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Subclinical Hyperthyroidism: Features and Treatment: Endocrinology 35
Subclinical Hyperthyroidism: Features and Treatment: Endocrinology 35
Subclinical
hyperthyroidism:
features and treatment
Subclinical hyperthyroidism is an entity that is being increasingly recognised, probably because
of the ageing of the population and the development of assays with enhanced thyroid-stimulating
hormone sensitivity. It is characterised by a clearly low serum concentration of thyrotropin and
the absence of obvious symptoms of overt hyperthyroidism. In this two part article, Dr Nabil
Aly reviews the clinical features and treatment options in older adults.
S
ubclinical hyperthyroidism is defined as a level of TSH suppression that determines these
normal serum free thyroxin (T4) and free negative effects, and the management and treatment
triiodothyronine (T3) levels with a thyroid- of this condition remain controversial issues3,4. In fact,
stimulating hormone (TSH) level suppressed below although in the normal reference range, serum thyroid
the normal range and usually undetectable. It has hormones (FT3 and FT4) would be increased for the
many relevant effects on the cardiovascular system individual with low or undetectable serum TSH levels,
and predominantly depletes skeletal sites that are thus determining a mild tissue hyperthyroidism.
rich in cortical bone. Consistent evidence indicates Indeed, the reference ranges for individual test results
that ‘subclinical’ hyperthyroidism reduces the over a period of 12 months were narrower than the
quality of life, affecting both the psychological and group reference ranges on which laboratory reference
somatic components of well-being, and produces ranges are based5.
relevant signs and symptoms of excessive thyroid
hormone action, often mimicking adrenergic Accordingly, conventional population-based
overactivity1. In addition, it is becoming increasingly reference intervals for thyroid function tests may not
apparent that subclinical hyperthyroidism may identify values that are outside the normal range for
accelerate the development of osteoporosis and the individual being tested1. The pituitary gland is
DR NABIL ALY is a consultant physician at
hence increased bone vulnerability to trauma, sensitive to minor changes in serum thyroid hormone
particularly in postmenopausal women with a pre- levels, and serum TSH responds with logarithmically
existing predisposition. Subclinical hyperthyroidism amplified variations to such changes1,6. Therefore, the
University Hospital Aintree, Liverpool
and its related clinical manifestations are reversible distinction between subclinical and overt
or may be prevented by timely treatment. hyperthyroidism, which is based on the population-
based reference range for thyroid hormone levels, is
somewhat arbitrary and diagnosis depends on the
Definition position of the patient’s set point for thyroid hormones
The definition of subclinical hyperthyroidism is based within the laboratory reference range. The view that
only on laboratory, not clinical, criteria and the term individuals with an undetectable serum TSH level
probably represents a misnomer2. Subclinical suffer from a mild form of tissue hyperthyroidism is
hyperthyroidism is characterised by a low or supported by the finding of relevant changes in several
undetectable concentration of serum thyrotropin cardiovascular measures and in bone structure and
(TSH) with free triiodothyronine (FT3) and free metabolism in these individuals1. Importantly, these
thyroxin (FT4) levels within laboratory reference changes significantly impair quality of life and,
ranges. Although there is evidence that subclinical especially in the elderly, greatly increase the risk of
hyperthyroidism may have adverse tissue effects, the cardiovascular morbidity and mortality, and of bone
• Multi-nodular goitre
Key points
Cardiovascular effects
The cardiovascular risk of subclinical • Subclinical hyperthyroidism is characterised by
hyperthyroidism is related to short-term effects due low serum concentration of TSH and the absence
to the electrophysiological effects of thyroid of obvious symptoms of hyperthyroidism.
• Excessive TSH-suppressive therapy with
hormones, and to long-term effects resulting from
levothyroxin for benign thyroid nodular disease or
increased left ventricular mass and increased cardiac differentiated thyroid cancer, or hormone over-
workload (Table 2). In most studies, patients with replacement in patients with hypothyroidism is the
subclinical hyperthyroidism, whether exogenous or most frequent causes.
endogenous, have tachcardia and increased • It can produce relevant signs and symptoms
prevalence of supraventricular arrhythmias, as of excessive thyroid hormone action, often
mimicking adrenergic overdrive.
assessed by 24-hour electrocardiographic
monitoring1. Subclinical hyperthyroidism may
precipitate re-entrant atrioventricular nodal hyperthyroidism, the prevalence of atrial fibrillation
tachycardia in individuals with a shorter P–R was increased to a similar degree in older people
interval28. In addition, data from a 10-year follow-up with overt and subclinical hyperthyroidism30 : 2.3 per
study of elderly patients with endogenous or cent in euthyroid subjects, 13.8 per cent in patients
exogenous subclinical hyperthyroidism indicate this with overt hyperthyroidism and 12.7 per cent in
disorder is associated with a threefold higher patients with subclinical hyperthyroidism. The
incidence of atrial fibrillation compared with relative risk of atrial fibrillation was 5.8 and 5.2
euthyroid healthy subjects29. respectively compared with euthyroid subjects30.
Moreover, subclinical hyperthyroidism was found to
Similarly, in a retrospective study of 1,338 be an independent risk factor for atrial fibrillation in
consecutive subjects with endogenous subclinical patients with other pre-existing cardiac risk factors
40 Endocrinology
References
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The most consistent cardiac abnormality nodular disease, differentiated thyroid cancer, or
reported in patients with exogenous and endogenous hormone over-replacement in patients with
subclinical hyperthyroidism, regardless of the hypothyroidism is the most frequent causes.
underlying aetiology, is a significant increase in left Consistent evidence indicates that subclinical
ventricular mass, with unchanged or increased at- hyperthyroidism reduces the quality of life, affecting
rest systolic function, and usually impaired diastolic both the psychological and somatic components of
function that is mainly due to slowed ventricular well-being, and produces relevant signs and symptoms
relaxation1. The mechanism responsible for the of excessive thyroid hormone action, often mimicking
increased left ventricular mass and diastolic adrenergic over-activity. Subclinical hyperthyroidism
dysfunction in both exogenous and endogenous exerts many significant effects on the cardiovascular
subclinical hyperthyroidism is unclear1. All the system and the resulting abnormalities are potentially
cardiac abnormalities mentioned might play a role in contributing to the increased cardiovascular
determining the increased cardiovascular mortality morbidity and mortality observed in these patients.
and morbidity in elderly patients with subclinical
hyperthyroidism1. The second part of this article in the November
edition will look at the effects on osteoporosis and
increased bone vulnerability to trauma.
Conclusion
Subclinical hyperthyroidism is a fairly common Conflict of interest: none declared.