From the Guidelines
Hypothyroidism is primarily caused by autoimmune thyroiditis, specifically Hashimoto's disease, where the immune system attacks the thyroid tissue, leading to inflammation and impaired function. The pathophysiology of hypothyroidism involves the thyroid gland's failure to produce sufficient thyroid hormones, primarily thyroxine (T4) and triiodothyronine (T3) 1. This condition can result from various causes, including chronic autoimmune thyroiditis, surgical removal of the thyroid, radiation treatment, certain medications, iodine deficiency, and pituitary or hypothalamic disorders.
Key factors that contribute to the development of hypothyroidism include:
- Female sex
- Advancing age
- White race
- Type 1 diabetes
- Down syndrome
- Family history of thyroid disease
- Goiter
- Previous hyperthyroidism
- External-beam radiation in the head and neck area 1
When thyroid hormone production decreases, the pituitary gland increases thyroid-stimulating hormone (TSH) production in an attempt to stimulate the thyroid, which is why elevated TSH is a key diagnostic marker. Reduced thyroid hormones affect virtually all body systems by slowing cellular metabolism, leading to symptoms like fatigue, cold intolerance, weight gain, constipation, dry skin, hair loss, bradycardia, and cognitive impairment. At the cellular level, thyroid hormones normally regulate gene transcription and mitochondrial function, so their deficiency reduces energy production and cellular activity throughout the body.
The primary screening test for thyroid dysfunction is the serum TSH test, and treatment typically involves levothyroxine (synthetic T4) replacement, usually starting at 1.6 mcg/kg/day for adults, adjusted based on TSH levels measured every 6-8 weeks until stabilized 1.
From the FDA Drug Label
Thyroid hormone drugs are indicated: As replacement or supplemental therapy in patients with hypothyroidism of any etiology, except transient hypothyroidism during the recovery phase of subacute thyroiditis primary hypothyroidism resulting from functional deficiency, primary atrophy, partial or total absence of thyroid gland, or the effects of surgery, radiation, or drugs, with or without the presence of goiter; and secondary (pituitary) or tertiary (hypothalamic) hypothyroidism
The pathophysiology of hypothyroidism involves a functional deficiency of the thyroid gland, which can result from various etiologies, including:
- Primary atrophy or partial/total absence of the thyroid gland
- Surgery, radiation, or drugs that affect thyroid function
- Secondary (pituitary) or tertiary (hypothalamic) hypothyroidism 2 Key factors include a decreased level of adrenocortical activity and a lowered metabolic state, which can lead to adrenocortical insufficiency when thyroid-replacement therapy is administered 2
From the Research
Pathophysiology of Hypothyroidism
The pathophysiology of hypothyroidism is characterized by a decrease in the functioning of the thyroid gland, leading to an under-secretion of thyroid hormones, mainly thyroxine (T4) and triiodothyronine (T3) 3, 4, 5, 6. This condition affects people of every age group, but is more commonly found in women and older people.
Causes of Hypothyroidism
The causes of hypothyroidism include:
- Autoimmune diseases, such as Hashimoto's thyroiditis 7
- Radiation therapy
- Thyroid gland removal surgeries
- Certain medications, such as amiodarone, lithium, and immune checkpoint inhibitors 5
- Chronic autoimmune thyroiditis (Hashimoto's thyroiditis) is the most common cause of hypothyroidism 5
Clinical Presentation of Hypothyroidism
The clinical presentation of hypothyroidism can range from asymptomatic to life-threatening and includes:
- Fatigue
- Lethargy
- Weight gain
- Cold intolerance
- Constipation
- Dry skin (xeroderma)
- Change in voice
- These symptoms are mostly the result of a low metabolic rate in the body 3, 4, 5
Diagnosis and Treatment of Hypothyroidism
The diagnosis of hypothyroidism is based on laboratory tests that measure the levels of thyroid hormones (T3 and T4) in the blood 3, 6. Treatment typically involves lifelong hormone replacement therapy with synthetic thyroid hormone replacement medication, such as levothyroxine, to help regulate hormone levels in the body 3, 4, 5, 6. The dose of levothyroxine used for treatment is based on the degree of preserved thyroid functionality and lean body mass 7.