| +
!
Early
!
|NL
!
 
!
or ↓
!
|↑↑
!
|Neg
!
|NL
|↓
|NL
|Normal
 
histology
|Thyroixine
 
intake
|-
|-
!acute suppurative thyroiditis
|Acute suppurative  
!Present
thyroiditis
!Small painful mass
| +
!Present late
|Small
!Present early
painful
!
 
!
mass
!
| +
!
Late
!
| +
!
Early
!
|NL
!
 
or ↓
|↑↑
|Neg
|↑
|↓
|Variable
heterogeneous
 
texture
 
perithyroidal
 
hypoechoic
 
space due to
 
abscess
|Polymorphonuclear
leukocytes
 
lymphocytes
 
exudates
|Viral, Bacterial
|-
|-
! rowspan="3" |Destructive hyperthyroidism
! rowspan="3" |Destructive
![[De Quervain's thyroiditis|Subacute (de Quervain's) thyroiditis]]
hyperthyroidism
!Present
| rowspan="3" |4-6
!Small painful mass
|[[De Quervain's thyroiditis|Subacute (de Quervain's)]]
!Present late
[[De Quervain's thyroiditis|granulomatous thyroiditis]]
!Present early
| +
!
|Small
!
painful  
!
 
!
mass
!
| +
!
Late
!
| +
!
Early
|NL
 
or ↓
|↑↑
|Neg
|↑
|↓
|Diffusely
enlarged
 
& normal or
 
decreased
 
 vascularity
|Gaint cells
 
granulomas
 
|Systemic
 
viral
 
infections
|-
|-
![[Postpartum thyroiditis]]
|[[Postpartum thyroiditis|Postpartum]]
!Present
[[Postpartum thyroiditis|thyroiditis]]
!Small painless goiter
| +
!Present late
|Small
!Present early
painless
!
 
!
goiter
!
| +
!
Late
!
| +
!
Early
!
|NL
!
 
or ↓
|↑↑
|>80% 
|↑
|↓
|Hypoechoic
diffusely
 
enlarged&
 
normal or
 
decreased
 
vascularity
|Lymphocytic
infiltration &
follicles
|Reg
 
T-cell
 
gain in
 
function
 
mutation
|-
|-
!acute suppurative thyroiditis
|Acute suppurative  
!Present
thyroiditis
!Small painful mass
| +
!Present late
|Small
!Present early
painful  
!
 
!
mass
!
| +
!
Late
!
| +
!
Early
!
|NL
!
 
or ↓
|↑↑
|neg
|↑
|↓
|Variable
heterogeneous
 
texture
 
perithyroidal
 
hypoechoic
 
space due to
 
abscess
|Polymorphonuclear leukocytes
 
lymphocytes
 
exudates
 
|Viral,
 
Bacterial
|-
|-
| rowspan="4" |'''Transient hypothyroidism'''
! rowspan="4" |'''Transient'''
|[[Postpartum thyroiditis]]
'''hypothyroidism'''
|Present
| rowspan="4" |2-4
|Small painless goiter
|[[Postpartum thyroiditis|Postpartum]]
|Present late
[[Postpartum thyroiditis|thyroiditis]]
|Present early
| +
|
|Small
|
painless
|
 
|
goiter
|
| +
|
Late
|
| +
|
Early
|NL
 
or ↑
|
|>80% 
|
|
| Hypoechoic
diffusely
 
enlarged
 
& normal or
 
decreased
 
vasclarity
|Lymphocytic
infiltration &
follicles
|Reg
 
T-cell
 
gain in
 
function
 
mutation
|-
|-
|[[Silent thyroiditis]]
|[[Silent thyroiditis|Silent]]
|Present
[[Silent thyroiditis|thyroiditis]]
|Small painless goiter
| +
|Present late
|Small
|Present early
painless
|
 
|
goiter
|
| +
|
Late
|
| +
|
Early
|
|NL
|
 
or ↑
|
| +
|NL
|
|Markedly
decreased
 
vascularity
 
variable
 
heterogeneous
 
texture
 
|Lymphocytic infiltration
& follicles
 
|CD4
 
T-cell
 
activation
 
mutation
|-
|-
|[[De Quervain's thyroiditis|Subacute (de Quervain's) thyroiditis]]
|[[De Quervain's thyroiditis|Subacute (de Quervain's)]]
|Present
[[De Quervain's thyroiditis|granulomatous thyroiditis]]
|Small painful mass
| +
|Present late
|Small
|Present early
painful
|
 
|
mass
|
| +
|
Late
|
| +
|
Early
|
|NL
|
 
or ↑
|
|Neg
|
|
|Diffusely
enlarged
 
normal or
 
decreased
 
 vasclarity
|Giant cells &
 
granulomas
 
|Systemic
 
viral
 
infections
|-
|-
|[[Infectious thyroiditis|acute suppurative thyroiditis]]
|Acute suppurative
|Present
thyroiditis
|Small painful mass
| +
|Present late
|Small
|Present early
painful
|
 
|
mass
|
| +
|
Late
|
| +
|
Early
|
|NL
|
 
or ↑
|
|Neg
|
|
|Variable
heterogeneous
 
texture
 
perithyroidal
 
hypoechoic
 
space due to
 
abcess
|Polymorphonuclear leukocytes
 
lymphocytes
 
exudates
|Infections
 
viral,bacterial
|-
|-
| rowspan="4" |'''Persistent hypothyroidism'''
! rowspan="4" |'''Persistent'''
|[[Riedel's thyroiditis]]
'''hypothyroidism'''
|Present
| rowspan="4" |6
|Small painful mass
|[[Riedel's thyroiditis|Riedel's]]
|Present late
[[Riedel's thyroiditis|thyroiditis]]
|Present early
| +
|
|Small
|
painful
|
 
|
mass
|
| +
|
Late
|
| +
|
Early
|
|
|75%
|
|
|Homogeneously
hypoechoic
 
fibrotic
 
invasion of the
 
adjacent
 
structures
|Lymphocytes, plasma cells, and eosinophils in a dense matrix of hyalinized connective tissue
|Viral
Bacterial
|-
|-
|[[Postpartum thyroiditis]]
|[[Postpartum thyroiditis|Postpartum]]
|Present
[[Postpartum thyroiditis|thyroiditis]]
|Small painless goiter
| +
|Present late
|Small
|Present early
painless  
|
 
|
goiter
|
| +
|
Late
|
| +
|
Early
|
|
|
|
|>80% 
|
|
|Hypoechoic
diffusely
 
enlarged&
 
normal
 
or decreased
 
vasclarity
|Variable
 
heterogeneous
 
texture,
 
hypoechogenic
|Reg
 
T-cell
 
gain in
 
function
 
mutation
|-
|-
|[[Hashimoto's thyroiditis]]
|[[Hashimoto's thyroiditis|Hashimoto's]]
|Present
[[Hashimoto's thyroiditis|thyroiditis]]
|Painful mass
| +
|Present late
|Painful
|Present early
mass
|
| +
|
Late
|
| +
|
Early
|
|
|
|
|
|95%
|
|
|
|Heterogeneous
echotexture
 
decreased
 
vasclarity
 
hypoechoic
 
micronodules
|Lymphoid
 
follicles
 
germinal centers
 
Hurthle cells
 
|Reg T-cell
 
dysfunction
|-
|-
|Acute suppurative thyroiditis
|Acute suppurative
|Present
thyroiditis
|Small painful mass
| +
|Present late
|Small
|Present early
painful  
|
 
|
mass
|
| +
|
Late
|
| +
|
Early
|
|
|
|
|Neg
|
|
|Variable
heterogeneous
 
texture
 
perithyroidal
 
hypoechoic
 
space due to
 
abcess
 
|Polymorphonuclear leukocytes
 
lymphocytes
 
exudates
|Systemic
 
viral
 
infections
|}
|}



Latest revision as of 19:21, 25 February 2019

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Furqan M M. M.B.B.S[2]Sunny Kumar MD [3]

Overview

Postpartum thyroiditis must be differentiated from other causes of thyroiditis, such as De Quervain's thyroiditis, Hashimoto's thyroiditis, Riedel's thyroiditis, and suppurative thyroiditis. Postpartum thyroiditis must also be differentiated from other diseases which cause hypothyroidism. As postpartum thyroiditis may cause transient thyrotoxic symptoms, the diseases causing thyrotoxicosis must also be considered in the differential diagnosis.

Differentiating Postpartum Thyroiditis from other Diseases

Differentiating postpartum thyroiditis from other causes of thyroiditis

Conditions Causes Age of onset (years) Pathological findings Diagnostic approach
Hashimoto's thyroiditis
  • All ages, peak at 30-50
  • Lymphocytic infiltration
  • Germinal centers
  • Fibrosis (in some variants)
Painful subacute (De Quervain's) thyroiditis
  • Unknown
  • 20-60
Silent thyroiditis
  • All ages, peak at 30-40
  • Lymphocytic infiltration
  • Lymphoid follicles
Postpartum thyroiditis
  • Childbearing age
  • Lymphocytic infiltration
Riedel's thyroiditis
  • Unknown
  • 30-60
Suppurative thyroiditis
  • Children, 20-40

Differentiating postpartum thyroiditis from other causes of hypothyroidism

  • Postpartum thyroiditis must be differentiated from other causes of hypothyroidism on the basis of history and symptoms and laboratory findings:[4][5][1][6][7][8]
Disease History and symptoms Laboratory findings Additional findings
Fever Pain TSH Free T4 T3 T3RU Thyroglobin TRH TPOAb^
Primary hypothyroidism Autoimmune

(Hashimoto's thyroiditis)

- - * Normal/ Normal/↓ Normal/ Normal Present (high titer)
Riedel's thyroiditis - - Normal/↑ Normal/↓ Normal/↓ Normal/↓ Normal Normal Usually present
Infectious thyroiditis + + Normal Normal Normal Normal Normal Normal Absent
Transient hypothyroidism Subacute (de Quervain's) thyroiditis +/- +/- ↑/ ↓/ Normal Normal Low/absent
Postpartum thyroiditis +/- +/- ↑/ ↓/ Normal Normal/↑ Present (high titer)
Silent thyroiditis - - ↑/ ↓/ Normal Normal Present (high titer)
Others Drug-induced - - /↓ /↑ Normal Normal/ Normal Absent**
  • History of hyperthyroidism
  • History of trauma
  • History of drug use, surgery, or radiation
Radiation-induced
Trauma induced
Radioiodine induced
Thyroidectomy
Subclinical hypothyroidism - - Normal Normal Normal Normal Normal Normal/
  • Asymptomatic


(†)T3RU; Triiodothyronine Resin uptake. (^)TPOAb; Thyroid peroxidase antibodies. (*)TSH may be decreased transiently in the thyrotoxicosis. (**)TPOAb may be present in drug-induced hypothyroidism or hyperthyroidism such as Interferon-alpha, interleukin-2, and lithium.

Differentiating postpartum thyroiditis from other causes of thyrotoxicosis

Disease History and symptoms Laboratory findings Additional findings
Fever Pain TSH Free T4 T3 T3RU Thyroglobin TRH TSH Receptor Antibody TPOAb^
Thyroiditis Postpartum thyroiditis +/- +/- ↑/ ↓/ Normal Normal/↑ Absent Present (high titer)
Hashimoto's thyroiditis (Hashitoxicosis) - - * Normal/ Normal/↓ Normal/ Normal Absent Present (high titer)
Subacute (de Quervain's) thyroiditis +/- +/- ↑/ ↓/ Normal Normal Absent Low/absent
Silent thyroiditis - - ↑/ ↓/ Normal Normal Absent Present (high titer)
Primary hyperthyroidism Grave's disease - - Normal/ Normal Present Absent
Toxic thyroid nodule - - Normal/↑ ↑(hot nodule) Normal/ Normal Absent Absent

-

Secondary hyperthyroidism Pituitary adenoma - - Normal/↑ Normal/ Normal Absent Absent
  • Inappropriately normal or increased TSH
Tertiary hyperthyroidism Tertiary hyperthyroidism - - Normal/ Absent Absent
  • Inappropriately normal or increased TSH
Drug induced Amiodarone type 1 - - Normal/↑ Normal/ Normal Absent Absent
Amiodarone type 2 - - Normal/↑ Absent/↓ Normal/ Normal Absent Absent
Others Factitious thyrotoxicosis - - Normal/↑ Normal Absent Absent
Trophoblastic disease - - Normal/↑ - Normal Absent Absent

-

Struma ovarii - - Normal/↑ - Normal Absent Absent

-

(†)T3RU; Triiodothyronine Resin uptake. (^)TPOAb; Thyroid peroxidase antibodies.

Differentiating various diseases on the basis of type of thyroid dysfunction

Stages Peek

presenting purpural month

Disease Symptoms and Signs Labs Mechanisum
Fatiuge Neck

swelling

Low

mood

Irritability TSH FT4 TPO ab ESR RAI

U

Thyroid U/S Microscopic

Picture

Persistent

hyperthyroidism

4-6 Grave's disease + Small

painful

mass

+ +

Early

↑↑ Neg Diffusely

enlarged

hypervascular

heterogeneous

echotexture

hyperplastic

follicles due to

eosinophilic

cytoplasm

scalloping

TSHR

activating

antibodies

Transient

hyperthyroidism

2-4 Silent thyroiditis + Small

painless

goiter

+

Late

+

Early

NL

or ↓

↑↑ 50% NL Markedly

decreased

vascularity

variable

heterogeneous

texture

Lymphocytic

infiltration & follicles

CD4

T-cell

activation

mutation

Postpartum thyroiditis + Small

painless goiter

+

Late

+

Early

NL

or ↓

↑↑ >80%  Hypoechoic

diffusely

enlarged

with

normal

or decreased

vascularity

Lymphocytic

infiltration & follicles

Reg

T-cell

gain in

function

mutation

Subacute (de Quervain's)

granulomatous thyroiditis

+ Small

painful

mass

+

late

+

early

nl

or ↓

↑↑ neg Diffusely

enlarged &

normal or

decreased

 vascularity

Giant cells

granulomas

Systemic

viral

infections

Factitious

thyrotoxicosis

+ Nl Neg +

Early

NL

or ↓

↑↑ Neg NL NL Normal

histology

Thyroixine

intake

Acute suppurative

thyroiditis

+ Small

painful

mass

+

Late

+

Early

NL

or ↓

↑↑ Neg Variable

heterogeneous

texture

perithyroidal

hypoechoic

space due to

abscess

Polymorphonuclear

leukocytes

lymphocytes

exudates

Viral, Bacterial
Destructive

hyperthyroidism

4-6 Subacute (de Quervain's)

granulomatous thyroiditis

+ Small

painful

mass

+

Late

+

Early

NL

or ↓

↑↑ Neg Diffusely

enlarged

& normal or

decreased

 vascularity

Gaint cells

granulomas

Systemic

viral

infections

Postpartum

thyroiditis

+ Small

painless

goiter

+

Late

+

Early

NL

or ↓

↑↑ >80%  Hypoechoic

diffusely

enlarged&

normal or

decreased

vascularity

Lymphocytic

infiltration & follicles

Reg

T-cell

gain in

function

mutation

Acute suppurative

thyroiditis

+ Small

painful

mass

+

Late

+

Early

NL

or ↓

↑↑ neg Variable

heterogeneous

texture

perithyroidal

hypoechoic

space due to

abscess

Polymorphonuclear leukocytes

lymphocytes

exudates

Viral,

Bacterial

Transient

hypothyroidism

2-4 Postpartum

thyroiditis

+ Small

painless

goiter

+

Late

+

Early

NL

or ↑

>80%   Hypoechoic

diffusely

enlarged

& normal or

decreased

vasclarity

Lymphocytic

infiltration & follicles

Reg

T-cell

gain in

function

mutation

Silent

thyroiditis

+ Small

painless

goiter

+

Late

+

Early

NL

or ↑

+ NL Markedly

decreased

vascularity

variable

heterogeneous

texture

Lymphocytic infiltration

& follicles

CD4

T-cell

activation

mutation

Subacute (de Quervain's)

granulomatous thyroiditis

+ Small

painful

mass

+

Late

+

Early

NL

or ↑

Neg Diffusely

enlarged

normal or

decreased

 vasclarity

Giant cells &

granulomas

Systemic

viral

infections

Acute suppurative

thyroiditis

+ Small

painful

mass

+

Late

+

Early

NL

or ↑

Neg Variable

heterogeneous

texture

perithyroidal

hypoechoic

space due to

abcess

Polymorphonuclear leukocytes

lymphocytes

exudates

Infections

viral,bacterial

Persistent

hypothyroidism

6 Riedel's

thyroiditis

+ Small

painful

mass

+

Late

+

Early

75% Homogeneously

hypoechoic

fibrotic

invasion of the

adjacent

structures

Lymphocytes, plasma cells, and eosinophils in a dense matrix of hyalinized connective tissue Viral

Bacterial

Postpartum

thyroiditis

+ Small

painless

goiter

+

Late

+

Early

>80%  Hypoechoic

diffusely

enlarged&

normal

or decreased

vasclarity

Variable

heterogeneous

texture,

hypoechogenic

Reg

T-cell

gain in

function

mutation

Hashimoto's

thyroiditis

+ Painful

mass

+

Late

+

Early

95% Heterogeneous

echotexture

decreased

vasclarity

hypoechoic

micronodules

Lymphoid

follicles

germinal centers

Hurthle cells

Reg T-cell

dysfunction

Acute suppurative

thyroiditis

+ Small

painful

mass

+

Late

+

Early

Neg Variable

heterogeneous

texture

perithyroidal

hypoechoic

space due to

abcess

Polymorphonuclear leukocytes

lymphocytes

exudates

Systemic

viral

infections

References

  1. 1.0 1.1 1.2 "Thyroiditis — NEJM".
  2. Akuzawa N, Yokota T, Suzuki T, Kurabayashi M (2017). "Acute suppurative thyroiditis caused by Streptococcus agalactiae infection: a case report". Clin Case Rep. 5 (8): 1238–1242. doi:10.1002/ccr3.1048. PMC 5538065. PMID 28781832.
  3. Akuzawa N, Yokota T, Suzuki T, Kurabayashi M (2017). "Acute suppurative thyroiditis caused by Streptococcus agalactiae infection: a case report". Clin Case Rep. 5 (8): 1238–1242. doi:10.1002/ccr3.1048. PMC 5538065. PMID 28781832.
  4. 4.0 4.1 Bindra A, Braunstein GD (2006). "Thyroiditis". Am Fam Physician. 73 (10): 1769–76. PMID 16734054.
  5. 5.0 5.1 McDermott MT (2009). "In the clinic. Hypothyroidism". Ann. Intern. Med. 151 (11): ITC61. doi:10.7326/0003-4819-151-11-200912010-01006. PMID 19949140.
  6. 6.0 6.1 Aoki Y, Belin RM, Clickner R, Jeffries R, Phillips L, Mahaffey KR (2007). "Serum TSH and total T4 in the United States population and their association with participant characteristics: National Health and Nutrition Examination Survey (NHANES 1999-2002)". Thyroid. 17 (12): 1211–23. doi:10.1089/thy.2006.0235. PMID 18177256.
  7. 7.0 7.1 Lania A, Persani L, Beck-Peccoz P (2008). "Central hypothyroidism". Pituitary. 11 (2): 181–6. doi:10.1007/s11102-008-0122-6. PMID 18415684.
  8. 8.0 8.1 De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A, Stockigt J. "Clinical Strategies in the Testing of Thyroid Function". PMID 25905413.
  9. "Clinical Finding and Thyroid Function in Women with Struma Ovarii".
  10. Vaidya B, Pearce SH (2014). "Diagnosis and management of thyrotoxicosis". BMJ. 349: g5128. PMID 25146390.
  11. "Think thyrotoxicosis factitia - measure thyroglobulin | The BMJ".

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