Thyroid Gland Disorders

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Multinodular goitre is the most common cause of thyroid enlargement in the elderly.
Patients with nodular enlargement of thyroid may seek treatment, usually for cosmetic
reasons or because compression symptoms may develop due to pressure on the trachea.
Such symptoms are particularly likely when the main enlargement is in the thyroid isthmus, with the large nodule passing behind the manubrium (retrosternal goitre).
Multinodular goitre produces irregular hyperplastic enlargement of the thyroid due to the development of well-circum-scribed nodules of varying size.
As many of the larger nodules are filled with brown gelatinous colloid, the larger goitres are often called multinodular colloid goitres. A few nodules may show evidence of haemorrhage and fibrous scarring. Sometimes, there are smaller, creamy coloured, fleshy nodules, which contain little colloid and are mainly composed of thyroid follicle cells.
Most patients with multinodular goitre have normal thyroid function but, occasionally, one of the nodules becomes functionally, as well as structurally, hyperplastic and secretes excess T3 and T4 .
The cause of multinodular colloid goitre is uncertain, but it may represent the uneven responsiveness of various parts of the thyroid to fluctuating TSH levels over a period of many years.
The nodules in multinodular goitre are composed of hyperplastic thyroid acini.
Many contain gelatinous colloid; others are solid and cream coloured. Cystic
degeneration and fibrosis are common.
Excessive secretion of TH produces hyperthyroidism

Hyperthyroidism is caused by excessive secretion of TH. Most of the clinical
features (collectively known as thyrotoxicosis) are manifestations of a permanently raised
meta-bolic rate, and the pathological changes that occur include loss of subcutaneous
fat, reduction of skeletal muscle bulk and, sometimes, cardiomyopathy. In addition, there
may be a visible or palpable enlargement of the thyroid gland (goitre).
Thyrotoxicosis may result from an autonomous nodule of hyperactive thyroid tissue that
is out of TSH control. This autonomous 'hot' nodule may be a solitary thyroid adenoma,
or may be a component of a multinodular enlargement of the thyroid (multinodular goitre).
Thyroid hyperactivity due to diffuse hyperplasia is seen in Grave's disease.
The epithelial cells are increased in number and size, and the edges of the colloid are
scalloped, indicating active removal of stored colloid for processing into thyroxine.
Reduced output of thyroid hormone produces the symptoms and physical signs of hypothyroidism
In infants, hypothyroidism produces the clinical syndrome called cretinism, which produces
a puffy face and enlarged tongue (coarse features), a protuberant abdomen, and delayed physical
and mental developmental milestones.

The main causes of cretinism are:
Untreated maternal hypothyroidism. This is now rare, due to better prevention, recognition and treatment
of maternal hypothyroidism. It is still a problem in some areas of the world where endemic goitre due to dietary iodine deficiency is seen.
Inherited enzyme defect. This produces sporadic cretinism and is due to failure of normal T3 and T4
synthesis.
In adults, hypothyroidism manifests as the syndrome called myxoedema, which is due
to reduced metabolic rate. There is progressive slowing of physical and mental activity, increasing
lethargy and sensitivity to cold, puffy face, coarse dry skin, thinning of hair (particularly
of the eyebrows), hoarseness and deepening of voice, and various internal abnormalities, partic-ularly
heart failure and a predisposition to hyperlipidaemia and hypothermic coma.

The main causes of myxoedema are:
Surgical ablation of the thyroid gland, which is usually as a result of total thyroidectomy for malignant disease, or aggressive subtotal thyroidectomy for hyperthyroid Graves' disease.
Hashimoto's disease.
Some drug therapy, e.g. lithium.
Reduced output of thyroid hormone produces the symptoms and physical signs of hypothyroidism
However, many patients with myxoedema present for the first time in old age, and only a few have
a history of previous thyroid surgery or disease.
At post mortem examination, these patients have a uniformly shrunken fibrous gland with very
little residual follicular tissue and often only a scanty lymphocytic infiltrate, representing
an 'end-stage' thyroid. There are no clues in either the history or the histology as to the
aetiology of the thyroid shrinkage, but some patients have demonstrable anti-thyroid antibodies.
These cases are sometimes called primary atrophic thyroiditis. It is speculated that
some patients with so-called focal lymphocytic thyroiditis may progress to this state, as may
patients with sub-clinical Hashimoto's disease or previous de Quervain's thyroiditis.
Graves' disease is the most important cause of hyperthyroidism
Graves' disease is a form of autoimmune disorder that presents with symptoms of hyperthyroidism,
diffuse enlargement of the thyroid gland, and exophthalmos (protuberant, staring eyes due to
expansion of retro-orbital soft tissue, mainly expansion of adipose tissue).
The disease is due to the presence of an IgG antibody called LATS, which acts directly
on thyroid follicle cells, stimulating them to divide (to produce increased cell
numbers - hyperplasia) and to synthesize and secrete TH continuously, out of the control
of TSH from the pituitary. TH is therefore synthesized and secreted irrespective of the
requirement, and the normal feedback mechanism is bypassed. The thyroid shows diffuse, fleshy
enlargement, and the follicles are lined by large, active follicle cells, the follicle lumina
containing virtually no stored colloid.
Another histological feature of the disease is the presence of increased numbers of lymphoid
aggregates, including some lymphoid follicles.
There is a high incidence of the HLA antigen HLA-DR3 in patients with Graves' disease.
In this disease the thyroid is focally infiltrated by lymphoid cells. Antibody-stimulated hyperplastic
thyroid acini are enlarged, with large nuclei and a scalloped appearance to the colloid.

Hashimoto's disease is most common in middle age, affecting women more than men. It is an example
of organ-specific autoimmune disease.
The most common auto-antibodies are an anti-microsomal antibody and an antibody against
thyroglobulin. Hashimoto's disease is particularly seen in patients with the HLA antigen, HLA-DR5.
The initial clinical manifestations include diffuse enlargement of the thyroid, occasionally with
a preliminary phase of hyperthyroidism, but by the time most patients seek medical attention,
they have passed through hyperthyroid and euthyroid phases and are becoming progressively hypothyroid.
On clinical examination, the thyroid is usually symmetrically enlarged and firm, with a bosselated
surface. As a result of the disappearance of brown (iodine-rich) colloid, and its replace-ment
by lymphocytes, the cut surface is white rather than the normal brown colour.
It may be that some Hashimoto thyroids proceed to primary atrophic thyroiditis. Laboratory
demonstration of the anti-thyroid antibodies forms the basis of the diagnosis of Hashimoto's
disease, rendering biopsy unnecessary.
Patients with Hashimoto's disease (and Graves' disease) show a high incidence of other
autoimmune diseases (e.g. vitiligo, SLE etc.).
Solitary nodules in the thyroid usually require excision to confirm their nature
Because most malignant epithelial tumours of the thyroid initially present as a solitary
thyroid nodule, complete surgical excision with a safe margin of normal thyroid tissue is usually
necessary. However, an accurate pre-operative diagnosis can often be made after cytological
examination of cells obtained by fine-needle aspiration of the nodule.

THYROID TUMORS
Solitary palpable thyroid nodules may be due to:
A disproportionately prominent nodule in a multinodular goitre.
A solitary thyroid adenoma, which may either be full of colloid or have a more cellular follicular
pattern. The latter may appear fleshy on cut surface.
A malignant thyroid tumour (mainly carcinomas derived from the follicle epithelium). Only histological
examination can distinguish these tumours from solitary
thyroid adenomata with the more cellular follicular find pattern.
The three main types of malignant tumour derived from thyroid follicle cells,
have very different natural histories, behaviour and prognosis. The most common type is
papillary carcinoma, a well-differentiated tumour that arises most frequently in young adults.
It is often multifocal within the thyroid, and tends to metastasize via lymphatics to nodes in
the neck. It is slow-growing and has an excellent prognosis; even metastatic tumours grow slowly
and can be cured by surgical resection.
Follicular carcinoma most commonly affects middle-aged people. Metastasizing via the bloodstream,
it is one of the tumours that characteristically spreads to bone. Patients may occasionally present
with a spontaneous fracture due to metastatic disease, before the primary tumour is detected.
It has a good prognosis.
Entirely confined to the elderly, anaplastic carcinoma grows very rapidly, extensively
invading tissues near the thyroid, such as the trachea and soft tissues of the neck. It may present
with a rapidly enlarging thyroid mass causing tracheal compression or jugular vein invasion.
The prognosis is very poor. The cells of the tumour, which are usually small, undifferentiated and round,
must be distinguished histologically from malignant lymphoma; the latter can also affect
the thyroid in the elderly, but is more responsive to treatment.
(a) This gross specimen shows an extensively infiltrating carcinoma in the thyroid, causing tracheal compression. Its behaviour is that of an anaplastic carcinoma.
(b) Histology of papillary carcinoma showing an easily recognizable papillary pattern.
(c) Histology of follicular carcinoma. Although the tumour attempts to reproduce the follicular pattern
of the normal thyroid, it is much less cellular, with less colloid being formed. There has been local
invasion into vessels (arrow).
(d) Histology of anaplastic carcinoma. The tumour is composed of undifferentiated, small, round cells
arranged in sheets, with no evidence of follicular or papillary differentiation. Histologically it is difficult to distinguish this type of tumour from a lymphoma.
The only significant abnormality of the parafollicular or 'C' cells of the thyroid is
the tumour known as medullary carcinoma Medullary carcinoma has the features of
a neuroendocrine tumour, being composed of small cells containing neuroendocrine granules.
An unusual feature is the occasional presence of amyloid in the supporting stroma. Occurring in
the middle-aged and elderly, these tumours are occasionally seen in children and young adults,
as a component of the multiple endocrine neoplasia (MEN) Type II syndrome.
The tumours are slow-growing, metastasize to local lymph nodes
and have a good prognosis. Those arising in patients with the MEN syndrome are
sometimes more aggressive and are associated with a poorer prognosis. However, the poor
prognosis is usually due to the adverse effects of the other endocrine tumours rather
than that in the thyroid. The tumours secrete calcitonin, and the diagnosis can be supported
by the demonstration of raised plasma calcitonin levels. The increased calcitonin produces
no systemic manifestations.
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