Wednesday, November 18, 2009

Goitre

Development of Thyroid gland

Thyroid gland develops from the endoderm of the 1st and 2nd pharyngeal pouches.
It started off with the formation of a median diverticulum, which descends down from the developing pharynx, passing in front of the hyoid bone to the neck. The upper end of this thyroglossal duct is located at the foramen of caecum (at the junction in between the anterior 2/3rds and the posterior 1/3rds). The lower end bifurcates at the level of the 2nd-4th tracheal rings, eventually proliferates to form the gland.

It also receives neural crest cells of the ectoderm from the 4th pharyngeal pouches, forming the parafollicular C-cells which secretes calcitonin.

The superior parathyroid glands -> derived from 4th pharyngeal pouch
The inferior parathyroid glands -> derived from 3rd pharyngeal pouch

Some congenital anomalies

1) Thyroglossal cyst




A cyst can be formed anywhere along the course of the thyroglossal duct.
Usually presented with a mid-line neck swelling, infrahyoid in location.
Moves upwards on deglutition and tongue protrusion.
Lined by columnar epithelium, containing fluid rich in cholesterol.

2) Thyroglossal fistula

Either present at birth, or due to ruptured thyroglossal cyst, or even in case of incomplete excision of thyroglossal cyst.
Presented at the midline, with a hood of skin at the upper margin of a discharging sinus.
Moves upwards on deglutition and tongue protrusion.

3) Ectopic thyroid gland


Any cessation of the descend of thyroid gland along the course of thyroglossal duct leads to formation of ectopic thyroid gland.
It can be a lingual thyroid, or even found within the superior mediastinum.
Such thyroid gland should be preserved since it might the only functioning thyroid gland.

Anatomy of the thyroid gland



The thyroid gland weights around 20gm.
It's situated slightly below and on the thyroid cartilage.
It has 2 lateral lobes, with the shape of a pear, connected in between by an isthmus, which overlies the 2nd-4th tracheal rings.
The gland is wrapped around the larynx, bound to it by the deep layer of cervical fascia, known as the pre-tracheal fascia.
The fascia is thickened over the posterior surface of the glands to form the Berry's ligament, which adheres the gland to the trachea. This explains why the gland moves upwards during degluttition.
The lateral lobes of thyroid gland is covered anteriorly by straps of sternohyoid and sternothyroid muscles.
Occasionally, there's a pyramidal lobe, extending from the isthmus (left to the midline).

Arterial supply of thyroid gland

The thyroid gland is supplied by :

1) A pair of superior thyroid arteries, branch of the external carotid artery.
2) A pair of inferior thyroid arteries, originating from the thyrocervical trunk. The inferior thyroid arteries passes behind the carotid sheath, which later emerges out from behind of the common carotid arteries before supplying the gland.

Venous drainage of the gland

1) Superior and middle thyroid veins -> drained into the internal jugular veins
2) Inferior thyroid veins -> brachiocephalic veins

Lymphatic drainage of the gland

Pretracheal, deep cervical and paratracheal nodes

Relation to the recurrent laryngeal nerves

Recurrent laryngeal nerve is a branch of vagus nerve.
The left RLN hooks around the aortic arch, whilst the right RLN hooks around the subclavian artery.
Both RLN then passes through the tracheo-esophageal grooves, then posteriorly through the lateral lobes of the gland.
It then pierces through the cricopharyngeus muscles, to gain entry into the larynx before innervating the intrinsic muscles of larynx.
This nerve can be injured in cases of thyroid surgery or even during malignant infiltration from the thyroid gland.
Unilateral damage causing hoarsness of voice.
Bilateral damage causing vocal cord paralysis and eventually the patient requires permanent tracheostomy.

Physiology




The gland comprises of about 1 million follicles, where each of them is lined by a single layer of follicular cells. At rest, the cells are cuboidal in shape, and after stimulation by TSH, it becomes columnar in shape. Noticed from the above diagram, there's colloidal space in the centre of the follicle. Thyroglobulin is produced by the cells into the colloid.

Thyroid hormone synthesis




Inorganic iodine is absorbed from the blood stream into the gland, which is oxidised to form free iodine.
These free iodine later combines with the amino acid tyrosine to form mono-iodothyrosine (MIT).
Two molecules of MIT produces di-iodothyronine (DIT)
One MIT and DIT produces tri-iodothyronine (T3)
Two molecules of DIT produces tetra-iodothyronine (T4)
These T3 and T4 molecules combines with the thyroglobulin molecules and are stored within the colloid of thyroid follicles.
When the gland is stimulated by TSH secreted from the anterior pituitary gland, the thyroglobulin molecules are absorbed by the follicular cells and are broken-down.
This releases the T3 and T4 molecules into the blood stream.
Within the blood stream, T3 and T4 are carried by the thyroxine-binding globulin (TBG).
Free T4 is the hormonal storage form, since only free T3 are metabolically active.

The feedback mechanism




First, the cerebral cortex detect the thyroid hormone level in the blood stream.
It sends signal through an unknown mechanism to stimulate the hypothalamus, and TRH is produced.
TRH stimulates the anterior pituitary gland to produce TSH.
TSH binds to the TSH-receptors of the gland, stimulating it to produce T3 and T4.
Once optimal level of thyroid hormone in the blood is achieved, autoregulation occurs as to maintain constant level of such hormone.

However, in cases like in Graves disease, since the body produces auto-antibodies, known as the Long-Activating Thyroid Stimulator (LATS), which competes with the TSH receptor over the gland, and hence stimulating it, results in thyrotoxicosis.

But in cases of secondary and tertiary thyrotoxicosis, such autoantibodies doesn't exist.

Classification of goitre

1) Simple

Colloid goitre
Multinodular goitre
Colloid nodule

2) Toxic

Primary thyrotoxicosis (Grave's disease)
Secondary thyrotoxicosis (Plummer's disease - toxic changes in Multinodular goitre)
Tertiary thyrotoxicosis (Toxic solitiary nodule)
Other causes -> Pituitary adenoma

3) Neoplastic

a) Benign

Thyroid adenoma (Follicular/Papillary/Mixed)

b) Malignant

i) From thyroid hormone producing cells

Well differentiated - Papillary/Follicular carcinoma
Poorly differentiated - Anaplastic carcinoma

ii) From non-thyroid hormone producing cells

Medullary carcinoma (involving the parafollicular C-cells)

iii) From non-hormonal producing cells

Lymphoma, Sarcoma

c) Inflammatory

Riedel's thyroiditis
De Quervain's thyroiditis
Hashimoto's thyroiditis
Acute bacterial thyroiditis/Thyroid abscess

d) Others

Thyroid cyst
Amyloidosis

Points in history of a case of goitre

a) Symptoms related to pressure effects/infiltration

Insidious onset with gradual progression in colloid goitre, multi-nodular goitre and colloid nodule
Sudden appearance of painful lump or enlargement of pre-existing nodule
Pain is a feature of De Quervain's thyroidits
Pain can be a feature of late thyroid carcinoma
Goitre presses on the trachea and esophagus causing dyspnoea and dysphagia
Fever can be present in thyroid abscess and thyroid storm
Hoarness of voice in infiltrative thyroid malignancies (recurrent laryngeal nerve palsy)

b) Symptoms of :

i) Primary thyrotoxicosis (Graves)


Mainly neurological symptoms
Anxiety, irritability, excitability
Tremors
Heat intolerance
Cold preferance
Excessive sweating
Proximal myopathy

ii) Secondary thyrotoxicosis

Mainly CVS symptoms
Symptoms related to : Angina, High-output failure, Atrial fibrillation, Thyrotoxic cardiomyopathy

iii) GI symptoms

H/o of increased appetite, but weight lost despite of that
Diarrhoea

iv) Menstrual disturbances

Oligomenorrhoea/amenorrhoea


v) Symptoms of Hypothyroidism

Lethargy
Lost of appetite
Weight gain
Cold intolerance
Fat deposition over Supraclavicular region
Deep hoarse voice

General examination

1) Hyperthyroidism


General appearance
Anxious, sweating, irritable
Staring look
Thin (despite h/o of increased appetite)

Hands
Thyroid acropachy
Onycholysis
Warm, sweaty palm
Palmar erythema
Irregularly irregular pulse, tachycardia

Head
Fine, straight hair
Exopthalmos - forward buldging of eye balls (proptosis)
Lid retraction - sclera above superior limbus is visible
Lig lag - movement of upper eyelid lags behind the eye ball
Chemosis - oedema of the conjunctiva
Opthalmoplegia - failure to look upwards and outwards
Loss of convergence - Moebius sign

Chest
Look for features of heart failure
To confirm atrial fibrillation

Leg
Proximal muscle weakness
Pretibial myxedema
Hyperreflexia

2) Hypothyroidism

General appearance
Dull expression
Slowness of movements

Hands/Skin
Coarse, dry, cold
Puffy hands
Bradycardia
Carpal tunnel syndrome

Head
Alopecia
Loss of lateral 1/3 of eyebrows
Xanthelesma
Puffy face
Macroglossia
Hoarseness of voice
Deafness

Chest
Soft heart sound
Pericardial rub
Sign of heart failure

Leg
Proximal muscle weakness
Delayed relaxation in ankle jerk

Local examination


1) Inspection
Stand in front of the patient
Under good lighting, inspect for any thyroid swelling
Ask the patient to swallow and observe for any upward movement of the swelling
Observe whether the swelling appears smooth, nodular, or irregular
Check for any scars indicating previous surgeries
Check for any dilated veins over the upper thorax and neck (thoracic inlet obstruction)
Ask the patient to raise his/her arms above the head
Observe if there's any facial edema, congestion, dilated/prominent neck veins
If present, suspect retrosternal extension of goitre

2) Palpation

Palpate for the trachea whether it's central
Try feeling for the lower border of the gland (ask the patient to swallow if not possible)
Stand behind the patient, with his/her neck flexed, and start palpating for the gland.
Crile's method - palpation of the gland done as the patient is swallowing
Lahey's method - push the contralateral lobe of the gland medially so that it springs out for easy palpation of the nodules located over the posteior surface
Check for any tenderness, thrill
Comment on the consistency - soft, cystic, firm, hard?
Kocher's test - pressure applied over the lateral lobes and if it induces stridor, it means that the goitre is pressing against the trachea
Feel for any palpable cervical lymph nodes
Feel for the carotid pulsation. If not felt over normal area, try palpating it over the posterior triangle of the neck. (sometimes an adenoma might have pushed the carotid sheath posteriorly)
Still not possible -> try feeling for the superficial temporal pulsation
If it's not felt -> Positive Berry's sign since an infiltrative lesion might have encircled the carotid sheath

3) Percussion
Percuss over the clavicle for any dullness (retrosternal extension)

4) Auscultation
For any vascular bruits

Investigations

1) Full blood count

Before starting treatment of thyrotoxicosis, a baseline value of Hb and Total WBC is necessary (since anti-thyroid drugs might cause agranulocytosis)

2) X-ray neck

Check whether the trachea is deviated
Spiculated calcification might be suggestive of malignancy

3) Ultrasound of neck

First to determine morphology of gland (whether it's solitiary, diffuse, MNG)
To determine a nodule, of whether it's solid or cystic

4) Radio-isotope scan

Not routinely used
Useful in cases where there's presentation of both symptoms of thyrotoxicosis and solitiary nodules, in order to determine whether the gland or nodule is toxic

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