Thyroid & parathyroid
Thyroid endocrine abnormalities
Hypothyroidism
Last author update: 1 August 2016
Last staff update: 30 September 2021
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PubMed Search: hypothyroidism adult myxedema
Table of Contents
Definition / general | Essential features | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Laboratory | Radiology description | Prognostic factors | Case reports | Treatment | Gross description | Microscopic (histologic) description | Positive stains | Electron microscopy description | Videos | Additional referencesCite this page: Guilmette J, Chi A. Hypothyroidism. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/thyroidhypo.html. Accessed April 18th, 2024.
Definition / general
- Hypothyroidism is a common endocrine disorder resulting from a deficiency of thyroid hormone (Rev Endocr Metab Disord 2016 May 7 [Epub ahead of print])
- Presents as clinical or subclinical disease based on presence of symptoms and levels of serum TSH and free thyroxine / T4
- Further classified as primary, secondary and tertiary (Thyroid 2012;22:1200)
- Central hypothyroidism refers to decreased production of TSH / TRH due to pituitary or hypothalamic lesions (Thyroid 2012;22:1200)
- Complications include myxedema, characterized by thickened, nonpitting edematous soft tissue in markedly hypothyroid patients (J Clin Diagn Res 2014;8:YD01, An Bras Dermatol 2016;91:100)
- Myxedema can also occur in hyperthyroidism, such as Graves disease (J Clin Diagn Res 2014;8:YD01)
- Myxedema crisis / coma; a medical emergency and life threatening condition associated with a high mortality rate, which usually occurs following severe hypothyroidism decompensation (J Thyroid Res 2011;2011:493462)
- See also Hypothyroidism-lab diagnosis
Essential features
- Hypothyroidism is a common endocrine disorder resulting from a deficiency in thyroid hormone (Rev Endocr Metab Disord 2016 May 7 [Epub ahead of print])
- It is imperative to distinguish primary hypothyroidism from secondary / tertiary hypothyroidism (Indian J Endocrinol Metab 2011;15:S99), as the causes are very different
- In severe hypothyroidism decompensation, myxedema crisis / coma, a life threatening condition, can occur and prompt medical treatment is recommended (J Thyroid Res 2011;2011:493462)
- Myxedema describes thickened, nonpitting edema of soft tissue that may develop in patients with hypothyroidism (J Clin Diagn Res 2014;8:YD01, An Bras Dermatol 2016;91:100)
- Histologically, mucin accumulation is found between collagen fibers of the reticular dermis
- Other findings include perivascular lymphocytes, large fibroblasts and hemosiderin deposits (An Bras Dermatol 2016;91:100)
- Diagnosis relies primarily on clinical findings, biopsy and laboratory findings suggestive of hypothyroidism (Endotext - Severe Hypothyroidism in the Elderly)
Epidemiology
- Prevalence: clinical primary hypothyroidism, 0.3%; subclinical disease, 4.3% (Thyroid 2012;22:1200)
- Myxedema crisis / coma has a higher incidence among older females, affects about 220,000 people per year (J Thyroid Res 2011;2011:493462)
Sites
- Thyroid gland
- Involvement of pituitary gland or hypothalamus are usually observed in central hypothyroidism (Hippokratia 2010;14:82, J Clin Endocrinol Metab 2012;97:3068)
- Myxedema involves primarily bilateral pretibial areas (Am J Clin Dermatol 2005;6:295)
- Other sites include: cheeks, hands, supraclavicular fossae and soft tissue around the eyes (Ophthal Plast Reconstr Surg 2006;22:457 , Med J Aust 2003;179:211)
Pathophysiology
- Secretion of thyroid hormones are regulated by the hypothalamic pituitary thyroid axis
- In primary hypothyroidism, the following changes occur:
- Destruction of the thyroid gland leads to decreased secretion of thyroid hormones T3 and T4
- In response, TSH secretion increases (Neth J Med 2009;67:332, Hippokratia 2010;14:82)
- Myxedema: dermal mucinosis is caused by increased deposition of connective tissue components (glycosaminoglycans, hyaluronic acid and mucopolysaccharides) within the reticular dermis (Wikipedia - Myxedema)
- Protein mucopolysaccharide complex binds water, resulting in nonpitting edema
- Myxedema coma: patients with longstanding hypothyroidism often develop adaptive mechanisms, including chronic peripheral vasoconstriction, diastolic hypertension and diminished blood blood volume to preserve a normal body core temperature
- Myxedema coma occurs when a precipitating event disrupts this homeostasis (Endotext - Myxedema and Coma (Severe Hypothyroidism))
Etiology
- Primary hypothyroidism:
- Environmental iodine deficiency (most common etiology worldwide, Thyroid 2012;22:1200)
- Destruction or ablation of thyroid gland (surgery, radiation, developmental)
- In the United States, Hashimoto thyroiditis is the most common etiology (Thyroid 2012;22:1200)
- Interference with thyroid hormone synthesis (idiopathic, genetic [J Med Genet 2005;42:379], drugs [lithium, iodide, methimazole, PTU])
- Supraphysiologic Iodine exposure, especially in those with preexisting thyroid disease (Nat Rev Endocrinol 2014;10:136)
- Chronic renal failure (normal TSH, low T3 and T4) (Nucl Recept 2005;3:1)
- Secondary hypothyroidism:
- Any pituitary disorder that causes reduced TRF or TSH secretion
- Include genetics, tumors (e.g., pituitary adenoma), infection, autoimmune disorders, drugs, pituitary surgery or radiotherapy, trauma or pituitary apoplexy (Indian J Endocrinol Metab 2011;15:S99, Hippokratia 2010;14:82)
- Tertiary hypothyroidism:
- Any hypothalamic disorder that causes reduced TRF secretion
- Includes tumors, surgery or radiotherapy (Indian J Endocrinol Metab 2011;15:S99, Hippokratia 2010;14:82)
- Subclinical hypothyroidism:
- High TSH, normal T3 and T4
- No clinical symptoms of hypothyroidism (Am Fam Physician 2005;71:1763) but may have sensory neuropathy (Neurol Sci 2009;30:149)
Clinical features
- Most common symptoms are dry skin, fatigue, muscle cramps, cold sensitivity, voice changes and constipation
- In advanced disease: carpal tunnel syndrome, sleep apnea and pituitary hyperplasia (Thyroid 2012;22:1200)
- Rarely presents with myxedema pseudovolvulus (J Surg Case Rep 2016 Apr 22;2016(4)) or severe hyponatremia (Eur J Endocrinol 2017;176:R15)
- Myxedema coma is characterized by unconsciousness, respiratory failure, bradycardia, hypothermia (Case Rep Endocrinol 2015;2015:169194) and altered mental status (N Engl J Med 2015;372:764), including "myxedema madness" (psychosis due to marked hypothyroidism)
- Recently, arrythmias and coagulation disorders have been recognized as part of myxedema crisis (J Thyroid Res 2011;2011:493462)
Diagnosis
- For most outpatients with primary thyroid disease, serum thyrotropin (TSH) is the best screening test, although it may not be adequate for hospitalized patients (Thyroid 2012;22:1200)
- Primary hypothyroidism is suspected when TSH is elevated, a goitrous thyroid is present, associated pituitary hormone deficiencies are absent and the thyrotropin releasing hormone stimulation test is normal (Indian J Endocrinol Metab 2011;15:S99)
- Secondary / tertiary hypothyroidism (central hypothyroidism) is suggested by a normal to low normal TSH and low normal thyroid hormone, confirmed by the thyrotropin releasing hormone stimuation test (Indian J Endocrinol Metab 2011;15:S99)
Laboratory
- Low free T3 / T4, high TSH (Endotext - Severe Hypothyroidism in the Elderly)
- Elevated serum TPO antibody titers may indicate autoimmune thyroiditis, and provide prognostic information on the risk of developing hypothyroidism (Thyroid 2012;22:1200)
- In myxedema, CEA and CA125 may be elevated (Clin Ther 2007;29:2710)
- May have hyponatremia (Eur J Endocrinol 2017;176:R15)
- See also Hypothyroidism-lab diagnosis
Radiology description
- Primary hypothyroidism:
- Ultrasound reveals a hyperechoic multinodular thyroid (Med J Aust 2016;205:179), with a halo around nodules and no calcifications; benign nodules typically have ill defined margins (AJR Am J Roentgenol 2010;195:216)
- Pretibial myxedema:
- Multiple imaging modalities may be helpful in diagnosis
- Echo-Doppler of the lower legs may show venous and lymphatic insufficiency (An Bras Dermatol 2016;91:100)
- Digital infrared thermal imaging, which detects surface temperature (Eur J Endocrinol 2011;164:605), shows an abnormally low focal temperature over the lower legs
- High resolution ultrasonography shows composition changes in pretibial soft tissue (Eur J Endocrinol 2011;164:605)
- Increased skin thickness is demonstrated by hypoechoic substance deposition in the cutaneous tissue, and blurred boundary lines between dermal and subcutaneous tissue
Prognostic factors
- Poor compliance with thyroid hormone replacement may lead to myxedema coma (Case Rep Endocrinol 2015;2015:169194)
- Predictors of mortality in myxedema crisis or coma: bradycardia, hypotension, hypothermia, respiratory failure requiring mechanical ventilation, sepsis, intake of sedative drugs, high APACHE II score, SOFA (Sequential Organ Failure Assessment) scores greater than 6, and no response to treatment (J Thyroid Res 2011;2011:493462)
Case reports
- 22 year old woman with hypothyroidism due to bromide intoxication (Am J Clin Pathol 1988;89:802)
- 30 year old man with Graves disease (Dermatol Online J 2008;14:8)
- 37 year old man with HIV, hemophilia and Pneumocystis carinii infection presenting as thyroid mass with hypothyroidism (Am J Clin Pathol 1991;95:489)
- 38 year old woman with myxedema coma and cardiac ischemia (Clin Ther 2007;29:2710)
- A man in his late thirties with undiagnosed hypothyroidism presenting with sigmoid volvulus (J Surg Case Rep 2016 Apr 22;2016(4))
- 43 year old woman with cardiac death due to cardiovascular myxoedema and endocardial fibroelastosis (Int J Cardiol 2015;182:281)
- 54 year old woman with fatal cardiac tamponade due to myxedema pericarditis (Am J Clin Pathol 1986;86:113)
- 82 year old woman with myxoedema secondary to hypothyroidism treated with intramuscular injection of Levothyroxine (Case Rep Endocrinol 2015;2015:169194)
Treatment
- Thyroid hormone replacement therapy (L-thyroxine), tailored for each patient (Drugs Aging 2005;22:23, Thyroid 2012;22:1200)
- Pretibial myxedema usually resolves spontaneously
- In some cases, topical steroids, intralesional steroids, gamma globulin, pentoxifylline, surgery and radiotherapy may be required (J Clin Diagn Res 2014;8:YD01)
- Myxoedema coma can be successfully managed with levothyroxine and hydrocortisone (Case Rep Endocrinol 2015;2015:169194)
- Weekly administration of thyroxine may be useful for patients with cognitive deficits, chronic disabilities and poor medical compliance (Case Rep Endocrinol 2015;2015:169194, Postgrad Med J 2007;83:e3)
Gross description
- Diffusely enlarged, firm goiter (Thyroid 2012;22:1200)
- Pretibial myxedema: well defined, indurated, erythematous skin with large urticarial plaques often involving both legs and sparing the toes (J Clin Diagn Res 2014;8:YD01)
Microscopic (histologic) description
- Primary hypothyroidism (J Clin Endocrinol Metab 1993;76:466):
- Hyperplastic follicles, some with papillary folding
- Follicle cells range from cuboidal to columnar with clear cytoplasm and round nuclei
- Scant colloid material
- Lymphocytic infiltrate may be present
- Skin myxedema is usually characterised by (J Clin Diagn Res 2014;8:YD01):
- Collagen fibers in reticular dermis are separated by mucin accumulation
- Cutaneous mucinosis (Am J Dermatopathol 2010;32:196)
- Mild perivascular lymphocyte infiltrate
- Epidermis is spared
- Prominent fibroblasts (An Bras Dermatol 2016;91:100)
- Presence of hemosiderin deposits (An Bras Dermatol 2016;91:100)
Positive stains
- Pretibial myxedema: Alcian blue reveals mucin deposition across the entire dermal thickness (An Bras Dermatol 2016;91:100)
Electron microscopy description
- Primary hypothyroidism: severe interference with thyroid hormone biosynthesis within the follicular cells (J Clin Endocrinol Metab 1993;76:466)
Videos
Endocrinology overview
Additional references
