What is the most likely diagnosis for a patient with hypothyroidism symptoms, including fatigue, constipation, cold intolerance, and a puffy face, with a diffusely enlarged and nontender thyroid gland that feels lumpy and nodular on palpation?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: November 25, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

Chronic Autoimmune (Hashimoto) Thyroiditis

The most likely diagnosis is chronic autoimmune (Hashimoto) thyroiditis, which classically presents with a diffusely enlarged, non-tender, lumpy/nodular thyroid gland combined with hypothyroid symptoms including fatigue, constipation, cold intolerance, and facial puffiness. 1

Clinical Reasoning

Classic Presentation Features

The patient's presentation contains the pathognomonic features of Hashimoto thyroiditis:

  • Thyroid examination findings: The diffusely enlarged, non-tender, lumpy/nodular texture on palpation represents lymphocytic infiltration creating a firm, irregular texture characteristic of Hashimoto disease 1
  • Hypothyroid symptom constellation: Fatigue, constipation, cold intolerance, and puffy face represent the most common clinical presentation as thyroid destruction progresses to overt hypothyroidism 1, 2
  • Gradual onset: The one-month timeline of progressive symptoms aligns with the insidious nature of autoimmune thyroid destruction 3

Excluding Alternative Diagnoses

Graves disease is excluded because this patient has hypothyroid symptoms rather than hyperthyroid manifestations (heat intolerance, tachycardia, weight loss, tremor) 1. Additionally, Graves disease typically presents with a smooth, diffusely enlarged thyroid rather than the lumpy, nodular texture described here 4.

Lymphadenitis is excluded because the examination describes thyroid enlargement specifically, not cervical lymph nodes, and the gland is non-tender 1.

Lymphoma is unlikely given the non-tender nature, absence of constitutional B symptoms, and the classic hypothyroid symptom pattern that points toward functional thyroid pathology rather than malignancy 1.

Thyroid cancer is less likely because malignancy typically presents as discrete nodules rather than diffuse, lumpy enlargement, and would not explain the constellation of hypothyroid symptoms 1. However, discrete nodules developing during follow-up would warrant ultrasound evaluation for malignancy risk 1.

Diagnostic Confirmation

Laboratory testing should confirm primary hypothyroidism with elevated TSH and low free T4 levels 1, 3. Anti-thyroid peroxidase (TPO) antibodies will be positive in Hashimoto thyroiditis, providing serologic confirmation 1.

Management Approach

Initiate lifelong levothyroxine replacement therapy at 1.6 mcg/kg/day for overt hypothyroidism once biochemical confirmation is obtained 1, 3. Monitor TSH levels at 6-8 weeks after starting treatment and after any dose adjustment, then annually once at goal 1, 3.

Important Caveats

  • Imaging is not routinely indicated for diagnosis of hypothyroidism, but thyroid ultrasound should be performed if discrete nodules are palpable or develop during follow-up to evaluate malignancy risk 1
  • Lower starting doses (12.5-50 mcg daily) should be used in patients older than 60 years or with known/suspected ischemic heart disease 3
  • Hashimoto thyroiditis is the cause of primary hypothyroidism in up to 85% of patients living in areas with adequate iodine intake 5, 6

References

Guideline

Hashimoto Thyroiditis Diagnosis and Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Hypothyroidism Symptoms and Complications

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Hypothyroidism: Diagnosis and Treatment.

American family physician, 2021

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Hypothyroidism: A Review.

JAMA, 2025

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.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.