Hypothyroidism and Angina: Research

Although it is more common to consider angina in relation to hyperthyroidism, several articles have reported angina appearing in hypothyroid patients when treated with exogenous thyroid hormones (T4). They recommended gradual increases in T4 dosage, but mentioned that a satisfactory dose may not be achievable, leaving patients to accept a compromise between hypothyroidism and angina.

NOTE: The following review involves ethical copying of limited content from journal articles within Canadian Copyright Law. See the Wikipedia article “Fair dealing in Canadian copyright law” or the Law itself, at http://laws-lois.justice.gc.ca/eng/acts/c-42/page-18.html

Hypothyroidism & angina articles

Casella, F., Bossi, I., Pisano, G., & Montano, N. (2008). An atypical case of typical chest pain. Internal and Emergency Medicine, 3(4), 405–407. http://doi.org/10.1007/s11739-008-0156-9

Quotes

“A 68-year-old woman presented to emergency department (ED) for a 2-week history of fatigue and recurrent episodes of chest pain on exertion described as constrictive and
associated with dyspnea. The duration of each episode of pain was about 30 min.” (p. 405)
“When the patient was admitted to our division, the initial investigations revealed
  • a normal complete blood count,
  • normal kidney and liver function tests,
  • and normal values of lactate dehydrogenase (220 U/l), creatine kinase (129 U/l),
    D-Dimer (50 ng/dl) and cardiac troponin T (<0.01 ug/l).
  • Chest radiography was normal.
  • The electrocardiogram (ECG) showed sinus bradycardia (48 bpm), normal QRS
    voltages, inverted T-waves in anterolateral chest leads, normal QT interval (Fig. 1a).
  • Echocardiography revealed a normal left ventricular function without evidence of regional wall motion abnormalities, minimal posterior echolucent space, and a normal right ventricular size and function with a normal pulmonary pressure.
  • a coronary computed tomography angiogram was performed showing
    normal coronary arteries.
  • Gastroesophageal reflux was excluded by performing esophagogastroscopy that showed no signs of esophagitis.

“thyroid function tests were performed revealing

  • a markedly elevated thyroid-stimulating
    hormone (TSH[100 lU/ml)
  • and significantly reduced serum free hormones
    • (FT3 1.8 pg/ml;
    • FT4 3.2 pg/ml).
  • Thyroid autoantibodies were strongly positive (anti-thyreoglobulin
    385 UI/ml;
  • anti-thyroid peroxidase 1,737 Ul/ml).
  • A thyroid echography showed a global thyroid enlargement
    with diffuse hypoechogenity and no evidence of nodules.

“These findings were suggestive for a Hashimoto’s thyroiditis. Therapy with levothyroxine was started, which rapidly led to remission of chest pain.” (p. 406)

“In most patients with ischemic heart disease, angina can worsen after the initiation
of thyroid hormone therapy due to increase of myocardial oxygen demand.” (p. 407)
“In several cases of hypothyroidism, even elevations of cardiac troponin and evidence of actual myocardial damage by cardiac MRI have been described. In view of these findings, our hypothesis is that chest pain, ECG changes and cardiac troponin elevation described
in hypothyroid patients with normal coronary angiogram, may reflect actual diffuse myocardial injury.” (p. 407)
Review commentary by Healthy Researcher BlogThe description of the woman’s symptoms are useful to sufferers of angina-like pain.
Notice that most of her tests showed “normal” results, other than her thyroid tests showing severe hypothyroidism.
Her TSH was astronomical, and her Free T3 and Free T4 levels were both depressed, and antibodies proved she had Hashimoto’s.
Luckily she did not have further chest pain on T4-only treatment, though the authors are wise to note that many people can have their angina worsen after T4-administration. 
It’s also worthy of note that her troponin T levels were extremely low.
Only her follow-up ECG vindicated her angina pain as cardiac. Lucky her. If she had had no “beeping machine” validate the cardiac basis of her pain, I wonder if the article could have been published.

Gammage, M., & Franklyn, J. (1997). Hypothyroidism, thyroxine treatment, and the heart. Heart, 77(3), 189–190.

Quotes

“it is well known that angina and myocardial infarction may be precipitated by the initiation of thyroxine replacement treatment (even in low dose) in those with underlying coronary artery disease (whether this is evident clinically or  electrocardiographically)–this association was described more than 70 years ago.” (p. 189)

“For this reason, a recent United Kingdom consensus statement for good practice in the management of hypothyroidism recommends that in older patients, especially those with ischaemic heart disease, the initial dose of thyroxine should be 25 mcg and increased every three to four weeks by 25 mcg increments.”  (p. 189)

“There is little evidence that triiodothyronine [T3] treatment is better than thyroxine [T4] in patients with ischaemic heart disease, although there is a theoretical benefit [of T3] should angina worsen and thyroid hormone replacement be stopped because the half life of triiodothyronine [T3] is shorter than that of thyroxine [T4].” (p. 189)

While it is reported that up to 15% of patients starting thyroxine [T4] therapy will sustain a myocardial infarction within two years, it is also clear that chest pain improves or resolves in up to half of patients with this problem. [Toft, A. D., 1994]” (p. 189)

“Nonetheless, 40% of patients with angina are unable to tolerate full replacement doses of thyroxine [T4]. [Levine, 1961 (republished 1980)]” (p. 189)

“In those considered unsuitable for surgery or angioplasty, adequate doses of thyroxine [T4] may not be achieved, even if the daily dose of thyroxine is 25 mcg or less, with gradual incremental increases every few weeks.” (p. 189)

“The possible effects of thyroxine therapy on cardiac mass and arrhythmia risk raise concerns regarding adverse influences of mild thyroxine [T4] excess on cardiac risk” (p. 190)

Review commentary by Healthy Researcher BlogThe article emphasizes that T4 can cause angina in those with an already weakened heart. It seems logical that if angina is provoked by increased T4, then it is likely that the heart has been compromised already … perhaps by a chronic hypothyroid state over time. 
Notice that they are willing to admit that T3 therapy is theoretically a good option for these T4-sensitive people.
It was shocking to hear that “up to 15% of patients starting thyroxine [T4] therapy will sustain a myocardial infarction within two years.” It seems possible that those 15% of patients had hearts previously damaged by chronic hypothyroidism … or Low T3 syndrome … or perhaps during treatment, they became “thyrotoxic” to extremely high levels of T4.
This article is further analyzed in a later post: What we’ve known for 90 years regarding hypothyroidism and angina.

Leese, G. P., Jung, R. T., Guthrie, C., & Waugh, N. (1992). Morbidity in patients on l-thyroxine: a comparison of those with a normal TSH to those with a suppressed TSH. Clinical Endocrinology, 37(6), 500–503. http://doi.org/10.1111/j.1365-2265.1992.tb01480.x

Table 2: Rate of ischaemic heart disease (%) in thyroid population [1180 patients on thyroxine replacement] and general population according to age and sex

  • Age 45-64: Thyroid population (Female 2.7%, Male 6.4%); General population (Female 0.7%, Male 1.7%)
  • Age 65-74: Thyroid population (Female 2.6%, Male 6.7%); General population (Female 1.8%, Male 3.2%)
  • Age > 75: Thyroid population (Female 5.7%, Male 7.9%); General population (Female 3.6%, Male 4.6%)

Discussion

“Most of the patients on thyroxine replacement were female (90%) and of an older age group than the general population (75% over 50 years compared to 34% of the general population” (p. 502)

“In conclusion, patients under the age of 65 years on L-thyroxine [T4] had a higher incidence of ischaemic heart disease (IHD) than the general population.” (p. 502)

Review commentary by Healthy Researcher BlogIt frustrates me that hypothyroidism is still not asked about in standard risk assessments when a patient goes to Emergency with heart pain. If you happen to be younger than 65 and you’re healthy other than your thyroid (and your angina-like chest pain), then you might be classified as low-risk. but according to this article, especially if you are in your 40s, if you are on T4 thyroid treatment, you’re at significantly higher risk of heart disease than the general population in that age group.


Fowler, P. B. S., Ward, P. D., Alaghband-Zadeh, J., & Prentice, M. G. (1981). Management Of Angina And Hypothyroidism. British Medical Journal (Clinical Research Edition), 282(6282), 2135.

Quotes

“Reports of deaths from myocardial infarction or deterioration of angina in patients recently started on thyroid replacement treatment began to appear in the 1930s. Warnings were published of the dangers of too vigorous treatment of hypothyroidism and of the indiscriminate use of thyroid hormone, particularly in patients with chest pain. Forty years on, the problem persists: hypothyroidism is not infrequently associated with angina, and if coronary artery disease is present treatment with thyroid hormone, which increases the heart rate and stimulates myocardial contractility and oxygen consumption, will probably result in worsening of cardiac symptoms. This dilemma needs to be re-examined in the light of advances in the investigation and treatment of coronary artery disease and of improved methods of managing thyroid disease.” (p. 2135, italics added)

Hypothyroidism and angina are common conditions and may occur together coincidentally, but there is also a more direct association and hypothyroidism apparently predisposes to coronary artery disease.” (p. 2135, italics added)

“The dose of T4 can be increased cautiously by 25mcg increments to a maximum of 150mcg daily unless the severity of angina increases, when the dose will need to be reduced.” (p. 2135, italics added)

“Beta-blocking drugs such as propranolol are useful except in the presence of severe bradycardia. In addition to its antianginal action propranolol affects the biologically active thyroid hormone T3 by inhibiting deiodination of the prohormone T4.” (p. 2135, italics added)

“Occasionally anaemia associated with hypothyroidism may be a contributory factor, when cautious transfusion of red cells may help to alleviate the angina.” (p. 2135, italics added)

“Despite these measures, adequate replacement of T4 may be unattainable because of the severity of angina. Many patients have had to accept the unsatisfactory compromise of continuing hypothyroidism, with its attendant ill health, misery, and risk of neuropsychiatric disturbance.” (p. 2135, italics added)

Review commentary by Healthy Researcher Blog: See the long history of reports, since the 1930s, of angina and cardiac death on thyroid replacement.  This shows that even the T4 in Natural Dessicated Thyroid (pre-Synthroid pill) could be harmful to sensitive hearts.  However, it is frustrating that this article leaves these patients with an unsatisfactory compromise on T4-only treatment:  Either you have angina on a too high dose, or hypothyroid pathology on a too low dose.  Apparently they are unable to imagine the possibility of successful T3-only treatment.

References

  • Casella, F., Bossi, I., Pisano, G., & Montano, N. (2008). An atypical case of typical chest pain. Internal and Emergency Medicine, 3(4), 405–407. http://doi.org/10.1007/s11739-008-0156-9
  • Flynn, R. W., Bonellie, S. R., Jung, R. T., & MacDonald, T. M. (2010). Serum Thyroid-Stimulating Hormone Concentration and Morbidity from Cardiovascular Disease and Fractures in Patients on Long-Term Thyroxine Therapy. The Journal of Clinical Endocrinology & Metabolism, 95(1), 186–193.
  • Fowler, P. B. S., Ward, P. D., Alaghband-Zadeh, J., & Prentice, M. G. (1981). Management Of Angina And Hypothyroidism. British Medical Journal (Clinical Research Edition), 282(6282), 2135.
  • Hoshino, T., Aya, S., Yamazaki, H., et al. (1978). Akuter Myokardinfarkt bei einem jungeren Patienten mit Hypertyreose. Z Kardiol 67, 99-103.
  • Leese, G. P., Jung, R. T., Guthrie, C., & Waugh, N. (1992). Morbidity in patients on l-thyroxine: a comparison of those with a normal TSH to those with a suppressed TSH. Clinical Endocrinology, 37(6), 500–503. http://doi.org/10.1111/j.1365-2265.1992.tb01480.x
  • Levine, H. D. (1980). Compromise therapy in the patient with angina pectoris and hypothyroidism: A clinical assessment. The American Journal of Medicine, 69(3), 411–418. http://doi.org/10.1016/0002-9343(80)90013-3
  • Toft, A. D. (1994). Thyroxine therapy. The New England Journal of Medicine, 331(3), 174.
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