What is the likely diagnosis for a 35-year-old woman with hyperthyrotropinemia (elevated Thyroid-Stimulating Hormone (TSH)), low free thyroxine, and positive thyroid peroxidase antibodies (TPO Ab), presenting with depressed mood, fatigue, and a hoarse voice?

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Hashimoto Thyroiditis (Chronic Autoimmune Thyroiditis)

This patient has Hashimoto thyroiditis, the most common cause of primary hypothyroidism in iodine-sufficient areas, characterized by the classic triad of elevated TSH, low free thyroxine, and positive thyroid peroxidase antibodies in a patient with a diffusely enlarged, firm, nodular thyroid gland. 1

Diagnostic Confirmation

The diagnosis is definitively established by the following key features present in this case:

  • Elevated TSH (6.0) with low free thyroxine (0.8) confirms primary hypothyroidism, distinguishing this from central hypothyroidism where both TSH and free T4 would be low 2, 1

  • Positive thyroid peroxidase antibodies (TPO-Ab = 48) are the hallmark serologic marker of Hashimoto thyroiditis and are present in the vast majority of cases 1, 3

  • Diffusely enlarged, firm, nodular, non-tender thyroid gland represents the classic physical examination finding where lymphocytic infiltration creates an irregular texture on palpation 1, 4

  • Hypothyroid symptoms including fatigue, depressed mood, and hoarse voice are the most common clinical presentation as thyroid destruction progresses 1, 3

Key Distinguishing Features

This presentation clearly differentiates from other thyroid disorders:

  • Not Graves' disease: The patient has hypothyroid symptoms (fatigue, depression, hoarse voice) rather than hyperthyroid manifestations (heat intolerance, tachycardia, weight loss), and the thyroid is lumpy/nodular rather than smooth 1

  • Not toxic multinodular goiter: This would present with thyrotoxicosis, not hypothyroidism 1

  • Not drug-induced hypophysitis: While the patient takes lithium, the elevated TSH with low free T4 indicates primary thyroid failure, not central hypothyroidism (which would show low TSH with low free T4) 2

Important Clinical Context

Several factors in this patient's history are relevant:

  • Postpartum timing (14 months after delivery, recently weaned): Hashimoto thyroiditis can present as painless postpartum thyroiditis, though the persistent hypothyroidism at 14 months indicates chronic autoimmune thyroiditis rather than transient postpartum thyroiditis 4

  • Lithium use: While lithium can cause hypothyroidism, the positive TPO antibodies and classic thyroid examination findings confirm autoimmune etiology 1

  • Family history of hypothyroidism: Genetic susceptibility plays a significant role in Hashimoto thyroiditis development 3, 5

  • Depressed mood: This is both a symptom of hypothyroidism and potentially confounded by her bipolar disorder history, making thyroid hormone replacement particularly important 1, 3

Management Approach

Initiate levothyroxine replacement therapy at 1.6 mcg/kg/day based on lean body mass (note: with BMI 32.5, use ideal body weight for dosing calculation) 1, 6

  • Monitor TSH at 6-8 weeks after starting treatment and after any dose adjustment to achieve target TSH in normal range 1

  • Lifelong thyroid hormone replacement is required, as Hashimoto thyroiditis leads to progressive thyroid destruction 1, 6

  • Avoid T3 (triiodothyronine) therapy unless persistent symptoms despite optimal levothyroxine treatment, as evidence for combination therapy is limited 3, 6

Critical Monitoring Considerations

  • Evaluate for discrete thyroid nodules during follow-up, as Hashimoto thyroiditis carries 1.6 times higher risk of papillary thyroid cancer 6

  • Screen for other autoimmune disorders periodically, particularly given the 20-30% association with other organ-specific autoimmune conditions 2, 5

  • TPO antibody levels typically decline with levothyroxine treatment (mean 70% decrease after 5 years), though they rarely normalize completely (only 16% become negative) 7

References

Guideline

Hashimoto Thyroiditis Diagnosis and Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

[Autoimmune thyroid disease].

Deutsche medizinische Wochenschrift (1946), 2021

Research

Hashimotos' thyroiditis: Epidemiology, pathogenesis, clinic and therapy.

Best practice & research. Clinical endocrinology & metabolism, 2019

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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