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

Varicose Veins

1) Anatomy of the Venous system of lower limb

The venous system of the lower limb is divided into the superficial and deep system. The superficial system comprises of

a) Long saphenous veins
b) Short saphenous veins

Long saphenous veins

It begins from the medial end of dorsal venous arch, ascending in front of the medial malleolus, then along the medial aspect of the leg and knee, anteriorly along the thigh, finally pierces the cribiform fascia and joins with the femoral vein at the SF junction (located 4cm lateral and below of the pubic tubercle)

Tributaries :

1) In the leg - anterior and posterior arch veins
2) In the thigh - medial and lateral thigh veins
3) At the SF junction - superficial circumflex iliac, superficial inferior epigastric, and superficial external pudendal

Short saphenos vein

It begins from the lateral end of dorsal venous arch, ascends behind lateral malleolus, then towards the popliteal fossa, where it pierces the popliteal fascia and joins the popliteal vein

Perforators

These are communicating veins, that pierces the deep fascia, ensures unidirectional flow of blood from the superficial to the deep system. Note that all veins of the lower limb are equipped with venous valves to prevent backflow of blood.
The constant perforators for the long saphenous system : (4 in the leg + 1 in thigh)

a) Crockett's perforators : 3 in number, located 5cm, 10cm and 15cm above the tip of medial malleolus

b) Boyd's perforator : Single, located below the knee

c) Dodd's perforator : Single, located at the level of mid-thigh

There is only one constant perforator for the short saphenous system, which is located 10cm above the lateral malleolus.

The deep system comprises of :

Each artery of the lower limb, namely the anterior, posterior, and lateral tibial artery, is accompanied by 2 veins (known as vena comitantes). Hence, all the 6 veins join just below the popliteal fossa to form the popliteal vein, and becomes the superficial femoral vein as it passes through the hunterian's canal. Finally, as it joins with the deep femoral vein at the upper thigh, it forms the femoral vein.

Thread veins

These are small veins, with diameter of 1-2mm, appears reddish, bluish or purplish, and is usually asymptommatic (only cosmetically disfiguring). However, it might be an indicator of an underlying muscle pump failure, and varicose veins might develops in the future. 

Physiology

The calf muscles act as a pump, which ensures blood flow from superficial to deep system, and ascending upwards in the deep system.
However, this is only possible when there're competent venous valves.

Varicose veins

Defined as dilated, tortous, and elongated superficial veins of the lower limbs.

Usually secondary to chronic venous hypertension.

Pathophysiology :

1) More common in females
2) Occupation involving long hours of standing (policeman, conductors) are at risk of developing such conditions, due to chronic pooling of blood within these leg veins -> dilatation of these veins -> valvular incompetence

3) Pregnancy : Risk of developing varicosities increases, due to progresterone mediated venodilatation and the pressuring effect of the enlarging fetus to the inferior vena cava

4) In cases of post-thrombotic veins, where there's valvular damange, it causes reversal of blood flow

5) In cases of intravascular clotting (DVT) or extrinsic compression of the veins (eg, pelvic tumours), causing elevated venous pressure.

6) Lastly, primary varicosities seems to run in family.

Classification

1) Primary varicose veins

Due to unknown etiology
Probably due to inherited/congenital weakness of the vessel wall or even absence of venous valves

2) Secondary causes 

Might developed due to valvular destruction (secondary to venous thrombosis)
Pregnancy
Ovarian cyst/Fibroids
Pelvic cancers
Abdominal lymphadenopathy
Iliac vein thrombosis
Ascites
Retroperitoneal fibrosis
 
Important points in History taking :

1) During early phase of disease, symptoms are usually subjective :

Aching, dragging pain over the calf region
Burning sensation felt over the calf

Later followed by some skin changes (explained later)

2) Occupational history as mentioned above is important
3) Any family history of varicose vein
4) Any previous h/o of deep vein thrombosis
5) Any h/o of pregnancy, or even pelvic tumours
6) Any h/o of complications (ulcers, haemorrhage, ruptures, DVT, superficial thrombophlebitis)

On examination :

1) Make sure that you're examining the patient while he/she is standing
2) Inspect for any varicosities along the region of long and short saphenous veins
3) Inspect for any saphena varix at the upper end of the long saphenous vein (ask the patient to cough to appreciate any cough impulse and feel for a palpable thrill)

4) Look for complications :

a) Eczema and dermatitis : Due to chronic irritation secondary to RBC breakdown (hemosiderin deposition)

b) Lipodermatosclerosis : Thickening and induration of the pigmented skin of lower leg due to replacement of the subcutaneous fat with fibrous tissue.

c) Varicose ulcers

More common in females
Responsible for about 2/3 cases of leg ulcers
Located above medial malleolus (long saphenous system)
Located above lateral malleolus (short saphenous system)
Slopping edge, with unhealthy granulation tissue seen over the floor
Skin edges surrounded by pigmentation

d) Marjolin's ulcer

A type of squamous cell carcinoma developed due to excessive scarring of tissue, secondary to chronic venous ulcer (in this case)
There's extensive damage to the surrounding lymphatic vessels and vascular channels. Hence, there's no way for this malignant lesion to spread to distant areas.
Besides, it's radio and chemo-resistant
The only way of treatment is to peform wide-excision + extensive skin grafting.

e) Superficial thrombophlebitis

Due to inflammation of the superficial veins (red and tender cord)

Various specific test for varicose veins :