SA JOURNAL OF DIABETES & VASCULAR DISEASE
DRUG TRENDS
VOLUME 10 NUMBER 2 • JUNE 2013
67
Aim for tighter control in hypothyroid disorders
Priority patients requiring treatment for
their subclinical hypothyroidism
• Symptomatic patients under 65 years, with
TSH levels of 4-10mU/L
• Asymptomatic patients, under 65 years, with
TSH of 4-10mU/L and high antibody levels
• Pregnant patients or those wishing to fall preg-
nant, are infertile or have ovulatory dysfunction
The evidence to treat patients over the age of 65
is not clear
Key messages
Aim for tighter control of hypothyroid
•
disorders
Get TSH levels to target, titrating
•
therapy as required
Make therapy as convenient for the
•
patient as possible
W
hen it comes to the management of
hypothyroid disorders, it’s important
to aim for tighter control and to get thyroid-
stimulating hormone (TSH) levels to target.
This is the message conveyed by Dr Sindeep
Bhana, a Johannesburg endocrinologist who
works in the public sector. He was speaking
at the Johannesburg launch of Abbott
Laboratories’ Synthroid, a new levothyroxine
sodium formulation that gives healthcare
professionals an additional option for the
treatment of hypothyroidism.
The thyroid gland may be a small organ
but it drives the entire body’s metabolism,
affecting
inter alia
carbohydrate, protein,
lipid and bone metabolism, cardiovascular
and cognitive function as well as fertility,
among many other functions.
Hypothyroidism affects 5-10% of elderly
women in some studies. Predisposing
factors include age, female gender, subacute
lymphocytic thyroiditis and Turner’s disease.
Chronic autoimmune thyroiditis is the
commonest cause of hypothyroidism, but
the following are a few other causes:
Thyroidectomy
•
Radioactive iodine treatment
•
Iodine therapy, including amiodarone
•
External radiation therapy
•
Infiltrative causes (although these are
•
rare)
Enzyme defects
•
Hypothalamic and pituitary pathology are
secondary causes of hypothyroidism.
“Treatment requires the use of levothyrox-
ine with the aim of restoring the metabolic
state,” says Dr Bhana. “The dosage can vary
from 25 to 300 micrograms, but the average
is 112 micrograms. It’s important to remem-
ber, however, that patients are not average
and that we need to titrate according to
individual patient needs. The optimal dose
depends on clinical criteria and a very narrow
TSH band. TSH levels need to be measured
six-weekly until they fall within the normal
range and thereafter six-monthly.
“Where secondary causes are involved,
we need to look at T4 levels alone and aim
for the upper third of normal.”
When individualising treatment, various
factors need to be taken into account, includ-
ing age, weight, race, underlying cardiovas-
cular health and other co-morbidities. There
are various levothyroxine formulations on
the market to choose from. “With elderly
patients, start with a low dose of 25 micro-
grams and double that every 3-4 weeks until
TSH levels normalise, as increasing the meta-
bolic rate too quickly, with higher doses of
thyroxine, may precipitate an infarct,” says
Dr Bhana.
A number of factors may increase lev-
othyroxine requirements. These include preg-
nancy, small bowel disease, drugs and dietary
supplements that reduce absorption, drugs
that increase metabolism and drugs that
reduce T4 to T3 conversion. “It’s important
to be aware of drug interactions, particularly
with those used for treating upper gastroin-
testinal tract symptoms,” cautions Dr Bhana.
He advises doctors not to swap patients
from one product to another if the TSH levels
are within a tight range. “If a patient is well
controlled on a specific product, stay with it.”
Dr Bhana describes subclinical hypo-
thyroidism (SH) as a ‘whole new ballgame’,
characterised by a TSH level up to 10, in the
presence of a normal T4 level. The condition is
more common in women than in men. Type 1
diabetes is also a predisposing factor. Its aeti-
ology is usually autoimmune, but it can occur
post ablative therapy for hyperthyroidism or
be the result of surgery. Most commonly,
as the Colorado study showed, inadequate
replacement therapy is the aetiology. “Some
37% of patients with hypothyroidism are not
receiving adequate or appropriate replace-
ment therapy, and in this context swapping
products may allow us to address matters.”
If SH is untreated, there is the likelihood
of the condition progressing to overt hypo-
thyroidism. Different studies show different
progression rates, and population and iodine
status evidently matter. Dr Bhana feels that
most of the randomised controlled trials were
not adequately designed to answer the gaps
in this field. “In treating SH, we see mixed
outcomes with regard to echocardiogram
parameters. And while T4 replacement has
been associated with improved endothelial
function and increased intima media func-
tion, there were no significant changes in
other measures of cardiovascular function.”
SH is associated with weight gain, as
shown in the Rotterdam study. It also poses
risks in pregnancy and fertility by increasing
the possibility of miscarriage, preterm birth,
poor developmental outcomes and ovulatory
dysfunction.
Summarising the management of hypo-
thyroidism, Dr Bhana observes that while
various guidelines are not in total agreement,
the following is generally accepted. Treat
symptomatic patients under 65 who have
TSH levels of 4-10 mU/l; treat asymptomatic
patients under 65 who have TSH levels of
4-10 mU/l and have high antibody levels;
treat patients who are pregnant, who wish to
fall pregnant, are infertile or have ovulatory
dysfunction. But the evidence to treat patients
over the age of 65 is not clear.
The goal is to aim for TSH target levels in
normal range – 0.5-2.5 in younger patients,
3-5 in the elderly. There are three levothy-
roxine brands now available in South Africa
– the first comes in dosages of 50 and 100
micrograms (not scored), the second in dos-
ages of 25, 50 and 100 micrograms (scored).
The third – the newly launched Synthroid –
comes in five doses, viz. 25, 50, 88, 100 and
112 micrograms (partially scored and colour
coded). “If patients are well controlled and
symptom free, don’t change brands,” advises
Dr Bhana. “However, 60% of patients suf-
fering from thyroid conditions are not, and
we now have more options. Make the dose
as convenient as possible and titrate until
normal levels are reached.”
Synthroid is a levothyroxine sodium formula-
tion available in 14 dosages in the USA. The
five dosages now available in South Africa
were chosen by local key opinion leaders and
give healthcare professionals more options for
titration. “Our aim is to simplify treatment and
make it more accessible,” says product man-
ager Ntebeng Ramushi. “The 88 microgram
dose especially has become very popular.”
P Wagenaar, Gauteng correspondent
