Case Report: A Rare Association of Diffuse Thyroid Lipomatosis with Amyloid Deposition

Introduction

Diffuse thyroid lipomatosis is a histopathological condition of unknown etiology characterized by extensive diffuse fatty infiltration of the thyroid stroma. In some rare cases, it has been associated with the deposition of amyloid in the thyroid gland [1, 2]. This condition can lead to the enlargement of the gland and can result in compressive symptoms [1]. Extensive adipose tissue in the thyroid gland can be found in a broad spectrum of conditions, from malignant lesions (thyroid carcinomas) to benign conditions (such as Graves’ disease) [2, 3]. Diffuse thyroid lipomatosis (or thyrolipomatosis) and thyrolipoma (adenolipoma) are part of the benign spectrum of lesions of the thyroid gland. The diffuse form is even less common than thyrolipoma and is characterized by mature adipose tissue deposition without evidence of encapsulation [4]. On the other hand, amyloid goiter results from the deposition of insoluble proteins due to its abnormal folding process and also can lead to the deposition of adipose tissue within the thyroid gland [5, 6]. A case of diffuse thyroid lipomatosis with coexistent deposition of amyloid protein is presented.

Case Presentation

We report the case of a 46-year-old man with a history of bronchiectasis with multiple episodes of viral and bacterial respiratory infections since he was 19 years old, chronic otitis media, pansinusitis, and infertility due to idiopathic hypogonadotropic hypogonadism. The patient referred a history of consanguinity (2 grandparents are brothers, and his parents are first-degree cousins). He has 2 children, both born after medically assisted reproduction, diagnosed with severe immunodeficiency with frequent respiratory and central nervous system infections. The patient presented with a 2-year history of progressive weight loss (<10% of total body weight) associated with fatigue to mild effort. Physical examination showed a lobulated diffuse thyroid enlargement and multiple inflammatory lymph nodules in the lateral compartments of the neck. Routine blood tests were normal, including cell blood count, renal function, proteinogram, beta-2 microglobulin, immunoglobulins, and C-reactive protein. The sedimentation rate was 35 (normal range 0–22 mm/h).

Thyroid function tests were within normal range with free T4 1.46 pg/dL (NR 0.90–1.70), free T3 3.3 pg/mL (NR 2.0–4.5), and TSH 1.35 µUI/mL (NR 0.30–4.20). Serum anti-thyroperoxidase and anti-thyroglobulin antibodies as well as serum calcitonin levels were undetectable. Two months later, neck ultrasound (US) scan revealed thyroid enlargement with a right thyroid lobe of 65 × 32 × 34 mm and a left lobe of 64 × 31 × 28 mm with iso-hypoechogenic and solid nodules with 18 mm and 15 mm in the right and left lobes, respectively, without cervical lymphadenopathy. FNA was performed in both nodules, which showed colloid goiter. The CT scan revealed a diffuse enlarged thyroid with areas of lower density than the remaining parenchyma (Fig. 1). The trachea was slightly deviated to the left side without compression. No cervical or mediastinal suspicious lymph nodes were detected. Twelve months later, the goiter enlarged, and he developed symptoms of dyspnea, dysphonia, and dysphagia. Neck US revealed coalescent iso-hyperechogenic nodules in the thyroid gland, the largest with 20 mm (Fig. 2), and FNA was repeated in this nodule with the diagnosis of a follicular lesion of undetermined significance, showing scarce cellularity, abundant colloid, macrophages, and some follicular cells with nuclear alterations (slight nuclear increase, clear chromatin, membrane irregularity, and grooves).

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CT scan showing diffuse thyroid enlargement with hypodense areas.

Citation: European Thyroid Journal 10, 6; 10.1159/000518444

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Thyroid ultrasound: the thyroid left lobe showing diffuse hyperechogenicity.

Citation: European Thyroid Journal 10, 6; 10.1159/000518444

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A total thyroidectomy was performed without surgical complications. The macroscopic appearance of the resected thyroid showed a bosselated, homogenous 237-g thyroid with yellow and hemorrhagic areas, without visible nodules. The left lobe measured 111 × 40 × 26 mm and the right lobe 105 × 65 × 43 mm. Microscopic examination of multiple sections revealed normal follicular architecture, with normal appearing follicular cells. There was fatty infiltration of the perifollicular and perivascular stroma, with extracellular deposition of an amorphous eosinophilic material, consistent with amyloid. There was apple-green birefringence of Congo red-stained slides under polarized light, confirming the presence of amyloid protein (Fig. 3). A final diagnosis of diffuse lipomatosis of the thyroid gland with amyloid deposition was established. There was no evidence of systemic amyloidosis. Abdominal fat and bone marrow biopsies revealed no pathological alterations. ¹⁸FDG-PET scan presented a faint lung uptake probably related to the bronchiectasis. The electrocardiogram and echocardiogram showed no abnormalities. Alpha-1 antitrypsin deficiency, familial Mediterranean fever, inflammatory bowel disease, cystic fibrosis, and idiopathic pulmonary fibrosis were also ruled out. The patient remains asymptomatic under treatment with levothyroxine.

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a Histologically, there was infiltration of thyroid stroma by mature adipose tissue (black arrow). b Interstitial amyloid deposition stained with Congo red (black arrow) showing apple-green birefringence under polarized light (yellow arrow).

Citation: European Thyroid Journal 10, 6; 10.1159/000518444

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Discussion

This case represents one of few published cases of diffuse thyroid lipomatosis. With the keywords “diffuse thyroid lipomatosis,” “thyrolipoma,” and “thyrolipomatosis” in the PubMed, we could find only 39 case reports and only 6 also had concomitant amyloid deposition (Table 1). These patients usually presented with normal thyroid function and severe compressive symptoms [2, 3, 7, 8, 10]. Bakan et al. [9] and Loh et al. [8] described 3 patients with coexistent bronchiectasis as in our patient (Table 1) [11]. Amyloid deposition can also lead to massive goiters and be associated with variable amounts of adipose tissue within the thyroid gland; however, the majority of the cases of diffuse thyroid lipomatosis do not have significant amyloid content [5, 6].

Table 1.

Patient characteristics and imaging findings for the cases of diffuse thyroid lipomatosis and amyloid deposition reported in the English literature

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The patient and his children have an unclear immunodeficiency disorder with severe and recurrent infections, which is still under investigation. Although it is consensual that amyloid deposition can occur as a reaction to systemic disease, such as a chronic inflammatory disease or a chronic infection, the pathophysiology underlying the association between amyloidosis and fat tissue deposition (especially in a massive way) remains to be elucidated. One possibility is capillary injury induced by amyloid, which leads to ischemia and subsequent metaplasia of stromal fibroblasts [5, 6, 10]. In addition, adipose tissue proliferation within the thyroid has been associated by some authors with disturbed embryogenesis [3, 4]. To the best of our knowledge, this case represents one of the few patients reported with diffuse thyroid lipomatosis with coexistent deposition of amyloid. Despite its rarity, thyroid lipomatosis should be considered in the differential diagnosis of a patient presenting with a goiter, and the clinician must be aware of the possibility of underlying systemic diseases.

Acknowledgment

The case report has been presented in the 42nd Annual Meeting of the European Thyroid Association that was held in Budapest, Hungary, in September 2019.

Statement of Ethics

The authors declare that the procedures were followed according to the regulations established by the Clinical Research and Ethics Committee and the Helsinki Declaration of the World Medical Association. The authors declare that the manuscript, complete or in parts, does not infringe any copyright and does not violate any privacy rights. The authors declare that no experiments were performed on humans or animals for this investigation. The authors state that the subject has given his written informed consent to publish his case, including publication of images.

Conflict of Interest Statement

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding Sources

The authors received no financial support for the research, authorship, and/or publication of this article.

Author Contributions

We declare that all authors have contributed substantially to the manuscript, have approved the final version of the manuscript, and the manuscript is not under review or has been published, completely or partially, in any other journal.

Data Availability Statement

The authors confirm the data supporting the findings of this case report are available within the article. Raw data that support the findings of this case report are also available from the corresponding author, upon reasonable request.