Table 4.

Studies that estimated presence of symptoms in groups of subjects with overt and/or subclinical hypothyroidism compared to euthyroid subjects

Reference	Place	Sample	Age of participants	Symptoms	Frequency of symptoms
Cooper et al45 randomized clinical trial	US	14 receiving thyroxine and twelve receiving placebo	Mean age 55 years old	Symptoms of hypothyroidism	Symptoms improved in 57.1% in the active group and 25% in the placebo group; P < 0.05
Canaris et al44 cross-sectional	US	76 cases and 147 controls	Mean age 44.4 years (cases) and 45.8 years (controls) Range 19–86 years	Hoarse voice, deep voice, dry skin, coarse hair, cold sensitivity, tiredness, presence of puffy eyes, muscle cramps, muscle weakness, constipation, depression, slow thinking, poor memory, difficult for math, irregular menses, heavy menses	Hypothyroid: 30.2% Control: 16.5%; P < 0.0001 More frequent symptoms in hypothyroid patients: hoarse voice, dry skin, muscle cramps
Bemben et al (Part 2)46 retrospective	US	205 women and 78 men; 15.4% of men and 14.6% of women with subclinical hypothyroidism	≥60 years Range: 60–97 years	Clinical symptoms of hypothyroidism	No significant difference in the frequency of symptoms in subjects with subclinical hypothyroidism compared to subjects with normal thyroid function
Kong et al47 clinical trial	United Kingdom	Only women: 23 in the thyroxine group and 17 in placebo group	Mean age thyroxine group 53 (3) years; mean age in the placebo group 45 (4) years	Fatigue, weight gain, anxiety symptoms	Only a significant worsening of anxiety scores in the group receiving L-thyroxine
Engum et al48 cross-sectional	Norway	30,589 people; 745 men and women with subclinical hypothyroidism	40–89 years	Hospital Anxiety and Depression Scale	No association found between anxiety and depression symptoms and subclinical hypothyroidism
Grabe et al49 cross-sectional	Germany	3790, 18 cases of overt hypothyroidism, and 27 of subclinical hypothyroidism	Mean age overt hypothyroidism group 52.1 (14.2); mean age subclinical hypothyroidism group 51.9 (12.5); mean age euthyroid group 59.2 (46.9)	Zerrssen Complaint Scale	No difference in the number of symptoms and complaints in subjects with overt and subclinical hypothyroidism compared to euthyroid controls
Jorde et al50 clinical trial	Norway	36 subjects with subclinical hypothyroidism, and 33 controls	Mean age intervention group 61.6 ± 11.5 years; mean age placebo group 63 ± 12.4 years	14 tests of cognitive function, Beck Depression Inventory, General Health Questionnaire, questionnaire about symptoms of hypothyroidism	After 1 year of thyroxin there is no difference in the performance of cognitive tests, Beck Depression Inventory and in the frequency of hypothyroidism symptoms between the two groups; subjects with subclinical hypothyroidism scored significantly better than controls on the GHQ-30