Myxedema coma pathophysiology

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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, undiagnosed, or undertreated hypothyroidism. Myxedema coma is usually precipitated by a systemic illness. Thyroid hormone plays an important role in cell metabolism. Long-standing hypothyroidism is associated with reduced metabolic rate and decreased oxygen consumption, which affects all body 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.

Pathophysiology

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

Triggers

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.

Pathogenesis

Thyroid hormone plays an important role in cell metabolism.
Long-standing hypothyroidism is associated with reduced metabolic rate and decreased oxygen consumption, which affects all body systems.
Reduced metabolism results in hypothermia.
Reduced metabolism and decreased oxygen also results 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.

Hypothyroidism

Precipitating Factor

↓T4

↓ IntracellularT3

↓ Thermogenesis

↓ Inotropic
Bradycardia

↓ Volume status

Hypothermia

Hypoventilation

↓ Cardiac output
↓ Blood volume

↓ GFR
↑ ADH

Alteration of mental state

Cerebral anoxia

↓Arterial pressure/shock

Hyponatremia
Edema

Myxedema Coma

The following table summarizes the various effects of reduced thyroid hormone on different organ systems

Organ System	Effect due to Decreased Thyroid Hormone	Manifestation
Cardiovascular	Cardiac contractility is 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
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

Associated Conditions

Common conditions associated with myxedema coma include:

References

↑ 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.

[pmid28825577-1] 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)

[pmid11130234-2] Wall CR (2000). "Myxedema coma: diagnosis and treatment". Am Fam Physician. 62 (11): 2485–90. PMID 11130234.

[pmid21941682-3] 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.

[pmid17127141-4] 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.

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