What is the primary diagnosis for a patient with symptoms of weight gain, fatigue, constipation, feeling cold, dry skin, thinning hair, and forgetfulness, along with an elevated Thyroid-Stimulating Hormone (TSH) level and presence of thyroid peroxidase antibodies?

Primary Diagnosis: Hashimoto's Thyroiditis (Chronic Autoimmune Thyroiditis)

Emilee has primary hypothyroidism due to Hashimoto's thyroiditis, confirmed by elevated TSH (8.5 mIU/L), borderline-low free T4 (0.8 ng/dL), and markedly elevated thyroid peroxidase antibodies (120 IU/mL). 1

Three Differential Diagnoses with Rationales

1. Hashimoto's Thyroiditis (Primary Diagnosis)

• Most likely diagnosis given the combination of elevated TSH, borderline-low free T4, and significantly elevated thyroid peroxidase antibodies (120 IU/mL, normal <35 IU/mL) 1
• Hashimoto's disease is the most common cause of hypothyroidism in developed nations where dietary iodine is adequate 1
• Her family history of maternal hypothyroidism supports autoimmune thyroid disease clustering in families 2
• The enlarged, non-tender thyroid gland on palpation is consistent with chronic lymphocytic thyroiditis 1

2. Subclinical Hypothyroidism Progressing to Overt Disease

• TSH of 8.5 mIU/L with free T4 at the lower limit of normal (0.8 ng/dL) represents the transition zone between subclinical and overt hypothyroidism 3
• Subclinical hypothyroidism progresses to overt disease in approximately 2-5% of cases annually, with higher progression rates when anti-TPO antibodies are positive 3
• Her symptomatic presentation (fatigue, weight gain, cold intolerance, constipation, cognitive changes) indicates she requires treatment regardless of the subclinical vs. overt classification 4

3. Medication-Induced or Secondary Hypothyroidism (Less Likely)

• While amlodipine is not typically associated with thyroid dysfunction, this must be considered in any patient on chronic medications 3
• Secondary (central) hypothyroidism from pituitary/hypothalamic disease is unlikely given the elevated TSH—central hypothyroidism presents with low or inappropriately normal TSH 3
• No history of radioiodine therapy, thyroidectomy, or external neck irradiation that would cause primary hypothyroidism from other causes 1

Physical Exam Findings Supporting Primary Diagnosis

The following physical findings confirm hypothyroidism:

• Enlarged, non-tender thyroid gland (goiter) is characteristic of Hashimoto's thyroiditis, distinguishing it from atrophic thyroiditis 1
• Thinning of lateral eyebrows is a classic sign of hypothyroidism 2
• Dry skin reflects the decreased metabolic rate and reduced sebaceous gland activity in hypothyroidism 2, 4
• Bradycardia (HR 64 bpm) results from decreased metabolic demands and reduced cardiac output 5
• Low-normal body temperature (36.5°C) reflects decreased thermogenesis from reduced metabolic rate 2
• Tired appearance and slight overweight (BMI 28) are consistent with the fatigue and weight gain from decreased basal metabolic rate 4, 5

Diagnostic Findings Supporting Primary Diagnosis

Thyroid Function Tests

• Elevated TSH (8.5 mIU/L, normal 0.4-4.0) indicates primary thyroid gland failure with compensatory pituitary stimulation 3, 4
• Borderline-low free T4 (0.8 ng/dL, normal 0.8-1.8) at the lower limit of normal confirms inadequate thyroid hormone production 3
• Markedly elevated thyroid peroxidase antibodies (120 IU/mL, normal <35) definitively establishes autoimmune thyroiditis as the etiology 1, 4

Hematologic Findings

• Mild normocytic anemia (Hb 11.5 g/dL, Hct 34%) is commonly associated with hypothyroidism due to decreased erythropoietin production and reduced bone marrow stimulation 2
• MCV in upper normal range (95 fL) may reflect early macrocytic changes, as hypothyroidism can impair B12 and folate metabolism, though frank macrocytosis is not yet present 2

Supporting Clinical Features

• Classic symptom constellation: fatigue, weight gain, cold intolerance, constipation, dry skin, hair thinning, and cognitive impairment (forgetfulness) are all hallmark features of hypothyroidism 4, 5
• No imaging indicated: There is no role for thyroid ultrasound, CT, MRI, or radionuclide scanning in the workup of primary hypothyroidism in adults, as imaging does not differentiate among causes and all causes show decreased radioiodine uptake 1

Why MCV is in Upper Normal Range

The MCV of 95 fL (upper normal) likely reflects subclinical macrocytic changes from hypothyroidism's effects on erythropoiesis:

• Hypothyroidism impairs DNA synthesis and cell division in bone marrow, leading to larger red blood cells 2
• Thyroid hormone deficiency can interfere with vitamin B12 and folate metabolism, contributing to macrocytic tendencies even before frank deficiency develops 2
• As hypothyroidism progresses untreated, MCV typically increases further into the macrocytic range 2
• The upper-normal MCV combined with anemia suggests early bone marrow suppression from thyroid hormone deficiency 2

Why She Has Low Hematocrit

The low hematocrit (34%, normal 36-46%) results from multiple mechanisms of hypothyroidism-induced anemia:

• Decreased erythropoietin production: Thyroid hormones stimulate erythropoietin synthesis; deficiency reduces red blood cell production 2
• Reduced bone marrow activity: Hypothyroidism decreases overall metabolic demands, leading to compensatory reduction in red blood cell mass 2
• Decreased plasma volume: While less common, some hypothyroid patients have reduced plasma volume that can mask the degree of anemia 2
• Potential iron deficiency: Hypothyroidism causes decreased gastric acid production and impaired iron absorption, though her MCV is not microcytic 2
• Menstrual blood loss: If Emilee has menorrhagia (common in hypothyroidism), this contributes to iron loss and anemia 2

The anemia should improve with levothyroxine replacement therapy as metabolic function normalizes. 2, 4

Treatment Recommendation

Emilee requires immediate levothyroxine replacement therapy at 1.5-1.8 mcg/kg/day (approximately 100-125 mcg daily for her estimated weight), taken on an empty stomach 30-60 minutes before breakfast. 6, 4

• All patients with TSH >10 mIU/L should be treated, but given her TSH of 8.5 mIU/L with positive anti-TPO antibodies, symptomatic presentation, and free T4 at the lower limit of normal, treatment is clearly indicated 3, 4
• Critical timing consideration: Levothyroxine must be taken separately from her magnesium citrate supplement (at least 4 hours apart) and calcium/iron if she takes these, as they significantly impair absorption 6
• Target TSH should be 0.5-2.0 mIU/L, with reassessment in 6-8 weeks after initiation 3, 4
• Since she is 45 years old without known coronary artery disease, full replacement dosing can be started immediately rather than gradual titration 3, 4

1, 6, 2, 3, 4, 5