Snapshot A 32-year-old woman presents to the clinic complaining of fatigue and weight gain for the past 2 months. She endorses cold intolerance, constipation, and dry skin but denies fever, diarrhea, swelling, chest pain, or shortness of breath. A physical examination demonstrates a lethargic, stocky patient with brittle hair. Her past medical history is significant for asthma that is well controlled with her rescue inhaler. Her laboratory studies demonstrate elevated levels of thyroid stimulating hormone. (Hashimoto thyroiditis) Hypothyroidism Clinical definition disorder characterized by the under production of thyroid hormone Epidemiology Demographics iodine deficiency is the most common cause of hypothyroidism worldwide Hashimoto thyroiditis is the most common cause of hypothyroidism in iodine-sufficient areas ETIOLOGY Pathogenesis primarily due to thyroid disease (primary hypothyroidism) but can be caused by secondary and/or tertiary hypothyroidism primary hypothyroidism Hashimoto thyroiditis (chronic autoimmune thyroiditis) cell- and antibody-mediated destruction of thyroid tissue infiltrative disease (e.g., fibrous thyroiditis) iatrogenic disease thyroidectomy radioiodine treatment external radiation therapy iodine deficiency and/or excess thyroid hormone resistance most commonly caused by defective thyroid hormone receptor beta; inherited in autosomal dominant pattern characterized by elevated T4/T3 and non-suppressed TSH medications lithium amiodarone interferon alpha interleukin-2 tyrosine kinase inhibitors checkpoint inhibitor immunotherapy (e.g., ipilimumab, pembrolizumab, and nivolumab) secondary and tertiary hypothyroidism secondary hypothyroidism caused by TSH deficiency secondary to any of the causes of hypopituitarism most commonly due to a pituitary tumor other causes include Sheehan syndrome, trauma, craniopharyngiomas, or infiltrative diseases tertiary hypothyroidism caused by any disorder that damages the hypothalamus or interferes with hypothalamic-pituitary portal blood flow (e.g., radiation therapy) Hyperthyroidism Clinical definition disorder defined by the over activity of the thyroid leading to excess thyroxine, leading to an acceleration of the body’s metabolism Epidemiology Demographics more common in women than men (5:1 ratio) Grave disease is the most common cause of hyperthyroidism ETIOLOGY Pathogenesis increased synthesis of thyroxine or from the release of preformed hormone secondary to inflammation or destruction of thyroid tissue causing a low TSH increased de novo synthesis of thyroxine Grave disease autoimmune disorder resulting from thyroid-stimulating hormone (TSH) receptor antibodies stimulates thyroid gland growth and thyroid hormone synthesis and release toxic adenoma/toxic multinodular goiter hyperplasia of thyroid follicular cells that are independent of TSH regulation presents with a nontender palpable nodule and focal uptake on radioactive iodine uptake studies trophoblastic disease/germ cell tumors high level human chorionic gonadotropin (hCG) from these conditions will lead to thyrotropic activity ectopic TSH secretion TSH-producing pituitary adenomas release of preformed hormone thyroiditis inflammation of thyroid tissue exogenous ingestion ectopic production of thyroid hormone struma ovarii Presentation Hypothyroidism Hyperthyroidism Cold intolerance (↓ heat production) Heat intolerance (↑ heat production) Weight gain and ↓ appetite Weight loss and ↑ appetite Hypoactivity, lethargy, fatigue, and weakness Hyperactivity Constipation Diarrhea ↓ Reflexes ↑ Reflexes Bradycardia Tachycardia, palpitations, arrhythmias Dry, cool skin and coarse, brittle hair Warm, moist skin and fine hair Diastolic hypertension Systolic hypertension Myxedema (facial/periorbital) Osteoporosis and hypercalcemia "Myxedema madness": syndrome characterized by psychosis, confusion, and disorientation Apathetic thyrotoxicosis Studies Diagnostic testing diagnostic approach diagnosis is based on clinical suspicion and confirmed via thyroid function tests Labs Hypothyroidism Hyperthyroidism ↑ TSH (best first test) ↓ TSH (best first test) ↓ Total T4 ↑ Total T4 ↓ Free T4 ↑ Free T4 Hypercholesterolemia (↓ LDL receptor synthesis) Hypocholesterolemia (↑ LDL receptor synthesis) Treatment Hypothyroidism Hyperthyroidism Levothyroxine Dose should be increased during pregnancy due to increased TBG Thionamides (e.g.,methimazole) Ablative131I therapy Propranolol (rate/symptom control) Complications Myxedema coma (hypothyroidism) Thyroid storm (hyperthyroidism)