Hypothyroidism: Overview & Hashimoto's Thyroiditis

Hypothyroidism is characterized by decreased thyroid hormone, leading to a reduced basal metabolic rate (BMR). It can arise from primary thyroid gland dysfunction or central issues involving the hypothalamus and pituitary gland.

Clinically, exhibit a variety of symptoms. Cold intolerance results from the diminished BMR and consequent decreased heat production. Dermatological manifestations like cool, dry skin & brittle hair are due to reduced metabolic activity in skin and hair follicles. Myxedema, characterized by periorbital edema and macroglossia, is a form of non-pitting edema caused by the accumulation of glycosaminoglycans like hyaluronic acid. Neuromuscular symptoms such as numbness or tingling in the first three and a half fingers can occur due to myxedema-induced median nerve compression in the carpal tunnel,

Metabolic and cardiovascular symptoms also develop in hypothyroidism. Patients often experience weight gain, primarily due to decreased BMR and fluid retention. Hypercholesterolemia is commonly observed due to downregulation of LDL receptors. Cardiovascular symptoms like bradycardia and decreased cardiac output emerge from downregulated beta-adrenergic receptors and impaired calcium flux in cardiac myocytes. Hypertension is also common due to increased systemic vascular resistance (SVR).

Hypothyroidism manifests with various GI and muscular symptoms. Constipation arises due to reduced gastrointestinal motility, while hypothyroid myopathy presents with proximal muscle weakness, cramps, and myalgias. It is characterized by atrophy of fast twitch type II fibers, resulting in elevated serum levels of creatinine kinase (CK).

Reproductive and psychiatric symptoms can also be prominent. Irregular menses occur as a result of hormonal imbalances, and psychiatric disturbances can range from depression and anxiety to cognitive impairment.

Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis, stands as the predominant cause of hypothyroidism in iodine-sufficient regions. This autoimmune condition leads to irreversible hypothyroidism by destroying the thyroid gland. It commonly affects older women between the ages of 45 and 65 and is often concomitant with other autoimmune disorders such as Celiac disease, T1DM, and primary adrenal insufficiency. Genetically, the disease is associated with MHC class 2 genes HLA-DR3 and DR5. The pathogenesis involves both type II and type IV hypersensitivity reactions. Specifically, CD8+ cytotoxic T cells inflict direct damage to thyroid follicular cells, while activated CD4+ T cells release cytokines that recruit macrophages, thereby intensifying the autoimmune response.

Anti-thyroid antibodies are a hallmark of Hashimoto’s. Patients frequently exhibit anti-thyroglobulin (anti-Tg) and anti-thyroid peroxidase (TPO) antibodies. Occasionally, anti-TSH receptor antibodies may also be present, acting to block the function of TSH and further diminish thyroid hormone production.

Special conditions associated with hypothyroidism include congenital hypothyroidism and myxedema coma. Congenital hypothyroidism is caused by inadequate thyroid hormone in utero due to factors like fetal thyroid dysgenesis, maternal hypothyroidism, or iodine deficiency. It manifests as intellectual disability, a pot-belly, protruding umbilicus, pallor, & a puffy face. Myxedema coma, an extreme form of hypothyroidism, is generally precipitated by acute stressors or chronic severe hypothyroidism. It leads to symptoms such as confusion, lethargy, hypothermia, hypotension, & even cardiovascular collapse.

For diagnosis, in primary hypothyroidism, low T4 & increased TSH. subclinical hypothyroidism results in normal T4 and increased TSH. Central hypothyroidism can either be secondary, arising from pituitary dysfunction, or tertiary, stemming from hypothalamic dysfunction. Both types present with low levels of T4 and TSH. The gold-standard treatment for hypothyroidism is oral levothyroxine, a synthetic form of T4.

Hashimoto's thyroiditis can initially manifest as transient hyperthyroidism due to the sudden release of preformed, stored thyroid hormones during the initial stages of glandular destruction. Over time, patients develop a painless goiter from the chronic elevation in TSH levels that induce glandular hypertrophy.

Histologically, it shows a lymphocytic infiltrate and atrophic follicles lined by Hurthle cells. It is also a significant risk factor for primary lymphoma of the thyroid, particularly B-cell non-Hodgkin lymphoma.