Myxedema coma pathophysiology

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

Overview

Myxedema coma occurs as a result of long-standing, un-diagnosed, or untreated hypothyroidism and is usually precipitated by a systemic illness. Thyroid hormone plays an important role in cellular metabolism. Long-standing hypothyroidism results in reduced metabolic rate and decreased oxygen consumption, which affects all organ systems. Reduced metabolism and decreased oxygen results in hypothermia and decreased drug metabolism leading to overdosing of medications particularly sedatives, hypnotics, and anesthetic agents and can precipitate myxedema coma.

Myxedema coma occurs as a result of long-standing, undiagnosed, or untreated hypothyroidism.^[1]^[2]^[3]^[4]
Myxedema coma is usually precipitated by a systemic illness.

Thyroid hormone plays an important role in cellular metabolism.
Long-standing hypothyroidism is associated with reduced metabolic rate and decreased oxygen consumption, which affects all organ systems.
Reduced metabolism results in hypothermia.
Reduced metabolism and decreased oxygen also result in decreased drug metabolism leading to overdosing of medications particularly sedatives, hypnotics, and anesthetic agents; this can precipitate myxedema coma.
Even in severe hypothyroidism, a balance of metabolic homeostasis is achieved through adaptive neurovascular mechanisms. However, in conditions such as respiratory or urinary tract infections, cardiac, acute myocardial infarction or stroke interfere with this adaptive mechanisms by decreasing the blood volume and ventilation triggering myxedema coma.

Myxedema coma can result from any of the causes of hypothyroidism, most commonly chronic autoimmune thyroiditis.
Myxedema coma can also occur in patients who had thyroidectomy or underwent radioactive iodine therapy for hyperthyroidism.
Rare causes may include secondary hypothyroidism and medications such as lithium and amiodarone.

Precipitating Factor

↓T4

↓ IntracellularT3

↓ Volume status

↓ GFR
↑ ADH

Cerebral anoxia

↓Arterial pressure/shock

Myxedema Coma

Organ System	Effect due to Decreased Thyroid Hormone	Manifestation
Cardiovascular	Cardiac contractility impaired: Leading to reduced stroke volume Low cardiac output Bradycardia Hypotension Reduced stroke volume Accumulation of fluid rich in mucopolysaccharides within the pericardial sac	Hypotension Narrowed pulse pressure Edema Pericardial effusions
Neurologic	Altered brain function due to: Reduced oxygen delivery and consumption Decreased glucose utilization Reduced cerebral blood flow	Altered consciousness
Pulmonary	Central depression of ventilatory drive: Hypoxia Hypercapnia	Hypoventilation
Renal	Reduced glomerular filtration rate because of: Low cardiac output Peripheral vasoconstriction Rhabdomyolysis Low volume stimulates Antidiuretic hormone impairs water excretion leading to hyponatremia	Dysuria Urinary frequency Nocturia
Gastrointestinal	Mucopolysaccharide infiltration and edema results in: Malabsorption Gastric atony Impaired peristalsis Paralytic ileus Megacolon	GI bleeding Ascites Constipation
Hematologic	Coagulopathy Due to decrease in production of factors V, VII, VIII, IX, and X Hemorrhage and vitamin B12 deficiency	Bleeding Anemia

Common conditions associated with myxedema coma include:

↑ Rizzo L, Mana DL, Bruno OD, Wartofsky L (2017). “[Myxedema coma]”. Medicina (B Aires) (in Spanish; Castilian). 77 (4): 321–328. PMID 28825577. Vancouver style error: initials (help)
↑ Wall CR (2000). “Myxedema coma: diagnosis and treatment”. Am Fam Physician. 62 (11): 2485–90. PMID 11130234.
↑ Mathew V, Misgar RA, Ghosh S, Mukhopadhyay P, Roychowdhury P, Pandit K, Mukhopadhyay S, Chowdhury S (2011). “Myxedema coma: a new look into an old crisis”. J Thyroid Res. 2011: 493462. doi:10.4061/2011/493462. PMC 3175396. PMID 21941682.
↑ Wartofsky L (2006). “Myxedema coma”. Endocrinol. Metab. Clin. North Am. 35 (4): 687–98, vii–viii. doi:10.1016/j.ecl.2006.09.003. PMID 17127141.