What is the differential diagnosis for a patient 6 months postpartum with a low Thyroid-Stimulating Hormone (TSH) level, elevated Thyroxine (T4) level, elevated Thyroglobulin Antibody (TgAb), and negative Thyroid Peroxidase Antibody (anti-TPO)?

Differential Diagnosis: Postpartum Thyroid Dysfunction with Low TSH, Elevated T4, Positive TgAb, Negative Anti-TPO

The most likely diagnosis is postpartum thyroiditis in the thyrotoxic phase, which occurs in approximately 5-9% of postpartum women and classically presents with transient hyperthyroidism followed by hypothyroidism. 1, 2

Primary Differential Diagnosis

1. Postpartum Thyroiditis (Most Likely)

Postpartum thyroiditis is the leading diagnosis given the timing (6 months postpartum), biochemical hyperthyroidism (low TSH, elevated T4), and presence of thyroid autoantibodies (elevated thyroglobulin antibody). 3

• The classic triphasic presentation occurs in only 22% of cases, with isolated thyrotoxicosis occurring in 30% and isolated hypothyroidism in 48% of affected women 1
• The thyrotoxic phase typically occurs at 14 weeks postpartum, while the hypothyroid phase occurs at 19 weeks postpartum, making 6 months (24 weeks) consistent with either late thyrotoxic phase or transition to hypothyroid phase 2
• Up to 50% of women who are thyroid antibody positive (TPO and/or thyroglobulin antibody) in the first trimester will develop postpartum thyroiditis 1
• The presence of elevated thyroglobulin antibody, even with negative anti-TPO, still supports autoimmune thyroid disease, as approximately 50% of anti-TPO positive women do not develop thyroid dysfunction 2

Key distinguishing features:

• Destructive thyroiditis causes release of preformed thyroid hormone, resulting in elevated thyroglobulin levels and increased urinary iodine excretion 2
• Diffuse or multifocal hypoechogenicity on thyroid ultrasound would support this diagnosis 2
• Symptoms in the thyrotoxic phase are typically milder than Graves' disease and include lack of energy and irritability 2, 4

2. Graves' Disease (Less Likely but Must Exclude)

Graves' disease must be excluded as it requires different management and can occur postpartum, though it is specifically excluded from the definition of postpartum thyroiditis. 1

• Graves' disease would present with more severe hyperthyroid symptoms including significant tachycardia, tremor, heat intolerance, and weight loss 3
• TSH receptor antibodies (TRAb) would be positive in Graves' disease, distinguishing it from postpartum thyroiditis 3
• Radioactive iodine uptake would be elevated in Graves' disease but low or absent in postpartum thyroiditis (destructive process) 2
• Graves' disease requires antithyroid medication (propylthiouracil or methimazole), while postpartum thyroiditis thyrotoxic phase is managed symptomatically with beta-blockers 3

3. Transition Phase of Triphasic Postpartum Thyroiditis

During the transition from thyrotoxic to hypothyroid phase, TSH may remain suppressed while T4 begins to normalize or even become low, potentially mimicking central hypothyroidism. 5

• This biochemical pattern can cause diagnostic confusion, as TSH suppression with declining T4 resembles secondary hypothyroidism 5
• The obstetric history, absence of headaches, successful breastfeeding, presence of goiter, and normal adrenocorticotropic hormone levels help distinguish this from central hypothyroidism 5
• Serial thyroid function testing over 4-6 weeks will clarify the diagnosis, as postpartum thyroiditis follows a predictable temporal pattern 3

4. Subclinical Hyperthyroidism from Other Causes (Less Likely)

Other causes of biochemical hyperthyroidism in the postpartum period are less likely but should be considered:

• Toxic adenoma or toxic multinodular goiter would show focal uptake on thyroid scan and typically occurs in older women 2
• Exogenous thyroid hormone ingestion (factitious thyrotoxicosis) would show low thyroglobulin levels, opposite to the elevated levels in postpartum thyroiditis 2
• Subacute (de Quervain's) thyroiditis typically presents with painful thyroid gland and elevated inflammatory markers, which are not characteristic of postpartum thyroiditis 2

Critical Diagnostic Workup

To establish the definitive diagnosis, the following investigations are essential:

• TSH receptor antibodies (TRAb): Positive in Graves' disease, negative in postpartum thyroiditis 3
• Thyroid ultrasound: Diffuse or multifocal hypoechogenicity supports postpartum thyroiditis; increased vascularity suggests Graves' disease 2
• Serum thyroglobulin level: Elevated in destructive thyroiditis (postpartum thyroiditis), low in factitious thyrotoxicosis 2
• Radioactive iodine uptake scan (if not breastfeeding): Low/absent uptake in postpartum thyroiditis, elevated in Graves' disease 2
• Serial thyroid function tests every 4-6 weeks: Will demonstrate the natural progression of postpartum thyroiditis 3

Management Implications

Treatment depends on the phase and severity of symptoms:

• Thyrotoxic phase: Beta-blockers (propranolol or atenolol) for symptomatic relief; antithyroid drugs are not indicated as this is a destructive process, not increased hormone synthesis 3
• Hypothyroid phase: Levothyroxine is indicated for symptomatic relief and in women who are breastfeeding or attempting to conceive 1
• Monitoring: Continue surveillance as 20-40% of women develop permanent primary hypothyroidism after postpartum thyroiditis 1
• Future pregnancies: Risk of recurrent postpartum thyroiditis is 70% if previous episode occurred 2

Critical Pitfalls to Avoid

• Do not start antithyroid medication without confirming Graves' disease with TRAb testing, as postpartum thyroiditis thyrotoxic phase is self-limited and antithyroid drugs are ineffective 3
• Do not assume euthyroidism based on a single normal TSH, as the transition phase can mimic central hypothyroidism and requires serial monitoring 5
• Do not dismiss symptoms as "normal postpartum changes", as even TPO-positive women without overt thyroid dysfunction experience more severe symptoms than antibody-negative controls 4
• Do not fail to arrange long-term follow-up, as 50% of women with postpartum thyroiditis will be hypothyroid 7-9 years later 2