From the Guidelines
Multinodular goitre develops through a complex pathophysiological process involving both genetic predisposition and environmental factors, primarily triggered by iodine deficiency, which stimulates increased thyroid-stimulating hormone (TSH) production, causing compensatory thyroid growth, as supported by the most recent evidence from the espen micronutrient guideline 1. The condition begins with focal hyperplasia of thyroid follicular cells, which leads to the formation of multiple nodules within the thyroid gland. This hyperplasia is often triggered by iodine deficiency, which stimulates increased TSH production, causing compensatory thyroid growth. Over time, these hyperplastic areas become autonomous, functioning independently of normal regulatory mechanisms. The nodules develop heterogeneously, with some becoming hyperfunctioning (producing excess thyroid hormones), while others remain hypofunctioning or even develop cystic degeneration. Key factors contributing to the development of multinodular goitre include:
- Iodine deficiency, which is a significant global health threat, as highlighted in the espen micronutrient guideline 1
- Genetic mutations, particularly in the TSH receptor and GNAS genes, which contribute to autonomous growth
- Environmental factors, such as diet and exposure to certain substances As the goitre enlarges, it can cause compressive symptoms affecting the trachea, esophagus, and recurrent laryngeal nerves. Blood supply to the enlarged gland increases, sometimes leading to areas of hemorrhage within nodules. The condition typically progresses slowly over years, with gradual nodule enlargement and increasing gland heterogeneity, potentially transitioning from a euthyroid state to subclinical or overt hyperthyroidism as autonomous nodules accumulate. The use of imaging studies, such as ultrasound (US) and radionuclide uptake scans, can help evaluate thyroid morphology and identify suspicious features of malignancy, as discussed in the acr appropriateness criteria 1. However, the primary trigger for multinodular goitre development is iodine deficiency, emphasizing the importance of adequate iodine intake and supplementation, especially during pregnancy and breastfeeding, as noted in the espen micronutrient guideline 1.
From the Research
Pathophysiology of Multinodular Goitre
The pathophysiology of multinodular goitre (MNG) is complex and involves multiple factors. Some of the key factors include:
- Iodine deficiency, which can lead to an increase in serum thyroid-stimulating hormone (TSH) level 2, 3, 4, 5
- Genetic predisposition, with heredity playing an important role in the etiology of goiter 3, 4, 5
- Environmental factors, such as exposure to natural goitrogens, smoking, and lack of selenium and iron 2, 4, 5
- Acquired factors, such as chronic malnutrition and lack of zinc 5
Etiology of Multinodular Goitre
The etiology of MNG can be classified into iodine-dependent and non-iodine dependent factors 2. Iodine-dependent factors include iodine deficiency, which can lead to an increase in serum TSH level and subsequent growth of the thyroid gland. Non-iodine dependent factors include genetic predisposition, environmental factors, and acquired factors.
Development of Multinodular Goitre
The development of MNG involves the growth of multiple nodules within the thyroid gland. This can occur through a variety of mechanisms, including:
- Autonomous growth of goiters, often accompanied by subclinical or overt thyrotoxicosis 3
- Inverse relationship between goiter size and serum TSH 3
- Multifocal, heterogeneous, and nodular growth pattern 3
- Heterogeneity of function, with patchy iodine metabolism on scintiscans 3
- Growth of clonal and polyclonal nodules 3
Diagnosis and Treatment of Multinodular Goitre
The diagnosis of MNG typically involves biochemical tests, such as serum TSH measurement and thyroid hormone measurement, as well as imaging methods, such as thyroid ultrasonography 2, 4. Fine-needle aspiration biopsy and cross-sectional imaging methods, such as computed tomography and magnetic resonance imaging, may also be used 2, 4. Treatment options for MNG include medical follow-up, surgery, and radioiodine therapy 2, 6, 5. The choice of treatment depends on the size of the goiter, the presence of symptoms, and the patient's overall health.