ANALYSIS AND COMMENTARY • • • • • •

The authors surmised that the decreases in thyroid-related mortality they found were likely due to improvements in the treatment of the thyroid conditions—stating that they were not aware of any evidence that the incidence of these thyroid conditions has declined over time; or that physicians have come to believe that fewer patients are dying from these disorders, but rather that the patients are merely dying with them; or that there was increasing reluctance to list these diseases as a cause of death.

We note that the marked improvement in the TSH assay over the period studied has made it embarrassingly clear that our record of maintaining a patient’s TSH within the normal range is often less-than-perfect. When completing a death certificate, it is easy to overlook an earlier thyroid disorder if the thyroid function tests were normal at the time the patient died. True, there is evidence the therapy used to treat certain forms of hyperthyroidism has recently undergone change (1), but shifts in racial/ethnic make-up, dietary iodine levels (2) and smoking incidence (3) have been documented in the UK, and newer drugs like amiodarone may also have altered the incidence and/or severity of several causes of hyperthyroidism and/or hypothyroidism. Better assays for TSH and TSH-receptor antibodies were introduced, which have helped physicians recognize and treat more subtle diseases, like silent thyroiditis, and hyper- and hypothyroidism in elderly patients, who often lack classical symptoms. These improved assays have also instigated growing concern about morbidity and mortality in so-called subclinical hyperthyroidism and hypothyroidism. Finally, one should note that patients with autoimmune diatheses underlying Graves’ and Hashimoto’s disease can suffer later mortality due to “unrelated” autoimmune diseases.

Therefore, it might be more credible to ascribe at least some of the decrease in mortality to advances in the care of common disorders like pneumonia, dementia, hypertension, chronic ischemic heart disease, atrial fibrillation and heart failure. This would seem to be consistent with the authors’ finding that total mentions of hyperthyroidism decreased the most in the 65-74 age group, in which these diseases may prove fatal. Disregarding the possible effects of thyroid disorders on pre-existing conditions, it is clear that thyroid disorders also can predispose to new medical conditions. Despite some methodological drawbacks, an increasing number of papers indicate that hyperthyroidism and hypothyroidism are associated with an increased risk of mortality, independent of any medical conditions present before the thyroid disorder was diagnosed (4,5). (The association between thyroid disorders and cardiovascular deaths seems to be more well-recognized, thus far, than deaths from osteoporotic hip fractures).

It is striking that less than 1% of patients with a diagnosis of hyperthyroidism or hypothyroidism have that diagnosis listed on their death certificates. (In the United Kingdom, the 2010 death rate was about 5 per 1000 for women and 7 per 1000 in men. A rough estimate of the annual incidence of primary hypothyroidism in women is about 4 per 1000 per year in surviving women and about 0.6 per 1000 in surviving men. The annual incidence of hyperthyroidism is about 1 per 1000 in women and 0. 15 per 1000 in men). The death certificates, on the other hand, mentioned hypothyroidism in only about 0.02 per 1000 women and 0.01 per 1000 in men , and mentioned hyperthyroidism in only about 0.004 per 1000 women and 0.001 per 1000 in men. Interestingly, the mortality rates for women were only 3 times those for men, although their prevalence in women is closer to 10-to-1. Despite the infrequency with which these disorders were mentioned in death records, a substantial fraction of patients with these thyroid diagnoses can have associated comorbidities, and presumably some die because of them. It is also striking that in the 2001–2010 period, 17% of the death certificates that mentioned hypothyroidism actually gave it as the underlying cause of death, and almost a quarter of all certificates that mentioned hyperthyroidism gave it as the underlying cause of death. This fraction of thyroid disorders as the direct cause of death, rather than as associated causes, seems high. What are the reasons for a physician to attribute a death directly to one of these thyroid conditions? An obvious reason would be deaths connected with thyroid storm/crisis or myxedema coma, but these are rare. Another reason could be fatal complications from treatment for the thyroid disorders (although the appropriate coding probably would fall under complications of surgery or of side effects of drugs or of radioiodine administration, while the thyroid disorder would probably be listed as an associated cause).

Unfortunately, death certificates cannot be used to determine the length of time between when the initial diagnosis of a thyroid disorder was made and the time death occurred, what therapies were given, or any associated laboratory or clinical information. Although concerns about privacy remain, the introduction of universal medical records would make it possible someday to devise guidelines for when thyroid disorders should be included on a death certificate as a possible associated cause. Should an associated thyroid disorder be included for all deaths from pneumonia, dementia, hypertension, chronic ischemic heart disease, atrial fibrillation and heart failure? Probably yes, if the death occurred within the first year after the thyroid disorder was diagnosed. But what about a patient who died of chronic ischemic heart disease at age 85 after having been “adequately treated” for hypothyroidism for 30 years? What if the hypothyroidism was due to ¹³¹I therapy for Graves’ disease: shouldn’t hyperthyroidism also be included on the death certificate?

References

1. Turner M, Driver I, Salotti JA, Pearce MS, Cheetham T. Increasing use of radioiodine in young people with thyrotoxicosis in Great Britain. Eur J Endocrinol 2013 e-pub before print September 6, 2012, doi: 10.1530/EJE-12-0542.
2. Vanderpump MPJ. Commentary: Iodine deficiency as a new challenge for industrialized countries: a UK perspective. Int J Epidemiol. 2012;41:601–604.
3. Ikuko F, Funatogawa T, Yano E. Impacts of early smoking initiation: long-term trends of lung cancer mortality and smoking initiation from repeated cross-sectional surveys in Great Britain. BMJ Open 2012;2:e001676. DOI:10.1136/bmjopen-2012-001676.
4. Spaulding SW. How Important Are Preexisting Comorbidities and Genetic Proclivities in Explaining the Increased Risk of Mortality in Hyperthyroidism. 2013. Clin Thyroidol 2013;25:37–39.
5. Thvilum M., Brandt F, Almind D, Christensen K, Hegedüs L., Brix TH. Excess Mortality in Patients Diagnosed With Hypothyroidism: A Nationwide Cohort Study of Singletons and Twins. J Clin Endocrinol Metab 2013. Published online, doi: 10.1210/jc.2012-3375.