The thyroid gland lies as a paired organ in the peritracheal fascia at the caudoventral aspect of the larynx. In humans, both thyroid lobes are connected by an "isthmus," but dogs and cats usually lack this connection, which makes each lobe a separate organ. In close relation with each thyroid gland are two small round to oval parathyroid glands. The localisation of these parathyroid glands is quite variable in both species. The intracapsular parathyroid gland can usually be found in the thyroid gland parenchyma in the center or at the dorsal side of the middle or caudal third of the thyroid gland. The superficially located extracapsular parathyroid gland lies close to the cranial pole of the thyroid gland.
The blood supply to the thyroid comes from the cranial and caudal thyroid arteries, which originate from the A. carotis communis or directly from the brachiocephalic artery. In the cat, often only the cranial thyroid artery is present, while in the dog there is usually also a caudal blood supply. The venous drainage is into the internal jugular veins.
The deep cervical lymph nodes (Lnn. cervicales profundi) are the tributary lymph nodes of the thyroid gland and can be found alongside the trachea. Lymphatic anastomoses also allow for a lymphatic drainage to the contralateral side.
Canine Thyroid Tumors
In former times, when dogs were frequently fed an iodine deficient diet, thyroid neoplasia was common and goiter was a common condition in dogs (and humans) in certain geographic areas.
Today, most canine thyroid neoplasias are malignant, the majority are unilateral, but bilateral tumors occur in up to 30% of the cases. A breed predisposition has been reported for the Boxer, Beagle, Golden Retriever, Collie and Airedale terrier. The average age of affected animals is 10 years, and there is no known sex predilection.
Most carcinomas originate from the follicular epithelium, and according to their histologic differentiation, they are grouped into follicular, papillary, solid, and anaplastic carcinomas, which is of prognostic significance. The rare medullary carcinomas originate from the parafollicular calcitonin, producing "c-cells" and are therefore also termed c-cell carcinomas. In the dog, thyroid carcinomas are usually not hormonally active. Hormone production can only be found in less than 20% of the patients and in these cases, both hyper- and hypothyroidism can occur. T4 and cTSH should be measured in all patients. Tumor metastases can occur to the lungs and the deep cervical, mandibular and retropharyngeal lymph nodes. In addition, distant metastases have been reported to arise in many organs: e.g., adrenals, kidneys, heart, liver, and brain. At time of diagnosis, about 40% of all dogs have metastases. Vascular invasion is common and finger-like projections into the vessels of the neck can be detected by Doppler sonography or, better, by contrast-CT.
All thyroid tumors are highly vascular, and Tru-Cut or incisional biopsies frequently lead to severe bleeding. The author therefore prefers fine needle aspiration for confirmation of diagnosis. Aspirates can be quite bloody, but usually contain an adequate number of cells and cell aggregates to ascertain a diagnosis. It has to be noted that the cellular characteristics of thyroid carcinoma are quite "benign," which is typical for endocrine neoplasia.
Contrast-CT or MRI are the imaging modalities of choice. Besides determining the extent of the tumor, these modalities are superior in demonstrating invasion into surrounding soft tissues and vessels as well as changes of the local lymph nodes regarding size and contrast uptake. If these techniques are not available, sonography can help assess invasion. Scintigraphic exams using Technetium pertechnetate (99mTc) can be helpful in diagnosis and staging of thyroid tumors; however, in the author's experience, in addition to their limited availability, their diagnostic value is not superior to CT or MRI.
From a clinical and therapeutical standpoint, two forms of canine thyroid tumors have to be differentiated: 1) clinically moveable and non-macro-invasive forms; 2) macro-invasive tumors that present as non- or poorly moveable, poorly circumscribed masses. These tumors can cause coughing, dyspnea, difficulty swallowing, and laryngeal paralysis from affection of the recurrent laryngeal nerve resulting in dyspnea and voice changes.
The type of therapy is based on the degree of invasion of the tumor. In noninvasive, moveable tumors, surgical resection is the therapy of choice. Because large tumors may compress on the trachea, rapid intubation after induction of anaesthesia is important. Patients with hyperthyroidism should not receive anticholinergic drugs, which could induce severe tachyarrhythmias.
The surgeon has to be well familiar with the anatomic structures of the ventral neck area. The animal is placed in dorsal recumbency and a ventral median skin incision is made from the cricoid to the manubrium. The long ventral neck muscles (Mm. sternohyoidei) are separated in the ventral midline, and the tumorous thyroid gland is exposed. Unilateral moveable tumors are resected within their capsule and include the parathyroid glands. The author recommends performing the tumor resection from the caudal, followed by the lateral, the dorsal and finally cranial aspects. Exposition of the anatomic structures cranially and caudally to the tumor help to identify the recurrent laryngeal nerve which lies dorsolateral to the trachea and the vagosympathetic trunk, which runs with the carotid artery. Injury to these nerves causes laryngeal paralysis and Horner's syndrome, respectively. If macroscopic invasion of larger vessels is apparent, these vessels are resected en bloc together with the tumor. Transsection of the carotid artery or jugular vein(s) does not cause clinical problems. Meticulous hemostasis is mandatory. Invasion into the neck musculature requires resection of the affected muscles. Bilateral tumors can be resected in a staged manner in which (at least) one extracapsular parathyroid gland is preserved and implanted into the surrounding soft tissue followed by the resection of the contralateral side 6–8 weeks later. Some authors advocate performing a bilateral thyroidectomy in one session and (initially) substitute for parathyroid hormone using vitamin D and calcium and thyroid hormone (Tuohy et al. 2012).
Macro-invasive tumors, which involve the esophagus, trachea or larynx, are considered inoperable and surgery is not indicated. In these cases, external beam radiation is preferred and can lead to acceptable survival times (Mayer et al. 2007).
The prognosis of operable thyroid tumors is quite favourable. In one study, median survival time of 20 patients was longer than 36 months (Klein 1995). In a study by the author, median survival time in 57 surgically treated cases was 18 months (Jores and Kessler, unpublished). According to the literature, tumor capsule, vascular or lymphatic invasion is associated with a poorer prognosis (Verschueren 1992). In the aforementioned study of the author, this could not be confirmed and invasive growth into or through the tumor capsule or microscopic or macroscopic vascular invasion was not a prognostic factor (Jores and Kessler, unpublished). Postoperative complications include bleeding, injury to the recurrent laryngeal nerves, and hypocalcemia from resection of the parathyroid glands.
Postoperative substitution of thyroid hormone in all cases has been advocated by some authors independent of the hormonal status because (re)growth of the tumor may be stimulated by endogenous TSH (Verschueren 1992). However, it has to be noted that most tumor metastases bear no or only very low numbers of TSH receptors.
Rare Thyroid Carcinoma Subtypes in Dogs
Medullary carcinoma (C-cell carcinoma) is a neoplasia of the parafollicular Calcitonin producing C-cells. For this reason C-cell carcinomas can go along with hypocalcemia. The histologic appearance is similar to that of low differentiated thyroid tumors, therefore immunohistologic verification is sometimes necessary (immunohistochemical documentation of Calcitonin). Most C-cell carcinomas are circumscribed, minimally invasive and therefore resectable. According to one study 10 of 12 tumors were resectable, 3 of these 10 dogs survived longer than 1 year (Carver 1995).
Ectopic thyroid tumors originate from "ectopic" or "accessory" thyroid tissue, which can be found alongside the entire trachea, in the mediastinum, and in the base of the tongue. Most commonly, they are located at the heart base close to the aorta between the origin of the brachiocephalic artery and the ductus arteriosus (Botalli).
Mediastinal ectopic thyroid carcinomas make up 5–10% of all tumors at the heart base and may go along with a chylothorax. They behave similarly to their normotopic counterparts with local invasion and a tendency for metastasis and are only rarely hormonally functional. Surgery is frequently problematic due to invasion into the pericardium, the heart itself or the cranial vena cava. Postoperative complications are common. In one study of 8 dogs, 6 were considered operable out of which 2 dogs died postoperatively. Median ST was 243 days (Liptak et al. 2008).
Ectopic thyroid tumors originating from the thyroglossal duct present as a subepiglottic mass and may cause dysphagia and coughing. This duct is an embryological anatomical structure, which represents a connection between the initial location of development of the thyroid gland and its final position. It atrophies during development of the fetus. Since it is located exactly on the midline in the posterior third of the tongue and involves the hyoid apparatus, ectopic thyroid tumors from this tissue usually cause osteolysis of the basihyoid and other hypoid bones. Resections of these tumors therefore include parts of the hyoid apparatus. This has not resulted in functional deficits in two cases treated by the author.
Multiple endocrine neoplasia (MEN-syndrome) goes along with simultaneous occurrence of tumors in several endocrine tissues. In Boxers and Boston Terriers, simultaneous occurrence of thyroid tumor and chemodectoma has been described.
Feline Thyroid Tumors
The normal thyroid glands in the cat are 14–25 mm long and 2.5–4 mm wide and have an extracapsular parathyroid gland on the cranial pole and an intracapsular parathyroid gland in the middle or caudal part. In the cat, the cranial thyroid artery branches off the A. carotis communis and supplies the entire gland while venous drainage is via cranial and caudal thyroid veins. Ectopic thyroid tissue is quite common in the cat and can be found anywhere between the base of the tongue and the base of the heart.
Thyroid tumors and hyperplasias are seen in cats, especially in USA, Europe, Australia, and New Zealand, but they have only rarely been reported in other parts of the world. Masses in the thyroid are usually seen in older cats (average age for adenomas and carcinomas 12.4 and 15.8 years, respectively. Today, hyperthyroidism is the most important endocrine disease in the cat. In the USA, benign changes (thyroid adenomas or hyperplasias) make up 98% of all thyroid masses; however, the incidence of carcinomas seems to be rising.
The frequency and geographic distribution of hyperthyroidism in cats point towards environmental, nutritional, and/or genetic cofactors in the development of this disease. Extensive research has been performed in this respect, but a convincing conclusion has not yet been reached. The feeding of canned food (esp. with fish and liver) and variable iodine content of the diet have been brought into connection with feline hyperthyroidism. In this respect, resorcinol, which is a component of the inner lining of food cans, has been found to promote struma formation. Environmental exposure to certain substances; e.g., some cat litter types, antiparasitics, plant fertilizers, herbicides, polybrominated diphenyl ether (PBDE, used as flame retardants in textiles), phthalates (found in many PVC plastics), polyphenols, PCBs, as well as an autoimmune component and genetic factors have been discussed to play a role in the development of the disease. There is an increasing prevalence of cats that have received Thiamazole derivatives for long-term treatment of hyperthyroidism and developed carcinomas in their thyroid glands. Therefore, malignant progression from benign neoplasia to carcinoma is suspected (Peterson 2010).
Most feline thyroid masses are benign hyperplasias or adenomas. They usually occur bilaterally and are hormonally functional leading to hyperthyroidism resulting predominantly in weight loss despite increased food uptake, hyperactivity, and secondary kidney and cardiac changes. Benign masses are usually small and have a tendency to displace towards the thoracic aperture following gravity. Cystic adenomas can reach several centimeters in diameter. Ectopic thyroid tumors can be found in about 10% of the patients. Adenocarcinomas are rare in cats and are usually larger than adenomas. Histologically, they are invasive into the capsule or the surrounding tissues as well as into blood and lymphatic vessels, and display increased pleomorphism of the cells and mitotic activity. Clinically, they tend to infiltrate the trachea, larynx and esophagus, making them less moveable. Metastasis occurs in 40 to 70 % of the cases and primarily affects regional lymph nodes and lungs.
In most cases of feline hyperthyroidism, documentation of an increased total T4 is sufficient to establish a diagnosis. Measurement of T3 does not offer any advantage over T4 and is therefore not recommended. In cases in which T4-levels remain in the upper reference range ("occult hyperthyroidism") measurement of free T4 (fT4) may be helpful, but has to be performed by equilibrium dialysis. Determination of feline TSH is offered by various laboratories today and confirms the diagnosis by demonstrating low to subnormal fTSH-levels.
Thyroid scintigraphy using Technetium Pertechnetate (Tc99m) is of great value in cats with presumed hyperthyroidism and may also detect ectopic thyroid tissue. It is not possible to differentiate benign from malignant disease by scintigraphy. Sonography of the thyroid is possible using high-resolution ultrasound probes. Physiologically, the feline thyroid gland has a fine and homogeneous echotexture. Adenomas usually lead to a thickening of the gland with rounding of the diameter and a more inhomogeneous echotexture. CT and MRI are also helpful in diagnosing masses in the thyroid glands.
About 1/3 of all hyperthyroid cats are azotemic. Since hyperthyroidism tends to mask the true degree of renal insufficiency, the renal condition may deteriorate after successful therapy of hyperthyroidism. In azotemic cats, thyrostatic drug therapy is recommended before definitive therapy (thyroidectomy, radioiodine therapy) is carried out, to determine the true degree of renal compromise.
Due to the effects of hyperthyroidism, benign tumors have to be treated. Today, the treatment of choice is medical management using thiamazole derivatives (methimazole, carbimazole) or radioiodine treatment. Surgery is reserved for those cases where medical therapy is not possible, not effective or has inacceptable side effects and when radioiodine treatment cannot be delivered. Choice of therapy also depends on the presence of secondary renal or cardiac compromise.
Surgery plays a minor part in the therapeutic cascade in all countries were radioiodine treatment can be performed. The goal of surgical therapy is the removal of all altered tissue under preservation of at least one functional parathyroid gland. Some surgeons prefer a preoperative therapy with methimazole to reach a euthyroid condition and therefore reduce the anaesthetic risk. Surgery is in most cases curative and results in rapid normalisation of T4-levels. If possible, scintigraphy is performed prior to thyroidectomy to detect all diseased thyroid tissue including ectopic masses. Malignant tumors frequently invade the glandular capsule and surrounding structures and therefore have to be regarded as inoperable.
The thyroid glands are exposed by a ventral midline approach dissecting through the sphincter colli muscle and median separation of the sternohyoid muscles. The peritracheal tissue is separated bluntly and both thyroid glands are exposed and examined grossly. Thyroid tumors can be found on the entire distance between the larynx and thoracic aperture. The extracapsular parathyroid glands are identified by their whitish colour and any attempt should be made to preserve at least one parathyroid gland together with its blood supply. Intracapsular and extracapsular thyroidectomy techniques have been described. In the intracapsular technique, the capsule is incised on the ventral aspect and the thyroid parenchyma is dissected out of the capsule using moistened Q-tips or ocular gauze sponges, thereby preserving the extracapsular parathyroid gland together with its blood supply. To reduce the risk of recurrence, a modification of this technique has been advocated in which the remaining capsule is resected under preservation of the cranial part containing the parathyroid gland and its blood supply. Using this modification of the intracapsular technique 5 (5.8%) of 86 cats in one study experienced a postoperative hypocalcemia (Naan et al. 2006).
With the extracapsular technique, the thyroid is completely removed including the capsule. This procedure is usually reserved for unilateral tumors and the removed parathyroid gland can be dissected from the resected tumor, chopped and reimplanted into adjacent musculature. In a modification of this technique, the capsule around the extracapsular parathyroid gland is incised and the parathyroid dissected away from the gland with a small rim of capsular tissue. However, with this technique postoperative hypocalcemia is still quite common and has been reported to occur in 23% of the cases (Flanders et al. 1999).
Since adenomas or hyperplasias are bilateral in about 80% of the cases, both thyroid lobes usually need to be removed. With unilateral excision, recurrence has to be expected within one year. True unilateral disease can be expected only if the contralateral side is atrophied, therefore bilateral thyroidectomy is usually indicated. Bilateral thyroidectomy can be performed in one session. The author recommends removing the more abnormal gland first. If overt damage to the blood supply of its parathyroid gland occurs, it is advisable to reimplant this parathyroid gland and perform the resection of the contralateral side one to two months later.
The most important postoperative complication is hypocalcemia, which usually develops between the 2nd and 5th postoperative day. Clinical symptoms include restlessness, weakness, muscle twitching (especially at the pinnae), tetanies and epileptic seizures. Revascularisation of the parathyroid gland takes at least two weeks and, in addition, ectopic parathyroid tissue is present in 35–50% of the cats in the peritracheal fascia, mediastinum or pericardium. Severe hypocalcemias are treated by 10% Ca-gluconate (0.5–1.5 ml/kg IV over 10–20 minutes) followed by constant infusion of 10 ml of a 10% Ca-gluconate in 250 ml Ringer's solution at 60 ml/kg/day). In contrast to other calcium salts, Ca-Gluconate can also be administered subcutaneously. After the acute symptoms have subsided, or in cases of minor hypocalcemia, oral therapy using calcium (25 mg/kg BID-TID) and vitamin D3 (Rocaltrol®, 1,25-dihydroxycholecalciferol, 0, 0,3–0,06 µg/kg oral SID) is instituted. The goal of substitution therapy is to keep the serum calcium in the low reference range. After several weeks the oral substitution can be tapered under constant control of the calcium levels.
Other surgical complications include bleeding, Horner's syndrome and laryngeal paralysis. Hypothyroidism is rarely a problem, since ectopic thyroid tissue is usually activated. A recurrence of hyperthyroidism is observed if not all hyperplastic or adenomatous tissue has been removed or if ectopic thyroid tissue is involved. According to one study, 5% of the cats experience a recurrence (Naan et al. 2006). In these cases, thyroid scintigraphy is indicated to locate the abnormal tissue. Usually radioiodine or medical management is used in these cases.
References
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