the thyroid gland embryology, anatomy, and physiology.

Learning objectives
• To understand the development and anatomy of the
thyroid gland
• To know the physiology and investigation of thyroid
function
• To be able to select appropriate investigations for thyroid
swellings

1. The thyroid
gland
BY: MUHAMMAD KHOSHKANI

2. Learning objectives
• To understand the
development and
anatomy of the thyroid
gland
• To know the physiology and investigation of
thyroid function

3. EMBRYOLOGY
The embryology of the thyroid and parathyroid glands underlies the anatomical position,
anatomical variations and congenital conditions of these structures; it is therefore vital for
surgery (Figure 55.1). The thyroglossal duct develops from the median bud of the
pharynx. The foramen caecum at the junction of the anterior two-thirds and posterior
one-third of the tongue is the vestigial remnant of the duct. This initially hollow
structure migrates caudally and passes in close continuity with, and sometimes through,
the developing hyoid cartilage. The parathyroid glands develop from the third and fourth
pharyngeal pouches. The thymus also develops from the third pouch. As it descends, the
thymus takes the associated parathyroid gland with it, which explains why the inferior
parathyroid, which arises from the third pharyngeal pouch, normally lies inferior to the
superior gland. However, the inferior parathyroid may be found anywhere along this line
of descent The developing thyroid lobes amalgamate with the structures that arise in the
fourth pharyngeal pouch, i.e. the superior parathyroid gland and the ultimobranchial
body. Parafollicular cells (C cells) from the neural crest reach the thyroid via the
ultimobranchial body.

5. SURGICAL ANATOMY
The normal thyroid gland weighs 20–25 g. The functioning unit is the lobule supplied by
a single arteriole and consists of 24–40 follicles lined with cuboidal epithelium. The
follicle contains colloid in which thyroglobulin is stored (Figure 55.2). The arterial supply
is rich, and extensive anastomoses occur between the main thyroid arteries and the
branches of the tracheal and oesophageal arteries (Figure 55.3). There is an extensive
lymphatic network within and around the gland. Although some lymph channels pass
directly to the deep cervical nodes, the subcapsular plexus drains principally to the
central compartment juxtathyroid – ‘Delphian’ and paratracheal nodes and nodes on the
superior and inferior thyroid veins (level VI) – and from there to the deep cervical (levels
II, III, IV and V) and mediastinal groups of nodes (level VII) (Figure 55.4).
The relationship between the recurrent laryngeal nerve (RLN) and the thyroid is of
supreme importance to the
operating surgeon.

6. A branch of the vagus, the nerve recurs round the arch of the aorta on the left and the
subclavian artery on the right. The clinical significance of this is that on the left the nerve
has more distance in which to reach the tracheo-oesophageal groove and therefore runs
in a medial plane. On the right, there is less distance and the nerve runs more obliquely
to reach the tracheo-oesophageal groove. Approximately 2% of nerves on the right are
non-recurrent and will enter the larynx from above.
The nerve runs posterior to the thyroid and enters the larynx at the cricothyroid joint.
This entry point is at the level
of Berry’s ligament, a condensation of pretracheal fascia that binds the thyroid to the
trachea. This is the point at which the nerve is at most risk of injury during surgery. In
terms of surgical anatomy, the nerve can be located in the tracheooesophageal groove,
where it forms one side of Beahrs’ triangle (the other two sides are the carotid artery and
the inferior thyroid artery) or at the cricothyroid joint. The nerve will normally be found
as the thyroid lobe is mobilised laterally, lying under the most posterolateral portion of
the gland called the tubercle of Zuckerkandl.

10. PHYSIOLOGY
Thyroxine
The hormones tri-iodothyronine (T3) and l-thyroxine (T4) are bound to thyroglobulin
within the colloid. Synthesis within the thyroglobulin complex is controlled by several
enzymes, in distinct steps:
● trapping of inorganic iodide from the blood; ● oxidation of iodide to iodine;
● binding of iodine with tyrosine to form iodotyrosine;
● coupling of monoiodotyrosines and di-iodotyrosines to form T3 and T4.
When hormones are required, the complex is resorbed into the cell and thyroglobulin is
broken down. T3 and T4 are liberated and enter the blood, where they are bound to
serum proteins: albumin, thyroxine-binding globulin (TBG) and thyroxine-binding
prealbumin (TBPA). The small amount of hormone that remains free in the serum is
biologically active. The metabolic efects of the thyroid hormones are due to unbound
free T3 and T4 (0.3% and 0.03% of the total circulating hormones, respectively). T3 is
the more important physiological hormone and is also produced in the periphery by
conversion from T4. T3 is quick acting (within a few hours), whereas T4 acts more slowly
(4–14 days).

11. Calcitonin
The parafollicular C cells of the thyroid are of neuroendocrine origin and arrive in the
thyroid via the ultimobranchial body (Figure 55.1). They produce calcitonin.

12. The pituitary–thyroid axis
Synthesis and release of thyroid hormones from the thyroid is controlled by thyroid-
stimulating hormone (TSH) from the anterior pituitary. Secretion of TSH depends upon
the level of circulating thyroid hormones and is modifed in a negative feedback manner.
In hyperthyroidism TSH production is suppressed, whereas in hypothyroidism it is
stimulated. Regulation of TSH secretion also results from the action of thyrotrophin-
releasing hormone (TRH) produced in the hypothalamus.
Thyroid-stimulating antibodies
A family of IgG immunoglobulins bind with TSH receptor sites (TRAbs) and activate
TSH receptors on the follicular cell membrane. They have a more protracted action than
TSH (16–24 versus 1.5–3 hours) and are responsible for virtually all cases of
thyrotoxicosis not due to autonomous toxic nodules. Serum concentrations are very low
but their measurement is not essential to make the diagnosis.

13. Serum thyroid hormones
Serum thyroid-stimulating hormone
TSH levels can be measured accurately down to very low serum concentrations with an
immunochemiluminometric assay. Interpretation of deranged TSH levels depends on
knowledge of the T3 and T4 values. In the euthyroid state, T3, T4 and TSH levels will
all be within the normal range. Florid thyroid failure results in depressed T3 and T4
levels, with gross elevation of TSH. Incipient or developing thyroid failure is
characterised by low normal values of T3 and T4 and elevation of TSH. In toxic states,
the TSH level is suppressed (Table 55.1).

14. Thyroid autoantibodies
Serum levels of antibodies against thyroid peroxidase (TPO) and thyroglobulin are useful
in determining the cause of thyroid dysfunction and swellings. Autoimmune thyroiditis
may be associated with thyroid toxicity, failure or euthyroid goiter. Levels above 25
units/mL for TPO antibody and titers of greater than 1:100 for antithyroglobulin are
considered significant, although a proportion of patients with histological evidence of
lymphocytic (autoimmune) thyroiditis are seronegative. The presence of
antithyroglobulin antibody interferes with assays of serum thyroglobulin, with implications
for follow-up of thyroid cancers. TSH receptor antibodies (TSH-RAb or TRAB) are
often present in Graves’ disease. They are largely produced within the thyroid itself.

16. Thyroid imaging
The workhorse investigation in thyroid disease for the surgeon is ultrasonography. This
modality allows assessment of the gland and the regional lymphatics. Not only can the
characteristics of the gland substance be quantifed, but critically the presence and features
of thyroid nodules can be described. Number, size, shape, margins, vascularity and
specifc features such as the presence of microcalcifcations can be used to predict the risk
of malignancy within a specifc nodule. Regional lymphatics, particularly in the lateral
neck, can be assessed accurately for the presence of metastatic deposits. During
ultrasonography, fne-needle aspiration (FNA) can be performed more accurately than
free-hand techniques allow.
Ultrasonography has the advantages that it is not associated with ionising radiation and is
non-invasive and cheap (Figure 55.5). Visualisation of the central neck nodes, in
particular those behind the sternum, is however limited. For this reason, when metastatic
disease is detected cross-sectional imaging is required to fully stage the disease.

17. Retrosternal extension, which can often be predicted on a plain chest radio-graph (Figure
55.6), also requires more advanced techniques to determine the extent adequately prior
to considering management. For most of these indications, the imaging modality of
choice is CT. Rapid acquisition times minimise artefacts secondary to breathing and the
lung felds can be accurately assessed simultaneously.
In the setting of an invasive primary thyroid cancer, both CT and MRI may have a role.
Contrast-enhanced CT is useful
for determining the extent of airway invasion (Figure 55.7) and MRI is superior at
determining the presence of prevertebral fascia invasion.
Positron emission tomography (PET) scans have limited application in thyroid disease.
They may be considered in the setting of recurrent thyroid cancer. This is particularly
useful when the disease does not concentrate iodine, at which point fuorodeoxyglucose
(FDG) uptake increases and lesions become positive on PET scans.

18. Figure 55.5 Ultrasonography. (a) Transverse scan of a normal thyroid. R, right lobe; L, left
lobe; T, trachea. (b) Longitudinal scan of normal jugular lymph nodes (white arrows).

19. Figure 55.6 Chest radiograph showing a retrosternal goitre with calci-fcation and tracheal
displacement (courtesy of Dr Achleshwar Dayal, Hoshangabad, MP, India).

20. Figure 55.7 (a) Scout flm showing retrosternal goitre. (b) Axial computed tomography (CT)
section showing goitre extending to below the aortic arch with tracheal compression.

21. Figure 55.7 (c) Coronal CT section showing goitre extending to the tracheal bifurcation.

22. Figure 55.7 (d) Sagittal CT section showing goitre flling the posterior mediastinum.

23. Isotope scanning
The uptake by the thyroid of a low dose of either radiolabelled iodine (
123
I) or the
cheaper technetium (
99m
Tc) will demonstrate the distribution of activity in the whole
gland. Routine isotope scanning is unnecessary and inappropriate for distinguishing
benign from malignant lesions because the majority (80%) of ‘cold’ swellings are benign
and some (5%) functioning or ‘warm’ swellings will be malignant. Its principal value is in
the toxic patient with a nodule or nodularity of the thyroid. Localisation of overactivity in
the gland will differentiate between a toxic nodule with suppression of the remainder of
the gland and toxic multinodular goitre with several areas of increased uptake with
important implications for therapy (
Figure 55.8).
Whole-body scanning is used to demonstrate metastases. However, the patient must have
all normally functioning thyroid tissue ablated by either surgery or radioiodine before the
scan is performed because metastatic thyroid cancer tissue cannot compete with normal
thyroid tissue in the uptake of iodine.

24. Figure 55.8 Technetium thyroid scan
showing the appearance of a 1-cm
‘toxic’ adenoma in the right thyroid
lobe with suppression of uptake in the
left lobe. The intense uptake gives a
false impression of the size of the
swelling.

25. Fine-needle aspiration cytology
FNAC is the investigation of choice in discrete thyroid swellings. FNAC has excellent
patient compliance, is simple and quick to perform in the outpatient department and is
readily repeated. This technique, developed in Scandinavia 40 years ago, is now routine
throughout the world. FNAC results should be reported using standard terminology
(Table 55.2). Ultrasound guidance allows more accurate sampling and reduces the rate of
unsatisfactory aspirates.

26. Thank you for lestening