Goiter simply refers to the enlargement of the thyroid gland. It can be due to various causes, dietary iodine deficiency being the most common cause worldwide. In the United States, however, Graves disease and Hashimoto disease are more common. Goiter has been classified as per different categories, morphology (nodular/diffuse), functional status (hyper/hypo/euthyroid), malignancy, etc. By definition, a 'diffuse, toxic" Goiter refers to a diffusely hyperplastic thyroid gland that is excessively overproducing the thyroid hormones.
The following are common causes of goiter:
Diffuse, toxic goiter is most commonly caused by autoimmune disorders like Graves disease in the United States.
The most common cause of diffuse, toxic goiter, is Graves disease. It is the most common cause of hyperthyroidism in the United States and affects 1 in 200 people.
It usually affects people between 30 and 50 years of age, but can occur in any age group. It is 7 to 10 times more common in females than in males. A marked increase in familial incidence has been observed, as well.
Diffuse, toxic goiter consists of a diffusely enlarged, vascular gland with rubber-like consistency. Microscopically, the follicular cells are hypertrophic and hyperplastic with little colloid in them. Lymphocytes and plasma cells infiltrate into the gland and can ultimately aggregate into lymphoid follicles.
All cases of diffuse, toxic goiter are not Graves disease and may have various non-autoimmune causative processes. But the majority of cases are auto-immune in nature. In Graves disease, antibodies are directed towards the thyroid-stimulating hormone receptor (TSHr) present on follicular cells. The chronic stimulation of these receptors results in the production of excess amounts of T3, T4, and the eventual enlargement of the thyroid gland resulting in a goiter.
This disease has the following histological characteristics:
Due to the last point above, there have been controversies regarding the association between Graves disease and papillary thyroid carcinoma, and whether the coexistence of the two affects the prognosis. On systematic review of various studies, it has been seen that if a papillary carcinoma is discovered after surgical removal of the gland the prognosis is excellent, whereas on discovering a tumor in a patient of Graves disease, the local characteristics of the tumor (size, extent, margins, functionality, etc.) decide the prognosis.
The common findings in a patient with the diffuse, toxic goiter on physical exam are as follows:
The primary evaluation consists of a complete thyroid profile, including serum T3, T4, TSH levels.
The treatment modalities for diffuse toxic goiter include:
Antithyroidthyroid Drugs (ATD)
Radio-iodine Therapy (I-31, RAI) 
Although diagnosed with the various forms of evaluation, as mentioned above, the differential diagnosis of diffuse, toxic goiter include:
Patients with diffuse toxic goiter, especially due to Graves disease, are expected to become hypothyroid during the natural course of their disease regardless of treatment. Prolonged thyrotoxicosis may cause ventricular thickening and, therefore, an increased risk of cardiac mortality.
Treatment with RAI is done with the aim of permanent hypothyroidism, thus making the patient dependant on life long thyroid hormone supplementation. ATDs have an average remission rate of 50% but an excellent prognosis after 4 years, devoid of relapse.
Diffuse, toxic goiter may present with the usual hypermetabolic(ex. heat intolerance, sweating, weight loss, etc.) and adrenergic symptoms(ex. palpitations, tremors, emotional lability, etc.) of hyperthyroidism, along with the swelling of the goiter. But elderly patients may not present with adrenergic symptoms, rather with apathy, atrial fibrillation, etc. which might also be presentations for depression, malignancy, or cardiac abnormalities.
Diagnosing diffuse, toxic goiter is an amalgamation of clinical signs and investigations. Evaluating radiological and blood investigations are important to reach a conclusion to the underlying cause of the disease. Once diagnosed, it is the physician's responsibility to help the patient pick the best treatment option based on their profile, and with a thorough understanding of potential side effects. Women need to be especially careful and well informed as being pregnant or breastfeeding requires them to change their form of therapy if contraindicated. Since this condition can also lead to cosmetic concerns (ex. bulging eyes,etc.) physicians, need to be sensitive and perceptive to them and counsel patients about treatment options available, along with having a realistic approach to the treatment response.
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