Basic Science 36 Thyroid - Anatomy and Physiology

Pharyngeal Cleft /Groove - Series of invaginations in ectoderm in primitive pharynx

Pharyngeal Arch 

Pharyngeal Pouch -  Series of invagination in endoderm in primitive pharynx.

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1st - Epithelial lining of Auditory tube, middle ear cavity and mastoid antrum

2nd - Epithelial lining of crypts of Palatine tonsil

3rd - Thymus and Inferior Parathyroid gland

4th - Superior Parathyroid gland and Ultimobranchial Body

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Remember, in Sensory/Motor/Both mnemonic 'Some Say Marry Money But My Brother Says Bad Boys Marry Money, the B's also give Branchial arch nerves in order:

• o But (CN V3): 1st arch
• o Brother (CN VII): 2nd arch
• o Bad (CN IX): 3rd arch
• o Boys (CN X): 4th and 6th arch - 4th gives superior laryngeal of vagus, 6th gives recurrent laryngeal of vagus

1st - Maxillary artey

2nd - Stapedial artery 

3rd - Common carotid artery 

4th - Arch of aorta

6th - Right and left pulmonary arteries, Ductus arteriosus 

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1st - muscles of mastication, tensor tympani, tensor veli palatini

2nd - Muscles of facial expression 

3rd - Stylopharyngeus muscle 

4th - Cricothyroid muscle, soft palate, phaynx 

6th - Intrinsic muscles of larynx except cricothyroid muscle

• o 1st groove gives rise to external auditory meatus 
• o All other groves do not give rise to any structures because the 2nd arch becomes very large and covers all the surface behind it and thus filling all the grooves.
• o In adult, this overgrown 2nd arch gives rise to platysma muscle.

A second arch fistula has a typical course, the knowledge of which can help in the total surgical extirpation of the tract.

• It has:
• o An external opening at the junction of lower and middle of the anterior border of sternomastoid. 
• o A tract which ascends just deep to deep cervical fascia along the carotid artery.
• o The tract passes deep to second arch structures, i.e. external carotid artery, stylohyoid and posterior belly of digastric but superficial to third arch structure, i.e. internal carotid artery (the tract passes between internal and external carotid arteries). It also runs superficial to hypoglossal nerve.
• o Pierces the pharyngeal wall and ends in the tonsillar fossa.

Branchial cyst is a vestigial remnant of 2nd branchial cleft and is lined by squamous epithelium. It appears in young adults and protrudes from beneath the anterior border of the upper 1/3rd of the sternocleidomastoid muscle as a fluctuant swelling that may transilluminate

• The tissue bud that becomes the thyroid gland initially arises as a midline diverticulum in the floor of the pharynx. This tissue originates in the primitive alimentary tract and consists of cells of endodermal origin. This point of origin corresponds to the foramen cecum of the base of the tongue in a fully developed human. The main portion of this cellular structure descends into the neck and develops into a bilobed solid organ. This structure becomes the thyroglossal duct, which is usually reabsorbed after 6 weeks of age. The distal aspect of this path of descent may be retained as a pyramidal lobe in the adult thyroid.
• Calcitonin-producing C cells arise from the fourth pharyngeal pouch and migrate from the neural crest into the thyroid. These C cells are the only component of the adult gland not of endodermal origin.

• Thyroglossal cyst is the remnant of thyroglossal duct. It is lined by endoderm.
• A thyroglossal cyst may be present in any part of thyroglossal tract but the most common site is beneath the hyoid (subhyoid).
• It is present in midline except in the region of thyroid cartilage where it is pushed to one side usually to the left.
• o It is very important to remember that due to its attachment to the foramen cecum, it moves upwards on protrusion of the tongue and on swallowing.

• Thyroglossal fistula is always acquired and never congenital, it occurs after infection or inadequate removal of a thyroglossal cyst. 
• As a thyroglossal tract is closely related to the body of thyroid,  this part must be excised along with the cyst or fistula, otherwise recurrence is certain.
• Sistrunk’ s operation is the treatment of choice - resection of the cyst and the midportion of the hyoid bone in continuity and resection of a core of tissue from the hyoid upwards toward the foramen cecum

Thyroid tissue found in lateral neck compartments was known as “lateral aberrant thyroid” and was explained as an embryologic variation. This concept has essentially been disproved, and it is thought that thyroid tissue found in the neck lateral to the jugular vein represents metastatic deposits from differentiated thyroid carcinoma (DTC), typically papillary cancer, and may be the initial presentation of this disease.

• The lobes lie lateral to the trachea and esophagus; anteromedial to the carotid sheath; and posteromedial to the sternocleidomastoid, sternohyoid, and sternothyroid muscles. The two lateral lobes are joined at the midline by an isthmus, whose superior edge is situated at or just below the cricoid cartilage.
• A pyramidal lobe is present in approximately 30% of patients and represents the most distal portion of the thyroglossal duct
• A thin layer of connective tissue surrounds the thyroid. This tissue is part of the fascial layer that invests the trachea. This pretracheal fascia is different from the thyroid capsule, and it can easily be separated from the capsule during surgery, whereas the true capsule of the thyroid cannot be separated. This fascia coalesces with the thyroid capsule posteriorly and laterally to form a suspensory ligament termed the ligament of Berry, which is the primary point of fixation of the thyroid to surrounding structures.

• SLN - Although such loss may not be as clinically devastating as RLN damage, it is extremely bothersome to patients whose occupation or avocation demands good voice quality
• RLN - paralysis of the vocal cord on the affected side - cord remains in a midline position or paramedian position. A grossly normal voice may occur if the remaining functioning contralateral cord is able to approximate the paralyzed cord. If the vocal cord remains paralyzed in adducted position and closure cannot occur, a severely impaired voice and ineffective cough also may result. If the RLNs are damaged bilaterally, complete loss of voice or airway obstruction may occur and possibly require an emergency surgical airway

• The arterial supply to the thyroid gland consists of four main arteries, two superior and two inferior
• The superior thyroid artery is the first branch of the external carotid artery after the bifurcation of the common carotid artery. The superior thyroid artery gives off the superior laryngeal artery and courses medially onto the surface of the inferior pharyngeal constrictor muscle and enters the apex of the superior pole. As the superior thyroid artery proceeds medially, it is adjacent to the external branch of the superior laryngeal nerve, and care must be taken not to damage it when controlling the artery
• The inferior thyroid artery takes its origin from the thyrocervical trunk. This artery originates from the subclavian artery and ascends into the neck on either side posterior to the carotid sheath and then arches medially and enters the thyroid gland posteriorly, usually near the ligament of Berry. Despite the name “inferior thyroid artery,” no direct arterial supply generally enters the inferior aspect of the thyroid.
• However, an arteria thyroidea ima may be present in less than 5% of patients and usually arises directly from the innominate artery or from the aorta
• The inferior thyroid artery typically supplies the superior and the inferior parathyroid glands, and care must be taken to evaluate the parathyroids after division of the inferior thyroid artery. For this reason, the inferior thyroid artery should be divided at the distal branches into the thyroid, rather than at its main trunk.

• Three pairs of venous systems drain the thyroid.
• Superior venous drainage is immediately adjacent to the superior arteries and joins the internal jugular vein at the level of the carotid bifurcation.
• Middle thyroid veins may be single or multiple and course immediately laterally into the internal jugular vein.
• The inferior thyroid veins are usually two or three in number and descend directly from the lower pole of the gland into the innominate and brachiocephalic veins.
• These veins often descend in association with the cervical horn of the thymus gland.

• The normal parathyroid gland is small, weighing approximately 40 mg.
• The designation of a parathyroid gland as “superior” or “inferior” is not based on the relative cranial to caudal position of the gland. What is more consistent is that the inferior parathyroid glands lie anterior to the RLN, and the superior parathyroid glands lie posterior to the RLN.
• The superior and inferior parathyroid glands most often have a single end artery that supplies them medially from the inferior thyroid artery. If the main trunk of the inferior thyroid artery is sacrificed for dissection, both parathyroids on that side become devascularized because there is no collateral blood supply in most cases to maintain viability.
• The inferior parathyroid blood supply is invariably from the inferior thyroid artery, whereas 15% to 20% of superior parathyroids have significant arterial supply from the superior thyroid artery.

• 
• Organification - Iodine binds with TG to form MIT and DIT.

• Inhibit hormone synthesis (antithyroid drugs) - Propylthiouracil, Methimazole, Carbimazole
• Inhibit iodine trapping (ionic inhibitors) - Thiocyanates, Perchlorate, Nitrates
• Inhibit hormone release - Iodine, Iodides of Na and K, Organic Iodide, Lugol’s Iodine (Potassium iodide plus iodine)
• Destroy thyroid tissue - Radioactive iodine, I131, I125, I123
• Inhibit peripheral conversion - Propylthiouracil, Beta blockers

• T3 is significantly more bioactive than T4.
• Most T4 is converted to T3, which has a high affinity for the peripheral nuclear thyroid hormone receptor (TR), a member of the steroid hormone receptor family
• Of circulating T3 and T4, 80% is bound to thyroxine-binding globulin (TBG) in the periphery
• Most T3 and T4 are bound to the extent that free T4 constitutes less than 1% of peripheral hormone
• Most T3 is peripherally derived from the deiodination of T4, which takes place largely in the plasma and liver
• Peripheral conversion of T4 to T3 can be impaired in many clinical circumstances, such as overwhelming sepsis and malnutrition, thionamide (propylthiouracil [PTU]) use, high-dose corticosteroids, beta blockers, iodinated contrast agents, and amiodarone use resulting in thyroid imbalance.

• Free T3 - 
• Free T4 (thyroxine) - 0.8-1.8 ng/dl 
• TSH - 0.45 - 4.5 mIU/L

• RAI uptake involves the oral administration of iodine-123 (123I) and calculated uptake with radioscintigraphy. A normal result is 15% to 30% uptake of the radionuclide after approximately 24 hours.
• 123I is preferable because of its shorter half-life and lesser radiation exposure with use than 131I, which is used for radioablation of thyroid neoplasms.
• Indications for the use of radioscintigraphy include the evaluation of a solitary thyroid nodule when the initial TSH is low (Fig. 36-8), to help delineate the cause of hyperthyroidism and, detection of functioning thyroid cancer metastases after remnant iodine ablation

The chronic physiologic changes that result from a lifetime of iodine deficiency involve anatomic and metabolic alterations of varying significance.

• Chronic preferential production of T3 rather than T4 and enhanced peripheral conversion of T4 to T3 occur. By making the production of T3 and clearance of the metabolically active hormone as efficient as possible, clinical hypothyroidism is largely avoided by a biochemical pattern of low serum T4 levels with elevated TSH levels and normal or above-normal levels of T3.
• In the most severe cases, serum T3 and T4 concentrations are low, and the serum TSH level is elevated. Iodine deficiency can lead to a preventable disease termed endemic goiter.
• Thyroid follicles demonstrate a hypertrophic response, with a reduction in follicular spaces. As iodine deficiency becomes more severe, follicles can become inactive and distended with colloid. Focal areas of nodular hyperplasia may develop and form nodules, some of which may become hot nodules and have an autonomous function. Others become inactive and inert. Necrosis, scarring, and hemorrhage can occur and result in fibrous ingrowth; all these disorders are accompanied by marked enlargement of the gland, often in an asymmetrical pattern.

• Antithyroid drugs –
• Amiodarone,
• lithium,
• Interferon alpha
• Interleukin 2