Silent thyroiditis differential diagnosis

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

Overview

Silent thyroiditis must be differentiated from other causes of thyroiditis, such as De Quervain's thyroiditis, Hashimoto's thyroiditis, Riedel's thyroiditis, and suppurative thyroiditis.

Differentiating Silent Thyroiditis from other Diseases

Silent thyroiditis must be differentiated from other causes of thyroiditis, such as De Quervain's thyroiditis, Hashimoto's thyroiditis, Riedel's thyroiditis, and suppurative thyroiditis.^[1]

Conditions	Causes	Age at onset	Pathological findings	Diagnostic approach
Silent thyroiditis	Autoimmune	All ages, peak at 30-40	Lymphocytic infiltration Lymphoid follicles	Increased TSH (hypothyroidism) and/or Decreased TSH (transient hypothyroidism) TPO antibodies present in high titer I-123 uptake usually decreased
Hashimoto's thyroiditis	Autoimmune	All ages, peak at 30-50	Lymphocytic infiltration Germinal centers Fibrosis (in some variants)	Increased TSH (hypothyroidism) TPO antibodies present in high titer I-123 uptake usually decreased
Painful subacute (De Quervain's) thyroiditis	Unknown	20-60	Giant cells Granulomas	Increased TSH (hypothyroidism) and/or Decreased TSH (Thyrotoxicosis) TPO antibodies absent or very low titer I-123 uptake decreased
Postpartum thyroiditis	Autoimmune	Childbearing age	Lymphocytic infiltration	Increased TSH (hypothyroidism) and/or Decreased TSH (transient hypothyroidism) TPO antibodies present in high titer I-123 uptake usually decreased
Riedel's thyroiditis	Unknown	30-60	Dense fibrosis	Normal TSH (euthyroidism) TPO antibodies usually present I-123 uptake decreased or normal
Suppurative thyroiditis	Infection	Children, 20-40	Abscess formation	Normal TSH (euthyroidism) TPO antibodies absent I-123 uptake normal

Silent thyroiditis must be differentiated from other causes of hypothyroidism on the basis of history and symptoms and laboratory findings:^[2]^[3]^[1]^[4]^[5]^[6]

Disease		History and symptoms		Laboratory findings							Additional findings
Disease		Fever	Pain	TSH	Free T4	T3	T3RU†	Thyroglobin	TRH	TPOAb^	Additional findings
Transient hypothyroidism	Silent thyroiditis	-	-	↑/↓	↓/↑	Normal	↓	↑	Normal	Present (high titer)	May present primarily with hyperthyroidism
	Postpartum thyroiditis	+/-	+/-	↑/↓	↓/↑	Normal	↓	↑	Normal/↑	Present (high titer)	May present primarily with hyperthyroidism
	Subacute (de Quervain's) thyroiditis	+/-	+/-	↑/↓	↓/↑	Normal	↓	↑	Normal	Low/absent	May present primarily with hyperthyroidism
Primary hypothyroidism	Autoimmune (Hashimoto's thyroiditis)	-	-	↑*	↓	Normal/↓	Normal/↓	Normal/↑	Normal	Present (high titer)	May be accompanied by other autoimmune diseases
	Riedel's thyroiditis	-	-	Normal/↑	Normal/↓	Normal/↓	Normal/↓	Normal	Normal	Usually present	Riedel's thyroiditis usually presents with hard and fixed thyroid mass.
	Infectious thyroiditis	+	+	Normal	Normal	Normal	Normal	Normal	Normal	Absent	Infectious thyroiditis associated with neck pain
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 hypo/hyperthyroidism such as Interferon-alpha, interleukin-2, and lithium.

Painless thyroiditis must be differentiated from other causes of hyperthyroidism such as Grave's disease and toxic nodular goiter.

Cause of thyrotoxicosis	TSH receptor antibodies	Thyroid US	Color flow Doppler	Radioactive iodine uptake/Scan	Other features
Graves' disease	+	Hypoechoic pattern	?	?	Ophthalmopathy, dermopathy, acropachy
Toxic nodular goiter	-	Multiple nodules	-	Hot nodules at thyroid scan	-
Toxic adenoma	-	Single nodule	-	Hot nodule	-
Subacute thyroiditis	-	Heterogeneous hypoechoic areas	Reduced/absent flow	?	Neck pain, fever, and elevated inflammatory index
Painless thyroiditis	-	Hypoechoic pattern	Reduced/absent flow	?	-
Amiodarone induced thyroiditis-Type 1	-	Diffuse or nodular goiter	?/Normal/?	? but higher than in Type 2	High urinary iodine
Amiodarone induced thyroiditis-Type 2	-	Normal	Absent	?/absent	High urinary iodine
Central hyperthyroidism	-	Diffuse or nodular goiter	Normal/?	?	Inappropriately normal or high TSH
Trophoblastic disease	-	Diffuse or nodular goiter	Normal/?	?	-
Factitious thyrotoxicosis	-	Variable	Reduced/absent flow	?	? Serum thyroglobulin
Struma ovarii	-	Variable	Reduced/absent flow	?	Abdominal RAIU

Disease		Findings
Thyroiditis	Direct chemical toxicity with inflammation	Amiodarone, sunitinib, pazopanib, axitinib, and other tyrosine kinase inhibitors may also be associated with a destructive thyroiditis.^[7]^[8]
	Radiation thyroiditis	Patients treated with radioiodine may develop thyroid pain and tenderness 5 to 10 days later, due to radiation-induced injury and necrosis of thyroid follicular cells and associated inflammation.
	Drugs that interfere with the immune system	Interferon-alfa is a well-known cause of thyroid abnormality. It mostly leads to the development of de novo antithyroid antibodies.^[9]
	Lithium	Patients treated with lithium are at a high risk of developing painless thyroiditis and Graves' disease.
	Palpation thyroiditis	Manipulation of the thyroid gland during thyroid biopsy or neck surgery and vigorous palpation during the physical examination may cause transient hyperthyroidism.
Exogenous and ectopic hyperthyroidism	Factitious ingestion of thyroid hormone	The diagnosis is based on the clinical features, laboratory findings, and 24-hour radioiodine uptake.^[10]
	Acute hyperthyroidism from a levothyroxine overdose	The diagnosis is based on the clinical features, laboratory findings, and 24-hour radioiodine uptake.^[11]
	Struma ovarii	Functioning thyroid tissue is present in an ovarian neoplasm.
	Functional thyroid cancer metastases	Large bony metastases from widely metastatic follicular thyroid cancer cause symptomatic hyperthyroidism.
Hashitoxicosis		It is an autoimmune thyroid disease that initially presents with hyperthyroidism and a high radioiodine uptake caused by TSH-receptor antibodies similar to Graves' disease. It is then followed by the development of hypothyroidism due to the infiltration of the thyroid gland with lymphocytes and the resultant autoimmune-mediated destruction of thyroid tissue, similar to chronic lymphocytic thyroiditis.^[12]
Toxic adenoma and toxic multinodular goiter		Toxic adenoma and toxic multinodular goiter are results of focal/diffuse hyperplasia of thyroid follicular cells independent of TSH regulation. Findings of single or multiple nodules are seen on physical examination or thyroid scan.^[13]
Iodine-induced hyperthyroidism		It is uncommon but can develop after an iodine load, such as administration of contrast agents used for angiography or computed tomography (CT), or iodine-rich drugs such as amiodarone.
Trophoblastic disease and germ cell tumors		Thyroid-stimulating hormone and HCG have a common alpha-subunit and a beta-subunit with considerable homology. As a result, HCG has weak thyroid-stimulating activity and high titer HCG may mimic hyperthyroidism.^[14]

References

↑ ^1.0 ^1.1 "Thyroiditis — NEJM".
↑ Bindra A, Braunstein GD (2006). "Thyroiditis". Am Fam Physician. 73 (10): 1769–76. PMID 16734054.
↑ McDermott MT (2009). "In the clinic. Hypothyroidism". Ann. Intern. Med. 151 (11): ITC61. doi:10.7326/0003-4819-151-11-200912010-01006. PMID 19949140.
↑ 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.
↑ Lania A, Persani L, Beck-Peccoz P (2008). "Central hypothyroidism". Pituitary. 11 (2): 181–6. doi:10.1007/s11102-008-0122-6. PMID 18415684.
↑ 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.
↑ Lambert M, Unger J, De Nayer P, Brohet C, Gangji D (1990). "Amiodarone-induced thyrotoxicosis suggestive of thyroid damage". J. Endocrinol. Invest. 13 (6): 527–30. PMID 2258582.
↑ Ahmadieh H, Salti I (2013). "Tyrosine kinase inhibitors induced thyroid dysfunction: a review of its incidence, pathophysiology, clinical relevance, and treatment". Biomed Res Int. 2013: 725410. doi:10.1155/2013/725410. PMC 3824811. PMID 24282820.
↑ Vialettes B, Guillerand MA, Viens P, Stoppa AM, Baume D, Sauvan R, Pasquier J, San Marco M, Olive D, Maraninchi D (1993). "Incidence rate and risk factors for thyroid dysfunction during recombinant interleukin-2 therapy in advanced malignancies". Acta Endocrinol. 129 (1): 31–8. PMID 8351956.
↑ Cohen JH, Ingbar SH, Braverman LE (1989). "Thyrotoxicosis due to ingestion of excess thyroid hormone". Endocr. Rev. 10 (2): 113–24. doi:10.1210/edrv-10-2-113. PMID 2666114.
↑ Jha S, Waghdhare S, Reddi R, Bhattacharya P (2012). "Thyroid storm due to inappropriate administration of a compounded thyroid hormone preparation successfully treated with plasmapheresis". Thyroid. 22 (12): 1283–6. doi:10.1089/thy.2011.0353. PMID 23067331.
↑ Fatourechi V, McConahey WM, Woolner LB (1971). "Hyperthyroidism associated with histologic Hashimoto's thyroiditis". Mayo Clin. Proc. 46 (10): 682–9. PMID 5171000.
↑ Laurberg P, Pedersen KM, Vestergaard H, Sigurdsson G (1991). "High incidence of multinodular toxic goitre in the elderly population in a low iodine intake area vs. high incidence of Graves' disease in the young in a high iodine intake area: comparative surveys of thyrotoxicosis epidemiology in East-Jutland Denmark and Iceland". J. Intern. Med. 229 (5): 415–20. PMID 2040867.
↑ Oosting SF, de Haas EC, Links TP, de Bruin D, Sluiter WJ, de Jong IJ, Hoekstra HJ, Sleijfer DT, Gietema JA (2010). "Prevalence of paraneoplastic hyperthyroidism in patients with metastatic non-seminomatous germ-cell tumors". Ann. Oncol. 21 (1): 104–8. doi:10.1093/annonc/mdp265. PMID 19605510.

Template:WikiDoc Sources

[urlThyroiditis_—_NEJM-1] 1.0 ^1.1 "Thyroiditis — NEJM".

[pmid16734054-2] Bindra A, Braunstein GD (2006). "Thyroiditis". Am Fam Physician. 73 (10): 1769–76. PMID 16734054.

[pmid19949140-3] McDermott MT (2009). "In the clinic. Hypothyroidism". Ann. Intern. Med. 151 (11): ITC61. doi:10.7326/0003-4819-151-11-200912010-01006. PMID 19949140.

[pmid18177256-4] 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.

[pmid18415684-5] Lania A, Persani L, Beck-Peccoz P (2008). "Central hypothyroidism". Pituitary. 11 (2): 181–6. doi:10.1007/s11102-008-0122-6. PMID 18415684.

[pmid25905413-6] 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.

[pmid2258582-7] Lambert M, Unger J, De Nayer P, Brohet C, Gangji D (1990). "Amiodarone-induced thyrotoxicosis suggestive of thyroid damage". J. Endocrinol. Invest. 13 (6): 527–30. PMID 2258582.

[pmid24282820-8] Ahmadieh H, Salti I (2013). "Tyrosine kinase inhibitors induced thyroid dysfunction: a review of its incidence, pathophysiology, clinical relevance, and treatment". Biomed Res Int. 2013: 725410. doi:10.1155/2013/725410. PMC 3824811. PMID 24282820.

[pmid8351956-9] Vialettes B, Guillerand MA, Viens P, Stoppa AM, Baume D, Sauvan R, Pasquier J, San Marco M, Olive D, Maraninchi D (1993). "Incidence rate and risk factors for thyroid dysfunction during recombinant interleukin-2 therapy in advanced malignancies". Acta Endocrinol. 129 (1): 31–8. PMID 8351956.

[pmid2666114-10] Cohen JH, Ingbar SH, Braverman LE (1989). "Thyrotoxicosis due to ingestion of excess thyroid hormone". Endocr. Rev. 10 (2): 113–24. doi:10.1210/edrv-10-2-113. PMID 2666114.

[pmid23067331-11] Jha S, Waghdhare S, Reddi R, Bhattacharya P (2012). "Thyroid storm due to inappropriate administration of a compounded thyroid hormone preparation successfully treated with plasmapheresis". Thyroid. 22 (12): 1283–6. doi:10.1089/thy.2011.0353. PMID 23067331.

[pmid5171000-12] Fatourechi V, McConahey WM, Woolner LB (1971). "Hyperthyroidism associated with histologic Hashimoto's thyroiditis". Mayo Clin. Proc. 46 (10): 682–9. PMID 5171000.

[pmid2040867-13] Laurberg P, Pedersen KM, Vestergaard H, Sigurdsson G (1991). "High incidence of multinodular toxic goitre in the elderly population in a low iodine intake area vs. high incidence of Graves' disease in the young in a high iodine intake area: comparative surveys of thyrotoxicosis epidemiology in East-Jutland Denmark and Iceland". J. Intern. Med. 229 (5): 415–20. PMID 2040867.

[pmid19605510-14] Oosting SF, de Haas EC, Links TP, de Bruin D, Sluiter WJ, de Jong IJ, Hoekstra HJ, Sleijfer DT, Gietema JA (2010). "Prevalence of paraneoplastic hyperthyroidism in patients with metastatic non-seminomatous germ-cell tumors". Ann. Oncol. 21 (1): 104–8. doi:10.1093/annonc/mdp265. PMID 19605510.

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Silent thyroiditis differential diagnosis

Overview

Differentiating Silent Thyroiditis from other Diseases

References

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