Thyroid hormones play a fundamental role in cardiovascular function. They influence how the heart responds to adrenaline, how the heart uses energy and how constricted or relaxed blood vessels are. However, their effect on the strength of cardiac contraction is less understood.
To better examine the role of thyroid hormones in cardiac contractility, endocrinology clinicians at UC Davis Health examined patients with myxedema coma, the most severe form of hypothyroidism. This life‑threatening condition offers a rare opportunity to observe the heart in a state of profound thyroid hormone deprivation.
Cardiac effects of hypothyroidism and critical illness
Individuals with low thyroid hormone levels (hypothyroidism) often exhibit changes in cardiac function, including delays in the onset of contraction, prolonged contraction and relaxation times and abnormalities in blood flow during cardiac filling.
A similar pattern of cardiac dysfunction is commonly observed in septic shock, a leading cause of death in intensive care units. In this setting, low circulating triiodothyronine (T3) levels occur in up to 95% of patients, a phenomenon often referred to as non‑thyroidal illness syndrome.
At the same time, approximately 30 - 40% of patients with septic shock develop septic cardiomyopathy, characterized by impaired myocardial contractility and reduced cardiac output.
"These observations raise an important question," explained Joaquin Lado, chief of Endocrinology, Diabetes and Metabolism at UC Davis Health. "Is it possible that untreated low thyroid hormone levels contribute to heart dysfunction?"
Traditionally, endocrinologists have been reluctant to treat low thyroid hormone levels during acute illness, viewing them as an adaptive metabolic response rather than a true hormone deficiency. However, this long‑held assumption is increasingly being challenged.
"If thyroid hormone deficiency weakens the heart," Lado added, "why wouldn't a prolonged deficiency worsen septic cardiomyopathy?"
"If thyroid hormone deficiency weakens the heart, why wouldn't a prolonged deficiency worsen septic cardiomyopathy?"-Joaquin Lado
About the Study
To explore thyroid hormone's role in cardiac contractility, Lado and colleagues conducted a multicenter study examining cardiac function in hospitalized patients with severe hypothyroidism, including those with myxedema coma. Their findings were published in The Journal of Clinical Endocrinology & Metabolism.
The study evaluated 112 intensive care unit patients using detailed echocardiographic analysis. The results revealed widespread cardiac dysfunction:
- More than one‑third of patients had reduced left ventricular ejection fraction, a traditional marker of systolic dysfunction
- Two‑thirds exhibited abnormal diastolic function
- Nearly 70% demonstrated impaired myocardial strain, a sensitive and early indicator of myocardial performance
Notably, these issues were present even in patients with preserved ejection fraction and occurred at similar rates in individuals with and without overt myxedema coma. This suggests that severe hypothyroidism exerts a direct and measurable impact on myocardial function, even when conventional markers appear normal.
Despite the high prevalence of cardiac dysfunction, short‑term, in‑hospital mortality remained relatively low, at 4.5%, highlighting both the resilience of the cardiovascular system and the opportunity for therapeutic intervention.
"These findings support the concept that severe hypothyroidism directly impairs cardiac performance," Lado explained. "Unlike other organs affected during critical illness, the heart retains thyroid hormone receptors and transport mechanisms. It is not unresponsive; it is hormonally deprived. In this context, particularly during septic shock, the heart may function as a purely hypothyroid organ, making it a compelling target for thyroid hormone replacement therapy."
What's next?
Building on these clinical observations, Lado and his team are now exploring the direct effects of thyroid hormones on cardiac muscle cells. Early laboratory studies using isolated cardiomyocytes suggest that thyroid hormones can enhance contractility within minutes. These rapid responses point to non‑genomic mechanisms, which may be especially relevant in acute, life‑threatening illness.
Translating these findings to patient care is the next critical step. To that end, Lado has developed an approved clinical trial protocol to study thyroid hormone replacement therapy in patients with septic shock. However, conducting such research presents significant challenges.
"Critically ill patients are difficult to consent, thyroid hormone therapy lacks industry backing because it is inexpensive, and ICU‑based research involves complex ethical and logistical hurdles," Lado noted. "However, this question is too important to leave unanswered."
As understanding of thyroid hormone function in critically ill patients grows, this research may challenge established medical thinking. It also may create new opportunities to improve outcomes for patients with severe heart dysfunction.
