SA JOURNAL OF DIABETES & VASCULAR DISEASE
REVIEW
VOLUME 8 NUMBER 1 • MARCH 2011
17
Intervention strategies for thyroid disorders
Among the intervention strategies for hyperthyroidism,
conventional treatment modalities include antithyroid drugs,
radio-iodine or surgery. Hypothyroidism is conventionally treated
with replacement doses of levothyroxine. As regards sub-clinical
forms of both conditions, due to the paucity of conclusive data
derived from clinical trials, evidence-based recommendations are
cautious and sometimes not conclusive when TSH levels are slightly
deranged.
42
Individualisation of therapy is most probably the answer
in these patients. The presence of several cardiovascular risk factors
in diabetic patients with sub-clinical thyroid impairment should be
taken into consideration for therapeutic purposes.
Some special situations must be considered with regard to the
pharmacological aspects of the drugs commonly used to treat
diabetic and thyroid patients. It has been reported that certain
sulphonylureas can inhibit the synthesis of thyroid hormone. They
include older-generation drugs such as carbutamide, tolbutamide,
methahexamide, and possibly chlorpropamide.
43
Moreover, met-
formin has been shown to reduce thyrotropin levels in diabetic
patients with primary hypothyroidism on thyroxine replacement
therapy.
44
Thiazolidinediones, on the other hand, have been
reported to induce thyroid-associated orbitopathy.
45
Another
situation in which to apply caution is with the use of statins in
diabetes. Myopathy can be much more common in statin-treated
diabetic patients with undiagnosed hypothyroidism.
46
Thyroid hormone analogues are still under development. They
retain some of the beneficial aspects of thyroid action on liver,
fat and muscle while sparing the detrimental effects of thyroid
hormones on the heart.
47
Some of these compounds have been
shown to lower glucose levels in mice and are promising treatment
modalities for diabetes.
48
Diabetes plus thyroid disorders: long-term mortality
or morbidity
As previously mentioned, sub-clinical hypothyroidism and
hyperthyroidism have both been linked to increased cardiovascular
risk.
49
Only a few studies have explored the effects of sub-clinical
thyroid dysfunction in the diabetic population. One of these studies
was performed in 588 Taiwanese type 2 diabetic patients with sub-
clinical hypothyroidism compared with euthyroid patients. In the
cross-sectional analysis, sub-clinical hypothyroidism was associated
with a higher frequency of nephropathy (after adjustment for,
among other factors, age, gender and HbA
1C
). After four years,
sub-clinical hypothyroidism was associated with a higher rate of
incident cardiovascular events in patients with type 2 diabetes,
although this became non-significant after additional adjustment
for urinary albumin:creatinine ratio.
50
In line with these findings are
the results of another cross-sectional study of 1 170 type 2 diabetic
patients.
51
Patients with sub-clinical hypothyroidism had a higher
prevalence of retinopathy, especially the sight-threatening form,
when compared with their type 2 diabetic euthyroid counterparts.
51
Mortality has been explored in 382 women with type 2 diabetes
belonging to the Fremantle Disease Study, which has a follow-up of
nine years. Only a borderline significance for the effect of serum TSH
status on all-cause and cardiac mortality was observed in the lowest
serum TSH category.
12
This study was included in a meta-analysis
by Haentjens
et al
.
52
which reported that compared with euthyroid
control subjects, sub-clinical hyperthyroidism yielded a significant
1.49-fold increase in relative likelihood of death from all causes. In
the general calculation, global mortality was not increased in sub-
clinical hypothyroidism. However, after the analysis was stratified by
studies with patients with co-morbidities (atomic bomb survivors,
type 2 diabetes, cardiac, stroke, or hip-fracture patients) all-cause
mortality was significantly higher than in the euthyroid population.
On the other hand, a retrospective analysis of a diabetes database
of 6,540 patients showed a lower mortality rate in patients with
elevated TSH levels at baseline (mean age of patients was 73 years)
versus an age-matched euthyroid group.
53
These results support
the previous notion that the higher mortality risk in a sub-clinical
hypothyroid patient is mainly observed in patients below 65 years
of age.
54,55
Conclusions
The impact of thyroid alterations on glucose metabolism has
been known for a long time. Thyrotoxic patients usually lose their
glucose control when thyroid decompensation is not promptly
solved. Most recently, new pathways of thyroid hormone action at
the tissue level have been unveiled and may be of relevance to the
understanding of insulin resistance present both in the hypothyroid
and hyperthyroid state.
While thyroid disorders are more prevalent in people with type 1
diabetes, due to common autoimmune origin, a similar prevalence
of thyroid disease has been reported in type 2 diabetes. On the
other hand, a much higher frequency of sub-clinical hypothyroidism
has been reported in metabolic syndrome patients. These findings
are not surprising since several metabolic syndrome traits are
associated with hypothyroidism.
The co-existence of both diabetes and thyroid disorders has
been associated with increased long-term morbidity and mortality.
Although the benefits of treating overt thyroid disease are clear,
the management of sub-clinical hypothyroidism or hyperthyroidism
is not yet solved and conclusive intervention studies are required. It
has been suggested that the decision to treat should be taken on an
individual approach. In this case, insulin-resistant, dyslipidaemic or
diabetic patients, who are at higher risk of cardiovascular disease,
might be special cases for whom treatment of sub-clinical thyroid
disease has to be seriously considered.
Key messages
•
In diabetes mellitus, the development of thyrotoxicosis
is associated with deranged metabolic control, increased
insulin requirements and ketoacidosis
•
Insulin resistance is evident in overt and sub-clinical
hypothyroidism
•
Prevalence of AITD
– is higher in type 1 diabetes
– is similar in the general population and type 2 diabetes
•
In type 2 diabetes
– AIDT increases cardiovascular risk
– concomitant sub-clinical hypothyroidism increases risk of
nephropathy and retinopathy
