thyroid enlargment, goitre, including its types, causes, diagnosis, treatment options, and potential complications.

The document provides comprehensive information on various aspects related to goitre, including its types, causes, diagnosis, treatment options, and potential complications. It covers details on different subtypes of goitre, such as multinodular goitre, Graves disease, and toxic adenoma, as well as benign and malignant forms. The section also discusses the investigation of thyroid function, emphasizing the importance of measuring serum TSH levels and using isotope scanning in cases of hyperthyroidism. Surgical treatment options for multinodular goitre are outlined, highlighting the choice between total thyroidectomy and partial resection. Complications of goitre, such as tracheal obstruction and secondary thyrotoxicosis, are addressed, along with the importance of evaluating nodules for signs of malignancy. The etiology of simple goitre is explained, focusing on factors like TSH stimulation and dietary iodine deficiency. Prevention and treatment methods for simple goitre are also discussed, emphasizing the role of iodised salt and the consideration of surgery for specific cases. Additionally, the document touches on the considerations for thyroidectomy procedures, the classification of thyroid enlargement, and the diagnosis of thyroid swellings using imaging techniques.

1. THYROID
ENLARGEMENT
BY: MUHAMMAD KHOSHKANI

2. The normal thyroid gland is impalpable. The term goitre (from the
Latin guttur = the throat) is used to describe generalised enlargement of
the thyroid gland. A discrete swelling (nodule) in one lobe with no
palpable abnormality elsewhere is termed an isolated (or solitary)
swelling. Discrete swellings with evidence of abnormality elsewhere in
the gland are termed dominant.
A scheme for classifying thyroid enlargement is given in Table 55.3.

4. Simple goitre

5. Aetiology
Simple goitre may develop as a result of stimulation of the thyroid gland by TSH,
either as a result of inappropriate secretion from a microadenoma in the anterior
pituitary (which is rare) or in response to a chronically low level of circulating
thyroid hormones. The most important factor in endemic goitre is dietary
defciency of iodine (see Iodine defciency), but defective hormone synthesis
probably accounts for many sporadic goitres (see Dyshormonogenesis).
TSH is not the only stimulus to thyroid follicular cell proliferation as other growth
factors, including immunoglobulins, exert an infuence. The heterogeneous
structural and functional response in the thyroid resulting in characteristic
nodularity may be due to the presence of clones of cells particularly sensitive to
growth stimulation.

6. Iodine defciency
The daily requirement of iodine is about 0.1–0.15 mg. In nearly all districts where
simple goitre is endemic, there is a very low iodide content in the water and food.
Endemic areas are in the mountainous ranges, such as the Rocky Mountains, the
Alps, the Andes and the Himalayas, and in the UK areas of Derbyshire and
Yorkshire. Endemic goitre is also found in lowland areas where the soil lacks
iodide or the water supply comes from far away mountain ranges, e.g. the Great
Lakes of North America, the plains of Lombardy, the Struma Valley, the Nile
Valley and the Congo. Calcium is also goitrogenic and goitre is common in low-
iodine areas on chalk or limestone, for example Derbyshire and southern Ireland.
Although iodides in food and water may be adequate, failure of intestinal
absorption may produce iodine defciency.

7. Dyshormonogenesis
Enzyme defciencies of varying severity may be responsible for many sporadic
goitres, i.e. in non-endemic areas (Figure 55.9). There is often a family history,
suggesting a genetic defect. Environmental factors may compensate in areas of high
iodine intake; for example, goitre is almost unknown in Iceland where the fsh diet
is rich in iodine. Similarly, a low intake of iodine encourages goitre formation in
those with a metabolic predisposition.
Figure 55.9 Total thyroidectomy for dyshormonogenetic
goitre in a 14-year-old girl.

9. Goitrogens
Well-known goitrogens are the vegetables of the brassica family (cabbage, kale and
rape), which contain thiocyanate, drugs such as para-aminosalicylic acid (PAS) and
the antithyroid drugs. Thiocyanates and perchlorates interfere with iodide trapping;
carbimazole and thiouracil compounds interfere with the oxidation of iodide and
the binding of iodine to tyrosine.
Surprisingly, iodides in large quantities are goitrogenic because they inhibit the
organic binding of iodine and produce an iodide goitre. Excessive iodine intake
may be associated with an increased incidence of autoimmune thyroid disease.

10. The natural history of simple goitre
Stages in goitre formation are:
● Persistent growth stimulation causes difuse hyperplasia; all lobules are composed
of active follicles and iodine uptake is uniform. This is a difuse hyperplastic goitre,
which may persist but is reversible if stimulation ceases.
● Later, as a result of fuctuating stimulation, a mixed pattern develops with areas of
active lobules and areas of inactive lobules.
● Active lobules become more vascular and hyperplastic until haemorrhage occurs,
causing central necrosis and leaving only a surrounding rind of active follicles.
● Necrotic lobules coalesce to form nodules flled either with iodine- free colloid or
a mass of new but inactive follicles.
● Continual repetition of this process results in a nodular goitre . Most nodules are
inactive, and active follicles are present only in the internodular tissue.

11. Diffuse hyperplastic goitre
Difuse hyperplasia corresponds to the frst stages of the natural history. The goitre
appears in childhood in endemic areas; in sporadic cases, it usually occurs at
puberty, when metabolic demands are high. If TSH stimulation ceases the goitre
may regress, but tends to recur later at times of stress such as pregnancy. The goitre
is soft, difuse and may become large enough to cause discomfort.
A colloid goitre is a late stage of difuse hyperplasia, when TSH stimulation has
fallen of and when many follicles are inactive and full of colloid (Figure 55.10).

13. Nodular goitre
Nodules are usually multiple, forming a multinodular goitre (Figure 55.11).
Occasionally, only one macroscopic nodule is found, but microscopic changes will
be present throughout the gland; this is one form of a clinically solitary nodule.
Nodules may be colloid or cellular, and cystic degeneration and haemorrhage are
common, as is subsequent calcifcation. Nodules appear early in endemic goitre and
later (between 20 and 30 years) in sporadic goitre, although the patient may be
unaware of the goitre until his or her late forties or ffties. All types of simple goitre
are more common in the female than in the male owing to the presence of
oestrogen receptors in thyroid tissue.

15. Diagnosis
Diagnosis is usually straightforward. The patient is euthyroid and the nodules are
palpable and often visible; they are smooth, usually frm and not hard and the goitre
is painless and moves
freely on swallowing. Hardness and irregularity, due to calcifcation, may simulate
carcinoma. A painful nodule, sudden appearance or rapid enlargement of a nodule
raises suspicion of carcinoma but is usually due to haemorrhage into a simple
nodule. Diferential diagnosis from autoimmune thyroiditis may be difcult and the
two conditions frequently coexist.

16. Investigations
Thyroid function should be assessed to exclude hyperthyroidism, and the presence
of circulating thyroid antibodies tested to diferentiate from autoimmune thyroiditis.
Ultrasonography is the gold standard assessment when undertaken by a suitably
trained and experienced operator. FNAC is only required for a nodule within the
goitre that demonstrates ultrasonographic features of concern. This may or may
not be the largest ‘dominant’ nodule. The biopsy should be performed under
ultrasound guidance to ensure that the correct nodule is sampled. If there are
swallowing or breathing symptoms then a CT scan of the chest and neck is the best
modality to assess tracheal or oesophageal deviation or compression.

17. Complications
Tracheal obstruction may be due to gross lateral displacement or compression in a
lateral or anteroposterior plane by retrosternal extension of the goitre (Figure 55.7).
Acute respiratory obstruction may follow haemorrhage into a nodule impacted in
the thoracic inlet.
Secondary thyrotoxicosis
Transient episodes of mild hyperthyroidism are common, occurring in up to 30%
of patients.
Carcinoma
An increased incidence of cancer (usually follicular) has been reported from
endemic areas. Dominant or rapidly growing nodules in longstanding goitres
should always be subjected to aspiration cytology.

19. Prevention and treatment of simple goitre
In endemic areas the incidence of goitre has been strikingly reduced by the
introduction of iodised salt. In the early stages, a hyperplastic goitre may regress if
thyroxine is given in a dose of 0.15–0.2 mg daily for a few months.
Although the nodular stage of simple goitre is irreversible, more than half of benign
nodules will regress in size over 10 years. Most patients with multinodular goitre
are asymptomatic and do not require operation. Surgery is indicated for nodular
goitres with features of underlying malignancy, for pressure symptoms if other
causes have been excluded or for cosmetic reasons if the patient fnds the goitre
unsightly. If the goitre is causing tracheal compression then surgery should be
considered. Many such patients are found incidentally and are asymptomatic and
often very elderly. As these goitres often grow very slowly the risks and benefts of
surgery should be considered carefully, particularly if a sternal split may be
required for access.

20. There is a choice of surgical treatment in multinodular goitre: total thyroidectomy
with immediate and lifelong replacement of thyroxine or some form of partial
resection to conserve sufcient functioning thyroid tissue to subserve normal
function while reducing the risk of hypoparathyroidism that accompanies total
thyroidectomy. Historically subtotal thyroidectomy involves partial resection of
each lobe, removing the bulk of the gland and leaving up to 8 g of relatively normal
tissue in each remnant. The technique is essentially the same as described for toxic
goitre, as are the postoperative complications. A signifcant problem with this
approach is the propensity for regrowth. Therefore, unless there is a local shortage
of thyroxine, most surgeons now favour total thyroidectomy in the setting of
bilateral disease.

21. More often, however, the multinodular change is asymmetrical, with one lobe
more signifcantly involved than the other. In these circumstances, particularly in
older patients, total lobectomy on the more afected side is the appropriate
management. Although this can be used in combination with subtotal resection of
the contralateral lobe (Dunhill procedure), most surgeons now prefer no
intervention on the less afected side because of the potential for regrowth and the
increased rate of complications associated with reoperation. In many cases, the
causative factors persist and recurrence is likely.

22. Reoperation for recurrent nodular goitre is more difcult and hazardous and, for
this reason, an increasing number of thyroid surgeons favour total thyroidectomy in
younger patients. However, when the frst operation comprised unilateral
lobectomy alone for asymmetric goitre, reoperation and completion total
thyroidectomy is straightforward if required for progression of nodularity in the
remaining lobe. Total lobectomy and total thyroidectomy have the additional
advantage of being therapeutic for incidental carcinomas.

23. Clinically discrete swellings

24. Discrete thyroid swellings (thyroid nodules) are common and are palpable in 3–4%
of the adult population in the UK and USA. They are three to four times more
frequent in women than in men.

25. Diagnosis
A discrete swelling in an otherwise impalpable gland is termed isolated or solitary,
whereas the preferred term is dominant for a similar swelling in a gland with
clinical evidence of generalised abnormality in the form of a palpable contralateral
lobe or generalised mild nodularity. About 70% of discrete thyroid swellings are
clinically isolated and about 30% are dominant. The true incidence of isolated
swellings is somewhat less than the clinical estimate. Clinical classifcation is
inevitably subjective and overestimates the frequency of truly isolated swellings.
When such a gland is exposed at operation or examined by ultrasonography, CT
or MRI, clinically impalpable nodules are often detected. The true frequency of
thyroid nodularity compared with the clinical detection rate by palpation is shown
in Figure 55.12.

27. Demonstrating the presence of impalpable nodules does not change the
management of palpable discrete swellings and begs the question of the necessity of
investigating incidentally found nodules. The importance of discrete swellings lies
in the risk of neoplasia compared with other thyroid swellings. Some 15% of
isolated swellings prove to be malignant and an additional 30–40% are follicular
adenomas. The remainder are non-neoplastic, largely consisting of areas of colloid
degeneration, thyroiditis or cysts. Although the incidence of malignancy or
follicular adenoma in clinically dominant swellings is approximately half of that of
truly isolated swellings, it is substantial and cannot be ignored (Figure 55.13).

28. Figure 55.13 The risk of malignancy in thyroid
swellings (‘rule of 12’). The risk of cancer in a
thyroid swelling can be expressed as a factor of
12. The risk is greater in isolated versus
dominant swellings, solid versus cystic
swellings and in men versus women.

29. Investigation
Thyroid function
Serum TSH and thyroid hormone levels should be measured. If hyperthyroidism
associated with a discrete swelling is confrmed biochemically, it indicates either a
‘toxic adenoma’ or a manifestation of toxic multinodular goitre. The combination
of toxicity and nodularity is important and is an indication for isotope scanning to
localise the area(s) of hyperfunction.
Autoantibody titres
The autoantibody status may determine whether a swelling is a manifestation of
chronic lymphocytic thyroiditis. The presence of circulating antibodies increases
the risk of thyroid failure after lobectomy.
Isotope scan
Isotope scanning used to be the mainstay of investigation of discrete thyroid
swellings but has been abandoned except when toxicity is associated with
nodularity.

30. Ultrasonography
This is used to determine the physical characteristics of thyroid swellings. There
are a number of ultrasonographic features in a thyroid swelling associated with
thyroid neoplasia, including microcalcification and increased vascularity, but only
macroscopic capsular breach and nodal involvement are diagnostic of malignancy.
Ultrasonography should be used as the primary investigation of any thyroid nodule
as a reassuring appearance mitigates the need for FNAC (see
Fine-needle
aspiration cytology).

31. Fine-needle aspiration cytology
FNAC should be used, ideally under ultrasound guidance, on all nodules that do
not fulfil a fully benign (U2) classification on ultrasonography. FNAC is reliable in
identifying papillary thyroid carcinoma (PTC) but cannot distinguish between a
benign follicular adenoma (Figure 55.14) and follicular carcinoma, as this
distinction is dependent not on cytology but on histological criteria, which include
capsular and vascular invasion.
FNAC is both highly specific and sensitive. Using ultrasonography improves this
further, particularly in part cystic, part solid nodules in which ultrasonography
allows targeting of the solid element for biopsy.

32. Figure 55.14 Thy3
aspiration cytology (Table
55.2). Follicular neoplasm
showing increased
cellularity with a follicular
pattern.

34. Radiology
Plain films have previously been used to assess tracheal compression and deviation,
but the modality of choice now is CT scanning. CT scanning is also useful if
ultrasonography has identified metastatic disease in the neck as it can assist surgical
planning and also assess the superior mediastinum and lungs.
Laryngoscopy
Flexible laryngoscopy has rendered indirect laryngoscopy obsolete and is widely
used preoperatively to determine the mobility of the vocal cords. The presence of
a unilateral cord palsy coexisting with an ipsilateral thyroid nodule of concern is
usually diagnostic of malignant disease.
Core biopsy
Core biopsy is rarely indicated in thyroid masses owing to the vascularity of the
thyroid gland and the risk of postprocedure haemorrhage. It can be useful in the
rapid diagnosis of widely invasive malignant disease, for example anaplastic
carcinoma, or in the diagnosis of lymphadenopathy.

35. Indication for surgery
The main indication for operation is the risk of neoplasia, which includes follicular
adenoma as well as malignant swellings. The reason for advocating the removal of
all follicular neoplasms is that it is seldom possible to distinguish between a
follicular adenoma and carcinoma cytologically. Even when the cytology is negative,
the age and sex of the patient and the size of the swelling may be relative
indications for surgery, especially when a large swelling is responsible for
symptoms.
There are useful clinical criteria to assist in selection for operation according to the
risk of neoplasia and malignancy.

36. Hard texture alone is not reliable as tense cystic swellings may be suspiciously hard
but a hard, irregular swelling with any apparent fxity, which is unusual, is highly
suspicious. Evidence of RLN paralysis, suggested by hoarseness and a non-
occlusive cough and confirmed by laryngoscopy, is almost pathognomonic.
Cervical lymphadenopathy along the internal jugular vein in association with a
clinically suspicious swelling is almost diagnostic of PTC. In most patients,
however, such features are absent. The incidence of thyroid carcinoma in women
is about three times that in men, but a discrete swelling in a male is much more
likely to be malignant than in a female. The risk of carcinoma is increased at either
end of the age range and a discrete swelling in a teenager of either sex must be
provisionally diagnosed as carcinoma.

37. Thyroid cysts

38. Thyroid cysts
Routine FNAC (or ultrasonography) shows that over 30% of clinically isolated
swellings contain fluid and are cystic or partly cystic. Tense cysts may be hard and
mimic carcinoma. Bleeding into a cyst often presents with a history of sudden
painful swelling, which resolves to a variable extent over a period of weeks if
untreated. Aspiration yields altered blood but reaccumulation is frequent. About
55% of cystic swellings are the result of colloid degeneration or are of uncertain
aetiology because of an absence of epithelial cells in the lining. Although most of
the remainder are the result of involution in follicular adenomas (
Figure 55.15),
some 10–15% of cystic follicular swellings are histologically malignant (30% in men
and 10% in women). PTC is often associated with cyst formation (Figure 55.16).
Most patients with discrete swellings, however, are women, aged 20–40 years, in
whom the risk of malignancy, although significant, is low and the indications for
operation are not clear-cut.

39. Ultrasonography is the most useful tool for assessing cysts. If there is no discernible
solid element, the cyst is almost certainly benign and does not need to be further
investigated. As stated above, simple aspiration is associated with high rates of
reaccumulation. However, ablation using either ethanol or thermal probes
(radiofrequency, microwave, laser or high-frequency ultrasound) achieves cyst
resolution in up to 90% of cases and should be considered for recurrent,
symptomatic cysts. If there is an associated solid element, then consideration
should be given to targeting that area with ultrasound-guided FNAC.
The indications for operation in isolated or dominant thyroid swellings are listed in
Table 55.4.

44. Selection of thyroid procedure
The choice of thyroid operation depends on:
● diagnosis (if known preoperatively);
● risk of thyroid failure;
● risk of RLN injury;
● risk of recurrence;
● Graves’ disease;
● multinodular goitre;
● diferentiated thyroid cancer;
● risk of hypoparathyroidism.

45. Total and near-total thyroidectomy do not conserve suffcient thyroid tissue for
normal thyroid function and thyroid replacement therapy is necessary. In two-
thirds of patients with negative antithyroid antibodies, one thyroid lobe will
maintain normal function.
Subtotal resections for colloid goitre or Graves’ disease run the risk of later growth
of the remnant and, if a second operation is required years later, this greatly
increases the risk to the RLN and parathyroid glands. In young patients, total
thyroidectomy should be considered. It may be preferable to leave the least afected
lobe untouched to permit a straightforward lobectomy in the future if required,
rather than carry out subtotal resections.
In Graves’ disease, preserving large remnants increases the risk of recurrence of
the toxicity and, in these cases, it is better to err on the side of removing too much
thyroid tissue rather than too little (
Table 55.5). Thyroid failure should not be
regarded as a failure of treatment, but recurrent toxicity is.
Therelativemeritsofroutinetotalversusselectivetotalthyroidectomyindiferentiatedthyroidcancerarediscussedbelow.

48. RETROSTERNAL
GOITRE

49. Retrosternal goitre tends to arise from the slow growth of a multinodular gland
down into the mediastinum. As the gland enlarges within the thoracic inlet,
pressure may lead to dysphagia, tracheal compression and eventually airway
symptoms. The vast majority of patients have minimal symptoms. Patients should
be considered for surgery if there is signifcant airway compression, if symptoms are
present or in young patients in whom symptoms are likely to develop. In elderly
patients with incidentally discovered retrosternal goitres , most surgeons would
observe rather than treat prophylactically. Clearly a balance between risk and
beneft must be made.
If a decision is made to proceed to surgery, assessment of the extent of disease is
critical. The vast majority (>95%) of retrosternal goitres can be removed
transcervically.

50. Patients most at risk of requiring conversion to an open sternotomy approach
include those with malignant disease or who are undergoing revision, those whose
goitres that extend into the posterior mediastinum and those in whom the diameter
of the goitre exceeds that of the thoracic inlet. In such cases a joint case with
thoracic surgery should be planned.
All patients should have cross-sectional imaging. Ideally this is performed in the
surgical position and, when interpreting CT chest scans, the surgeon should pay
attention to the arm position. If the arms are up (as for standard CT chest) there
will be a great deal of diference in thyroid position compared with when the arms
are down and the neck extended.
The approach to surgery is as described in Surgical technique of thyroidectomy.

51. A longer incision is required. The surgeon may mobilise the sternomastoid muscle
from the strap muscles to improve access. The ligamentous tissue between the
sternal heads of the clavicles may be gently divided to increase the opening for
gland delivery. Blunt dissection on the capsule of the gland allows mobilisation.
Gentle traction is applied to deliver the gland into the neck. If the goitre has
developed from a posteriorly positioned nodule there is a risk that the RLN may
be displaced anteriorly, so great care must be taken in dividing apparent fascial
bands that overlie the gland. The blood supply is from the neck, reducing the risk
of catastrophic bleeding from the great vessels. Nonetheless, care should be taken
in the region of the major blood vessels in the neck and chest.
If the gland is fxed and immobile or too large to deliver through a cervical
approach, a midline sternotomy is performed and the gland can be dissected from
below to achieve a safe total thyroidectomy.

52. Thank you for listening