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Mauro Boronat Section of Endocrinology and Nutrition, Complejo Hospitalario Universitario Insular Materno-Infantil, Las Palmas de Gran Canaria, Spain
Research Institute in Biomedical and Health Sciences, University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain

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Summary

Isolated, adult-onset central hypothyroidism is very rare, and its diagnosis can be challenging. A 42-year-old patient was referred for evaluation of a 2.8 cm thyroid nodule. She referred symptoms that could be attributed to hypothyroidism and thyroid tests showed low TSH and normal-low levels of free T4. However, evaluation of the remaining pituitary hormones and pituitary MRI were normal, yet a radionuclide scanning revealed that the thyroid nodule was ‘hot’ and the tracer uptake in the remaining thyroid tissue was suppressed. Interpretation of these studies led to a misdiagnosis of subclinical hyperthyroidism and the patient was treated with radioiodine. Soon after treatment, she developed a frank hypothyroidism without appropriate elevation of TSH and the diagnosis of central hypothyroidism was made a posteriori. Long term follow-up revealed a progressive pituitary failure, with subsequent deficiency of ACTH and GH. This case should alert to the possibility of overlooking central hypothyroidism in patients simultaneously bearing primary thyroid diseases able to cause subclinical hyperthyroidism.

Learning points:

  • Although rarely, acquired central hypothyroidism can occur in the absence of other pituitary hormone deficiencies.

  • In these cases, diagnosis is challenging, as symptoms are unspecific and usually mild, and laboratory findings are variable, including low, normal or even slightly elevated TSH levels, along with low or low-normal concentrations of free T4.

  • In cases with low TSH levels, the coexistence of otherwise common disorders able to cause primary thyroid hyperfunction, such as autonomous nodular disease, may lead to a misdiagnosis of subclinical hyperthyroidism.

Open access
Shanika Samarasinghe Division of Endocrinology and Metabolism, Loyola University Medical Center, Maywood, Illinois, USA

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Simge Yuksel Division of Internal Medicine, Loyola University Medical Center, Maywood, Illinois, USA

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Swati Mehrotra Department of Pathology and Laboratory Medicine, Loyola University Medical Center, Maywood, Illinois, USA

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Summary

We report a rare case of concurrent medullary thyroid cancer (MTC) and papillary thyroid cancer (PTC) with intermixed disease in several of the lymph node (LN) metastases in a patient who was subsequently diagnosed with clear cell renal cell carcinoma (RCC). A 56 year old female presented with dysphagia and was found to have a left thyroid nodule and left superior cervical LN with suspicious sonographic features. Fine needle aspiration biopsy (FNAB) demonstrated PTC in the left thyroid nodule and MTC in the left cervical LN. Histopathology demonstrated multifocal PTC with 3/21 LNs positive for metastatic PTC. One LN in the left lateral neck dissection exhibited features of both MTC and PTC within the same node. In the right lobe, a 0.3 cm focus of MTC with extra-thyroidal extension was noted. Given persistent calcitonin elevation, a follow-up ultrasound displayed an abnormal left level 4 LN. FNAB showed features of both PTC and MTC on the cytopathology itself. The patient underwent repeat central and left radical neck dissection with 3/6 LNs positive for PTC in the central neck and 2/6 LNs positive for intermixed PTC and MTC in the left neck. There was no evidence of distant metastases on computed tomography and whole body scintigraphy, however a 1.9 x 2.5 cm enhancing mass within the right inter-polar kidney was discovered. This lesion was highly suspicious for RCC. Surgical pathology revealed a 2.5 cm clear cell RCC, Fuhrman grade 2/4, with negative surgical margins. She continues to be observed with stable imaging of her triple malignancies.

Learning points:

  • Mixed medullary-papillary thyroid neoplasm is characterized by the presence of morphological and immunohistochemical features of both medullary and papillary thyroid cancers within the same lesion. Simultaneous occurrence of these carcinomas has been previously reported, but a mixed disease within the same lymph node is an infrequent phenomenon.

  • Prognosis of mixed medullary-papillary thyroid carcinomas is determined by the medullary component. Therefore, when PTC and MTC occur concurrently, the priority should be given to the management of MTC, which involves total thyroidectomy and central lymph node dissection.

  • Patients with thyroid cancer, predominantly PTC, have shown higher than expected rates of RCC. To our knowledge, this is the first report describing the combination of MTC, PTC, and RCC in a single patient.

Open access
J K Witczak Section of Endocrinology, Department of Medicine, Prince Phillip Hospital
Centre for Endocrine and Diabetes Sciences, University Hospital of Wales, Heath Park, Cardiff, UK

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N Ubaysekara Centre for Endocrine and Diabetes Sciences, University Hospital of Wales, Heath Park, Cardiff, UK

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R Ravindran Centre for Endocrine and Diabetes Sciences, University Hospital of Wales, Heath Park, Cardiff, UK

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S Rice Section of Endocrinology, Department of Medicine, Prince Phillip Hospital

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Z Yousef Department of Cardiology, University Hospital of Wales, Heath Park, Cardiff, UK

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L D Premawardhana Centre for Endocrine and Diabetes Sciences, University Hospital of Wales, Heath Park, Cardiff, UK

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Summary

Graves’ disease is associated with tachydysrythmia, cardiac ischaemia and cardiomyopathy – all uncommon in young adults without previous cardiac disease. We present three young individuals who developed cardiac complications after periods of uncontrolled Graves’ disease. Subject 1: A 34-year-old female had severe thyrotoxic symptoms for weeks. Investigations showed fT4: 98.4 (11–25 pmol/L), fT3: 46.9 (3.1–6.8 pmol/L), TSH <0.01 (0.27–4.2 mU/L) and thyrotrophin receptor antibody (TRAb): 34.8 (<0.9 U//l). She had appropriate treatment but several weeks later she became breathless despite improving thyroid function. Echocardiography showed a pericardial effusion of 2.9 cm. She responded well to steroids and NSAIDs but developed active severe Graves’ orbitopathy after early total thyroidectomy. Subject 2: A 28-year-old male developed thyrotoxic symptoms (fT4: 38 pmol/L, fT3: 13.9 pmol/L, TSH <0.01 (for over 6 months) and TRAb: 9.3 U/L). One month after starting carbimazole, he developed acute heart failure (HF) due to severe dilated cardiomyopathy – EF 10–15%. He partially recovered after treatment – EF 28% and had early radioiodine treatment. Subject 3: A 42-year-old woman who had been thyrotoxic for several months (fT4: 54.3; fT3 >46.1; TSH <0.01; TRAb: 4.5) developed atrial fibrillation (AF) and heart failure. Echocardiography showed cardiomegaly – EF 29%. She maintains sinus rhythm following early total thyroidectomy (EF 50%). Significant cardiac complications may occur in previously fit young adults, who have had uncontrolled Graves’ disease for weeks to months. Cardiac function recovers in the majority, but early definitive treatment should be discussed to avoid Graves’ disease relapse and further cardiac decompensation.

Learning points:

  • Cardiac complications of Graves’ disease are uncommon in young adults without previous cardiac disease.

  • These complications may however occur if Graves’ disease had been poorly controlled for several weeks or months prior to presentation.

  • Persistent symptoms after adequate control should alert clinicians to the possibility of cardiac disease.

  • Specific treatment of Graves’ disease and appropriate cardiac intervention results in complete recovery in the majority and carries a good prognosis.

  • Early definitive treatment should be offered to them to prevent cardiac decompensation at times of further relapse.

Open access
Maria Tomkins Department of Endocrinology and Diabetes, Beaumont Hospital Dublin, Dublin, Ireland

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Roxana Maria Tudor Department of Endocrinology and Diabetes, Beaumont Hospital Dublin, Dublin, Ireland

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Diarmuid Smith Department of Endocrinology and Diabetes, Beaumont Hospital Dublin, Dublin, Ireland

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Amar Agha Department of Endocrinology and Diabetes, Beaumont Hospital Dublin, Dublin, Ireland

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Summary

This case is the first to describe a patient who experienced concomitant agranulocytosis and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis as an adverse effect of propylthiouracil treatment for Graves’ disease. A 42-year-old female with Graves’ disease presented to the emergency department (ED) with a 2-week history of fevers, night sweats, transient lower limb rash, arthralgia, myalgia and fatigue. She had been taking propylthiouracil for 18 months prior to presentation. On admission, agranulocytosis was evident with a neutrophil count of 0.36 × 109/L and immediately propylthiouracil was stopped. There was no evidence of active infection and the patient was treated with broad-spectrum antibodies and one dose of granulocyte colony-stimulation factor, resulting in a satisfactory response. On further investigation, ANCAs were positive with dual positivity for proteinase 3 and myeloperoxidase. There was no evidence of end-organ damage secondary to vasculitis, and the patient’s constitutional symptoms resolved completely on discontinuation of the drug precluding the need for immunosuppressive therapy.

Learning points:

  • Continued vigilance and patient education regarding the risk of antithyroid drug-induced agranulocytosis is vital throughout the course of treatment.

  • ANCA-associated vasculitis is a rare adverse effect of antithyroid drug use.

  • Timely discontinuation of the offending drug is vital in reducing end-organ damage and the need for immunosuppressive therapy in drug-induced ANCA-associated vasculitis.

  • Similarities in the pathogenesis of agranulocytosis and drug-induced ANCA-associated vasculitis may offer insight into an improved understanding of vasculitis and agranulocytosis.

Open access
Alexa Clark Department of Medicine, Department of Medicine, Queen’s University, Kingston, Ontario, Canada

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Marosh Manduch Department of Pathology and Molecular Medicine, Department of Medicine, Queen’s University, Kingston, Ontario, Canada

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Russell Hollins Department of Otolaryngology, Department of Medicine, Queen’s University, Kingston, Ontario, Canada

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Sara Awad Division of Endocrinology and Metabolism, Department of Medicine, Queen’s University, Kingston, Ontario, Canada

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Summary

We report a case of metastatic papillary thyroid carcinoma presenting with a recurrent right-sided cervical lymph node necrotic cyst. A 55-year-old woman presented with a 3-month history of a right-sided upper neck mass following an upper respiratory tract infection. Past medical history includes a right-sided nephrectomy secondary to a benign renal tumor and hypertension. She was evaluated by Otolaryngology, and fine-needle aspiration was performed. The mass recurred 2 months following aspiration. Ultrasound of the neck showed a 2.2 × 1.4 × 1.9 cm right cervical lymph node with a small fatty hilum but a thickened cortex. Neck computed tomography (CT) scan showed a well-defined 2.3 cm mass in the right upper neck corresponding to a necrotic cervical lymph node at level IIA. It also revealed a 7 mm calcified left thyroid nodule. Cytology revealed a moderate collection of murky fluid with mildly atypical cells presumed to be reactive given the clinical history of infection. The cyst had re-grown 2 months following aspiration. Excisional biopsy was performed and revealed metastatic classic papillary thyroid carcinoma (PTC). Subsequently, a total thyroidectomy and right neck dissection was performed. Pathology confirmed metastatic unifocal classic PTC of the right thyroid lobe and two lymph node metastases out of a total of 17 resected lymph nodes. The patient underwent radioactive iodine ablation. Subsequent I-131 radioiodine whole-body scan showed no evidence of metastases. In conclusion, metastatic PTC should be considered in the differential diagnosis of a recurrent solitary cystic cervical lymph node.

Learning points:

  • Metastatic PTC should be considered in the differential diagnosis of a recurrent solitary cystic cervical lymph node.

  • A dedicated thyroid ultrasound is the preferred modality for identifying thyroid lesion over computed tomography.

  • There is a risk of non-diagnostic cytology following FNA for cystic neck lesions, largely predicted by the cyst content of the nodule.

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Haruhiko Yamazaki Department of Breast and Endocrine Surgery, Kanagawa Cancer Center, Yokohama, Japan

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Hiroyuki Iwasaki Department of Breast and Endocrine Surgery, Kanagawa Cancer Center, Yokohama, Japan

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Yoichiro Okubo Department of Pathology, Kanagawa Cancer Center, Yokohama, Japan

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Nobuyasu Suganuma Department of Breast and Endocrine Surgery, Kanagawa Cancer Center, Yokohama, Japan

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Katsuhiko Masudo Department of Breast and Thyroid Surgery, Yokohama City University Medical Center, Yokohama, Japan

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Hirotaka Nakayama Department of Surgery, Yokohama City University School of Medicine, Yokohama, Japan

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Yasushi Rino Department of Surgery, Yokohama City University School of Medicine, Yokohama, Japan

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Munetaka Masuda Department of Surgery, Yokohama City University School of Medicine, Yokohama, Japan

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Summary

The objective this study is to report two cases of thyroid gland invasion by upper mediastinal carcinoma. Mediastinal tumors are uncommon and represent 3% of the tumors seen within the chest. In reports on mediastinal masses, the incidence of malignant lesions ranged from 25 to 49%. The thyroid gland can be directly invaded by surrounding organ cancers. We report these cases contrasting them to the case of a thyroid cancer with mediastinal lesions. Case 1 was a 73-year-old woman who was diagnosed with papillary thyroid carcinoma, and she underwent surgery and postoperative radioactive iodine. Case 2 was a 74-year-old man who was diagnosed with non-small-cell lung carcinoma, favor squamous cell carcinoma, and he underwent chemoradiotherapy. Case 3 was a 77-year-old man who was diagnosed a thymic carcinoma based on pathological findings and referred the patient to thoracic surgeons for surgical management. The images of the three cases were similar, and the differential diagnoses were difficult and required pathological examination. Primary thyroid carcinoma and invading carcinoma originating from the adjacent organs need to be distinguished because their prognoses and treatment strategies are different. It is important to properly diagnose them by images and pathological findings.

Learning points:

  • The thyroid gland in the anterior neck can be directly invaded by surrounding organ cancers.

  • Primary thyroid carcinoma and invading carcinoma originating from the adjacent organs need to be distinguished because their prognoses and treatment strategies are different.

  • It is important to properly diagnose by images and pathological findings.

Open access
Tiago Nunes da Silva Department of Internal Medicine, ENETS Centre of Excellence, Erasmus MC, University Medical Centre, Rotterdam, the Netherlands

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(Loes) M L F van Velthuysen Department of Pathology, Erasmus MC, University Medical Centre, Rotterdam, the Netherlands

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Casper H J van Eijck Department of Surgery, Erasmus MC, University Medical Centre, Rotterdam, the Netherlands

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Jaap J Teunissen Department of Radiology & Nuclear Medicine, Erasmus MC, University Medical Centre, Rotterdam, the Netherlands

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(Hans) J Hofland Department of Internal Medicine, ENETS Centre of Excellence, Erasmus MC, University Medical Centre, Rotterdam, the Netherlands

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Wouter W de Herder Department of Internal Medicine, ENETS Centre of Excellence, Erasmus MC, University Medical Centre, Rotterdam, the Netherlands

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Summary

Non-functional pancreatic neuroendocrine tumours (NETs) can present with advanced local or distant (metastatic) disease limiting the possibility of surgical cure. Several treatment options have been used in experimental neoadjuvant settings to improve the outcomes in such cases. Peptide receptor radionuclide therapy (PPRT) using beta emitting radiolabelled somatostatin analogues has been used in progressive pancreatic NETs. We report a 55-year-old female patient with a 12.8 cm pancreatic NET with significant local stomach and superior mesenteric vein compression and liver metastases. The patient underwent treatment with [177Lutetium-DOTA0,Tyr3]octreotate (177Lu-octreotate) for the treatment of local and metastatic symptomatic disease. Six months after 4 cycles of 177lutetium-octreotate, resolution of the abdominal complaints was associated with a significant reduction in tumour size and the tumour was rendered operable. Histology of the tumour showed a 90% necrotic tumour with abundant hyalinized fibrosis and haemorrhage compatible with PPRT-induced radiation effects on tumour cells. This report supports that PPRT has a role in unresectable and metastatic pancreatic NET.

Learning points:

  • PRRT with 177Lu-octreotate can be considered a useful therapy for symptomatic somatostatin receptor-positive pancreatic NET.

  • The clinical benefits of PRRT with 177Lu-octreotate can be seen in the first months while tumour reduction can be seen up to a year after treatment.

  • PRRT with 177Lu-octreotate was clinically well tolerated and did not interfere with the subsequent surgical procedure.

  • PRRT with 177Lu-octreotate can result in significant tumour reduction and may improve surgical outcomes. As such, this therapy can be considered as a neoadjuvant therapy.

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Mads Ryø Jochumsen Department of Nuclear Medicine & PET Centre, Aarhus University Hospital, Aarhus, Denmark

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Peter Iversen Department of Nuclear Medicine & PET Centre, Aarhus University Hospital, Aarhus, Denmark

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Anne Kirstine Arveschoug Department of Nuclear Medicine & PET Centre, Aarhus University Hospital, Aarhus, Denmark

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Summary

A case of follicular thyroid cancer with intense focal Methionine uptake on 11C-Methionine PET/CT is reported here. The use of 11C-Methionine PET in differentiated thyroid cancer is currently being investigated as a surrogate tracer compared to the more widely used 18F-FDG PET. This case illustrates the potential incremental value of this modality, not only in the localizing of parathyroid adenoma, but also indicating that 11C-Methionine PET might have a potential of increasing the pretest likelihood of thyroid malignancy in a cold nodule with highly increased Sestamibi uptake.

Learning points:

  • 11C-Methionine PET/CT and 18F-Fluorocholine PET/CT often visualizes the parathyroid adenoma in case of negative Tc-99m-MIBI SPECT/CT.

  • A cold nodule in Tc-99m Pertechnetat thyroid scintigraphy with a negative Sestamibi scintigraphy has a very low probability of being malignant.

  • However, the pretest likelihood of thyroid cancer in a cold nodule with increased Sestamibi uptake is low.

  • 11C-Methionine PET might have a potential incremental value in increasing the pretest likelihood of thyroid malignancy in a cold nodule with highly increased Sestamibi uptake.

Open access
Christopher W Rowe Departments of Endocrinology and Diabetes
Schools of Medicine and Public Health

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Kirsten Murray Departments of Endocrinology and Diabetes

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Andrew Woods Maternity and Gynaecology, John Hunter Hospital, Newcastle, New South Wales, Australia

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Sandeep Gupta Department of Nuclear Medicine & PET, Hunter New England Imaging, John Hunter and Calvary Mater Hospital, Newcastle, New South Wales, Australia
Health Sciences, University of Newcastle, Newcastle, New South Wales, Australia

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Roger Smith Departments of Endocrinology and Diabetes
Schools of Medicine and Public Health

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Katie Wynne Departments of Endocrinology and Diabetes
Schools of Medicine and Public Health

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Metastatic thyroid cancer is an uncommon condition to be present at the time of pregnancy, but presents a challenging paradigm of care. Clinicians must balance the competing interests of long-term maternal health, best achieved by iatrogenic hyperthyroidism, regular radioiodine therapy and avoidance of dietary iodine, against the priority to care for the developing foetus, with inevitable compromise. Additionally, epidemiological and cellular data support the role of oestrogen as a growth factor for benign and malignant thyrocytes, although communicating the magnitude of this risk to patients and caregivers, as well as the uncertain impact of any pregnancy on long-term prognosis, remains challenging. Evidence to support treatment decisions in this uncommon situation is presented in the context of a case of a pregnant teenager with known metastatic papillary thyroid cancer and recent radioiodine therapy.

Learning points:

  • Pregnancy is associated with the growth of thyroid nodules due to stimulation from oestrogen receptors on thyrocytes and HCG cross-stimulation of the TSH receptor.

  • Thyroid cancer diagnosed during pregnancy has not been shown to be associated with increased rates of persistent or recurrent disease in most studies.

  • There is little evidence to guide the management of metastatic thyroid cancer in pregnancy, where both maternal and foetal wellbeing must be carefully balanced.

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Marco Russo Endocrinology, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy

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Ilenia Marturano Endocrinology, Department of Clinical and Experimental Medicine, University of Catania, Garibaldi-Nesima Hospital, Catania, Italy

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Romilda Masucci Surgical Oncology, Garibaldi-Nesima Hospital, Catania, Italy

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Melania Caruso Gynecology and Obstetrics, Garibaldi-Nesima Hospital, Catania, Italy

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Maria Concetta Fornito Nuclear Medicine, Garibaldi-Nesima Hospital, Catania, Italy

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Dario Tumino Endocrinology, Department of Clinical and Experimental Medicine, University of Catania, Garibaldi-Nesima Hospital, Catania, Italy

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Martina Tavarelli Endocrinology, Department of Clinical and Experimental Medicine, University of Catania, Garibaldi-Nesima Hospital, Catania, Italy

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Sebastiano Squatrito Endocrinology, Department of Clinical and Experimental Medicine, University of Catania, Garibaldi-Nesima Hospital, Catania, Italy

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Gabriella Pellegriti Endocrinology, Garibaldi-Nesima Hospital, Catania, Italy

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Summary

Struma ovarii is a rare ovarian teratoma characterized by the presence of thyroid tissue as the major component. Malignant transformation of the thyroidal component (malignant struma ovarii) has been reported in approximately 5% of struma ovarii. The management and follow-up of this unusual disease remain controversial. We report the case of a woman with a history of autoimmune thyroiditis and a previous resection of a benign struma ovarii that underwent hystero-annexiectomy for malignant struma ovarii with multiple papillary thyroid cancer foci and peritoneal involvement. Total thyroidectomy and subsequent radioiodine treatment lead to complete disease remission after 104 months of follow-up. The diagnosis and natural progression of malignant struma ovarii are difficult to discern, and relapses can occur several years after diagnosis. A multidisciplinary approach is mandatory; after surgical excision of malignant struma, thyroidectomy in combination with 131I therapy should be considered after risk stratification in accordance with a standard approach in differentiated thyroid cancer patients.

Learning points

  • Malignant struma ovarii is a rare disease; diagnosis is difficult and management is not well defined.

  • Predominant sites of metastasis are adjacent pelvic structures.

  • Thyroidectomy and 131I therapy should be considered after risk stratification in accordance with standard approaches in DTC patients.

Open access