Amyloidosis is a systemic disorder characterized by extracellular deposition of amyloid fibrillary proteins. ¹ This is an aggregation of more than 20 proteins belonging to families that do not exhibit structural or functional relationships. It can affect any organ and can manifest in a localized form or as a generalized disease. The mechanisms underlying its pathogenesis are poorly understood.

Pathological studies can identify this deposition by its affinity to the Congo Red stain and yellow-green birefringence under polarized light. ² Several types of amyloidosis exist, which are distinguished by the type of protein and the localization of the deposit.

A histological study of amyloid deposition in the thyroid gland revealed its presence in 30%–80% of cases. ³ However, the prevalence of amyloid goiter in multinodular goiters remains low with an estimated prevalence of 0.17. ⁴ The potential to simulate thyroid cancer by its volume and progression is also a concern. ⁵ The earliest documented case of amyloid goiter (AG) was reported by Beckman in 1858. ⁶ This article presents a comprehensive review of three cases of AG, complemented by a thorough literature review. This study aimed to elucidate the clinical, therapeutic, and evolutionary characteristics of this rare entity.

Amyloidosis is characterized by the deposition of amyloid, an insoluble, beta-pleated sheet protein. It can occur because of chronic inflammation in cases of secondary amyloidosis, which may be associated with rheumatoid arthritis, ankylosing spondylitis, and Familial Mediterranean Fever (FMF). In the present case series, three patients had a known chronic inflammatory disease. Conversely, amyloidosis can manifest as a primary condition without an identified underlying disease. The occurrence of amyloid goiter is rare, with case reports in the literature primarily focusing on adults between the ages of 40 years and 50. However, there have been reports of cases in children and elderly individuals, indicating no clear predilection for age or sex. Amyloidosis is most often a secondary complication of an underlying inflammatory disease. ^{7, 8}

Progressive enlargement of the thyroid was observed clinically, and compressive signs have been documented in numerous cases in the literature. In our case, this was reported in one patient and was the primary symptom that motivated her to consult. This rapid enlargement may be attributed to the inflammation of the thyroid gland. In most cases, surgical intervention is performed to exclude malignancy. Amyloid deposition is rarely associated with thyroid dysfunctions. Our three patients exhibited clinical and biological euthyroidism, and the literature on the subject reported only a few cases of thyroid dysfunction. ⁹

FNA has been demonstrated to be a valuable diagnostic tool in several cases; however, it does not appear to be a reliable indicator of amyloidosis. In our experience, FNA was performed in two cases, and amyloid deposition was identified on cytological examination in one. Nonetheless, as reported in some cases in the literature, core biopsy was more informative and amyloid deposition was revealed when it was performed. Definitive histological examinations remain the gold standard for diagnosis. Thyroidectomy serves a dual role as both a therapeutic and a diagnostic modality. Notably, amyloid deposition has the potential to affect other endocrine systems. As detailed in this report, one patient exhibited parathyroid amyloid deposits, which were substantiated through pathological examination despite normal calcium and phosphorus levels in the assessment. Adrenal amyloid deposition was suspected in another patient who presented with primary adrenal insufficiency. Patel et al. have also documented parathyroid amyloid deposits. ⁸

The patient with amyloidosis secondary to FMF was diagnosed with adrenal insufficiency. We hypothesized that the patient's adrenal amyloid deposition or a condition associated with FMF was the underlying cause. To expand on this finding, a comprehensive literature review was conducted using the term "amyloid goiter" in PubMed. The search was limited to publications published between 2019 and 2024. The results of this review are summarized in Table 1.

Ethical approval and consent were not required.

Written informed consent for the publication of the report and associated images was obtained from the patients prior to submission.