Prognosis

With early diagnosis, timely institution of L-T4 replacement therapy, regular patient follow-up care, and attention to other attendant complications, the prognosis in Hashimoto's thyroiditis (HT) is excellent with patients leading a normal life. Untreated myxedema coma has a poor prognosis and a high mortality rate, particularly in old age. Transient periods of thyrotoxicosis sometimes occur, and rarely full hyperthyroid Graves' disease with active ophthalmopathy. There is an increased prevalence of coronary artery disease in patients with untreated or undertreated HT. The relationship between papillary thyroid carcinoma (PTC) and HT has been controversial. Primary thyroid B-cell lymphoma affects less than one in a thousand persons, and it is more likely to affect those with long-standing autoimmune thyroiditis. Complications of over-replacement with L-T4 should be avoided. This chapter explores the prognosis of Hashimoto's disease.

Iodide Metabolism and Effects

Iodine (I2) is essential in the synthesis of thyroid hormones T4 and T3 and functioning of the thyroid gland. Both T3 and T4 are metabolically active, but T3 is four times more potent than T4. Our body contains 20-30 mg of I2, which is mainly stored in the thyroid gland. Iodine is naturally present in some foods, added to others, and available as a dietary supplement. Serum thyroid stimulating hormone (TSH) level is a sensitive marker of thyroid function. Serum TSH is increased in hypothyroidism as in Hashimoto's thyroiditis. In addition to regulation of thyroid function, TSH promotes thyroid growth. If thyroid hormone synthesis is chronically impaired, TSH stimulation eventually may lead to the development of a goiter. This chapter explores the iodide metabolism and effects of Hashimoto's disease.

Pathology

Grossly, thyroid enlargement in Hashimoto's thyroiditis (HT) is generally symmetrical, often with a characteristic conspicuous pyramidal lobe. The tissue involved by HT is pinkish-tan to frankly yellowish in color and tends to have a rubbery firmness. There is no necrosis or calcification. The capsule is intact and non-adherent to peri-thyroid structures. Microscopically, there is a diffuse process consisting of a combination of epithelial cell destruction, lymphoid cellular infiltration, and fibrosis. Lymphocytes are predominantly T-cells and plasma cells. Most infiltrating T-cells have α/β T-cell receptors. Gamma/delta T-cells are rare. Hashimoto's thyroiditis has been graded based on lymphocytic infiltration seen on cytology, into Grades 0-III, where Grade 0 means no lymphoid cells and Grade III severe lymphoid cell infiltration. Deposits of dense material representing IgG are found along the basement membrane on electron microscopy. This chapter explores the pathology of Hashimoto's disease.

Hashimoto's Encephalopathy

Hashimoto's encephalopathy is a relapsing encephalopathy occurring in association with Hashimoto's thyroiditis (HT) with high titers of anti-thyroid antibodies. The mechanism of pathogenesis is unknown. Auto-antibodies to α-enolase have been found to be associated with Hashimoto's encephalopathy. Recently, the crucial role of neuro-inflammation in the development of psychological disorders including depression and anxiety has received more attention. Because the majority of patients with Hashimoto's encephalopathy respond to steroids or immuno-suppressant treatment, this condition is now also referred to as “steroid-responsive encephalopathy.” Initial treatment is usually with oral prednisone (50–150 mg/day) or high-dose IV methyl-Prednisolone (1 g/day) for 3-7 days. Thyroid hormone treatment is also included if required. This chapter explores Hashimoto's encephalopathy.

Diagnosis

Clinically, a diffuse, firm goiter with pyramidal lobe enlargement, and without signs of thyrotoxicosis, should suggest the diagnosis of Hashimoto's thyroiditis (HT). The association of goiter with hypothyroidism is almost diagnostic. The thyroid stimulating hormone (TSH) is the sensitive marker of hypothyroidism and diagnosis of subclinical hypothyroidism. Thyroid perioxidase antibodies (TPO-Ab) and, less frequently, thyroglobulin antibodies (Tg-Ab) are elevated in the serum of patients with HT. Ultrasound may display an enlarged gland with normal texture, focal, or diffuse glandular enlargement with coarse, heterogenous, and hypo-echoic pattern, or a suggestion of multiple ill-defined micro-nodules. Color Doppler shows extensive hyper-vascularity. Histologically, the thyroid gland shows diffuse lymphocytic and plasma cell infiltration with formation of lymphoid follicles. Atrophy of the thyroid parenchyma is usually evident. It also reveals scant colloid, and a few epithelial cells, which may show Hurthle cell change. This chapter explores the diagnosis of Hashimoto's disease.

Etiology and Risk Factors

The etiology of Hashimoto's thyroiditis (HT) arises from an interaction between genetic and non-genetic factors. The genes implicated vary in different ethnic groups and the incidence is increased in people with chromosomal disorders. HT is usually associated with auto-antibodies against thyroglobulin (Tg) and thyro-perioxidase (TPO) leading to primary hypothyroidism. Having other autoimmune diseases is a risk factor to develop HT. First-degree relatives of persons with HT have greater risk of developing the disease. Female gender is associated with an eight-fold increased risk for HT possibly due to the effects of sex hormones, X-chromosome-encoded susceptibility, skewed X-chromosome inactivation, pregnancy, and fetal micro-chimerism. In genetically susceptible individuals, environmental factors, including high iodine intake, selenium deficiency, infectious diseases, stress, and certain drugs, have been implicated in initiating the autoimmune process. This chapter explores the etiology and risk factors of Hashimoto's disease.

Epidemiology

Hashimoto thyroiditis (HT) remains the most common cause of spontaneous hypothyroidism in areas of adequate iodine intake, such as North America. The incidence of HT is estimated to be 10-15 times higher in females. The most commonly affected age range is 30-50 years, with the peak incidence in men occurring 10-15 years later, but it may be seen in any age group, including children. Hashimoto's thyroiditis appears to occur in more than 10% of patients presenting with thyroid nodule and may be associated with other autoimmune disorders. The occurrence of papillary thyroid carcinoma in HT ranges widely from 0.5-30% of cases. The prevalence of thyroid antibodies is twice more common in women than in men, and higher in whites and Asians than Blacks or Mexicans. There is approximately a 30-fold increase in risk for developing HT in children and 20-fold increased risk in siblings of patients with HT, with females being significantly more often affected than males. This chapter explores the epidemiology of Hashimoto's disease.

Historical Review

Hashimoto thyroiditis (HT) is part of the spectrum of autoimmune thyroid diseases characterized by the destruction of thyroid cells by various cell- and antibody-mediated immune processes. It was first described by the Japanese surgeon Hakaru Hashimoto (1981-1934). It was not until 1956 when a link between antibodies to thyroid cells present in the serum of patients and HT was made. Over time, our understanding of the immunologic pathways involved in HT has evolved. We now recognize the association of this disease with other autoimmune diseases and thyroid cancer. The increasing use of the needle biopsy and serologic tests for antibodies have led to much more frequent recognition, and there is reason to believe that it may be increasing in frequency. It is now one of the most common thyroid disorders. This chapter gives a historical overview of Hashimoto's disease.

Dietary Management

The best diets for Hashimoto's thyroiditis (HT) patients are the gluten-free diet, paleo diet, and vegetarian and vegan diets. Micro-nutrients to integrate in diet for patients with HT are Iodine (150-290 µg/day), Selenium (55-75 µg/day), Zinc (34-40 mg/day), Vitamin D (1500-2500 IU/day), and Vitamin B12 (2.4-2.8 µg/day). The worst foods for patients with HT that should be avoided are gluten, goitrogens, alcoholic drinks, food additives, and supplements (gums, lecithin, and coffee and fiber supplements). This chapter explores the dietary management of Hashimoto's disease.

Management

Treatment of Hashimoto thyroiditis (HT) is mainly medical supplementing L-thyroxine (L-T4) for hypothyroidism. L-thyroxine has proved to reduce the volume of the thyroid gland in both hypothyroidism and euthyroid state. The dose of L-T4 is tailored according to the patient's needs; the standard dosage is 1.6-1.8 µ/kg/day. The level of TSH is frequently monitored for dose adjustment till euthyroid state is attained thereafter every 6-12 months. Thyroidectomy is considered in patients with cosmetic problem; with compressive symptoms (such as dysphagia, dyspnea, change of voice), suspicion of malignancy as papillary thyroid carcinoma is commonly associated. Surgery has a beneficial effect in cases of painful thyroiditis. Radioactive iodine treatment can be considered as a last option in elderly patients with large goiter who refuse surgery and their thyroiditis is not responding to L-T4 treatment. This chapter explores the management of Hashimoto's disease.