NEOPLASIA OF THE THYROID

The thyroid is the most common endocrine organ to undergo malignant transformation. Thyroid adenomas are identified as being functioning/hyperfunctioning (hot), nonfunctioning (cold), or photon deficient on tracer imaging. Hot nodules (which are typically adenomas) are more often benign than the cold lesions. They are slow growing over many years. Management for hyperfunctioning adenomas includes ablation with surgery or radioactive iodine.

Thyroid Carcinomas Papillary Carcinoma

It is the most common thyroid malignancy, representing approximately 80 percent of all thyroid malignant diseases. Radiation exposure, especially during childhood, is associated with the development of papillary thyroid carcinoma. There is usually single dominant nodule that is ‘cold’ on thyroid scan. There is a bimodal frequency with peaks in the second and third decades and then later in life. This tumor is slow growing and spreads via lymphatics after many years. An increased incidence of papillary cancer is hypothesized among patients with Hashimoto thyroiditis. It is also

known to be associated with Gardner syndrome (familial adenomatous polyposis). Histologically it presents with typical papillary structures within follicles that have epithelial cells that have nuclei with cleared centers (orphan annie eye).

Treatment: Is surgical excision whenever possible like.

With large tumors radiotherapy is used along with surgery. TSH suppression therapy is also used.

Follicular Carcinoma

Follicular carcinoma accounts for 15 percent of all thyroid cancers. It represents an increased proportion of thyroid cancers in regions where dietary intake of iodine is low and is more common in the elderly and in women. This tumor is more malignant than papillary carcinoma. It spreads hematogenously with distant metastasis to lung and bone.

Treatment: Near total thyroidectomy (NTT) is the preferred treatment. Postoperative radioiodine ablation is to be done. Small lesions can be treated with lobectomy alone. It has the best prognosis overall.

‘99er’-Keep level of TSH between 0.1-0.3mU/liter in papillary thyroid carcinoma because TSH stimulates the tumor. During remission of tumor, keep it low by increasing levothyroxine dose. For patient with metastatic papillary carcinoma, complete TSH suppression is required.

‘99er’-Thyroglobulin is used as tumor marker after NTT.

Anaplastic Carcinoma

Anaplastic carcinoma is one of the least common thyroid carcinomas. It has the most aggressive biologic behavior of all thyroid malignancies and one of the worst survival rates of all malignancies in general. It often presents with a painful enlargement.

Treatment: The progression of disease is rapid, and most patients die from local airway obstruction or complications of pulmonary metastases within 1 year despite all treatment efforts. Total or subtotal thyroidectomy is performed when the extent of carcinoma permits it.

Medullary Carcinoma

Medullary carcinoma accounts for 5 percent of all thyroid cancers and occurs in sporadic or familial form. Tumors arise from the parafollicular C cells of the thyroid gland.

C cells are neural-crest derivatives and produce

calcitonin. It is encapsulated but without any typical nuclear features and rarely involves lymph node, unlike papillary carcinoma.

Medullary carcinoma is component of MEN (multiple endocrine neoplasias). MEN type II is because of RET mutation.

• MEN type IIa (Sipple syndrome): Pheochromo-cytoma, medullary thyroid carcinoma, and (in one half of cases) parathyroid hyperplasia.

• MEN type IIb (mucosal neuroma syndrome):

Pheochromocytoma, medullary carcinoma, and neuromas occur. Patients also have marfanoid features.

‘99er’ - α blockade for 10-14 days is required in any patient of MEN type II undergoing surgery because of associated pheochromocytoma.

The only effective therapy is thyroidectomy.

Hürthle Cell Carcinoma/Oncocytic Carcinoma A variant of follicular carcinoma is a rare thyroid malignancy. About 75-100 percent of the tumor is composed of Hürthle cells (oxyphilic, oncocytic, Askanazy, or large cells) that contain abundant granular acidophilic cytoplasm. It typically manifests in the fifth decade of life.

Treatment: Hürthle cell carcinomas behave aggressively.

These tumors most often do not take up radioactive iodine. Patients with a diagnosis of Hürthle cell neoplasm based on FNAB findings undergo lobectomy and isthmectomy. If, the final pathologic result confirms Hürthle cell carcinoma, patients return to surgery for completion thyroidectomy. For tumors >5 cm or for palpable lymphatic metastases, total thyroidectomy is often performed during the initial operation.

Diagnosis: Thyroid carcinoma is suspected when there is recent growth of thyroid or an evident mass is seen with no tenderness or hoarseness. Patients with a history of radiation therapy of the head, neck, or upper mediastinum in childhood should also be suspected to develop carcinoma but the latency period may be very long. The presence of a solitary nodule or the production of calcitonin is also clue to malignancy.

Calcifications on X-rays such as psammoma bodies suggest papillary carcinoma (characteristic-diagnosis clincher); increased density is seen in medullary carcinoma.

Thyroid nodule: Most common thyroid nodule is colloid, followed by follicular adenoma. The first step in diagnosis of a thyroid nodule is measurement of TSH, with the subsequent steps (of T4, T3 measurement) all

dependent on TSH levels. If TSH is decreased, than the next step should be radionuclide scan.

‘99er’-If a thyroid nodule is > 1cm, go for FNAC (even if TSH is normal). Otherwise do yearly ultrasound.

Ultrasound is also recommended if nodule rapidly increases in size. Ultrasound is better than CT for imaging nodule. Radioactive scans not used here, as they are to be used only in diagnosing toxic nodules in thyrotoxic patients.

‘99er’-Follicular Adenoma: histologically demons-trates invasion of the capsule and blood vessels. FNAB shows large numbers of normal-appearing follicular cells.

It is almost impossible to differentiate follicular adenoma from follicular cancer.

Thyroiditis

It is the inflammation of thyroid gland and includes:

• Acute suppurative thyroiditis-due to bacterial infection

• Subacute thyroiditis: results from a viral infection of the gland

• Chronic thyroiditis: autoimmune in nature.

• Secondary thyroiditis: due to drugs like amiodarone and interferon-alpha

All have different clinical courses, and each can be associated at one time or another with euthyroid, thyrotoxic, or hypothyroid state.

Acute Suppurative Thyroiditis

Most cases involve the left lobe of the thyroid and are associated with a developmental abnormality or the persistence of a pyriform sinus from the pharynx to the thyroid capsule. Organisms responsible include S aureus, Streptococcus hemolyticus, and pneumococcus.

Clinical features: Presenting symptoms usually are fever, chills, neck pain, sore throat, hoarseness, and dysphagia.

Neck pain is frequently unilateral and radiates to the mandible, ears, or occiput. Neck flexion reduces the severity of the pain. The pain worsens with neck hyperextension.

Treatment: is immediate parenteral antibiotic therapy (penicillin or ampicillin) required before abscess formation begins.

Subacute Thyroiditis

It includes granulomatous, giant cell, or de Quervain thyroiditis. This can occur at any age, although most commonly in the fourth and fifth decades. It is generally

thought to be due to viral processes and usually follows a prodromal viral illness. It is one of the most common causes of thyrotoxicosis that shows reduced uptake on RAIU. It may be associated with post- partum period.

Clinical features: Presents with malaise, fever, pain over the thyroid or referred to the lower jaw, ears, neck, or arms.

The gland is enlarged, firm and tender (diagnosis clincher) in this setting. Labs show ↑ ESR, ↓RAIU, initial ↑ T3 and T4 followed by their decrease, and features of hypothyroidism.

Treatment: Since it is self-limiting, only symptomatic treatment with low dose aspirin, along with control of thyroid function is required. If aspirin does not relieve the discomfort, prednisone can be used. Propranolol can be used to reduce signs and symptoms of hyperthyroi-dism and low-dose levothyroxine may be used when hypothyroidism develops.

‘99er’-Causes of thyrotoxicosis with ↓RAIU: Subacute granulomatous (De Quervain) thyroiditis, thyrotoxicosis factitia, iodine induced thyrotoxicosis.

‘99er’-Thyrotoxicosis factitia- is characterized by exogenous administration of thyroid hormone.

‘99er’-No thyroglobulin detected in factitious thyrotoxicosis.

Hashimoto Thyroiditis

It is a chronic inflammatory process of the thyroid with lymphocytic infiltration of the gland. Commonly found antibodies are antithyroid peroxidase (anti-TPO) and antithyroglobulin (anti-Tg). It most frequently occurs in middle- aged women, and is the most common cause of sporadic goiter in children. Histology shows lymphocytic infiltration of gland.

Clinical features: Patients most commonly present with nonspecific symptoms suggestive of overt hypothyroi-dism. Diagnosis clincher will be a painless goiter on physical examination. The goiter is rubbery and not always symmetrical.

Diagnosis: History and physical examination are very helpful. High titers of antithyroid antibodies, namely antimicrosomal antibodies are present. Initially lab values are normal but as the disease progresses, TSH increases and T4 and T3 decrease. Histologic confirmation is rarely needed.

Treatment: Treatment of choice is thyroid hormone replacement and the drug of choice is orally administered levothyroxine sodium, usually for life.

‘99er’-When lymphoma is suspected along with Hashimoto thyroiditis then large bore needle biopsy is indicated. Suspicion for presence of lymphoma in a Hashimoto thyroiditis patient should arise from rapid increase in size of gland.

Lymphocytic (Silent, Painless, or Postpartum) Thyroiditis

It is a self-limiting episode of thyrotoxicosis associated with chronic lymphocytic thyroiditis. It is more common in women of any age. This disease may last for 2-5 months and be recurrent (as in postpartum thyroiditis).The thyroid is nontender, firm, symmetrical, and slightly to moderately enlarged. Its hallmark is a radioiodine uptake of less than 1 percent at 24 hours. T4 and T3 are very much elevated initially, and ESR is normal.

Treatment: is symptomatic with propranolol and hormone replacement if required later on.

‘99er’-Postpartum thyroiditis- 80 percent of these patients recover function and remaining may require replacement therapy. Serial thyroid function testing is therefore indicated in these patients.

Reidel Thyroiditis

It is a rare chronic inflammatory disease of the thyroid gland characterized by a dense fibrosis that replaces normal thyroid parenchyma and invades surrounding structures mediastinal and retroperitoneal fibrosis. It is said to be not primarily a thyroid disorder but rather a manifestation of a systemic disorder, namely multifocal fibrosclerosis.

Clinical features: Thyroid presents as hard fixed painless goiter. The character of the thyroid gland is often described as stony or woody (diagnosis clincher). Most patients are euthyroid. Hypothyroidism is noted in approximately 30 percent of cases. Local compressive symptoms, such as neck tightness or pressure, dyspnea, dysphagia, hoarseness, choking, and cough are frequent.

Treatment: Corticosteroid therapy is the medical treatment of choice for patients with Reidel thyroiditis.