This patient's history and presentation is classic for hypothyroidism. The best initial screening test for suspected hypothyroidism is a serum thyroid-stimulating hormone (TSH) level.
Hypothyroidism classically presents with complaints of weight gain, fatigue, cold intolerance, menstrual irregularities, myalgias, dry skin, and brittle hair or hair loss. Common physical exam findings include bradycardia, hypertension, a delayed relaxation phase of deep tendon reflexes, and goiter. Central hypothyroidism (i.e. hypothyroidism caused by pituitary or hypothalamic failure) can present with additional signs of hypogonadism and adrenal insufficiency. To diagnose hypothyroidism, a TSH level is used for screening; if abnormal, it is followed by a repeat TSH and free T4 to better characterize the type of thyroid dysfunction.
In their review of hypothyroidism, Gaitonde et al. reiterate the complications of untreated hypothyroidism, including hypertension, dyslipidemia, infertility, cognitive impairment, and neuromuscular dysfunction. Currently there is no evidence for screening asymptomatic individuals. If hypothyroidism is suspected and the initial TSH is elevated, then further workup for primary hypothyroidism should be performed. If the TSH level is low, then a central cause of hypothyroidism should be suspected (or alternatively, the possibility of a hyperthyroid state should be entertained).
Rodondi et al. review subclinical hypothyroidism and the risk of both coronary heart disease (CHD) and overall mortality. Subclinical hypothyroidism is defined as a biochemical elevation of TSH, with normal free T4 levels. In this study, the authors found an increased risk of CHD events and CHD-related mortality in patients with subclinical hypothyroidism. This risk correlated with the degree of TSH elevation and was greatest for patients with a TSH of 10 mIU/L or greater.
Illustration A shows a simple screening algorithm for patients with suspected hypothyroidism. Note that serum TSH is the initial test of choice. Also note that with a low TSH, a central cause of hypothyroidism should be considered. Illustration B summarizes the signs and symptoms of hypothyroidism. Illustration C shows an image of a goiter, which can be present in hyperthyroidism (Graves' disease) or hypothyroidism (Hashimoto's thyroiditis or iodine deficiency).
Answer 1: Anti-TPO antibodies are present in patients with Hashimoto's thyroiditis. Hashimoto's thyroiditis is the most common cause of hypothyroidism in adults in iodine-sufficient areas and is the most likely cause in this patient. However, the best initial test is to confirm the presence of hypothyroidism.
Answer 2: Morning cortisol and plasma ACTH (along with an ACTH stimulation test) are useful to diagnose adrenal insufficiency. Although chronic adrenal insufficiency does present with fatigue, it would more likely be accompanied by anorexia, weight loss, and hypotension as opposed to the weight gain and pre-hypertension seen in this patient.
Answer 3: Serum free T4 is appropriate as a follow-up test if an abnormal TSH level is discovered.
Answer 5: Hemaglobin and hematocrit would be helpful in evaluating for anemia. Although anemia can also present with fatigue, the presence of the other symptoms makes hypothyroidism more likely.
Gaitonde DY, Rowley KD, Sweeney LB. Hypothyroidism: an update. Am Fam Physician. 2012;86(3):244-51.
PMID:22962987 (Link to Abstract)
Rodondi N, Den elzen WP, Bauer DC, et al. Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA. 2010;304(12):1365-74.
PMID:20858880 (Link to Abstract)