A 28-year old woman was diagnosed with a toxic multi-nodal goiter. A goiter is a non-neoplastic, non-inflammatory enlargement of the thyroid gland that can compress the trachea, esophagus, and associated structures (6). She demonstrated shortness of breath, dysphagia, anxiety, excessive sweating, heat intolerance, weight loss, and irritability. The surgeon suggested a bilateral subtotal thyroidectomy following a two-week regimen of anti-thyroid drugs. A subtotal thyroidectomy involves removal of almost the entirety of the thyroid gland while leaving the posterior aspect intact to preserve the underlying parathyroid glands (2). The antithyroid drugs reduced vascularization to the thyroid gland to minimize the risk of postoperative hemorrhage.
The patient’s symptoms can be explained primarily by the physiological role of thyroid hormone. In the case of a toxic multi-nodal goiter, the nodules autonomously release an excess amount of thyroid hormone (credible source needed). Thyroid hormone exerts its effect on most tissues in the body by increasing enzymes involved with metabolism. The pituitary releases thyroid-stimulating hormone, which induces thyroid-releasing hormone from the hypothalamus to induce thyroid hormone production and secretion from the thyroid gland (8). Once released into the blood, the lipid-soluble thyroid hormone can diffuse across cell membranes to target receptors within the nucleus or the mitochondria. Once bound, they are able to regulate gene expression in the nucleus for proteins involved in metabolism and increase the body’s metabolic rate by stimulating the synthesis of enzymes involved in the electron transport chain and increasing the number of sodium-potassium ATPase pumps in the mitochondria (8). With increased pump activity, there are more energy-releasing reactions to maintain the electrochemical gradient. With increased metabolic activity in cells throughout the body, there are relevant clinical manifestations such as warm and moist skin due to heat production and excessive sweating, increased cardiac output, weight loss, nervousness, and increased proteolysis and lipolysis (8). However, the mechanism for hyperthyroidism-induced irritability is still unknown. The patient is experiencing a shortness of breath and dysphagia due to the enlargement of the thyroid gland which causes swelling in the neck and compresses the trachea, esophagus, and recurrent laryngeal nerves making it difficult to breathe and swallow (6).
The thyroid gland is located in the neck anteriorly at bony level C5-T1, deep to the sternothyroid and sternohyoid muscles (6). The right and left lobes of the thyroid gland sit superficial and anterolateral to the larynx and trachea and are connected by an isthmus at the level of the second and third tracheal rings (6). In about fifty percent of people, there is a pyramidal lobe arising from the isthmus and ascending superiorly, which is a remnant of epithelium and connective tissue from the thyroglossal duct (6). A thin fibrous capsule surrounds the gland, which is attached to the cricoid cartilage and trachea by dense connective tissue (6). On the posterior surface of each lobe, superficial to the thyroid capsule, lie the small, paired superior and inferior parathyroid glands (6).
The thyroid gland is the first endocrine gland to develop during gestation (10). The gland originates from the embryonic pharynx and neural crest. The formation of the thyroid gland begins at the foramen cecum, which is present at the junction between the first and second pharyngeal pouches (1). The gland begins as an outpouching of endodermal epithelial cells called the thyroid primordium. After further development, the primordium becomes the thyroid diverticulum, which is a bilobed structure consisting of the left and right lobes of the thyroid gland (10). Once the thyroid diverticulum is formed, the endodermal cells continue to proliferate and the outpouching continues to grow, becoming the thyroglossal duct. This structure pulls the thyroid from the foramen cecum inferiorly along the anterior aspect of the epiglottis to the thyroid gland’s final position on the superior portion of the trachea (10). Once the thyroid is in place, the thyroglossal duct typically disappears (9).
During a subtotal thyroidectomy, certain vessels should be ligated to prevent hemorrhaging in this area. The thyroid gland is supplied bilaterally by the superior and inferior thyroid arteries. The superior thyroid artery branches off the external carotid artery and the inferior thyroid artery branches off the thyrocervical trunk which branches off the subclavian artery (6). Superior thyroid arteries supply the anterior superior portion of the thyroid gland and inferior thyroid arteries supply the posteroinferior portion. Superior and inferior thyroid arteries anastomose within the thyroid gland to provide sufficient blood flow and serve as a potential collateral circulation between subclavian and external carotid arteries (6). In ten percent of people, a small unpaired thyroid ima artery may be present, typically arising from the brachiocephalic trunk artery (6).
On the anterior surface of the thyroid gland is the thyroid plexus of veins consisting of pairs of superior thyroid veins draining the superior poles, the middle thyroid veins draining the middle of the lobes, and the inferior thyroid veins draining the inferior poles (6). The superior and middle thyroid veins drain into the internal jugular veins, while the inferior thyroid veins drain directly into the brachiocephalic veins. The nerves of the thyroid gland come from the superior, middle, and inferior cervical ganglia through the cardiac, superior, and inferior thyroid-arterial plexuses (6). These nerves control dilation and constriction of the vessels supplying the thyroid gland; they have no control in regulatory endocrine secretion as that is regulated by the pituitary (6). The aforementioned arteries and veins must be ligated during surgery to prevent lasting damage due to postoperative hemorrhaging. The nerves around the thyroid should also be protected to prevent potentially lethal consequences. Parathyroid glands in this area also need to be protected during surgery for regulation of calcium metabolism (6).
The recurrent laryngeal nerve has a varying course depending on which side of the body it comes from. The right recurrent laryngeal nerve branches off of the right vagus nerve and wraps under the right subclavian artery before running superiorly to the larynx. An important note to keep in mind when performing a thyroidectomy is the fact that right recurrent laryngeal nerve runs intimately with the right inferior thyroid artery (6). The left recurrent laryngeal nerve, branching from the left vagus nerve, courses under the aortic arch artery before returning superiorly to the larynx (5). Both of these nerves pass posterior to the cricothyroid joint, which is the location in which the recurrent laryngeal nerve changes its name to the inferior laryngeal nerve (5). The motor functions of the recurrent laryngeal nerve/inferior laryngeal nerve include motor innervation to all intrinsic muscles of the larynx (except for the cricothyroid muscle, which is innervated by the external branch of the superior laryngeal nerve) (5). The recurrent laryngeal nerve also supplies sensory innervation to the mucosa of the infraglottic cavity (6).
Since recurrent laryngeal nerves innervate most of the intrinsic laryngeal muscles, damage to this nerve can lead to disrupted function in the speaking and breathing (6). Damage unilaterally to the recurrent laryngeal nerve typically causes aphonia (disturbance of voice production) and laryngeal spasms.. One of the intrinsic muscles of the larynx is the posterior cricoarytenoid muscle which is responsible for abducting the vocal cords. Damage to the innervation to this muscle may cause difficulty during heavy breathing.
In addition to the nerves and vessels at risk during subtotal thyroidectomy, the parathyroid glands also pose a significant concern for surgeons. The parathyroid glands are four small, oval glands located on the posterior aspect of the thyroid gland, though there is some variability in the number and location of these glands in the body (6). These glands are primarily responsible for releasing parathyroid hormone, which plays a critical role alongside vitamin D in maintaining calcium homeostasis (4). At low serum calcium levels, parathyroid hormone and vitamin D are stimulated to increase calcium mobilization, increase intestinal calcium reabsorption, and decrease calcium excretion through urine (4). In cases of damage or removal of the parathyroid glands, circulating calcium levels plummet, resulting in hypocalcemia. Prolonged hypocalcemia can cause tetany in the form of muscle twitches and cramps that may result in death due to prolonged laryngeal constriction (6). Additionally, hypocalcemia has been linked to seizures, hyporeflexia, papilledema, neurological disturbances, and skin changes (3). In cases of total thyroidectomies, it is possible to transplant the parathyroid glands to the arm in order to preserve parathyroid hormone function (6).