What is the most likely diagnosis for a 35-year-old female with depressed mood, fatigue, gravel voice, elevated Thyroid-Stimulating Hormone (TSH) level, low free thyroxine level, and positive thyroid peroxidase (TPO) antibodies?

Diagnosis: Chronic Autoimmune (Hashimoto's) Thyroiditis with Overt Hypothyroidism

This patient has chronic autoimmune thyroiditis (Hashimoto's thyroiditis) presenting with overt hypothyroidism, confirmed by elevated TSH (6 mIU/L), low free thyroxine (0.8 ng/dL), positive thyroid peroxidase antibodies (48), and a diffusely enlarged, firm, nodular thyroid gland. 1, 2

Clinical Reasoning

Biochemical Confirmation

• TSH of 6 mIU/L with free T4 of 0.8 ng/dL (below the normal reference range of 0.8-2.0 ng/dL) definitively establishes overt hypothyroidism, not subclinical disease 1
• The free T4 is at the absolute lower limit or below normal range, which combined with elevated TSH confirms thyroid hormone deficiency requiring treatment 1, 2

Autoimmune Etiology

• Positive thyroid peroxidase antibodies (TPO Ab = 48) confirm autoimmune thyroiditis as the underlying cause 3, 4
• Anti-thyroglobulin antibodies <20 (negative) does not exclude autoimmune disease, as TPO antibodies alone are sufficient for diagnosis 3
• The presence of TPO antibodies predicts progression to more severe hypothyroidism at a rate of 4.3% per year 1

Physical Examination Findings

• Diffusely enlarged, firm, nodular, nontender thyroid gland is the classic presentation of Hashimoto's thyroiditis 3, 4
• The firm, nodular texture reflects lymphocytic infiltration and fibrous replacement of thyroid tissue characteristic of chronic autoimmune thyroiditis 3
• Normal ESR (15) helps exclude subacute thyroiditis, which would present with tenderness and markedly elevated ESR 4

Clinical Presentation Alignment

• Depressed mood, fatigue, and gravel voice (hoarseness) are classic symptoms of hypothyroidism 2, 3
• The 6-month duration indicates chronic rather than acute thyroid dysfunction 2
• Postpartum timing (14 months after delivery) is significant, as postpartum thyroiditis can trigger or unmask underlying autoimmune thyroid disease 1

Important Clinical Context

Lithium Contribution

• Lithium carbonate for bipolar disorder is a known cause of hypothyroidism and can exacerbate underlying autoimmune thyroid disease 5
• However, the positive TPO antibodies indicate this is primarily autoimmune thyroiditis, with lithium potentially accelerating its progression 3

Family History Significance

• Family history of hypothyroidism substantially increases risk for autoimmune thyroid disease 1
• This genetic predisposition combined with environmental triggers (postpartum state, lithium) led to clinical manifestation 3

Postpartum Consideration

• While postpartum thyroiditis typically occurs within 12 months of delivery, this patient's presentation at 14 months with positive TPO antibodies and chronic symptoms indicates permanent autoimmune thyroiditis rather than transient postpartum thyroiditis 1

Why Not Other Diagnoses

• Not subclinical hypothyroidism: Free T4 is low, not normal 1
• Not postpartum thyroiditis: Too late (>12 months), chronic symptoms, and positive antibodies indicate permanent disease 1
• Not subacute thyroiditis: No thyroid tenderness, normal ESR, and chronic rather than acute presentation 4
• Not secondary hypothyroidism: TSH is elevated rather than low or inappropriately normal 2