Snapshot A 38-year-old woman presents to her primary care physician with complaints of increased fatigue. On further review, she also reports that she has been experiencing a 15-pound weight gain, cold intolerance, and constipation over the past few months. On physical exam, she is bradycardic, has a puffy face with periorbital edema, has thinning hair, exhibits delayed relaxation of deep tendon reflexes, and is without a goiter. Introduction Clinical definition primary hypothyroidism due to the autoimmune destruction of the thyroid gland Epidemiology most common cause of primary hypothyroidism predominantly female (10-15 x higher) 30-50 years of age Risk factors family history autoimmune disease Pathogenesis anti-thyroid antibodies destroy thyroid cells leading to insufficient production of thyroid hormone anti-thyroid peroxidase anti-thyroglobulin damaged thyroid cells can initially leak stored thyroid hormone into circulation leading to transient hyperthyroidism before the onset of hypothyroidism Associated conditions pernicious anemia celiac disease type 1 diabetes Prognosis excellent with treatment myxedema coma has a high mortality rate Presentation Symptoms weakness and fatigue cold intolerance constipation and ileus weight gain depression, slow mentation, and inability to concentrate heavy menstruation galactorrhea thyrotropin-releasing hormone can stimulate prolactin secretion hoarseness myopathy dementia/memory loss Physical exam dry and cold skin puffy face with periorbital edema non-pitting edema (myxedema due to glycosaminoglycan in the interstitium) thinning hair and nails bradycardia delayed relaxation of the deep tendon reflexes thyroid gland can be atrophic, normal, or enlarged Special presentation subclinical elevated thyroid stimulating hormone (TSH) but normal thyroid hormones does not require treatment unless auto-antibody positive or symptomatic Studies Diagnostic testing diagnostic approach screen and confirm with lab tests studies TSH and free T4 primary screening TSH is the most sensitive measure lab results may be confounded by high doses of biotin supplementation autoantibody diagnose Hashimoto versus other etiologies of hypothyroidism anti-thyroid peroxidase (90% of cases) anti-thyroglobulin (50% of cases) 10-15% are antibody negative imaging not routinely indicated biopsy fine needle aspiration for any dominant nodule or fast-growing goiter histopathology is the gold standard for diagnosis but invasive diffuse lymphocytic and plasma cell infiltration is characteristic of Hashimoto thyroiditis Diagnostic criteria ↑ TSH and ↓ free T4 in early disease, TSH and free T4 may be normal positive antithyroid autoantibodies Differential Euthyroid sick syndrome distinguishing factors ↓ thyroid hormone but also ↓TSH secondary to nonthyroidal systemic illness Thyroid lymphoma distinguishing factors rapidly enlarging goiter lymphoma on histopathology Panhypopituitarism distinguishing factor loss of pituitary hormones in addition to ↓ T4 including ↓ cortisol, ↓ sex steroids, ↓ growth hormone, and ↓ antidiuretic hormone Major depressive disorder distinguishing factor lack of cold intolerance, integumentary changes, myxedema, and goiter Treatment Management approach thyroid hormone replacement to achieve a euthyroid state within 2-4 weeks monitor clinically and with TSH monitor for other associated complications mild anemia ↑ total cholesterol, low-density lipoprotein, and triglycerides ↓ high-density lipoprotein hyponatremia First-line lifelong levothyroxine replacement requires adjustment during pregnancy adverse effects include overreplacement leading to osteoporosis and arrhythmias administer empirically without lab confirmation in myxedema coma Second line surgery indicated for obstructive symptoms (dysphagia, stridor, and hoarseness), malignancy, and cosmesis Complications Thyroid lymphoma or other thyroid malignancy Iatrogenic overreplacement Myxedema coma life threatening complication of hypothyroidism start empiric treatment with IV levothyroxine if high suspicion can support diagnosis with TSH and free T4 level