36 Thyroid Benign conditions

• Congenital neck mass - 
• Branchial cleft cyst
• Thyroglossal duct cyst
• Vascular anomalies
• Laryngocele
• Ranula
• Teratoma
• Dermoid cyst
• Thymic cyst

• Inflammatory neck mass - 
• Infectious inflammatory disorders
• - Reactive viral lymphadenopathy
• - Bacterial lymphadenopathy
• - Parasitic lymphadenopathy
• Noninfectious inflammatory disorders

• Neoplastic disorders - 
• Metastatic head and neck carcinoma
• Thyroid masses
• Salivary gland neoplasm
• Paragangliomas
• Schwannoma
• Lymphoma
• Lipoma and benign skin cysts

• Hashimoto Thyroiditis
• Acute Suppurative Thyroiditis 
• Sub-acute thyroiditis  (de Quervain's thyroiditis)
• Riedel thyroiditis (struma)

Hashimoto's thyroiditis or autoimmune thyroiditis is autoimmune-mediated destruction of thyrocytes, marked by an intense infiltration of the lymphocytes and plasma cells that virtually replace the thyroid parenchyma.

• Pathology:
• A complex immunologic phenomenon results in the formation of immune complexes and complement in the basement membrane of follicular cells.
• These cellular reactions ultimately result in the infiltration of lymphocytes and resultant fibrosis, which decreases the number and efficiency of individual follicles. As this immune phenomenon continues, the presence of TSH-blocking antibodies, such as thyroid peroxidase antibodies, can be detected.
• Thyroid peroxidase antibodies are probable key mediators in the initial complement fixation process

• Clinical features:
• o It is predominantly a disease of women (F:M ratio 10:1).
• o The enlargement of thyroid is generally painless and diffuse.
• o Most patients with long standing disease are in hypothyroid state, but a few of them develop hyperthyroidism in the mid-course known as Hashitoxicosis.
• o Clinically, there is enlarged thyroid and hypothyroidism.

• Treatment:
• The treatment is lifelong replacement therapy with thyroid hormone.

• Complications:
• Non-Hodgkin B-cell lymphoma - There is infiltration of thyroid by the lymphocytes and if they stay longer in the gland, there is transformation into lymphoma.

Subacute thyroiditis is also known as granulomatous or de Quervain's thyroiditis.  The disease is viral in origin.

• Symptoms:
• o Symptoms usually start after an episode of upper respiratory infection.
• o Asthenia, fever, malaise
• o Symptoms referable to stretching of the thyroid capsule, mainly pain over the thyroid or pain referred to the lower jaw, ear or occiput. [@ de Quervain is associated with pain.]

• Microscopic findings:
• Granulomatous as it contains giant cells, epitheloid cells and macrophages. This is the reason; sub-acute thyroiditis is also called as Granulomatous thyroiditis.

• Lab findings:
• o Elevated ESR,
• o Initial elevation of T4 and T3
• o Decreased radioactive iodine uptake.

The disease is usually self-limiting and acute cases should be managed with oral Prednisolone for 7 days and then, it is gradually tapered off over the next month.

• Firm thyroid secondary to a chronic inflammatory process involving the entire gland.
• Symptoms of severe discomfort can occur because of extension into the trachea, esophagus, and laryngeal nerve
• As a result, patients may have impending airway obstruction or dysphagia.
• Unilateral involvement of symptoms may suggest a malignancy and lead to surgical intervention.
• Surgical pathology reveals dense fibrous tissue and almost total obliteration of normal follicular architecture. 
• Treatment with thyroid hormone replacement, corticosteroids, or tamoxifen may be effective.
• Immediate tracheal or esophageal obstruction may require a surgical approach to relieve symptoms.

1. Diffuse toxic goitre—(Graves’ disease, Basedow’s disease. Primary thyrotoxicosis).

2. Toxic multinodular goitre (Secondary thyrotoxicosis) (Plummer disease).

3. Toxic nodule.

4. Hyperthyroidism due to rarer causes:

• a. Thyrotoxicosis factitia—drug induced. Due to intake of L-thyroxine more than normal.
• b. Jod Basedow thyrotoxicosis—because of large doses of iodides given to a hyperplastic endemic goitre.
• c. Autoimmune thyroiditis or de Quervain’s thyroiditis.
• d. Occasionally carcinoma thyroid.
• e. Neonatal thyrotoxicosis. It subsides in 3-4 weeks as TsAb titres fall in the baby’s serum.
• f. Struma ovarii.
• g. Drugs like amiodarone

Iodides inhibit the further release of hormone causing hypothyroidism (Hokkaido goitre). 

[@ WOLf - fLOW - Low (Hypothyridism)]

When the appearance of goiter and hyperthyroid symptoms occur simultaneously then it is called primary thyrotoxicosis. This usually affects young female patient. The thyroid enlargement is diffuse and the gland is hypervascular. Onset is usually acute but there may be relapse and remissions. Eye signs are usually common.

When the thyrotoxic feature develops at a later period on a pre-existing thyroid enlargement then it is called secondary thyrotoxicosis. Usually the goiter is nodular. Onset is insidious. Cardiovascular symptoms are more severe and patient may present with cardiac failure or atrial fibrillation. Eye signs except lid lag and lid retraction are rare.

Stages in goitre formation are:

• • Persistent growth stimulation causes diffuse hyperplasia; all lobules are composed of active follicles and iodine uptake is uniform. This is a diffuse hyperplastic goitre, which may persist for a long time but is reversible if stimulation ceases. 
• • Later, as a result of fluctuating stimulation, a mixed pattern develops with areas of active lobules and areas of inactive lobules. 
• • Active lobules become more vascular and hyperplastic until haemorrhage occurs, causing central necrosis and leaving only a surrounding rind of active follicles.
• • Necrotic lobules coalesce to form nodules filled either with iodine-free colloid or a mass of new but inactive follicles.  A colloid goitre is a late stage of diffuse hyperplasia when TSH stimulation has fallen off and when many follicles are inactive and full of colloid. 
• • Continual repetition of this process results in a nodular goitre. Most nodules are inactive, and active follicles are present only in the internodular tissue.

It is an autoimmune disease with a strong familial predisposition, female preponderance (5:1), and peak incidence between the ages of 40 and 60 years. Graves’ disease is characterized by- 

• (1) signs and symptoms of thyrotoxicosis,
• (2) a visibly enlarged neck mass consistent with a goiter that may demonstrate an audible bruit secondary to increased vascular flow, and
• (3) exophthalmos

• The ophthalmopathy is believed to be caused by stimulation of the overexpressed TSH-R in the retro-orbital tissues of patients with Graves disease.
• Proptosis, supraorbital and infraorbital swelling, and conjunctival swelling and edema, can be severe.

• „ Orbital proptosis
• „ Ophthalmoplegia
• „ Pretibial myxedema.

An enlarged smooth thyroid mass and signs and symptoms of thyrotoxicosis. 

TFT:  elevated T3 and T4, decreased level of TSH

• 123I radionuclide scan
• - elevated uptake throughout an enlarged gland versus in Graves disease
• - isolated area of increased uptake in a hyperfunctioning nodule
• - low uptake in exogenous thyroid misuse or thyroiditis.

Ultrasound or CT scan of the neck can be performed to evaluate clinical landmarks if needed for surgical planning.

Anti-Tg and anti-TPO antibodies are elevated in up to 75% of patients but are not specific. Elevated TSH-R or thyroid-stimulating antibodies (TSAb) are diagnostic of Graves’ disease and are increased in about 90% of patients.

Graves’ disease may be treated by any of three treatment modalities: antithyroid drugs, thyroid ablation with radioactive ¹³¹I, and thyroidectomy.

Following initial medical therapy, a decision must be made about long-term management of the hyperthyroid state. These medications are problematic, and a more definitive ablation of Graves disease via RAI or thyroidectomy is recommended for most patients.

American Thyroid Association (ATA) and the American Association of Clinical Endocrinologists (AACE) recommend total or near-total thyroidectomy as the procedure of choice for the surgical management of Graves’ disease.

• Patients with thyrotoxicosis have increased adrenergic stimulation.
• The peripheral adrenergic effects of thyrotoxicosis can be modulated by the use of beta-blocking agents such as propranolol, which should be initiated particularly in patients with tachycardia and in elderly patients.
• Beta blockers do not directly inhibit thyroid hormone synthesis.
• Although adrenergic symptoms such as an increased pulse rate, tremor, and anxiety can be improved, the hypermetabolic state can remain or progress with beta blocker treatment alone.

The thionamide class of antithyroid drugs includes PTU and methimazole (Tapazole).

This class of drugs effectively blocks synthesis of thyroid hormone and acts by inhibiting the organification of intrathyroid iodine as well as the coupling of iodotyrosine molecules to form T3 and T4

• Methimazole is preferred over PTU except for during the first trimester of pregnancy and in life- thyroid. Both drugs reduce thyroid hormone production
• by inhibiting the organic binding of iodine and the coupling of iodotyrosines (mediated by TPO). In addition, PTU also inhibits the peripheral conversion of T4 to T3, making it useful for the treatment of thyroid storm.

Both drugs can cause agranulocytosis, but this occurs in less than 1% of cases. Other side effects include rash, arthralgias,neuritis, and liver dysfunction (potentially worse with PTU).

When contemplating surgical treatment for Graves' disease, the patient should be initially treated with antithyroid drugs for 6–8 weeks to achieve a euthyroid or near euthyroid state before surgery to prevent development of thyroid crisis after surgery.

The catecholamine response of thyrotoxicosis can be alleviated by administering β-blocking agents. β-Blockade should be considered in all patients with symptomatic thyrotoxicosis and is recommended for elderly patients, those with coexistent cardiac disease, and patients with resting heart rates >90 bpm. These drugs have the added effect of decreasing the peripheral conversion of T4 to T3.

• Exogenous corticosteroids can effectively suppress the pituitary thyroid axis.
• Also, they act in the periphery to inhibit the peripheral conversion of T4 to T3; this effectively lowers serum T3 levels,allowing steroids to be used as a rapid inhibitory agent for hyperthyroid conditions.
• Steroids can also lower serum TSH concentration.
• The rapid action of steroids makes them a potentially important primary treatment of severe, previously untreated, or resistant hyperthyroidism, usually in conjunction with supportive care and the other agents

• Iodine, given in large doses in the form of SSKI or Lugol solution after the administration of an antithyroid medication, can inhibit thyroid hormone release by altering the organic binding process (Wolff-Chaikoff effect).
• This effect is transient, but iodine supplementation can be used to treat hyperactivity of the gland in preparation for surgery.
• Lugol’s iodide solution or saturated potassium iodide generally is administered beginning 7 to 10 days preoperatively (three drops twice daily) to reduce vascularity of the gland and decrease the risk of precipitating thyroid storm.

• Radioiodine in adequate dose can destroy the thyroid cells and control thyrotoxicosis. No surgery is required and prolonged drug therapy is not required.
• It is also a treatment option for - Graves disease, toxic adenoma and toxic multinodular goiter.
• Antithyroid drugs are given until the patient is euthyroid and then discontinued to maximize drug uptake.
• It ablates the thyroid within 6 to 18 weeks. Patients with mild, well-tolerated hyperthyroidism can safely proceed to RAI ablation immediately.
• However, patients who are older or severely thyrotoxic may require pretreatment with a thionamide.
• The overall cure rate with RAI is 90%. Hypothyroidism develops in cured individuals—hence the need for careful measurement of thyroid hormone and TSH levels at regular intervals after therapy.
• Most patients are candidates for RAI; exceptions include women who are pregnant or lactating or patients with a suspicious nodule.

• Indications of RAI in Graves disease - 
• - Older patients with small or moderate-sized goiters
• - Who have relapsed after medical or surgical therapy
• - In whom antithyroid drugs or surgery are contraindicated.

• Avoidance of surgery and the associated risks of RLN damage, hypoparathyroidism, or postsurgical recurrence.
• The use of 131I therapy might be more cost effective over time, but the financial advantage is not as clear if repeated 131I therapy is needed.

• Exacerbation of cardiac arrhythmias, particularly in older patients, possible fetal damage in pregnant women, worsening ophthalmic problems, and rare but possibly life-threatening thyroid storm.
• After 1 year, about 2.5% of patients develop hypothyroidism each year.
• Lead to progression of Graves’ ophthalmopathy (33% after RAI compared to 16% after surgery), and ophthalmopathy is more common in smokers.
• There is a small increased risk of nodular goiter, thyroid cancer, and hyperparathyroidism (HPT)
• Unexplained increase in their overall and cardiovascular mortality rates when compared to the general population.

• Surgery is recommended when RAI is contraindicated as in patients who -
• (a) have confirmed cancer or suspicious thyroid nodules,
• (b) are young,
• (c) desire to conceive soon (<6 months after treatment
• (d) have had severe reactions to antithyroid medications,
• (e) have large goiters (>80 g) causing compressive symptoms, and
• (f) are reluctant to undergo RAI therapy. 

Relative indications for thyroidectomy - smokers, with moderate to severe Graves’ ophthalmopathy, those desiring rapid control of hyperthyroidism with a chance of being euthyroid, and those demonstrating poor compliance to antithyroid medications.

• Concomitant hyperparathyroidism needing operative intervention
• Social factors that would expose family members to RAI.
• Ophthalmopathy may be transiently worsened by RAI therapy, and it may be the case that surgery more rapidly stabilizes ophthalmopathy.

• Thyroid storm is also referred to as thyrotoxic crisis.
• The condition may be precipitated by abrupt cessation of antithyroid medications, infection, thyroid or nonthyroid surgery, and trauma in patients with untreated thyrotoxicosis.
• This complication is rarely encountered if appropriately anticipated.
• Thyroid storm is manifested by severe tachycardia, fever, confusion, vomiting to the point of dehydration, and adrenergic over stimulation to the point of mania and coma after thyroid resection in a patient with uncontrolled hyperthyroidism.
• Treatment of a patient with overt thyroid storm includes rapid fluid replacement and institution of antithyroid drugs, beta blockers, iodine solutions, and steroids.
• In life threatening circumstances, plasmapheresis or plasma exchange may be effective in reducing T4 and T3 levels.

• Toxic multinodular goiters (Plummer disease) usually occur in older individuals, who often have a prior history of a nontoxic multinodular goiter.
• Over several years, enough thyroid nodules become autonomous to cause hyperthyroidism.
• Symptoms and signs of hyperthyroidism are similar to Graves’ disease, but extrathyroidal manifestations are absent.
• Treatment - Hyperthyroidism must be adequately controlled. Both RAI and surgical resection may be used for treatment. When surgery is performed, near-total or total thyroidectomy is recommended to avoid recurrence and the consequent increased complication rates with repeat surgery.

• The term multinodular goiter describes an enlarged, diffusely heterogeneous thyroid gland.
• Initial findings include diffuse enlargement,but asymmetric nodularity of the mass often develops.
• The cause of this mass is usually iodine deficiency. Initially, the mass is euthyroid, but with increasing size, elevations in T3 and T4 levels can occur and gradually progress to clinical hyperthyroidism.
• The workup and diagnosis involve evaluation of thyroid function test results.
• Ultrasound and radioisotopic scanning demonstrate heterogeneous thyroid substance.
• Nodules with poor uptake can appear as lesions suggestive of malignancy.
• The incidence of carcinoma in multinodular goiter has been reported to be 5% to10%.
• FNA for diagnosis and resection for suspicious lesions should be strongly considered.

A substernal goiter is an intrathoracic extension of an enlarged thyroid that generally occurs as a result of multinodular goiter. 

• Primary substernal goiter (1%)  
• - arises as aberrant thyroid tissue within the anterior or posterior mediastinum
• - is based on the intra thoracic vasculature and not supplied by the inferior thyroid artery.

• Secondary Substernal goiter (99%) -  
• - enlargements or extensions of multinodular goiters based on the inferior thyroid vasculature.
• - They expand downward into the anterior mediastinum