Case 2: Worsening Anxiety in an Adolescent: The Role of Anchoring Bias

Presented here are three patients who have a common chief complaint. All three cases have discussions on presentation, the differential diagnosis, and management that collectively serve as a Review article. Following the three cases, an expert weighs in in a short commentary with 5 questions for CME credit.An 18-year-old female patient with a medical history of posttraumatic stress disorder, generalized anxiety and panic disorder, cannabis use disorder, migraines with aura, and intermittent asthma presents to the adolescent clinic with 1 month of worsening anxiety, stating, “I am unable to calm myself with relaxation strategies.” During the past month, she has experienced heart palpitations, chest pain, shortness of breath on exertion, new headaches characterized by global pressure that awakens her from sleep and are not positional or related to Valsalva, and an unintentional 17.6-lb (8-kg) weight loss in 5 months. She denies nausea, vomiting, and any dietary or activity changes. Her only medication is medroxyprogesterone depot for contraception. She has a family history notable for cardiac disease in her father and paternal grandfather after age 50 years. Her psychosocial history is significant for sexual trauma, anxiety, and 5 years of daily inhaled marijuana use (1 joint per day mixed with tobacco). She denies using other substances and is not taking any prescribed or over-the-counter medications or supplements.Her initial vital signs are a temperature of 98°F (36.7°C), heart rate of 134 beats/min, respiratory rate of 20 breaths/min, pulse oxygen saturation of 100% in room air, and blood pressure of 151/61 mm Hg. Her weight is 144.4 lb (65.5 kg) (77th percentile); BMI is 25.25 (82nd percentile). At a visit 8 months earlier, she weighed 162.7 lb (73.8 kg) (91st percentile) with a BMI of 27.8 (91st percentile). She appears alert and anxious but does not appear to be in acute distress. On physical examination her head, ears, eyes, nose, and throat examination is notable for bilaterally injected conjunctiva, and there is no evidence of thyromegaly or palpable thyroid nodules. She is tachypneic, with increased work of breathing and expiratory wheezing. Her cardiac examination demonstrates tachycardia without irregular heart sounds or murmurs, and good distal perfusion without bounding pulses. On ophthalmic examination there are clearly defined optic discs. Her neurologic examination demonstrates a mild resting tremor in her hands; she has a normal gait and balance, 5/5 strength, and 2/4 reflexes throughout. The remainder of the examination findings are normal. She is transferred to the pediatric emergency department for further evaluation and management of unexplained tachycardia, tachypnea, and hypertension.The differential diagnosis for an adolescent patient with worsening anxiety, new headache, chest pain, heart palpitations, weight loss, hypertension, and dyspnea on exertion is extensive. In this case, the differential diagnosis included mental health disorders, substance-related toxicity, cardiopulmonary pathologies, infectious etiologies, intracranial pathologies, and endocrinologic diseases.Given the patient’s history of anxiety and trauma, this presentation could be mistaken for an exacerbation of her underlying mental health conditions. However, anxiety alone is a diagnosis of exclusion, and clinicians must evaluate other etiologic causes for this presentation. Furthermore, despite this patient’s prolonged history of cannabis use, she denied any change in her patterns of use or new substances; nevertheless, toxidrome from cannabis or other agents should be considered. In addition, the patient’s weight loss was unintentional and unrelated to body dysmorphia, changes in caloric intake, or excessive energy expenditure, making an eating disorder an unlikely cause of these symptoms.Considering cardiopulmonary etiologies, this presentation could have been consistent with pulmonary embolism; however, she did not have any risk factors for thrombosis, and a pulmonary embolism is unlikely without clinical signs or symptoms of deep venous thrombosis, hemoptysis, or oxygen desaturation. Although myocarditis and asthma exacerbation could have caused her shortness of breath, headache, and tachycardia, these diagnoses are not typically associated with hypertension. Similarly, tachycardia and palpitations could warrant further investigation for cardiac arrhythmias, but an arrhythmia would also be less likely to explain this patient’s hypertension.The neurologic examination findings were normal, and the patient had sharp optic discs on examination, making increased intracranial pressure unlikely. However, other disturbances within the neuroendocrinologic axis, which include catecholamine excess and thyroid abnormalities leading to hyperthyroidism, are critical to consider, especially because this patient has worsening anxiety, heart palpitations, weight loss, and hypertension. Although she previously had normal thyroid function (2 years before the current presentation), developing thyroid disease between ages 18 and 24 years in those assigned female at birth is common and deserves further evaluation. Although rare, thyroid malignancy can also present similarly. Pheochromocytoma can also be considered but is less likely because the symptoms are constant and not episodic in nature and there is no familial genetic history.The diagnostic studies performed are shown in Table 1. Given the findings of negligible thyrotropin and elevated free thyroxine (T4) levels, the patient was diagnosed as having hyperthyroidism. With the guidance of the pediatric endocrinology service, further thyroid studies were performed, as shown in Table 2, revealing that the patient had elevated thyroid peroxidase antibody (TPO) and thyroid-stimulating immunoglobulin (TSI) levels consistent with new-onset Graves disease. The thyroid ultrasonographic image shown in the Fig and the study results given in Table 2 confirmed the diagnosis.Graves disease is an autoimmune disease that causes increased thyroid hormone production and thyroid growth due to autoantibody stimulation of the thyrotropin receptor. The causes of Graves disease are multifactorial, including genetic predisposition and environmental factors. The clinical presentation of Graves’ disease is due to hyperthyroidism. Graves’ disease manifests as anxiety, tachycardia, widened pulse pressure, weight loss or failure to gain weight, tremors, proximal muscle weakness, sweating, and ophthalmopathy. Specifically, proptosis and periorbital edema are signature eye findings of Graves disease that distinguish it from other forms of hyperthyroidism. (1) Diagnosis of Graves disease is based on the clinical presentation of hyperthyroidism and the following laboratory findings: 1) reduced thyrotropin levels, 2) normal or elevated thyroid hormone levels (usually free T4), and 3) presence of thyroid receptor-stimulating antibodies such as TSI and TPO. (2) The binding of the autoantibodies will stimulate follicular cell growth and excessive development, leading to an enlarged thyroid gland (related to triiodothyronine [T3]) and increased thyroid hormone synthesis (related to T4). (3) Commonly, in the diagnosis of Graves disease, there is a higher elevated T3 than free T4 level, given that TSI antibodies stimulate the thyrotropin receptor to make thyroid hormone and the deiodinization of T4 to T3. The TSI antibodies help differentiate hyperthyroidism due to Graves disease from the thyrotoxic state seen with Hashimoto thyroiditis, which can mimic Graves disease. In cases with indeterminate laboratory findings, diagnosis of Graves can be further elucidated with a nuclear medicine thyroid uptake scan showing increased 24-hour iodine uptake. (2) Ultrasonography can also help exclude the presence of thyroid nodules in patients with hyperthyroidism and will show an enlarged thyroid gland with increased vascularity in Graves disease. (3)Graves disease is most commonly diagnosed in adolescents, making this age group particularly susceptible. (4) In parallel, diagnoses of anxiety peak during adolescence. Globally, anxiety symptoms in adolescents have doubled compared with estimates before the COVID-19 pandemic, with the highest rates seen in older female adolescents. (5) Adolescents with Graves disease are also reported to have higher rates of comorbid anxiety and attention-deficit/hyperactivity disorder, bipolar disorder, depression, and suicidality. (6) Clinicians treating patients already diagnosed as having mental health disorders and presenting with an exacerbation of those symptoms may be less likely to discover a new diagnosis of thyroid disease despite evidence that in greater than 40% of patients, the diagnosis of a mental health disorder precedes that of hyperthyroidism. (6) In this patient’s case, the primary presenting symptom and concern was worsening anxiety, and this presentation could distract the clinician from other diagnostic hypotheses, leading to anchoring bias.Anchoring bias refers to the excessive weighting of initial information and the inability to adjust the initial diagnostic hypothesis when further information becomes available. (7) It is among the most common heuristic cognitive biases in medical decision-making. (8) Therefore, it is critical that clinical providers identify and mitigate anchoring bias, specifically when diagnosing thyroid disease in adolescents with comorbid mental health disorders. The impact of anchoring bias in children and adolescents with both thyroid and psychiatric disorders likely contribute to abnormal thyrotropin levels being identified in up to 6% of children and adolescents hospitalized for psychiatric disorders. (9) Although there is a complex interplay between the symptomatic presentation of thyroid disease, thyroid levels, and mental health disorders, it is well-supported that the exacerbation of hyperthyroidism is strongly related to symptomatic anxiety and depression. (10) One way to address anchoring bias in the context of anxiety and mood symptom exacerbation in an adolescent previously diagnosed as having a mood or anxiety disorder is to conduct screening thyrotropin and T4 levels as part of their overall evaluation to determine whether thyroid disease may play a role in their symptoms.Graves disease management is aimed at 1) decreasing or eliminating TSI and TPO antibody production to decrease T4 production and 2) treating the effects of thyrotoxicosis. First-line treatment in children and adolescents includes antithyroid drugs, although refractory or severe cases may require definitive treatment with radioactive iodine therapy or surgical thyroidectomy. (11) In children and adolescents with Graves disease in the United States, methimazole is recommended as first-line treatment over propylthiouracil given the risk of rapidly progressive hepatotoxicity. (11) Although methimazole can cause liver dysfunction (usually cholestatic), neutropenia, and skin rash, a recent study found that these events occur in less than 15% of patients and are dose-dependent. (12) Thionamide carbimazole is an alternate form of methimazole commonly used in children and adolescents in Europe and worldwide, but this formulation is not available in North America. (13) Most children will become euthyroid within 4 to 8 weeks of starting these thyroid-blocking agents. (12)(13)In patients with symptomatic hyperthyroidism (resting heart rate >90 beats/min in adults or >100 beats/min in children), β-adrenergic blockade is recommended. (11) β-Blockade should be used with caution in children with a history of severe asthma. There is a lower risk of bronchoconstriction using cardioselective agents such as atenolol or metoprolol. (14) Treatment of orbitopathy and ophthalmopathy is based on the severity of eye disease. If the patient has mild eye disease, supportive therapy with ophthalmic lubricants is recommended, and selenium supplementation can be considered. (13) If moderate to severe disease, initial treatment with glucocorticoids is recommended. (13)After the diagnosis of Graves disease, the patient was promptly connected for ongoing/outpatient follow-up with the pediatric endocrinology service and adolescent medicine service. She was started on atenolol and methimazole. At the time of her diagnosis in the emergency department, the patient described profound relief that her worsening anxiety had “a reason,” indicating the importance of clinicians investigating beyond potential anchoring bias.Hyperthyroidism can exacerbate preexisting mental health conditions in children and adolescents.Anchoring bias is among the most common heuristic cognitive biases in medical decision-making and negatively impacts the care provided to children and adolescents with panic and anxiety disorders.To combat anchoring bias in mental health care, providers should consider alternative diagnoses that do not come intuitively through conscious consideration of diagnoses, thoughtful reasoning, and reflection.