Simple Goiter and Thyroid Enlargement

• Simple goiter and its complications involve swelling/enlargement of the thyroid gland.
• Normally, the thyroid gland is impalpable.

Types of Thyroid Enlargement

• Generalized enlargement (goiter).
• Discrete swelling (nodule) in one lobe.
• With no palpable abnormality elsewhere (isolated/solitary swelling).
• With evidence of abnormality elsewhere in the gland (dominant nodule).

Classifications of Thyroid Enlargement

• Simple (euthyroid) and toxic.
• Neoplastic and inflammatory.

Simple (Euthyroid) Goiter Types

• Diffuse hyperplastic: Physiological (puberty, pregnancy).
• 1ry Iodine deficiency: Endemic where dietary iodine intake is < 100 µg/day and linked to goitrogens (Brassica family, cabbage, soya bean) and is common in hill stations, as well excess dietary fluoride.
• 2ry Iodine deficiency: Drugs; para-aminosalicylic acid (PAS), Lithium and radioactive iodine, phenylbutazone, thiocyanates, potassium perchlorate, and antithyroid drugs along with Dyshormonogenetic goiter.
• Colloid goiter.
• Nodular goiter and Solitary nontoxic nodule.
• Recurrent nontoxic nodule, Wolff-Chaikoff effect and Hokkaido goiter

Wolff-Chaikoff Effect

• Large iodide intake inhibits thyroid hormone release (inhibits organification) by autoregulation, but later may cause escape phenomenon.

Toxic Goiter Types

• Diffuse (primary): Graves' disease.
• Multinodular (secondary): Plummer's disease.
• Toxic nodule (solitary) (tertiary) and recurrent toxicosis.

Neoplastic Goiter Types

• Benign: Adenomas (follicular, Hurthle cell).
• Malignant: Carcinomas (papillary, follicular, medullary, anaplastic) and lymphomas.

Inflammatory Goiter Types

• Autoimmune: Hashimoto's disease and chronic lymphocytic thyroiditis.
• Granulomatous: De-Quervain's thyroiditis.
• Fibrosing: Riedel's thyroiditis.
• Infective: Acute (bacterial/viral thyroiditis "subacute") and chronic (tuberculous, syphilitic).
• Others: Amyloid.

Etiology of Simple Goiter

• Simple goiter may develop due to stimulation of the thyroid gland by:
• TSH either by inappropriate secretion from a microadenoma (rare) or a chronic low thyroid hormone level.
• Other growth factors, including immunoglobulins, exert an influence.
• Iodine deficiency due to lowered iodides in food/water where the daily requirement of iodine is about 0.1-0.15 mg, and failure of intestinal absorption.
• Calcium is also goitrogenic.
• Goiter is common in low-iodine areas on chalk or limestone.
• Dietary deficiency of iodine is the most important factor in endemic goiter.
• Defective hormone synthesis is also responsible for sporadic goiters (in non-endemic areas).
• High iodine intake (like Iceland's fish diet) may compensate and reduce goiter prevalence.

Examples of Goitrogens

• Vegetables of the Brassica family (cabbage, kale, and rape) which contain thiocyanate along with drugs: para-aminosalicylic acid (PAS) & antithyroid or iodides in large quantities.
• How do goitrogens act?
• Thiocyanates & perchlorates interfere with iodide trapping.
• Carbimazole & thiouracil compounds interfere with Oxidation of iodide and Binding of iodine to tyrosine.
• Iodides in large quantities inhibit organic binding of iodine and produce an iodide goiter.
• Excessive iodine intake may be associated with ↑ incidence of autoimmune thyroid disease.

Stages of Goiter Formation (Natural History of Simple Goiter)

• Formation of Diffuse Hyperplastic Goiter: Persistent TSH stimulation causes diffuse hyperplastic goiter with active follicles, uniform iodine uptake, reversible if stimulation stops.
• Formation of Nodular Goiter: Fluctuating stimulation leads to development of a mixed pattern (active lobules & inactive lobules). Active lobules become more vascular & hyperplastic which causes hemorrhage and central necrosis, along with necrotic lobules coalascing to form nodules filled either with Iodine-free colloid or mass of new but inactive follicles with continuous process resulting in a nodular goiter.
• Most nodules are inactive where active follicles are present only in the internodular tissue with thyroid nodularity may resulting from clones of cells sensitive to growth stimulation.

Types of Simple Goiter

• Diffuse Hyperplastic Goiter
• Pathogenesis: Diffuse hyperplasia
• Epidemiology: Age (childhood in endemic areas, at puberty in sporadic cases.
• Clinical Picture: Signs where the goiter is soft, diffuse and patients may show Discomfort (if goiter becomes large).
• IV. Fate: If TSH stimulation decreases, the goiter may regress, but tends to recur later at times of stress (pregnancy).
• A colloid goiter (a late stage of diffuse hyperplasia) occurs when TSH stimulation has fallen off and many follicles are inactive and full of colloid.

Nodular Goiter

• Pathogenesis: As discussed in the stages of the natural history.
• Types: Multi-nodular Goiter where Nodules are usually multiple with Clinically Solitary Nodule which involves one macroscopic nodule but microscopic changes present throughout the gland.
• Epidemiology: Age (nodules appear early in endemic goiter, but later in sporadic goiter between 20 and 30 years), although patients are unaware of goiter until 40s or 50s with sex being more common in the female (estrogen receptors in thyroid tissue).
• Pathology : Nodules may be Colloid or cellular with cystic degeneration & hemorrhage commonly seen. Subsequentially calcification occurs too.
• Clinical Picture: Patients are usually euthyroid, where the nodules are Palpable, Smooth, Painless, Moves on swallowing and Firm which could possibly simulate carcinoma.
• Suspicion of carcinoma is ↑↑ in case of: Painful nodule along with Sudden appearance and rapid enlargement of a nodule.
• DDX: Autoimmune thyroiditis (DD is difficult since both conditions often coexist).

Investigations for Goiter

• Investigations: Thyroid function test & Thyroid antibodies to Differentiate it from thyroiditis with ultrasonography as The gold standard assessment for indications.
• Fine Needle Aspiration Cytology [FNAC]: Biopsy should be performed under ultrasound guidance to ensure that a correct nodule is sampled.
• Plain Radiographs [X-Rays]: X-Ray of the chest and thoracic inlet.
• CT scan (neck & chest) which best assesses Tracheal or esophageal deviation or compression if there are swallowing or breathing symptoms.
• Complications of Multinodular goiter
• Secondary thyrotoxicosis (30%), Follicular carcinoma of the thyroid (10%), Hemorrhage in the nodule, Tracheal obstruction Calcification, cosmetic problems.

Prevention & Treatment of Simple Goiter

• Lines of treatment for simple goiter:
• Medical with Thyroxine and iodine supplementation.
• Surgical via total thyroidectomy with immediate & lifelong replacement of thyroxine as a result of partial resection.
  • Subserve normal function and lowered risk of hypoparathyroidism.
• Radioactive iodine provides smaller size of recurrent nodular goiter after previous subtotal resection.
• How to deal with some type of goiter?
  • Endemic Goiter involves introduction of iodized salt.
  • Hyperplastic Goiter: Early hyperplastic goiter may regress with 0.15–0.2 mg thyroxine daily for a few months
• Multinodular goiter : Most patients are asymptomatic & do not require operation, except for cosmetic grounds, pressure symptoms, patient anxiety, retrosternal extension or a dominant area of enlargement that may be neoplastic.

Clinically Discrete Swellings (Thyroid Nodules)

• Incidence:
  • Common and more frequently seen in women > men (by 3 to 4 times).
• Etiology:
• Thyroid adenomas (almost all are follicular), carcinomas (papillary, follicular, medullary or anaplastic), thyroid cysts and thyroiditis presenting as a solitary nodule (localized form)
• Diagnosis:
• Incidence: 70% of thyroid swellings.
• Clinical Solitary nodule is clinically and radiologically distinct from surrounding tissue.
• Dominant nodule: Incidence of 30% of thyroid swellings that involve a gland with generalized abnormality, but only one nodule is palpable.
• Importance of discrete swellings lies in the risk of neoplasia since 15% of isolated swellings prove to be malignant.
• Thyroid function test interpretation: Hyperthyroidism -May indicate either Toxic adenoma or a manifestation of toxic multinodular goiter.
• The combination of toxicity and nodularity is important for isotope scanning that will localize the area(s) of hyperfunction.
• Autoantibody titers increase in chronic lymphocytic thyroiditis.
• Presence of circulating antibodies leads to an increased risk of thyroid failure after lobectomy.

Isotope Scan

• Importance: isotope uptake assesses functional activity relative to the surrounding area.
• Categorization of swellings via scanning of Hot (Overactive) nodule: Takes up isotope, while the surrounding thyroid tissue does not.
• Warm (Active) nodule: Takes up isotope & so does normal thyroid tissue around it.
• Cold (Underactive) nodule:
• No isotope uptake.
• About 80% of discrete swellings are cold, but only 15% malignant.
• The use of this criterion as an indication for operation lacks discrimination.

Ultrasonography (US)

• Demonstrate subclinical nodularity and cyst formation so its used for FNAC with US findings in thyroid swelling suggestive of neoplasia
  • Microcalcifications and increased vascularity revealed via doppler with macroscopic capsule breach and nodal involvement diagnostic of malignancy.
• Fine-Needle Aspiration Cytology (FNAC): How & When to use it Under ultrasound guidance all nodules that do not fulfill a fully benign (U2) classification on US.
  • Advantages: In identifying papillary thyroid carcinoma it is best combined with specific, sensitive, ultrasonography enhances accuracy, targeting solid parts in mixed nodules along with FNAC, in order to diagnosis colloid nodule, thyroiditis, papillary carcinoma, medullary or anaplastic carcinoma lymphoma.
  • Disadvantages: It Cannot distinguish between a benign follicular adenoma & follicular carcinoma for this distinction is dependent not on cytology but on histological criteria, which include capsular & vascular invasion.
• Radiology confirms or assesses, where the chest & thoracic inlet radiographs are.

Key aspects for Radiology when evaluating goiter

• Tracheal deviation or Compression and retrosternal extension that are used during indicated malignancy suspicions
• CT & MRI scans are Useful in retrosternal swelling and recurrent swelling and have no role in the first line of investigation.
• PET CT Scan is Useful in localizing disease which does not uptake radioiodine.
• Laryngoscopy: Medicolegally: is used preoperatively for vocal cords mobility for medicolegal, rather than clinical reasons with recognition that it is in Diagnosis of malignancy with unilateral cord palsy and a swelling.
• Core biopsy is rarely indicated in thyroid masses owing to the vascularity of the thyroid gland, as well as risk of postprocedural hemorrhage although, it can be useful for the rapid diagnosis of widely invasive malignant disease.

Treatment protocols

• Nontoxic benign nodule requires observation (without any therapy) and follow up with annual clinical examination & ultrasound neck.
• Solitary toxic nodule is resolved initially with antithyroid drugs and then with radioactive iodine therapy.
• Colloid nodule can be observed, while hemithyroidectomy is done for cosmosis.
• Malignant nodule requires A. Papillary carcinoma of thyroid: Total or near total thyroidectomy with or without radioactive iodine & hormonal replacement.
• B. Follicular adenoma: Requires Hemithyroidectomy if Total thyroidectomy is required for it to be found malignant pathologically.
• C. Medullary carcinoma of thyroid: Total thyroidectomy with bilateral neck nodal dissection including central compartment.
• Indications for surgery:
  • Risk of neoplasia (MAIN INDICATION), toxic nodule in young, recurrent cystic nodule during complex cyst examinations.
• Clinical criteria for surgery include Neoplasia and Malignancy, which involves a hard, irregular and.
• Fixed swelling is highly suspicious with recurrent laryngeal nerve paralysis.
• Deep cervical lymphadenopathy along the IJV is noted during suspicious swelling.
• Epidemiology: Thyroid carcinoma in women is about 3 times that in men, but the patient and physician should note if its discrete swelling in a male and that's much more likely to be malignant than in a female.

Retrosternal Goiter

• Definition: Having > 50% goiter below the suprasternal notch.
  • Has major Intrathoracic extension Requiring mediastinal dissection, extension into the anterior mediastinum >2 cm in depth, and that mass reaches the level of 4th thoracic vertebra.
• Etiology: Ectopic thyroid tissue from the mediastinum, not related to the existing thyroid which gets its blood supply from the mediastinum itself.
• Secondary (common) which Is commonly seen in the short neck or obese individuals due to negative intrathoracic pressure

Types of Goiter

• Substernal Type: Part of the nodule is palpable in the lower neck.
• Plunging goiter: Is forced into the neck by increased intrathoracic pressure.
• Intrathoracic goiter itself has a normal neck and most often effects men.
• Symptoms: Often symptomless, it's not rare for it to be Discovered on a routine chest radiograph, it is possible for severe symptoms to present: such as, Dyspnea (particularly at night), Cough and stridor (harsh sound on inspiration), dysphagia or recurrent nerve paralysis is rare.
• Inspection of patients shows +VE Pemberton's sign where lower border is not seen, its very significant when Raising the arm above the shoulder level: where Dilated veins are seen over neck, the upper part chest wall will constrict, and Stridor and rarely dysphagia may occur.

Other signs of possible Goiter

• Is important to note if lower border is not palpated with inspection from BY PALPATION by auscultation where a Dull note occurs over the sternum on percussion.
• X-RAY: Shows a soft-tissue shadow in the superior mediastinum which Sometimes accompanies Calcification Note that CT scans are Most accurate anatomical visualization, but may also Shows Significant tracheal compression and obstruction may be demonstrated.
• Antithyroid drugs are Contraindicated in case of thyrotoxicosis accompanied with obstructive symptoms which would only cause them to enlarge a goiter.
• For Surgery: its typically only resolved with Resection from the neck plus median sternotomy and that there is no injury to the recurrent laryngeal nerve because the surgeon has already carefully identified it .

Thyroid Incidentaloma

• Clinically, it comes as unsuspected and impalpable thyroid swellings.
• Management relies on the observation that the majority of impalpable thyroid swellings can be safely managed by a single annual review, unless certain criteria are met or if the swelling becomes palpable.

Thyroid Cysts

• Definition: thyroid swelling is cystic in nature & elicit positive fluctuation.
• A: fnac is indicated so that the cyst may cause regression of simple cysts.
• Common causes are Colloid degeneration (no epithelial lining) (50%) during involution in Follicular Adenomas like Cysts. Management involves observing any complex cyst that's greater then 4 cm in size to evaluate for reoccurrence after three repeated aspiration. Breathing difficulties in thyroid swellings are a reoccurring symptom:
• Retrosternal goiter shows Ve Pemberton's sign, Multinodular goiter of long duration has +Compressive stridor with Secondary toxic goiter - congestive cardiac failure and Carcinoma infiltrating the trachea that results in Stridor on rest (without compression with fingers).