Thyroid Gland - Anatomy, Embryology,  Developmental Abnormalities, Symptoms and Investigation 

Anatomy of Thyroid Gland

The thyroid weighs around 20 grams. Thyroid Gland is made of two lobes, one is on the right, and the other is on the left joined in the midline by Isthmus.  Isthmus is part of the thyroid Gland corresponding to 2nd, 3rd, and 4th tracheal rings. Lobes of the thyroid gland correspond to the upper and middle of the thyroid cartilage, till the  the 5th and 6tb tracheal rings. - The pyramidal lobe is seen in 30% of cases. The pyramidal lobe (PL), also known as the third lobe of the thyroid gland or lobe of Lalouette, is an embryological remnant of the distal end of the thyroglossal duct . There is a projection called the organ of Zuckerkandl  which is a very important and reliable landmark for the identification of recurrent laryngeal nerve during  the surgery. RLN passes posterior to the  organ of Zuckerkandl. Another important landmark for identification for the guide for RLN during  the surgery is called the ligament of the berry. Berry's ligament is formed by the joining of pretracheal fascia with the true capsule of thyroid gland in the posterior and the lateral aspect. RLN passes either through the ligament of the berry  or under  the ligament of the berry  to enter the larynx.

Blood Supply of the Thyroid Gland

The two constant arteries supplying the thyroid gland are the superior thyroid arteries, also the external carotid arteries. The second thyroid artery is the inferior thyroid artery which is the branch of the thyrocervical trunk which is the branch of the subclavian artery. The inferior thyroid artery arises proximally  from the thyrocervical trunk and ascends up and posterior to the carotid shealth and curves to enter the thyroid gland . 

In 5 % cases we can find the third artery i.e. Thyroidea  IMA artery. Thyroidea IMA is a branch of  the Brachiocephalic trunk and usually follows the midline course and goes to the isthmus or the  inferior poles of thyroid gland.

Veins Associated with the Thyroid Gland:

Venous drainage of thyroid gland: Three important veins drain Thyroid Gland.  Superior thyroid veins drain into the internal jugular vein. The middle thyroid vein is very important and is a short vein with variable locations. It is mainly seen in around 50% of individuals. It is the first vessel to be ligated during thyroid surgery . It drains into the internal jugular vein. The inferior thyroid vein can be two to three, and it drains into the brachiocephalic vein.

Nerves associated with the thyroid gland

• Recurrent laryngeal nerve: The recurrent laryngeal nerve (RLN) is a paired nerve and arises from the vagus nerve (cranial nerve X). 
• Left-sided recurrent laryngeal nerve: It arises from the vagus nerve and loops around the aortic arch at the level of  the ligamentum arteriousum , ascending upwards and at the level of lower poles of the thyroid gland enters  the tracheoesophageal groove and ascends upto the larynx.
• Right-sided recurrent laryngeal nerve: Arises from the vagus nerve and loops around the junction of right subclavian and right common carotid artery and then ascends up lateral to the trachea and enters  the tracheoesophageal groove in the middle part of the thyroid gland.

Also Read: Prune Belly Syndrome (Eagle Belly Syndrome)

Difference between left recurrent laryngeal nerve and right recurrent laryngeal nerve

1. The left recurrent laryngeal nerve has a longer course and a straight course. It lies in a deeper and more medial place. 
2. The right recurrent laryngeal nerve has a shorter and more oblique course than the left recurrent laryngeal nerve. It lies in a more superficial plane. 

Relation with the Inferior Thyroid artery- In the neck RLN usually lies posterior to the Inferior thyroid artery but at times it can lie anterior or pass between the branches of the Inferior thyroid artery.

Recurrent laryngeal nerves supply all the intrinsic muscles of the larynx except the cricothyroid. Along with this, recurrent laryngeal nerves also sensory supply to the larynx below the vocal cords. The recurrent laryngeal nerve may be seen as a non-recurrent laryngeal nerve.

• Non-recurrent laryngeal nerve arises  straight from Vagus and follows a straight path to the larynx. It is commonly seen on the right side and mostly in 0.5-1.5% of individuals. Non-recurrent laryngeal nerves can be commonly associated with aberrant right subclavian arteries. Left sided Non-recurrent laryngeal nerve are uncommon and when they occur they are associated with Situs inversus or right sided Aortic arch. 

External Branch of the Superior Laryngeal Nerve: 

• SLN at the level of hyoid bone gives two branches, an internal branch and an external branch. The internal branch of the superior laryngeal nerve provides the sensory supply to the larynx above the vocal cords. The external branch of the superior laryngeal nerve runs parallel to the upper part of the superior thyroid vessel. External branch of the superior laryngeal nerve supply cricothyroid  muscle. Superior thyroid vessel should be ligated as close to the thyroid gland as possible to prevent the injury to the external branch of the superior laryngeal nerve.

LYMPHATIC DRAINAGE

• Lymphatic from the thyroid gland predominantly drains into the central group of lymph nodes, which includes the level 6 lymph nodes, which include the following: Prelaryngeal- Delphian, nodes, Pretracheal, Paratracheal. Level 7 of the lymph nodes is also considered part of the central group of lymph nodes. Some of the lymphatics can also drain into the lateral group of lymph nodes, including levels 2,3,4, and 5b. These are the lymph nodes where we can inspect or suspect any problems associated with the thyroid carcinoma of the patients.

Histology of Thyroid gland

• The thyroid gland is made up of lobes, and lobes are made of lobules. Lobules are called the functional unit of the thyroid gland.Every lobule is supplied by single arteriole. Lobules are made of follicles and around 25-40 follicles in each lobule. The follicles are lined by single-layered flattened cuboidal cells in resting cells. The activity of the thyroid gland increases, and the height of the epithelial cells increases. In state of Hyperthyroidism Epithelial lining becomes High (tall) columnar epithelium.  The follicle contain the colloid which stores the T3 and T4 bound to the protein Thyroglobulin .

Also Read: RENAL STONES - Etiology, Investigation and Management

Physiology of Thyroid gland

• The thyroid gland produces three important hormones called T4, T3, and calcitonin. Follicles produce T3 and T4 hormones, while calcitonin is produced by C cells.
• Formation of T3 and T4: The trapping of iodine takes place in the form of inorganic iodide. Further, it undergoes oxidation, and there is binding to form monoiodotyrosine and diiodotyrosine. There is a coupling of diiodotyrosine and monoiodotyrosine to form T3 and T4 hormones.
• Organification and Binding are catalysed by enzyme Peroxidase. In  euthyroid state whole  T4 comes from the thyroid gland but only  20% of T3 comes from the thyroid gland, and the rest is formed in the blood by peripheral conversion of T4 to T3 by deiodination in the outer ring of T4.
• If there is deiodination from the inner ring of T4 it results in the formation of metabolic inactive compound rT3. Normally rT3 gets cleared from the circulatio but in cases of non thryoidal illness or Sick Euthyroid syndrome levels of rT3 rises.  In hyperactive states like Graves disease or Multinodular toxic goitre increased production of T3  directly from the  Thyroid gland. T3 is a more active biological hormone as compared to T4.
• Once in the circulation T4 AND T3 are in the bound form (99.9%) and free form (0.1%) . 80 % of the  bound form is bound to Thyroid binding globulin , along with that it can be bound to Albumin and prealbumin. TSH is responsible for the growth of the thyroid gland.
• Differentiation of the follicular cells uptake, and organification of iodine and release of T3 and T4 occurs in the stimulation of TSH. TRH, which is the Thyrotropin-releasing hormone, is a hypophysis tropic hormone produced by neurons in the hypothalamus that stimulates the release of thyroid-stimulating hormone and prolactin from the anterior pituitary.

Embryology of Thyroid gland

• The thyroid gland develops in the floor of mouth  at the middle of the base of the tongue, the development starts at the junction of the anterior 2/3 rd and the posterior 1/3 rd of the tongue which later  is called a foreman caecum.
• It arises as the midline thyroid diverticulum around the second week of gestation. Further, it descends into the neck along the thyroglossal duct  and forms the bilobed diverticulum. This bilobed diverticulum will give rise to solid bilobed thyroid gland. By the sixth week of gestation, this thyroglossal duct  starts getting absorbed and by the seventh week of gestation, the thyroid gland reaches its final location.
• C-cells of the thyroid gland: Parafollicular cells (C cells) These cells are derived from neural crest cells and get incorporated in the thyroid gland via  ultimobranchial bodies which arise from the 4th  or the 5th  Phyrangeal pouches. Ultimobranchial bodies form a part of the Lateral thyroid anlage which fuses with the midline thyroid anlage and incorporates th Ccels into the thyroid gland. C cells are located in  the superolateral aspect of the thyroid gland.

Developmental abnormalities of Thyroid Gland

1.Ectopic thyroid: 

• Ectopic thyroid can be located anywhere along the path of development and descent of the thyroid gland which means it can be anywhere from the foreman caecum to the anterior mediastinum. At times it may descent further into mediastinum and give rise to mediasinal thyroid gland .

2.Lingual thyroid:

It is an undescended thyroid located at the base of tongue. Due to inadequate production of thyroid hormones there is  increased levels of TSH, it leads to the increase  size of the thyroid gland which results in swelling at the base of the tongue. So the lingual  symptoms of thyroid  mainly presents as the swelling of the base of the tongue.

Lingual thyroid is mainly present with compressive thyroid symptoms. Further swelling interferes with speech, difficulty in swallowing, and respiration as well. The lingual thyroid requires surgery for the treatment and remove of the lingual thyroid.

Before surgery, it is crucial to make sure that there is only thyroid tissue present in the body or that there is some other thyroid tissue present in the body elsewhere as well. It is important to go for a thyroid scan before the surgical procedure such as a radioactive Iodine scan to see if it is the only thyroid tissue in the body or not. If it is the only thyroid tissue then the other options for the lingual thyroid include: TSH suppression by giving thyroxine to the patient. Radioactive Iodine ablation in case of TSH suppression doesn't work in the patient.

Related: Post Operative Thyroid Complications

THYROGLOSSAL CYST

• Investigation of choice of thyroglossal cyst includes ultrasound-guided FNAC.  Complications:  Infection, papillary carcinoma of the thyroid gland

• Treatment: Sistrunk's operation is the surgical procedure done for the thyroglossal cyst. Sistrunk's operation includes the following components:  Excision of the cyst, along with the entire tract,. Excise the central body of the hyoid bone. Excise the central core of lingual muscle as well. Incision and drainage are contraindicated and should not be done in a patient with a thyroglossal cyst. 

THYROGLOSSAL FISTULA

• Thyroglossal Fistula forms due to two main reasons: Infection in the thyroglossal cyst which can  ruptre spontaneously giving rise to Thyroglossal fistula. Inadequate removal of thyroglossal cyst. Thyroglossal Fistula is never congenital. Symptoms- Off and on discharge from the  small cutaneous opening covered by the hood of skin, the discharge can be mucoid or mucopurulent. Small cutaneous opening can go upwards in swallowing as well as while protrusion of the tongue. Treatment of choice is Sistrunk's operation.

INVESTIGATION

• The first investigation that we do in thyroid pathology or thyroid dysfunction is TFT. TFT is the thyroid function test. It includes the measurement of serum levels of TSH, T3, and T4. The most reliable, sensitive, and first-line screening investigation for thyroid pathology is TSH. The TSH is measured by third and fourth-generation ultrasensitive radioimmunoassay. Normal values of TSH are:

• We can measure total level of T3 and T4 but preferably Free T3 and T4 are measured. If the TSH level is normal or high then the next step of management is thyroid ultrasound or a neck ultrasound in all patients with MNG/ palpable solitary thyroid nodule and nodule detection on other imaging studies. If the TSH level is low then the next step of management is thyroid scan.

USG -Objective of Evaluation

• High-frequency probe- 7.5-16mHz, tells the size of the thyroid gland, confirmation of the presence of a nodule or diffuse enlargement, Solitary (STN) versus  multiple (MNG), location of the nodule (which includes anterior and posterior), omposition either solid or cystic, an accurate nodule size assessment is required for the follow-up. Ultrasound characterized the nodule to assess the risk of malignancy, helps to guide FNAC, extrathyroidal invasion, show the presence of lymph nodes and their following characteristics as well. Normal lymph nodes will be rounded with the loss of fatty hilum 

USG prediction or the malignancy:

• Hypoechoic solid nodule, taller than wider shape, loss of peripheral halo, microcalcification, chaotic intra-nodular vascularity, complex nodules, Infiltrative or micro lobulated margins

FNAC

• It is the most accurate invasive investigation. FNAC is the investigation of choice in patients with discrete thyroid swelling and discrete thyroid nodules. For the FNAC, a needle of 23-27 gauge is used.  FNAC has more than 80% sensitivity and more than 90% specificity. Drawback: FNAC cannot distinguish between a follicular adenoma or a follicular carcinoma because it cannot tell about the capsular and the vascular invasion which we find in a patient of follicular carcinoma. The adequate FNAC is defined as the six groups of follicular cells containing at least 10-15 cells from 2 aspirates. 

Thyroid Scan

• It is also called a radioisotope scan or thyroid scintigraphy. The main objective is to tell about the distribution of the activity in the gland. Radiotracers that can be used are:Iodine 123-t _1/2 -13 hours- More preferred, 99TC-t _1/2-6 hours. If given by IV route images can be obtained  at 30 mins  , but in oral route images are obtained at 6 and 24 hours. Normal thyroid gland has bilateral symetrical uptake and is 15-30 % at the end of 24 hrs. 

Images

Area of increased focal intake- Hot nodule/area ( risk of malignancy- <5%), Decrease uptake / non functional area – Cold nodule ( risk of malignancy- 15-20%). Indications of Thyroid scan- In pateints of hyperthyroidism – differentiate between differnt causes of hyperthyroidism  , to see distribution activity in mixed picture hyperthyroidism. Ectopic thyroid. Thyroid cancer- to look for residula disease or recurrent disease.

• Graves disease-uniformly increased uptake. Toxic adenoma- single area of incresed uptake. Thyroiditis- uniformly decreased uptake. Toxic Nodular goitre- mixed/ patchy distribution where there are  multiple area of incresed uptake and decresed uptake

Cross-sectional imaging: 

1.CT or MRI

• For certain indications, cross-section imaging is performed. Provides good anatomical images of the thyroid gland about the surrounding structure, especially the surrounding structure of the aerodigestive tract, such as the esophagus and trachea. It also tells about the surrounding structure of the muscles and evenly surrounding vessels.  Cross-section imaging is better than ultrasound in evaluating infra clavicular mediastinum. Indications: Retro sternal goiter (NCCT) and advanced or Locally advanced thyroid cancer (CECT).  For cross-section imaging, CT is widely preferred because of its easy interpretation and we order CT from skull base to the Tracheal bifurcation.

2.PET Scan

• It is useful in thyroid cancer which has become refractory to radioactive iodine. It is used in high risk or recurrent thyroid cancers.  35% of nodules picked at PET scans are more likely to be malignant. 

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