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Chapter 98 : Endocrinopathies: Chronic Thyroiditis, Addison Disease, Pernicious Anemia, Graves’ Disease, Diabetes, and Hypophysitis
Authors:
C. L. Burek1,
N. R. Rose2,
Giuseppe Barbesino3,
Jian Wang4,
Andrea K. Steck5,
George S. Eisenbarth†,
Liping Yu6,
Ludovica De Vincentiis7,
Adriana Ricciuti8,
Alessandra De Remigis9,
Patrizio Caturegli10
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Affiliations:
1: Johns Hopkins University, Department of Pathology, SOM, 720 Rutland Ave., Baltimore, MD 21205;
2: Johns Hopkins University, Department of Pathology, SOM, 720 Rutland Avenue, Baltimore, MD 21205;
3: Thyroid Unit, Massachusetts General Hospital — Harvard Medical School, 15 Parkman St., Boston, MA 02114;
4: Department of Endocrinology, Jinling Hospital, Nanjing, China;
5: Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, CO 80045;
6: Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, CO 80045;
7: Johns Hopkins University, Department of Pathology, Rutland Ave., Baltimore, MD 21205;
8: Johns Hopkins University, Department of Pathology, Rutland Ave., Baltimore, MD 21205;
9: Johns Hopkins University, Department of Pathology, Rutland Ave., Baltimore, MD 21205;
10: Johns Hopkins University, Department of Pathology, SOM, 720 Rutland Ave., Baltimore, MD 21205
Content Type: Reference
Publication Year:
2016
Category: Immunology
Book DOI:
10.1128/9781555818722
Chapter DOI:
10.1128/9781555818722.ch98
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Abstract:
Chronic lymphocytic thyroiditis (CLT), also known as Hashimoto thyroiditis, is an autoimmune disease characterized by lymphocytic infiltration of the thyroid gland, with the concomitant production of autoantibodies to thyroid antigens, primarily thyroglobulin and/or thyroperoxidase (TPO), formerly known as microsomal antigen (1). Although few epidemiological data are available, the prevalence of CLT is estimated to be 1 in 1,000 people, with an incidence of 0.2 to 2% and a female-to-male ratio of about 18:1 (1). Clinical signs and symptoms manifest slowly and may involve many systems of the body (1). Accumulations of hydrophilic mucoproteins with edema, a condition called myxedema, affects skin and connective tissue and can affect the appearance of the individual. Lethargy may ensue, with a loss of mental acuity. Systems commonly affected are the gastrointestinal tract, the hemopoietic system, the endocrine system, and the urogenital system (1). Enlargement of the thyroid gland due to lymphocyte invasion, called goiter, is a frequent manifestation, although there is an atrophic variation. Demonstration of autoantibodies to the thyroid antigens aids in the diagnosis of CLT, distinguishing it from other causes of hypothyroidism.
Citation:
Burek C, Rose N, Barbesino G, Wang J, Steck A, Eisenbarth G, Yu L, De Vincentiis L, Ricciuti A, De Remigis A, Caturegli P.
2016.
Endocrinopathies: Chronic Thyroiditis, Addison Disease, Pernicious Anemia, Graves’ Disease, Diabetes, and Hypophysitis,
p 930-953.
In
Detrick B, Schmitz J, Hamilton R (ed),
Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555818722.ch98
Figures
Endocrinopathies: Chronic Thyroiditis, Addison Disease, Pernicious Anemia, Graves’ Disease, Diabetes, and Hypophysitis
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Citation:
Burek C, Rose N, Barbesino G, Wang J, Steck A, Eisenbarth G, Yu L, De Vincentiis L, Ricciuti A, De Remigis A, Caturegli P.
2016.
Endocrinopathies: Chronic Thyroiditis, Addison Disease, Pernicious Anemia, Graves’ Disease, Diabetes, and Hypophysitis,
p 930-953.
In
Detrick B, Schmitz J, Hamilton R (ed),
Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555818722.ch98
/content/10.1128/9781555818722.ch98.ch98fig1
FIGURE 1
Indirect IF for antibodies to adrenal cortex using an unfixed, air-dried section of monkey adrenal cortex. All layers of the adrenal cortex are stained. Magnification, ×32.
10.1128/9781555818722/8722ch98fig1_thmb.gif
10.1128/9781555818722/8722ch98fig1.gif
FIGURE 1
Indirect IF for antibodies to adrenal cortex using an unfixed, air-dried section of monkey adrenal cortex. All layers of the adrenal cortex are stained. Magnification, ×32.
Citation:
Burek C, Rose N, Barbesino G, Wang J, Steck A, Eisenbarth G, Yu L, De Vincentiis L, Ricciuti A, De Remigis A, Caturegli P.
2016.
Endocrinopathies: Chronic Thyroiditis, Addison Disease, Pernicious Anemia, Graves’ Disease, Diabetes, and Hypophysitis,
p 930-953.
In
Detrick B, Schmitz J, Hamilton R (ed),
Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555818722.ch98
/content/10.1128/9781555818722.ch98.ch98fig2
FIGURE 2
Same as Fig. 1 but at a higher magnification. Only the cytoplasm of the adrenal cells is attained. Magnification, ×80.
10.1128/9781555818722/8722ch98fig2_thmb.gif
10.1128/9781555818722/8722ch98fig2.gif
FIGURE 2
Same as Fig. 1 but at a higher magnification. Only the cytoplasm of the adrenal cells is attained. Magnification, ×80.
Citation:
Burek C, Rose N, Barbesino G, Wang J, Steck A, Eisenbarth G, Yu L, De Vincentiis L, Ricciuti A, De Remigis A, Caturegli P.
2016.
Endocrinopathies: Chronic Thyroiditis, Addison Disease, Pernicious Anemia, Graves’ Disease, Diabetes, and Hypophysitis,
p 930-953.
In
Detrick B, Schmitz J, Hamilton R (ed),
Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555818722.ch98
/content/10.1128/9781555818722.ch98.ch98fig3
FIGURE 3
Indirect IF for antibodies to parietal cells using an unfixed, air-dried section of rodent stomach mucosa. The cytoplasm of only the parietal cells is stained. Magnification, ×100.
10.1128/9781555818722/8722ch98fig3_thmb.gif
10.1128/9781555818722/8722ch98fig3.gif
FIGURE 3
Indirect IF for antibodies to parietal cells using an unfixed, air-dried section of rodent stomach mucosa. The cytoplasm of only the parietal cells is stained. Magnification, ×100.
Citation:
Burek C, Rose N, Barbesino G, Wang J, Steck A, Eisenbarth G, Yu L, De Vincentiis L, Ricciuti A, De Remigis A, Caturegli P.
2016.
Endocrinopathies: Chronic Thyroiditis, Addison Disease, Pernicious Anemia, Graves’ Disease, Diabetes, and Hypophysitis,
p 930-953.
In
Detrick B, Schmitz J, Hamilton R (ed),
Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555818722.ch98
/content/10.1128/9781555818722.ch98.ch98fig4
FIGURE 4
Progression to diabetes in children positive for anti-islet cell autoantibodies in DAISY (Diabetes Autoimmunity Study in the Young) relative to the number of anti-islet cell autoantibodies expressed (autoantibodies to GAD65 [glutamic acid decarboxylase], ICA512 [IA-2, insulinoma-associated antigen], and insulin). Adapted with permission from Diabetes Care ( 60 ).
10.1128/9781555818722/8722ch98fig4_thmb.gif
10.1128/9781555818722/8722ch98fig4.gif
FIGURE 4
Progression to diabetes in children positive for anti-islet cell autoantibodies in DAISY (Diabetes Autoimmunity Study in the Young) relative to the number of anti-islet cell autoantibodies expressed (autoantibodies to GAD65 [glutamic acid decarboxylase], ICA512 [IA-2, insulinoma-associated antigen], and insulin). Adapted with permission from Diabetes Care ( 60 ).
Citation:
Burek C, Rose N, Barbesino G, Wang J, Steck A, Eisenbarth G, Yu L, De Vincentiis L, Ricciuti A, De Remigis A, Caturegli P.
2016.
Endocrinopathies: Chronic Thyroiditis, Addison Disease, Pernicious Anemia, Graves’ Disease, Diabetes, and Hypophysitis,
p 930-953.
In
Detrick B, Schmitz J, Hamilton R (ed),
Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555818722.ch98
/content/10.1128/9781555818722.ch98.ch98fig5
FIGURE 5
Current biochemical anti-islet autoantibody assays.
10.1128/9781555818722/8722ch98fig5_thmb.gif
10.1128/9781555818722/8722ch98fig5.gif
FIGURE 5
Current biochemical anti-islet autoantibody assays.
Citation:
Burek C, Rose N, Barbesino G, Wang J, Steck A, Eisenbarth G, Yu L, De Vincentiis L, Ricciuti A, De Remigis A, Caturegli P.
2016.
Endocrinopathies: Chronic Thyroiditis, Addison Disease, Pernicious Anemia, Graves’ Disease, Diabetes, and Hypophysitis,
p 930-953.
In
Detrick B, Schmitz J, Hamilton R (ed),
Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555818722.ch98
/content/10.1128/9781555818722.ch98.ch98fig6
FIGURE 6
General outline of high-throughput fluid-phase 96-well plate assays for anti-insulin autoantibodies. In the illustrated example, 125I-insulin is utilized, but the assay formats are identical for the GAD65, IA-2, and ZnT8 assays. Ag, antigen; Ab, antibody.
10.1128/9781555818722/8722ch98fig6_thmb.gif
10.1128/9781555818722/8722ch98fig6.gif
FIGURE 6
General outline of high-throughput fluid-phase 96-well plate assays for anti-insulin autoantibodies. In the illustrated example, 125I-insulin is utilized, but the assay formats are identical for the GAD65, IA-2, and ZnT8 assays. Ag, antigen; Ab, antibody.
Citation:
Burek C, Rose N, Barbesino G, Wang J, Steck A, Eisenbarth G, Yu L, De Vincentiis L, Ricciuti A, De Remigis A, Caturegli P.
2016.
Endocrinopathies: Chronic Thyroiditis, Addison Disease, Pernicious Anemia, Graves’ Disease, Diabetes, and Hypophysitis,
p 930-953.
In
Detrick B, Schmitz J, Hamilton R (ed),
Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555818722.ch98
/content/10.1128/9781555818722.ch98.ch98fig7
FIGURE 7
Standard curve for calculation of NIDDK units. The x axis is the number of cpm from the assay after removal of the background cpm, and the y axis is log 2 NIDDK units.
10.1128/9781555818722/8722ch98fig7_thmb.gif
10.1128/9781555818722/8722ch98fig7.gif
FIGURE 7
Standard curve for calculation of NIDDK units. The x axis is the number of cpm from the assay after removal of the background cpm, and the y axis is log 2 NIDDK units.
Citation:
Burek C, Rose N, Barbesino G, Wang J, Steck A, Eisenbarth G, Yu L, De Vincentiis L, Ricciuti A, De Remigis A, Caturegli P.
2016.
Endocrinopathies: Chronic Thyroiditis, Addison Disease, Pernicious Anemia, Graves’ Disease, Diabetes, and Hypophysitis,
p 930-953.
In
Detrick B, Schmitz J, Hamilton R (ed),
Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555818722.ch98
/content/10.1128/9781555818722.ch98.ch98fig8
FIGURE 8
Format of the electrochemiluminescence (ECL) assay. In the illustrated example, biotin and Sulfo-Tag proinsulin were utilized, but the assay format is identical for GAD65. Adapted with permission from Diabetes ( 86 ).
10.1128/9781555818722/8722ch98fig8_thmb.gif
10.1128/9781555818722/8722ch98fig8.gif
FIGURE 8
Format of the electrochemiluminescence (ECL) assay. In the illustrated example, biotin and Sulfo-Tag proinsulin were utilized, but the assay format is identical for GAD65. Adapted with permission from Diabetes ( 86 ).
Citation:
Burek C, Rose N, Barbesino G, Wang J, Steck A, Eisenbarth G, Yu L, De Vincentiis L, Ricciuti A, De Remigis A, Caturegli P.
2016.
Endocrinopathies: Chronic Thyroiditis, Addison Disease, Pernicious Anemia, Graves’ Disease, Diabetes, and Hypophysitis,
p 930-953.
In
Detrick B, Schmitz J, Hamilton R (ed),
Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555818722.ch98
/content/10.1128/9781555818722.ch98.ch98fig9
FIGURE 9
Detection of serum pituitary antibodies by indirect immunofluorescence using acetone-fixed cryostat sections cut from a human anterior pituitary gland. (A) A few isolated cells are recognized by the patient antibodies (type 1 pattern). The arrow shows the granularity, suggesting that antibodies recognize small vesicles scattered in the cytosol. (B) Multiple clustered cells are highlighted by the patient serum (type 2 pattern), which diffusely stains the entire cytosol (arrow).
10.1128/9781555818722/8722ch98fig9_thmb.gif
10.1128/9781555818722/8722ch98fig9.gif
FIGURE 9
Detection of serum pituitary antibodies by indirect immunofluorescence using acetone-fixed cryostat sections cut from a human anterior pituitary gland. (A) A few isolated cells are recognized by the patient antibodies (type 1 pattern). The arrow shows the granularity, suggesting that antibodies recognize small vesicles scattered in the cytosol. (B) Multiple clustered cells are highlighted by the patient serum (type 2 pattern), which diffusely stains the entire cytosol (arrow).
Citation:
Burek C, Rose N, Barbesino G, Wang J, Steck A, Eisenbarth G, Yu L, De Vincentiis L, Ricciuti A, De Remigis A, Caturegli P.
2016.
Endocrinopathies: Chronic Thyroiditis, Addison Disease, Pernicious Anemia, Graves’ Disease, Diabetes, and Hypophysitis,
p 930-953.
In
Detrick B, Schmitz J, Hamilton R (ed),
Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555818722.ch98
References
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Tables
Endocrinopathies: Chronic Thyroiditis, Addison Disease, Pernicious Anemia, Graves’ Disease, Diabetes, and Hypophysitis
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Citation:
Burek C, Rose N, Barbesino G, Wang J, Steck A, Eisenbarth G, Yu L, De Vincentiis L, Ricciuti A, De Remigis A, Caturegli P.
2016.
Endocrinopathies: Chronic Thyroiditis, Addison Disease, Pernicious Anemia, Graves’ Disease, Diabetes, and Hypophysitis,
p 930-953.
In
Detrick B, Schmitz J, Hamilton R (ed),
Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555818722.ch98
/content/10.1128/9781555818722.ch98.ch98tab1
TABLE 1
Biochemically characterized autoantigens
TABLE 1
Biochemically characterized autoantigens
Citation:
Burek C, Rose N, Barbesino G, Wang J, Steck A, Eisenbarth G, Yu L, De Vincentiis L, Ricciuti A, De Remigis A, Caturegli P.
2016.
Endocrinopathies: Chronic Thyroiditis, Addison Disease, Pernicious Anemia, Graves’ Disease, Diabetes, and Hypophysitis,
p 930-953.
In
Detrick B, Schmitz J, Hamilton R (ed),
Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555818722.ch98
/content/10.1128/9781555818722.ch98.ch98tab2
TABLE 2
Summary of techniques used to detect pituitary antibodies in human serum a
TABLE 2
Summary of techniques used to detect pituitary antibodies in human serum a
Citation:
Burek C, Rose N, Barbesino G, Wang J, Steck A, Eisenbarth G, Yu L, De Vincentiis L, Ricciuti A, De Remigis A, Caturegli P.
2016.
Endocrinopathies: Chronic Thyroiditis, Addison Disease, Pernicious Anemia, Graves’ Disease, Diabetes, and Hypophysitis,
p 930-953.
In
Detrick B, Schmitz J, Hamilton R (ed),
Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555818722.ch98
/content/10.1128/9781555818722.ch98.ch98tab3
TABLE 3
Summary of 42 cohort studies using IF and pituitary gland substrate to detect the presence of serum pituitary antibodies
TABLE 3
Summary of 42 cohort studies using IF and pituitary gland substrate to detect the presence of serum pituitary antibodies
Citation:
Burek C, Rose N, Barbesino G, Wang J, Steck A, Eisenbarth G, Yu L, De Vincentiis L, Ricciuti A, De Remigis A, Caturegli P.
2016.
Endocrinopathies: Chronic Thyroiditis, Addison Disease, Pernicious Anemia, Graves’ Disease, Diabetes, and Hypophysitis,
p 930-953.
In
Detrick B, Schmitz J, Hamilton R (ed),
Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition.
ASM Press, Washington, DC.
doi: 10.1128/9781555818722.ch98