Adults may benefit from routine screening for hypothyroidism

An adult screening program for hypothyroidism may help relieve symptoms of the condition in approximately 1% of the population in the United Kingdom.

Researchers in the United Kingdom conducted a randomized, double blind, crossover trial involving healthy women aged 50 to 79 years (35 to 49 years with family history of thyroid disease) and healthy men aged 65 to 79 years who were seen at five wellness centers for general health assessments.

According to the study, 8% of the 4,365 patients seen at the centers had serum TSH levels exceeding 4 mU/L. Of 64 eligible patients who agreed to participate, 49 women and seven men completed the trial (mean age, 58 years). Baseline TSH values ranged from 4.1 mU/L to 9 mU/L.

Thyroxine vs. placebo

Participants began a 4-month treatment period with one 50-mcg daily dose of thyroxine. Researchers raised doses monthly to 75 mcg and 100 mcg (mean dose, 72 mcg daily) as necessary until patients reached target TSH ranges of 0.6 mU/L to 2 mU/L. Participants then began a 4-month course of treatment with placebo. At the conclusion of each period, participants were examined for physical symptoms of hypothyroidism, blood pressure, pulse rate and body weight. They also completed questionnaires on quality of life and psychological well-being.

Nearly three-quarters of the 15 participants with repeat TSH measurements exceeding 4.5 mU/L benefited from treatment with thyroxine. Eleven reported feeling better on thyroxine vs. placebo, whereas none reported improvement on placebo (P=.001). Eight of these participants also noted that more than one symptom was alleviated. Tiredness and memory loss were reported as the symptoms most commonly resolved by treatment.

Results also indicated that 41 participants had repeat TSH measurements of 4.5 mU/L or less. Of these, 10 felt better on thyroxine when compared with placebo, and 16 reported feeling better on placebo (P=.42). Fifteen felt no difference.

“These results confirm that symptomatic response to thyroxine is a necessary diagnostic criterion of hypothyroidism; serum concentration of TSH or other markers alone does not accurately identify affected individuals as assessed by a benefit from thyroxine treatment,” the researchers wrote.

James Haddow, MD, who wrote an accompanying editorial, said the study design was “particularly well suited to exploring mild thyroid deficiency because symptoms are nonspecific.

“Allowing each subject to be his or her own control bypassed variations in the background noise associated with these nonspecific symptoms,” he told Endocrine Today.

Haddow also noted that using healthy people who were being seen for general health evaluations allowed the researchers to determine if routine screening in healthy patients with slightly elevated TSH levels would be beneficial.

Looking ahead

In light of their findings, the researchers contended that an adult hypothyroidism screening program would be worthwhile. Moreover, they pointed out that such a program would be unique because “it aims to improve the quality of life rather than extending the duration of life.”

In his editorial, Haddow, who is co-director of the division of medical screening and special testing at Women and Infants Hospital in Providence, R.I., said “a next step” would be testing of pilot programs to gather more evidence on the benefits of routine screening.

“Given the health benefit, ease and low cost of treatment, and virtual absence of undesirable side-effects, this next step deserves serious consideration,” Haddow wrote.

Haddow, also said these results are easily applicable to the US population as well.

“Rates of thyroid deficiency are higher in women and increase with age in both the U.K. and the US,” he said. “Given the insight gained from this study, I would encourage similarly designed pilot studies in the United States to confirm and extend the existing study’s observations.” – by Melissa Foster

For more information:

• Abu-Helalah M. J Med Screen. 2010;17:164-169.
• Haddow J. J Med Screen. 2010;17:163.

Disclosures: Dr. Haddow receives funding from the CDC to conduct a model statewide trial to detect and treat maternal hypothyroidism in pregnancy.

Abu-Helalah et al have reported their results on the utility of screening for thyroid disease in adults and treating those with mild hypothyroidism. In a population attending periodic health assessments, they identified about 8% of the population as having an elevated TSH. Following appropriate exclusions, 110 individuals were invited to participate in the randomized intervention study. Using a statistically powerful placebo-controlled crossover approach, 64 consented individuals were randomized to receive either L-thyroxine (LT₄) or identical placebo capsules. Monthly TSH measurements were used to adjust treatment to a goal TSH of 0.6-2.0 mU/L. At the end of each 4-month therapy block, the subjects were assessed for thyroid function, thyroid-related symptom scores, quality of life (QOL) and general psychological well being (GHQ-30) before receiving the opposite treatment and being re-evaluated 4 months later.

The odds of feeling subjectively better while on L-thyroxine increased proportionally with the degree of baseline TSH elevation although the subjects who were treated based on a single TSH elevation were not shown to have a statistically significant improvement. The authors do report a significant reduction in the total serum cholesterol in this study cohort of 56 individuals who completed the trial. The subgroup of subjects with two abnormal TSH values documented prior to initiation of LT₄ (27% of the total randomized) clearly benefited from the LT₄ intervention with a 73% response rate and a more than a fourfold increase in the odds of feeling better. I was unable to access the web tables where I suspect the negative data on the GHQ-30 and SG-36 are likely reported.

This study has some potentially important observations. First, screening the adult population resulted in the identification of a reasonable number of subjects deriving direct benefit from the screening. Secondly, mildly elevated TSH values often are found to be in the expected normal range upon re-assessment and treatment with LT4 based on the single sample seems to result in no clear benefit. Thirdly, significant clinical improvement (albeit not in the harder end points of the SF-36, GHQ-30 or standard Zulewski scores) was demonstrated in those with confirmed hypothyroidism. The value of the cross over design highlights the lack of sensitivity and statistical power of several recent interventional studies using single TSH values for entry and parallel group design. The largest of these studies, one by Jorde et al and another by Parle et al, both published in The Journal of Clinical Endocrinology & Metabolism, seem to indicate that LT₄ has no impact on the well being of the sometimes selectively asymptomatic subjects who are then treated with LT₄ without apparent success.

Finally, I for one, feel reassured by these results. Although not the hard neuro-cognitive end points I would prefer, I feel better offering my patients with non-specific symptoms and confirmed TSH elevations LT₄ therapy and titrating to a low normal TSH end point.

– James V. Hennessy, MD
Director, Clinical Endocrinology
Beth Israel Deaconess Medical Center

Disclosure: Dr. Hennessy reports to relevant financial disclosures.

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