Between July 1991 and December 1995, 76 case patients with newly diagnosed hypothyroidism and 147 control patients were enrolled. One case patient was enrolled into the study for approximately every 10 potential case patients recruited in Colorado, though this varied by institution. In Michigan, one case patient was enrolled for about every 14 potential case patients, also identified on the basis of having had thyroid function tests ordered. The exact number excluded for each criterion is unknown because exclusions occurred both through the laboratory and through the investigators. The above estimates of enrollment were made according to the mean number of all elevated T SH levels reported by each laboratory. Many thyroid function tests were ordered on patients for reasons other than suspected new hypothyroidism, accounting for our low “enrollment rate.” When subsequent interview or chart review excluded potential enrollees, this was most often because thyroid function tests had been ordered to monitor thyroid hormone replacement in known hypothyroid patients.
Among the 76 case patients, 36 were enrolled from Colorado and 40 from Michigan. Fifty-four (71.0%) were women. Age ranged from 20 to 85 years, and the mean age was 44.4 years. Of the 71 respondents to the question of family history, 30 (42.2%) reported at least one family member with thyroid illness (). Among the 147 control patients enrolled proportionately from the Colorado and Michigan hospitals, 104 (70.7%) were women. The mean age of the control group was 45.8 years (range 19–86 years), and 24 (16.8%) of 143 respondents reported a family history of thyroid disease. Case and control patients differed demographically in the reported family history and, as would be expected, in the mean TSH level (). The T4 levels were not compared statistically, as approximately half of the samples were tested by total T4 assay, while the other half were tested by free T4 according to the policies of the individual laboratories.
Case patients reported higher percentages of total positive hypothyroid responses than did controls (30.2% vs 16.5%, p < .0001). When positive symptoms were split according to severity, the difference between case and control patients in the percentage of reported symptoms remained significant regardless of level 4 or level 5 severity (). The number of symptoms correlated weakly with TSH (r = .35, p < .0001), showing increasing numbers of reported symptoms with decreasing thyroid function.
Univariate analysis showed that three “current” symptoms differed significantly between case and control subjects: hoarse voice, dry skin, and muscle cramps (). Among the “changed” symptoms, a hoarser voice, deeper voice, drier skin, feeling colder, feeling more tired, having puffier eyes, more muscle cramps, weaker muscles, more constipation, feeling more depressed, slower thinking, poorer memory, and having more difficulty with math were significant (p < .05) (). In general, the proportion of hypothyroid patients reporting individual symptoms was low. However, some symptoms were reported in very low percentages among the euthyroid group, such as having a hoarse voice.
Current Symptoms of Hypothyroidism
Changed Symptoms of Hypothyroidism
Symptoms were entered into conditional stepwise logistic regression analysis. Two current symptoms, hoarse voice and muscle cramps, were significant in both univariate and multivariate analysis. Of the 13 changed symptoms, only 2 remained significant in multivariate analysis: puffier eyes and being constipated more often.
In ROC analysis the area under the curve was equal to 0.72 when using the 13 changed symptoms, and 0.66 when using only the three current symptoms. When the numbers of changed symptoms were grouped, control patients reported zero, one, or two symptoms significantly more often, while case patients reported seven or more symptoms more often ().
Proportion of case and control patients reporting “changed” symptoms.
Likelihood ratios were reported for all individual symptoms ( and ), and increasing numbers of univariately significant symptoms ( and increasing numbers of univariately significant symptoms (). The LRs were small for many individual symptoms, corresponding to small changes in disease likelihood. When the number of symptoms was evaluated, the LR associated with no reported symptoms was 0.5, suggesting a somewhat greater likelihood of being euthyroid. Likelihood ratios had greater impact when patients reported more symptoms. Specifically, patients reporting seven or more changed symptoms were much more likely to be hypothyroid (LR = 8.7; 95% CI 3.8, 20.2).
Number of Symptoms Reported by Case and Control Patients