Thyroid: III Thyroid Pathophysiology
Mrs JA, a 41-year-old part-time nurse
presented to her GP with a 6-month history of weight loss of 10 kg. On
questioning she was eating well but complained of diarrhoea. She had also
noticed that she felt exhausted and had developed insomnia. On further
questioning she admitted to feeling increasingly hot and shaky and to having
muscle weakness of the legs, particularly climbing stairs. She was normally
well and had not seen the doctor since her last pregnancy 8 years before. A
blood test showed the following results: free T4 49.7 pmol/L; total
T4 225 nmol/L; TSH <0.01 mU/L.
She was referred to an endocrinologist
at the local hospital where initial investigations confirmed a diagnosis of
Graves’ disease. She was treated with carbimazole and propranolol for the first
month of treatment followed by carbimazole alone. Subsequently, after
discussing the therapeutic options, she opted to have 131I therapy
which was given as an outpatient when she had become euthyroid. She was
followed up at regular outpatient visits and 6 months later complained of
lethargy, weight gain and feeling cold all the time. Clinically she had
features of hypothyroidism and blood tests were as follows: free T4
crinologist commenced thyroid hormone
replacement therapy and 3 months later she was well and her blood tests were
normal.
Introduction
There are a number of causes of
hyperthyroidism but over 90% of cases are accounted for by autoimmune thyrotoxicosis
(Graves’ disease, approximately 75%), toxic multinodular goitre (approximately
15%) and solitary toxic adenoma (approximately 5%). Transient thyrotoxicosis
may be associ- ated with thyroiditis and certain drugs may be responsible,
particularly amiodarone. Very rarely patients present with thy- rotoxicosis
secondary to TSH-secreting tumours of the pitui- tary, pituitary thyroid
hormone resistance syndrome, extrathy- roidal hormone excess or secondary to
thyroid carcinoma.
Clinically, the features of
thyrotoxicosis may be divided into those caused by thyroid hormone excess and
seen in all cases of hyperthyroidism and those associated with autoim- munity
and seen in patients with Graves’ disease only (Fig. 15a and b; Table 15.1).
Treatment is either with antithyroid drugs (alone or in combination with
thyroxine replacement therapy), radioactive iodine ablation using 131I or
surgery. Choice of treatment depends on the underlying cause and may be
influenced by the patient’s age, other coexisting disease, particularly in the
elderly, or the presence of thyroid-associated ophthalmopathy.
Thyroid Function Tests
Thyroid hormone measurement
Only about 1% of thyroid hormones are
in the metabolically active ‘free’ state as both T4 and T3
are tightly bound to trans- port proteins in the plasma (Chapter 13). Assays of
‘total’ T4 or T3 measure mainly the protein-bound
hormone. This may be affected in a number of ways by conditions affecting
protein concentration. Thus spuriously high total T4 measurements
will occur in pregnancy and in women taking the oral contraceptive pill as
estrogen increases thyroxine binding globulin (TBG) synthesis. Inappropriately
low measurements may be found in individuals with congenital TBG deficiency or
severe liver disease.
Assays of ‘free’ thyroid hormones are
now widely available and are not generally affected by changes in plasma
binding protein concentrations.
Thyroid stimulating hormone
measurement Measurement of TSH is
the most widely used thyroid function test. It is less subject to assay
interference and reliably predicts thyroid function in accordance with the
principles of negative feedback. Thus in hyperthyroidism the TSH concentration
is undetectable. In primary hypothyroidism, TSH concentrations are elevated and
in secondary hypothyroidism the low free T4 level is accompanied by low TSH
concentrations.
Other biochemical tests of thyroid
function, such as TRH tests, have been used only rarely since the advent of
highly sensitive TSH assays.
Thyroid imaging
Biochemical tests of thyroid function
may be supplemented by imaging techniques to investigate thyroid structure and
function:
1. Thyroid ultrasonography will reveal the presence of single or multiple
nodules and cysts. Needle aspiration for cytology or cyst drainage and thyroid
biopsy may be conducted under ultrasound control.
2. Thyroid scintigraphy or radionuclide imaging is helpful in the
diagnosis of thyroiditis, when isotope uptake is greatly diminished in contrast
to the uniform increase seen in thyrotoxicosis. A clinically solitary nodule
may be revealed as a ‘cold’ nodule on scanning, requiring further investigation
for possible malignant disease.
Thyroid cancer
Thyroid cancer usually presents as a
swelling in the thyroid gland. It is a relatively rare malignancy and the
majority of thyroid nodules will prove to be benign. Investigations include
fineneedle aspiration cytology, with or without thyroid scintigraphy. Most
malignancies are papillary carcinomas; other tumours include the more
aggressive follicular carcinomas and rapidly progressive anaplastic lesions.
Medullary thyroid carcinomas arising in thyroid C cells may be found in
isolation or as part of the MEN 2 syndrome (see Chapter 50).
