Hypothyroidism

	Hypothyroidism Main page
Patient Information
Overview
Classification Primary hypothyroidism Hashimoto's thyroiditis Secondary hypothyroidism Tertiary hypothyroidism
Differentiating different causes of hypothyroidism
Screening
Diagnosis
History and symptoms

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

Synonyms and keywords: Myxedema; myxoedema; thyroid activity decreased; hypothyroid

Overview

Thyroxine (T4) and triiodothyronine (T3) are produced from the thyroid gland. Thyroid hormones are important in regulating different body functions, and their deficiencies are associated with different symptoms including the decrease in energy metabolism, decreased appetite, cold intolerance, and slightly low basal body temperature (low basal metabolic rate)^[1]. Iodine deficiency is recognized as the most common cause of hypothyroidism world widely. In developed countries and areas of iodine sufficiency, the most common cause of hypothyroidism is chronic autoimmune thyroiditis (Hashimoto’s thyroiditis) with a more prevalence in women than men^[2]^[3]. Symptom and signs of hypothyroidism is mostly related to the magnitude of the thyroid hormone deficiency, and the acuteness with which the deficiency develops rather than the cause of hypothyroidism^[4]. However, the typical clinical manifestations of hypothyroidism may vary depending on the origin of the disease. Clinical scenario- if associated with secondary and tertiary hypothyroidism, may present other coexisting endocrine deficiencies such as hypogonadism and adrenal insufficiency, that may mask the manifestations of hypothyroidism. Although hypothyroidism diagnosis is mainly a laboratory diagnosis^[5], the coexisting conditions and wide variation in clinical presentation may make the diagnosis hard. Subclinical hypothyroidism on the other hand is mostly asymptomatic, but may be transformed to clinical. Recent researches have shown subclinical hypothyroidism may have various consequences, such as hyperlipidemia and increased risk for the development of cardiovascular disease, even heart failure, somatic and neuromuscular symptoms, infertility and other complications ^[6]^[7].

Classification

The table below presents a classification of isolated thyroid disorders and its causes based on the classification^[8] ^[9]^[10]^[11]:

		Origin of the defect			Causes
		Origin of the defect			Endagenous causes	Exagenous causes
		Thyroid	Pituirtary	Hypothalamus	Endagenous causes	Surgery or radiation	Other causes
Primary hypothyroidism		+	-	-	Congenital hypothyroidism Autoimmune (Hashimoto's) thyroiditis Resistance to TSH	After hyperthyroidism or thyroid cancer treatment: Thyroidectomy Radioiodine therapy Radiation for non-thyroid-related head and neck malignancies including lymphoma	Iodine deficeincy Drug induced thyroiditis Amiodarone Lithium Thionamide Interferon Sunitinib Rifampicin Thalidomide Acute infectiuos thyroiditis Trauma-induced
Transient hypothyroidism		+	+	-	Subacute (de Quervain’s) thyroiditis Postpartum thyroiditis	Major surgeries
Central Hypothyroidism	Secondary OR Pituitary originated	-	+	-	Pituitary mass lesions, especially pituitary adenomas Brain cysts and abscesses Meningiomas Dysgerminomas Metastatic tumors Craniopharyngiomas Pituitary apoplexy Sheehan syndrome (postpartum pituitary necrosis) Idiopathic isolated TSH deficiency Lymphocytic or granulomatous hypophysitis	Surgery of pituitary adenomas Radiation therapy to: Pituitary adenomas Other mass lesions near pituitary gland	Head trauma with injury of the stalk
Central Hypothyroidism	Tertiary OR Hypothalamus originated	-	-	+	Hemochromatosis Histiocytosis Developmental abnormalities Internal carotid aneurysms Other central nervous system (CNS) tumors Idiopathic isolated TRH deficiency	Radiation in high doses to: Brain Infratemporal Nasopharyngeal Oropharyngeal	Infections Tuberculosis Syphilis Toxoplasmosis Sarcoidosis

Classification of thyroiditis based on the duration algorythm

Hypothyroidism diagnosis can be made based on the laboratory findings^[8] ^[9]^[10]^[11]:

History, signs, and symptoms suggestive of hypothyroidism

Measure FT4 and TSH

Normal FT4, Elevated TSH>5.5

Decresased level of FT4

Subclinical hypothyroidism

Elevated TSH > 5.5

Normal TSH level OR Decreased TSH level < 0.2

Check anti-thyroid autoantibodies and TPOAb

Check TRH

Increased

Normal

Normal or increased

Decreased

•Autoimmune thyroiditis
• Resistance to TSH

•Iodine deficeincy
•Thyroiditis

•Pituitary related hypothyroidism

•Hypothalamus related hypothyroidism

Differential diagnosis

^[1]^[3]^[5]

Disease		History and symptoms			Laboratory findings							Additional findings
Disease		Fever	Goiter	Pain	TSH	Free T4	T3	T3RU	Thyroglobin	TRH	TPOAb	Additional findings
Primary hypothyroidism	Autoimmune	+	+/- Diffuse	-	↑	↓	N/↓	Normal	N/↑	Normal	↑	May be accompanied by other autoimmune diseases
	Thyroiditis	+	+/-	+	↑	↓	Normal	Normal	N/↑	Normal	Normal	Infectious thyroiditis associated with neck pain
	Others	-	+/-	-	↑	↓	Normal	Normal	N/↑	Normal	Normal	History of hyperthyroiditis Drug history
Transient hypothyroidism		+/-	-	+/-	↑	↑	Normal	Normal	↑	Normal	Normal	May present primarily with hyperthyroiditis
Subclinical hypothyroidism		-	-	-	↑	Normal	Normal	Normal	↑	Normal	N/↑	Asymptomatic
Central Hypothyroidism	Pituitary	+	-	-	N/↓	N/↓	N/↓	↓	Normal	Normal	Normal	Other pituitary hormone deficiencies signs
Central Hypothyroidism	Hypothalamus	+	-	-	N/↓	N/↓	N/↓	↑	Normal	↓	Normal	Other pituitary hormone deficiency signs
Resistance to TSH/TRH		-	-	-	↑	N/↓	N/↓	Normal	Normal	↑/↓	Normal	Rare

History and symptom

The symptoms and signs of clinical hypothyroidism are listed in the table below. The appearance of symptoms depends on the degree of hypothyroidism severity^[12]^[13]^[14]:

Symptoms	Constituitional	HEENT	Neuromuscular	Complications
More common	Fatigue Cold intolerance Decreased sweating Hypothermia Coarse skin Weight gain	Hoarseness Goiter Fullness in the throat and neck	Depression Emotional lability Attention deficit	Macroglossia Obstructive sleep apnea Paresthesia Nerve entrapment syndromes (carpal tunnel syndrome) Blurred vision (central hypothyroidism)
Less common	Puffiness Hair loss Constipation Fever If accompanied by thyroiditis	Sore throat Periorbital edema	Slowed speech and movements	Pituitary hyperplasia followed by hyperprolactinemia Ataxia Myxedema coma (with non-pitting edema) Cardiomegaly Pericardial effusion Ascites Hyperlipidemia Galactorrhea Infertility

References

↑ ^1.0 ^1.1 McDermott MT (2009). "In the clinic. Hypothyroidism". Ann. Intern. Med. 151 (11): ITC61. doi:10.7326/0003-4819-151-11-200912010-01006. PMID 19949140.
↑ Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, Braverman LE (2002). "Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III)". J. Clin. Endocrinol. Metab. 87 (2): 489–99. doi:10.1210/jcem.87.2.8182. PMID 11836274.
↑ ^3.0 ^3.1 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.
↑ Zimmerman RS, Brennan MD, McConahey WM, Goellner JR, Gharib H (1986). "Hashimoto's thyroiditis. An uncommon cause of painful thyroid unresponsive to corticosteroid therapy". Ann. Intern. Med. 104 (3): 355–7. PMID 3753833.
↑ ^5.0 ^5.1 Lania A, Persani L, Beck-Peccoz P (2008). "Central hypothyroidism". Pituitary. 11 (2): 181–6. doi:10.1007/s11102-008-0122-6. PMID 18415684.
↑ O'Brien T, Dinneen SF, O'Brien PC, Palumbo PJ (1993). "Hyperlipidemia in patients with primary and secondary hypothyroidism". Mayo Clin. Proc. 68 (9): 860–6. PMID 8371604.
↑ Diekman T, Lansberg PJ, Kastelein JJ, Wiersinga WM (1995). "Prevalence and correction of hypothyroidism in a large cohort of patients referred for dyslipidemia". Arch. Intern. Med. 155 (14): 1490–5. PMID 7605150.
↑ ^8.0 ^8.1 Colon-Otero G, Menke D, Hook CC (1992). "A practical approach to the differential diagnosis and evaluation of the adult patient with macrocytic anemia". Med. Clin. North Am. 76 (3): 581–97. PMID 1578958.
↑ ^9.0 ^9.1 Gharib H, Tuttle RM, Baskin HJ, Fish LH, Singer PA, McDermott MT (2005). "Subclinical thyroid dysfunction: a joint statement on management from the American Association of Clinical Endocrinologists, the American Thyroid Association, and the Endocrine Society". J. Clin. Endocrinol. Metab. 90 (1): 581–5, discussion 586–7. doi:10.1210/jc.2004-1231. PMID 15643019.
↑ ^10.0 ^10.1 Rugge JB, Bougatsos C, Chou R (2015). "Screening and treatment of thyroid dysfunction: an evidence review for the U.S. Preventive Services Task Force". Ann. Intern. Med. 162 (1): 35–45. doi:10.7326/M14-1456. PMID 25347444.
↑ ^11.0 ^11.1 Garber JR, Cobin RH, Gharib H, Hennessey JV, Klein I, Mechanick JI, Pessah-Pollack R, Singer PA, Woeber KA (2012). "Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association". Thyroid. 22 (12): 1200–35. doi:10.1089/thy.2012.0205. PMID 22954017.
↑ Carlé A, Pedersen IB, Knudsen N, Perrild H, Ovesen L, Laurberg P (2014). "Hypothyroid symptoms and the likelihood of overt thyroid failure: a population-based case-control study". Eur. J. Endocrinol. 171 (5): 593–602. doi:10.1530/EJE-14-0481. PMID 25305308.
↑ Diaz A, Lipman Diaz EG (2014). "Hypothyroidism". Pediatr Rev. 35 (8): 336–47, quiz 348–9. doi:10.1542/pir.35-8-336. PMID 25086165.
↑ Samuels MH (2014). "Psychiatric and cognitive manifestations of hypothyroidism". Curr Opin Endocrinol Diabetes Obes. 21 (5): 377–83. doi:10.1097/MED.0000000000000089. PMC 4264616. PMID 25122491.

[pmid19949140-1] 1.0 ^1.1 McDermott MT (2009). "In the clinic. Hypothyroidism". Ann. Intern. Med. 151 (11): ITC61. doi:10.7326/0003-4819-151-11-200912010-01006. PMID 19949140.

[pmid11836274-2] Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, Braverman LE (2002). "Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III)". J. Clin. Endocrinol. Metab. 87 (2): 489–99. doi:10.1210/jcem.87.2.8182. PMID 11836274.

[pmid18177256-3] 3.0 ^3.1 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.

[pmid3753833-4] Zimmerman RS, Brennan MD, McConahey WM, Goellner JR, Gharib H (1986). "Hashimoto's thyroiditis. An uncommon cause of painful thyroid unresponsive to corticosteroid therapy". Ann. Intern. Med. 104 (3): 355–7. PMID 3753833.

[pmid18415684-5] 5.0 ^5.1 Lania A, Persani L, Beck-Peccoz P (2008). "Central hypothyroidism". Pituitary. 11 (2): 181–6. doi:10.1007/s11102-008-0122-6. PMID 18415684.

[pmid8371604-6] O'Brien T, Dinneen SF, O'Brien PC, Palumbo PJ (1993). "Hyperlipidemia in patients with primary and secondary hypothyroidism". Mayo Clin. Proc. 68 (9): 860–6. PMID 8371604.

[pmid7605150-7] Diekman T, Lansberg PJ, Kastelein JJ, Wiersinga WM (1995). "Prevalence and correction of hypothyroidism in a large cohort of patients referred for dyslipidemia". Arch. Intern. Med. 155 (14): 1490–5. PMID 7605150.

[pmid1578958-8] 8.0 ^8.1 Colon-Otero G, Menke D, Hook CC (1992). "A practical approach to the differential diagnosis and evaluation of the adult patient with macrocytic anemia". Med. Clin. North Am. 76 (3): 581–97. PMID 1578958.

[pmid15643019-9] 9.0 ^9.1 Gharib H, Tuttle RM, Baskin HJ, Fish LH, Singer PA, McDermott MT (2005). "Subclinical thyroid dysfunction: a joint statement on management from the American Association of Clinical Endocrinologists, the American Thyroid Association, and the Endocrine Society". J. Clin. Endocrinol. Metab. 90 (1): 581–5, discussion 586–7. doi:10.1210/jc.2004-1231. PMID 15643019.

[pmid25347444-10] 10.0 ^10.1 Rugge JB, Bougatsos C, Chou R (2015). "Screening and treatment of thyroid dysfunction: an evidence review for the U.S. Preventive Services Task Force". Ann. Intern. Med. 162 (1): 35–45. doi:10.7326/M14-1456. PMID 25347444.

[pmid22954017-11] 11.0 ^11.1 Garber JR, Cobin RH, Gharib H, Hennessey JV, Klein I, Mechanick JI, Pessah-Pollack R, Singer PA, Woeber KA (2012). "Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association". Thyroid. 22 (12): 1200–35. doi:10.1089/thy.2012.0205. PMID 22954017.

[pmid25305308-12] Carlé A, Pedersen IB, Knudsen N, Perrild H, Ovesen L, Laurberg P (2014). "Hypothyroid symptoms and the likelihood of overt thyroid failure: a population-based case-control study". Eur. J. Endocrinol. 171 (5): 593–602. doi:10.1530/EJE-14-0481. PMID 25305308.

[pmid25086165-13] Diaz A, Lipman Diaz EG (2014). "Hypothyroidism". Pediatr Rev. 35 (8): 336–47, quiz 348–9. doi:10.1542/pir.35-8-336. PMID 25086165.

[pmid25122491-14] Samuels MH (2014). "Psychiatric and cognitive manifestations of hypothyroidism". Curr Opin Endocrinol Diabetes Obes. 21 (5): 377–83. doi:10.1097/MED.0000000000000089. PMC 4264616. PMID 25122491.

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