What is the pathophysiology of multinodular goiter (MNG) of the thyroid?

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Last updated: April 6, 2025 • View editorial policy

From the Guidelines

The pathophysiology of multi-nodular goitre of the thyroid is primarily driven by chronic stimulation of the thyroid gland, often resulting from iodine deficiency, which leads to irregular growth and structural changes, as supported by the 2022 espen micronutrient guideline 1. The development of multi-nodular goitre is a complex process that involves both genetic and environmental factors. Key factors include:

  • Iodine deficiency, which increases the risk of developing autonomous thyroid nodules that are unresponsive to TSH control, as noted in the espen micronutrient guideline 1
  • Genetic mutations that affect thyroid growth and function, particularly in the TSH receptor gene
  • Hyperplasia of thyroid follicular cells, which form multiple nodules of varying sizes throughout the gland As these nodules grow, they can undergo degenerative changes, including:
  • Hemorrhage
  • Fibrosis
  • Calcification These changes contribute to the irregular appearance of the gland and can lead to symptoms such as difficulty breathing or swallowing due to compression of surrounding structures. The condition can progress slowly over years, with nodules gradually increasing in size and number, making it a chronic condition requiring ongoing monitoring. According to the espen micronutrient guideline, even mild or moderate iodine deficiency can have adverse effects on thyroid function and overall health, particularly during pregnancy and breastfeeding 1.

From the Research

Pathophysiology of Multinodular Goitre

The pathophysiology of multinodular goitre (MNG) is complex and involves multiple factors. Some of the key aspects include:

  • Iodine deficiency, which can contribute to the development of MNG, although it is not the sole cause 2, 3
  • Genetic predisposition, with hereditary factors playing a significant role in the etiology of goitre 2, 3, 4
  • Environmental factors, such as exposure to natural goitrogens, smoking, and lack of selenium and iron 4
  • Autonomous growth of goiters, often accompanied by subclinical or overt thyrotoxicosis 2, 3
  • Heterogeneity of function, with patchy iodine metabolism on scintiscans 3

Etiology

The etiology of MNG can be classified into iodine-dependent and non-iodine dependent factors 5. Non-iodine dependent factors include:

  • Genetic predisposition
  • Environmental factors
  • Autonomous growth of goiters
  • Heterogeneity of function

Development of MNG

The development of MNG is thought to involve the high intrinsic growth potential of a variable, genetically predetermined fraction of all thyrocytes 2. This leads to the formation of true benign neoplasias, which can grow and function independently of thyroid-stimulating hormone (TSH) 2, 3.

Clinical Features

MNG can present with a range of clinical features, including:

  • Enlargement of the thyroid gland
  • Presence of single or multiple nodules
  • Risk of malignancy
  • Toxicity
  • Local compressive symptoms
  • Subclinical or overt thyrotoxicosis 5, 6, 2, 3, 4

Diagnostic Evaluation

The diagnostic evaluation of MNG involves:

  • Measurement of TSH
  • Accurate imaging with high-resolution ultrasonography or computed tomography
  • Fine-needle aspiration biopsy 5, 6, 4
  • Thyroid scintigraphy may be used if there is abnormal TSH measurement 5

References

Guideline

espen micronutrient guideline.

Clinical Nutrition, 2022

Research

Multinodular goitre: 'much more to it than simply iodine deficiency'.

Bailliere's best practice & research. Clinical endocrinology & metabolism, 2000

Research

Nodular goiter and goiter nodules: Where iodine deficiency falls short of explaining the facts.

Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association, 2001

Research

Non-Toxic Multinodular Goiter: From Etiopathogenesis to Treatment.

Sisli Etfal Hastanesi tip bulteni, 2022

Research

Evaluation and management of multinodular goiter.

Otolaryngologic clinics of North America, 1996

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.