High-Dose Levothyroxine Effective for Myxedema Coma Treatment

Nancy A Melville

November 06, 2014

SAN DIEGO — Myxedema coma, a rare but potentially fatal form of decompensated hypothyroidism, can be identified according to key clinical signs and successfully treated in most patients with 500 µg of intravenous levothyroxine (L-thyroxine), according to a new study.

A first important step toward improving diagnosis of the syndrome, however, would be to assign it a more appropriate name, specifically "severely decompensated hypothyroidism" (SDH), asserted coinvestigator Dr Caroline T Nguyen, (Keck School of Medicine, University of Southern California, Los Angeles).

" 'Myxedema coma' is a misnomer, because most patients who present initially with this syndrome often do not have myxedema or coma," Dr Nguyen said.

"Rather, the term 'severely decompensated hypothyroidism' is more accurate and descriptive of this syndrome, and our thinking of it in this manner may lead to earlier diagnosis and initiation of treatment," she said.

Even with treatment, mortality rates from myxedema coma can be as high as 25% to 60%, yet, due to its rarity, reports on effective diagnosis and treatment in the literature are limited mainly to single case reports and small case series.

Altered Mental Status Most Helpful Clinical Parameter

In presenting her data on the case series of 47 patients and 50 episodes — said to be the largest case series to date — at the recent 2014 Annual Meeting of the American Thyroid Association, Dr Nguyen said she and her colleagues identified four key clinical signs of the syndrome. They include:

  • Hypothyroidism as determined by clinical exam, history, or biochemical findings.

  • A precipitating event, such as an infection, that takes a patient from a compensated to decompensated state.

  • Hypothermia or defective thermoregulation, whether absolute or relative. "For example, a septic patient with a normal temperature," Dr Nguyen said.

  • An altered mental status. "This can range from disorientation to coma, and in our experience, altered mental status has been the most helpful clinical parameter to distinguish between the compensated and decompensated hypothyroid patient."

Patients had a median free-T4 value of 0.39 ng/L, and median thyroid stimulating hormone (TSH), which was available for 38 patients with primary hypothyroidism, was 69.28 mIU/mL.

Patients were treated with 500 µg IV of L-thyroxine, with additional treatments including hydrocortisone and supportive care.

"The goal [the L-thyroxine therapy] is to partially reverse the hypothyroid state, enabling the patient to effectively adapt to the precipitating event that led to decompensation," Dr Nguyen said.

"The dose is designed to restore the total body thyroxine pool."

The average time from presentation to treatment with L-thyroxine was 27.3 hours.

From the time of treatment with L-thyroxine, 56% of patients showed improvements in mental status within 24 hours, 18% improved within 48 hours, and 6% improved in a week or less. In 16% of cases, the time to improvement was unknown.

Infection and sepsis were the leading precipitating events for 23 (41%) episodes.

Eighteen patients in the case series were aged 60 or older. When treated with 500 µg IV L-thyroxine within a 24-hour period, their survival rate was 89%.

Among 91% of patients who were followed for a week or longer, there were no cardiovascular complications, and most patients were followed for more than a month.

Four of the patients (8%) died, all between the ages of 72 and 82, and all had presented with sepsis or septic shock, requiring intubation.

High Rate of Infection/Sepsis as Precipitating Factor

Dr Nguyen noted that the high percentage of patients presenting with infection underscores the need to consider myxedema coma.

"The high incidence of infection and sepsis (in the case series) emphasizes the importance of having a strong suspicion for infection in the severely decompensated hypothyroidism patient, even in the setting of a normal white blood cell count," she said.

"In severely decompensated hypothyroidism, the patient is unable to effectively adapt to the precipitating events, leading to central nervous system and cardiovascular dysfunction, which, if not reversed, can be fatal."

Dr Giuseppe Barbesino (Massachusetts General Hospital, Boston), who comoderated the session, commented that the combination of hypothyroidism and various comorbidities cloud the issue, leaving many unanswered questions.

"This remains an unresolved issue to me. These are very sick hypothyroid patients — some sicker than others," he told Medscape Medical News. "The question is whether these patients are sick and hypothyroid or sick because they are hypothyroid.

"We certainly see patients with similar degrees of hypothyroidism who are not that sick; we also see people who are similarly sick with sepsis and other issues who are not hypothyroid.

"Of course they all receive treatment for hypothyroidism and for the other underlying issues, so we will never know."

No Name Change for Syndrome Yet

While noting that the research offers valuable input on the treatment of myxedema coma, Dr Barbesino was not in agreement regarding the assertion of the name change for the syndrome.

"I think the importance of the paper is in the observation that restoring euthyroidism rapidly with high-dose levothyroxine is safe," he said. "I think that a new nomenclature without solid pathophysiologic basis is not warranted" at this time.

The authors have reported they have no relevant financial relationships. Dr Barbesino is on the advisory board for Tirosint, a form of levothyroxine.

2014 Annual Meeting of the American Thyroid Association; November 1, 2014; Boston, MA. Abstract 221.

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