Thyroid Disorders
Table 1: Studies on Overt (OH) or Subclinical Hypothyroidism (H) and Outcome Compared with Euthyroid Controls Publication Population Type of Study Number Male/Female Age (Years)* TSH Cut-off Follow-up
Imaizumi et al.19
Parle et al.10 Japanese UK
Gussekloo Dutch et al.16
Van den Beld Dutch et al.17
Walsh et al.18
Cappola et al.11
Sgarbi et al.36
Razvi et al.13
Epidemiological 257 (H) with euthyroid controls
Epidemiological 94 (H) with euthyroid controls
96/61 2,293 (C) 15/79 1,026 (C)
Epidemiological 30 (H) with euthyroid controls
Epidemiological 6 (H) with euthyroid controls
189/369 472 (C) All males 459 (C)
Australian Epidemiological 119 (H) with euthyroid controls
US 51 (H) 37/82 1,906 (C) 994/912
Epidemiological 47 (OH) with euthyroid controls
Japanese– Epidemiological 99 (H) Brazilian
with euthyroid controls
UK
Epidemiological 97 (H) with euthyroid controls
913 (C) 21/30 175/321
2,639 (C) 1,096/1,543 36/63
444/469 23/74 2,279 (C) 1,096/1,183
58.5±12.3 56.4±12.4
49.9±17.9 45.3±15.8
58 49
>65 4.0 >10
>20 4.5
4.5 6-15 13 7 20 20
Death IHD**
Death IHD
>73 4.3 4 Death
M 62.7 F 60.8
Level (mU/l) (Years) 5
10 >10
M 70 (60–90) 5 F 71 (60–94)
85 4.8 ≥ 10 3
Outcome Result Measure
Death IHD**
Death Death RR 2.2 M
Not significant F RR 3.6 M 1.6 F Not significant
RR 0.77 p<0.009
Not significant***
Not significant RR 1.6 <10mU/L RR 2.6 >10 mU/L Not significant Not significant
Death**** RR 2.3 p<0.01
Death**** Not significant IHD death RR 1.8 p<0.5
*Mean and/or range. **No proof of association between subclinical hypothyroidism and cardiovascular death. ***Very small number and only males. ****All-cause mortality. C = euthyroid controls; F = female; H = subclinical hypothroidism; M = male; OH = overt hypothyroidism; RR = relative risk; TSH = thyroid-stimulating hormone.
combination of TSH–T4 could mean euthyroidism in one individual and subclinical hypothyroidism in another.6
These differences in
defining the condition are also part of the reason for the reported prevalence of subclinical hypothyroidism varying from 4 to 17% of a normal population.
Some of the above controversial issues are elegantly considered in an article by Beckett and MacKenzie,7 Weetman.8
accompanied by an editorial by
Their review of current guidelines highlighted another often overlooked reason for circumspection in using apparently precise TSH decision limits for treatment recommendations. As they pointed out, the reasons for having guidelines is to simplify and standardise treatment. The danger in simplification is obvious in that it fails to take the patient as an individual into account, as is frequently made clear in ripostes to the onslaught of evidence-based medicine. It also must be admitted that much evidence will never be gathered in areas of established clinical endocrinology practice, while in others such as the evidence supporting treatment of subclinical hypothyroidism, there are still surprising gaps and uncertainties6 that may for other reasons never be investigated in the full evidence-based manner (see below).
Cardiac Morbidity and Mortality in Subclinical Hypothyroidism
Although it is the general clinical impression that patients with overt hypothyroidism have increased cardiac morbidity and mortality, real evidence is scarce. More controversial is the morbidity and mortality when considering mild or subclinical hypothyroidism. Most available evidence is based on surrogate markers such as adverse lipid profile, endothelial dysfunction, increased arterial stiffness and cardiac performance.6,9
54
However, some population studies have provided a reasonable level of evidence for the mortality and cardiovascular morbidity rates in hypothyroidism (see Table 1). As seen in Table 1, the studies are widely different both in population selection, follow-up period and definition of the degree of thyroid dysfunction (by choice of TSH decision levels). The general picture from these studies is that of only a questionable or at best minor association between hypothyroidism and cardiovascular death, although many of them do find an association with cardiovascular risk. A large population study from the UK10
of a 10-year
follow-up of 1,191 persons in the community over 60 years of age described no association between raised serum TSH at screening and higher mortality, quite the opposite to persons with suppressed TSH. Similarly, the large cross-section Cardiovascular Health Study from the US including 3,678 subjects found no increased cardiovascular morbidity in those with subclinical hypothyroidism compared with those with normal TSH levels11 subjects from the Wickham study12
However, in a recent re-analysis of this cohort13
and the 20-year follow-up of 2,779 did not find such association either. with exclusion of
individuals with known thyroid disease or ischaemic heart disease and on medications that could affect thyroid function, the majority of participants at baseline were euthyroid (95.9%; mean age 45.3 years, range 18–92). The prevalence of subclinical hypothyroidism (between six and 15mU/litre) was 4.1% (mean age 49.9 years, range 18–87) and was higher in women, older individuals, non-smokers and those with positive thyroid antibodies. These patients had a higher mortality rate from ischaemic heart disease with a relative risk (RR) of approximately 1.8. Furthermore, in a cross-sectional study of 1,149 women aged 69±7.5 years from Rotterdam Hak et al.14
described an increased risk
for atherosclerosis and acute myocardial infarction (AMI) in subjects with subclinical hypothyroidism defined as serum TSH >4.0mU/litre and normal levels of T4 and T3, but there were no data on mortality.
EUROPEAN ENDOCRINOLOGY
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68