Prophylactic Thyroidectomy Research Articles

The Long-Term Cure of Patients With Hereditary Medullary Thyroid Carcinoma: 40 Years of Follow-Up in a Single Center.

The cure rate of patients with hereditary medullary thyroid carcionoma (MTC) can be decisively improved by screening for elevated calcitonin (Ctn) levels and RET gene mutations in patients from families affected by multiple endocrine neoplasia type 2 (MEN2), followed by prophylactic thyroidectomy in persons with mutated RET genes. In this long-term observational study, we investigated whether postoperative cures are indeed maintained decades after the procedure. From 1979 to 2021, 277 patients with MEN2 who underwent thyroidectomy were observed postoperatively for 14.4 ± 10.3 years (mean, standard deviation). They were classified as either cured or not cured depending on the last measured serum Ctn level (cured, Ctn < 10 pg/mL or < 2 pg/mL; not cured, Ctn ≥ 10 pg/mL). Depending on their RET mutation status, they were categorized as moderate, high, or highest risk (121, 130, and 26 patients, respectively). 154 patients (55.6%) obtained a long-term cure (Ctn <10 pg/mL). The median age at surgery was 27, 14, and 4 years in patients at moderate, high, and highest risk. All 52 patients who had undergone prophylactic thyroidectomy before the age of 6 years, 9 years, or 6 months had a Ctn level below 2 pg/mL and were cured at the end of the follow-up period. In a multivariable analysis, prognostic factors for a long-term cure were a lower tumor stage and, by tendency, classification as belonging to the moderate as opposed to the highest-risk group. In patients receiving an early diagnosis of MEN2 via family screening, prophylactic thyroidectomy taking into account the RET mutation risk group can achieve a long-term cure of MTC with undetectable serum Ctn levels.

30years of prophylactic thyroidectomy for hereditary medullary thyroid cancer : Amilestone in translational medicine

Medullary thyroid cancer (MTC) is the most frequent manifestation of multiple endocrine neoplasia type 2 (MEN2) that determines the oncological outcome. Germline mutations in the rearranged during transfection (RET) protooncogene, atumor suppressor gene on chromosome 10q11.2, were identified 30 years ago as the genetic basis of MEN2 and published in 1993 and 1994. These seminal findings gave rise to the concept of prophylactic thyroidectomy for asymptomatic gene mutation carriers based on apositive RET gene test, which has become the standard of care ever since. Clinical genetic investigations showed genotype-phenotype correlations with respect to the individual gene mutation regarding the penetrance and onset of MTC and to alesser extent also with respect to the other components of MEN2, pheochromocytoma and primary hyperparathyroidism. From this a clinically relevant risk stratification could be derived. Initially, the optimal timing of prophylactic thyroidectomy was primarily based on the RET genotype alone, which was not sufficient for a precise age recommendation and subsequently required additional consideration of calcitonin serum levels for fine tuning. Calcitonin levels first show the risk of lymph node metastasis when they exceed the upper normal limit of the assay independent of carrier age and RET mutation. Routine calcitonin screening of patients with nodular thyroid disease, screening of families on identification of MEN2 index patients, and pre-emptive thyroidectomy in carriers of gene mutations with normal calcitonin levels have led to the fact that nowadays, 30years after the first description of the gene mutations causing the disease, the life-threatening hereditary MTC has become curable: ashining example for the success of translational transnational medical research for the benefit of patients.

Does Genotype-Specific Phenotype in Patients with Multiple Endocrine Neoplasia Type 2 Occur as Current Guidelines Predict?

The clinical manifestation of multiple endocrine neoplasia type 2 (MEN2) in terms of developing medullary thyroid cancer (MTC), pheochromocytoma (PCC), and/or primary hyperparathyroidism (PHPT) is related to the respective pathogenic variant of the RET proto-oncogene. The aim of this study is to retrospectively analyze the individual, genotype-dependent clinical manifestations of a large cohort of MEN2 patients. By comparing their clinical profile with currently existing evidence-based knowledge, an optimal therapy and prevention strategy in terms of prophylactic thyroidectomy and clinical follow-up could be ensured. This is a retrospective single-center study of 158 MEN2 patients who were diagnosed and/or surgically treated at a tertiary referral care center between 1990 and 2022. All participants were categorized according to their pathogenic variant of the RET proto-oncogene. Subsequently, the clinical manifestation of the disease and its time of occurrence was documented. Our analysis showed results in line with existing studies, except for a considerably lower-than-predicted occurrence of PCC in patients with V804M/L mutations. This study supports the current recommendation regarding the pathogenic variant-dependent management of this rare cancer-associated syndrome.

Impact of Early Diagnostic and Therapeutic Interventions and Clinical Course in Children and Adolescents with Multiple Endocrine Neoplasia Types 1 and 2.

Multiple endocrine neoplasia types 1 (MEN1) and 2 (MEN2) are inherited endocrine tumor syndromes caused by mutations in the MEN1 or RET genes. This study aimed to investigate clinical outcomes and molecular characteristics among children with MEN. This study included eight patients from seven unrelated families. Data on clinical course, biochemical findings, and radiologic studies were collected by retrospective chart review. All diagnoses were genetically confirmed by Sanger sequencing of MEN1 in three MEN1 patients and RET in four patients with MEN2A and one patient with MEN2B. Three patients with MEN1 from two families presented with hypoglycemia at a mean age of 11±2.6 years. Four patients with MEN2A were genetically diagnosed at a mean of 3.0±2.2 years of age by family screening; one of them was prenatally diagnosed by chorionic villus sampling. Three patients with MEN2A underwent prophylactic thyroidectomy from 5 to 6 years of age, whereas one patient refused surgery. The patient with MEN2B presented with a tongue neuroma and medullary thyroid carcinoma at 6 years of age. Subsequently, he underwent a subtotal colectomy because of bowel perforation and submucosal ganglioneuromatosis at 18 years of age. This study described the relatively long clinical course of pediatric MEN with a mean follow-up duration of 7.5±3.8 years. Insulinoma was the first manifestation in children with MEN1. Early diagnosis by family screening during the asymptomatic period enabled early intervention. The patient with MEN2B exhibited the most aggressive clinical course.

A rare case of medullary carcinoma

Medullary thyroid cancer (MTC) accounts for 5–10 % of all thyroid cancers. Most cases (75 %) are sporadic, but the proportion of patients with MTC and a familial predisposition syndrome is the highest among those with any hereditary cancer syndrome (about 25 %), and this possibility should be considered when examining a patient with MTC. Familial syndromes include multiple endocrine neoplasia (MEN) 2A, MEN 2B, and non-MEN familial MTC (familial MTC). Familial MTC syndromes occur in approximately one case per 30,000 of the population. Reduced penetrance and clinical variability are well-established features of many monogenic disorders, particularly phenotypes associated with the RET proto-oncogene. They require an individual assessment of the pathogenic effects and clinical significance of any identified new sequence of the RET va­riant as prerequisites for individual genetic counseling and planning of medical monitoring and treatment. Diagnostic criteria for the disease have been outlined, molecular and genetic aspects have been discussed, and the determination of treatment and further observation has been addressed. The article describes a clinical case of a rare variant of MTC. Treatment of this pathology with radical extrafascial thyroidectomy is under consideration. Given the ineffectiveness of radioiodine and chemotherapy, the main task in the treatment of MTC is early diagnosis, radical surgical intervention, and active monitoring aimed at early detection of disease recurrence. When planning prophylactic thyroidectomy, it is recommended to focus on the stratification of the level of RET gene mutations and the timing of prophylactic thyroidectomy proposed by the American Thyroid Association. The introduction of molecular genetic research into clinical practice for the purpose of diagnosing MTC allows for the objective assessment of the genetic lineage of the disease within a biological family. A timely diagnosis of MTC makes it possible to prescribe an adequate treatment at the stage of preclinical manifestations of the disease, which can significantly increase the quality and duration of life.

SAT561 Pathogenic RET V804M Germline Variant Without Clinical Manifestations Of Multiple Endocrine Neoplasia Type 2 In An Elderly Male

Abstract Disclosure: R. Ghosh: None. G. Al-Naqeeb: None. P. Veeraraghavan: None. C. Craig: None. J. Klubo-Gwiezdzinska: None. S. Gubbi: None. Background: Germline pathogenic variants in the RET protooncogene give rise to multiple endocrine neoplasia (MEN) types 2A and 2B. MEN2A is mainly characterized by MTC (∼100%), pheochromocytoma (PHEO; 4% - 88%), and primary hyperparathyroidism (HPTH; 2% - 30%), while MEN2B predominantly manifests with MTC (100%), PHEO (50%), mucocutaneous neuromas, and marfanoid habitus. Both MEN2A and 2B follow an autosomal dominant mode of inheritance. While certain pathogenic RET variants (M918T, A883F, and C634X) have high penetrance and present with aggressive disease, other variants such as V804M are of low penetrance and manifest with clinically mild disease.Clinical case: A 75-year-old male was referred to our center for further evaluation of the finding of an abnormal RET gene that was identified on a peripheral blood whole-exome gene sequencing research panel performed at an outside center. The patient was noted to have a germline RET c.2410 G&amp;gt;A, p.V804M heterozygous pathogenic variant. The patient denied any history of lump in the neck, symptoms of hyper- or hypothyroidism, tremors, headaches, fatigue, facial flushing, palpitations, constipation, diarrhea, anxiety, depression, or history of fragility fractures. Medical history consisted of hypertension, nephrolithiasis, type 2 diabetes mellitus, obstructive sleep apnea, interstitial pulmonary fibrosis, and colonic diverticula and polyps. Family history was significant for leukemia, colon, and breast cancers, but none of the relatives had a history of MTC, PHEO, or MEN2, and his children, while healthy, had not undergone RET germline testing. Physical examination showed no evidence of hypothyroidism or hyperthyroidism. Neck examination showed no evidence of thyromegaly or cervical lymphadenopathy. Laboratory investigations were unremarkable [serum calcitonin: 7.9 pg/ml (NL: &amp;lt;/=14.3), CEA 2.8 mcg/L (NL: 0.8-3.4), thyrotropin (TSH): 1.92 microIU/ml (NL: 0.35-4.94), free thyroxine: 0.9 ng/dl (NL: 0.7-1.5), plasma free normetanephrine: 0.31 nmol/L (NL: &amp;lt;0.9), plasma free metanephrines 0.24 nmol/L (NL: &amp;lt;0.5), parathyroid hormone: 28.2 pg/ml (NL: 15-65), and ionized calcium 1.23 mmol/l (NL: 1.09-1.30)]. Thyroid sonogram was normal. We recommended active annual surveillance with biochemical markers and imaging along with genetic testing of the RET gene in his children. Conclusion: The V804M RET variant has been often associated with MTC or MEN2A phenotypes [1]. However, the variable expression of this variant may lead to a mild clinical phenotype or even absence of MTC/MEN2A manifestations. Hence, active surveillance as opposed to radical surgery like prophylactic thyroidectomy would be more beneficial in patients with no clinical or biochemical evidence of disease. Reference: Pinna et al., 2007, V804M is the most frequent mutation and may be associated with FMTC/MEN-2A phenotype. Thyroid, 17(2), 101-104. Presentation Date: Saturday, June 17, 2023

SAT574 Thyroglossal Duct Papillary Thyroid Cancer With Normal Eutopic Thyroid Gland: A Management Dilemma

Abstract Disclosure: H. Belal: None. J.T. Batch: None. G.Y. Gandhi: None. Background: The incidence of thyroglossal duct cyst carcinomas is less than 1%, the majority being papillary thyroid cancer. One-third arise de novo from the thyroglossal duct. The rest are direct metastasis of eutopic papillary thyroid cancer. Management in the setting of a normal eutopic thyroid gland is challenging. Clinical Case: A 35-year-old female presented with transient right facial paresthesia. CT angiogram revealed an incidental 2.3 cm thyroglossal duct cyst with internal ectopic thyroidal tissue and micro-calcifications. She denied any compressive symptoms, radiation exposure, or family history of thyroid cancer and was euthyroid. Ultrasound noted a normal thyroid gland and complex solid-cystic mass measuring 2.3 x 2.0 x 1.5 cm superior to the isthmus. Satisfactory fine needle aspiration of the mass revealed benign-appearing epithelial cells, macrophage, and colloid-like material. Due to new anterior neck pain, a Sistrunk Procedure (SP) was performed. Pathology revealed a 1.2 cm papillary thyroid carcinoma, conventional type (confirmed by TTF-1 and thyroglobulin stains), arising within the thyroglossal duct cyst. Surgical margins were free of cancer, and there was no lymphovascular invasion. A thyroid ultrasound seven months after the procedure revealed heterogenous thyroid tissue, no thyroid nodules, and several small benign-appearing reniform-shaped cervical lymph nodes in zones 1 and 2. The patient was offered yearly thyroid ultrasound surveillance versus prophylactic thyroidectomy. She elected to proceed with thyroidectomy due to concerns about disease recurrence. Final pathology results revealed right lobe 2 mm papillary microcarcinoma limited to the thyroid. Conclusion: Fine needle aspiration of thyroglossal duct cysts can have a high false negative rate, as in our patient. There is currently no consensus on treatment of thyroid carcinomas arising from thyroglossal duct cysts. There are four possible surgical strategies: 1) SP alone 2) SP with concurrent thyroid lobectomy or pyramidal lobe resection 3) SP with total or near total thyroidectomy in all patients and 4) SP and selective addition of total or near total thyroidectomy in high-risk patients. The role of radio-iodine ablation and levothyroxine suppression after SP is also unclear. Management recommendations are Grade C, relying on case reports, case series, and expert opinion. Whether or not to proceed with total thyroidectomy, especially in the setting of a normal thyroid gland, remains highly controversial. Some experts even argue for an early aggressive surgical approach with SP, total thyroidectomy, and level I lymph node sampling in all patients to provide accurate staging and allow for the use of thyroglobulin and whole-body scintigraphy in surveillance. Multisite comparative data on the long-term outcomes of patients who receive early aggressive versus conservative management is needed. Presentation: Saturday, June 17, 2023

Clinic Heterogeneity and Management of Pediatric Patients With Germline RET Proto-oncogene Mutation: Single-center Experience.

Inherited forms of medullary thyroid carcinoma (MTC) can cause serious problems in diagnosis and follow-up. Family screening is performed, and prophylactic thyroidectomy at an appropriate age can be life-saving. This study aimed to investigate the diagnostic, clinical, laboratory characteristics, and treatment methods of cases with rearranged during transfection ( RET) mutation in the childhood age group. Patients diagnosed with hereditary MTC and patients who were evaluated by detecting MTC and/or RET mutations in their families were included in this study. Nine cases from 6 families were included in the study. Seven patients were evaluated as a result of screening, whereas 2 patients, one of whom was MEN2B, were symptomatic. Prophylactic thyroidectomy was performed in 7 cases. Medullary microcarcinoma was found in all, and additional papillary thyroid carcinoma in one. An inoperable tumor was detected in one patient, and sorafenib treatment was applied. A very heterogeneous clinical presentation can be seen in a group of pediatric patients with RET mutation. In rare RET mutations, the genotype-phenotype relationship is still unclear, and different clinical pictures can be seen. Although prophylactic thyroidectomy is life-saving, it can cause iatrogenic hypothyroidism and hypoparathyroidism. Concomitant papillary microcarcinomas may occur in very young children with germline RET mutation.

Prominent corneal nerves in pure mucosal neuroma syndrome, a clinical phenotype distinct from multiple endocrine neoplasia type 2B

BackgroundPure mucosal neuroma syndrome (MNS), an autosomal dominant neurocutaneous disorder, is a rare discrete subgroup in multiple endocrine neoplasia (MEN) type 2B, which present without associated endocrinopathies of MEN2B but with typical physical features such as prominent corneal nerves.Case presentationThis report describes a 41-year-old patient with complaint of itchy eyes and irritation, presenting with blocked gland orifices in the upper and lower eyelids, light conjunctival hyperemia, a semitransparent neoplasm measuring 2 mm*2 mm on the nasal limbus suggestive of neuromas, and prominent corneal nerves. In vivo confocal microscopy (IVCM) revealed structural alterations—namely a prominent hyperreflective, thickened nerve plexus and a normal endothelium—in both eyes. Testing for SOS1 mutation was positive. This patient may represent a discrete subgroup termed pure mucosal neuroma syndrome (MNS), which presents with the characteristic appearance of MEN2B but without RET gene mutations.ConclusionProminent corneal nerves have been described in some diseases, such as multiple endocrine neoplasia (MEN) type 1 and type 2A and 2B, congenital ichthyosis, Refsum’s disease, leprosy, etc. Ophthalmic assessment including prominent corneal nerves has proven valuable in asymptomatic individuals of MEN2B. Our case illustrates the importance of recognizing the ocular features of MNS, a rare presentation of MEN2B, in order to prevent prophylactic thyroidectomy in these patients for prophylactic thyroidectomy is not mandatory in MNS. However, regular monitoring and genetic counseling are still necessary.

Abstract #1399269: Never Too Old for Genetics: An Unusually Late Presentation of Medullary Thyroid Cancer in MEN2A

Virtually all germline RET pathogenic variant carriers develop medullary thyroid carcinoma (MTC). If possible, thyroidectomy should be performed prophylactically, before developing MTC. We describe a patient with pheochromocytoma found to have a germline RET p.Cys634Ser pathogenic variant at age sixty years who would be categorized as high risk based on genotype classification described by the American Thyroid Association and would have warranted prophylactic thyroidectomy at a young age. A 60-year-old man with history of hypothyroidism and osteopenia was found to have an adrenal mass during evaluation for kidney stones. It measured 4.1 x 3.2 x 3.8 cm on CT scan of abdomen and pelvis. MRI with and without gadolinium revealed a 4 cm left adrenal mass with T2 enhancement. Diagnosis of pheochromocytoma was confirmed with elevated levels of plasma free metanephrine and normetanephrine. The adrenal nodule showed avid uptake on PET CT Gallium-68 DOTATATE scan. No uptake was noted on the contralateral adrenal gland or in the neck. Patient underwent left adrenalectomy. Surgical pathology confirmed pheochromocytoma. Patient also had evidence of primary hyperparathyroidism (pHPT). Germline genetic analysis revealed a RET c.1900T >A(p.Cys634Ser) pathogenic variant confirming the diagnosis of multiple endocrine neoplasia type 2A (MEN2A). Calcitonin level was noted to be mildly elevated at 27.8 pg/ml. Subsequently, patient underwent total thyroidectomy, subtotal parathyroidectomy and bilateral central neck dissection. Surgical pathology revealed multifocal MTC, diffuse C-cell hyperplasia, and a foci of papillary thyroid microcarcinoma. Immunohistochemistry for calcitonin revealed diffuse C-cell hyperplasia. Patient was doing well on postoperative follow up and calcitonin level downtrended to < 2 pg/ml. Nearly all patients with MEN2A have either C-cell hyperplasia (CCH) or MTC, approximately 50% have a pheochromocytoma and 20-30% have pHPT. Age-related penetrance of CCH and hMTC is mutation dependent. Peak incidence in index patients is in the third decade of life in MEN2A. Our patient presented in the sixth decade of life. We decided to pursue genetic testing. The DOTATE scan did not show uptake in the neck and the calcitonin was only mildly elevated. However, as there is known complete penetrance of MTC in patients with MEN2A syndrome, patient underwent total thyroidectomy with central neck dissection with results of surgical pathology confirming presence of MTC. This case highlights the importance of considering genetic syndromes even in patients who present at older ages and challenges the classic genotype-phenotype correlation of the RET p.Cys634Ser pathogenic variant and MTC.

"Graded early warning system" of RET germline mutation carriers in MEN2A/MEN2B families and total thyroidectomy (report of 7 cases)

Objective: To explore the reasonable time of prophylactic thyroidectomy for RET gene carriers in multiple endocrine neoplasia(MEN) 2A/2B families. Methods: From May 2015 to August 2021, RET gene carriers in MEN2A/MEN2B families were dynamically followed up at the Department of Thyroid Head and Neck Surgery, Beijing Tongren Hospital of Capital Medical University. The high-risk patients were encouraged to undergo prophylacitc total thyroidectomy according to the principle of "graded early warning system", namely the evaluation of gene detection, calcitonin value and ultrasound examination successively. Seven cases underwent the surgery, including 3 males and 4 females, aged from 7 to 29 years. According to the risk stratification listed in the guidelines of the American Thyroid Association in 2015, there were 2 cases of the highest risk, 2 cases of the high risk and 3 cases of the modest risk. Calcitonin index remained within the normal range in 3 cases and elevated in 4 cases before operation. All 7 patients underwent thyroidectomy with lymph node dissection of the level Ⅵ performed in 4 patients. Results: The time from suggestion to operation was 2 to 37 months, with an average of 15.1 months. The 6 patients were medullary thyroid carcinoma and 1 case with C-cell hyperplasia. The follow-up time was 2 to 82 months, with an average of 38.4 months. Postoperative serum calcitonin levels of all cases decreased to normal level, with biochemical cure. There was no sign of recurrence on ultrasound examination. All 7 patients had no serious complications, no obvious thyroid dysfunction. Their height, weight and other indicators of pediatric patients were similar to those of their peers, with normal growth and development. Conclusion: For healthy people with MEN2A/MEN2B family history, prophylactic thyroidectomy can be carried out selectively based on the comprehensive evaluation of "graded early warning system" with strict screening and close monitoring.

Pediatric thyroid surgery: Retrospective analysis on the first 25 pediatric thyroidectomies performed in a reference center for adult thyroid diseases.

Pediatric thyroid carcinoma represents about 4-5% of all pediatric carcinoma with an incidence of 0.5 cases/100,000, compared to 2-10/100000 cases in the adult population. The aim of this study is to present the experience of a reference adult endocrine surgery unit in charge of the treatment of pediatric thyroid diseases. From January 2019 to September 2022, 25 patients, aged 5-17, underwent thyroid surgery. We analysed indications for surgery, use of intraoperative nerve monitoring (IONM), definitive histological examination, postoperative outcomes and risk factors related. Surgical indication was performed for Graves' disease (27%) and for nodular pathology (73%): of these, four were malignant lesions (TIR4/TIR5), eight with indeterminate characteristics (TIR3A/TIR3B) and four characterized as benign (TIR1/TIR2). Total thyroidectomy (TT) was performed in 76% of cases, three of which were prophylactic for the activation of the RET gene mutation in MEN 2A. IONM was used in eight cases (32%), all patients aged 11 years or less. FNA's accuracy was 100% for lesions typified as benign and malignant (TIR1/TIR2 and TIR4/TIR5). The overall malignancy rate achieved was 40% and in the final histological examination 75% of the TIR 3B lesions were malignant. Six patients (24%) developed hypoparathyroidism in the first postoperative day, with normalization of calcium values within thirty days in 5 patients. Pediatric thyroid nodules are rare and distinguished from adult thyroid disease by a worse prognosis and higher malignancy rates. Our work reports a much higher malignancy rate among indeterminate TIR 3B lesions than observed in the adult population and the three patients who underwent prophylactic total thyroidectomy for activating RET gene mutation had all a definitive histological diagnosis of medullary carcinoma. Post-surgical hypoparathyroidism is a common finding in these patients: in most cases the condition is transient and it benefits from supportive therapy. Intraoperative finding of a thinner recurrent laryngeal nerve in younger patients makes nerve isolation more difficult than in adult surgery: IONM is recommended in patients under 12. Pediatric thyroid surgery is challenging, we sustain it requires referral thyroid Centers for thyroid disease with highly skilled general endocrine surgeons.

Hereditary medullary thyroid cancer

ParafollicularC cells progress via C cell hyperplasia to medullary thyroid cancer (MTC), which can be present even in the first years of life in multiple endocrine neoplasia (MEN) type2A and 2B patients. Basal calcitonin and carcinoembryonic antigen (CEA) are useful tumor markers for the diagnosis and monitoring. The prognosis depends on the stage when the disease is diagnosed and there is a good genotype-phenotype correlation with the RET proto-oncogene, which can be used for estimation of the risk. The risk-stratified prophylactic thyroidectomy plays a decisive role in the prognosis of known gene mutation carriers.

Pediatric Thyroidectomy: Experience From a Portuguese Hospital.

Background and objective Pediatric thyroid disease requiring surgery is rare. Thyroid nodules are a frequent indication for surgery and are mostly benign. However, up to 25% of cases can be malignant. In this study, we aimed to describe our center's experience with regard to pediatric thyroid surgery. Methods This was a retrospective transverse study involving pediatric patients who underwent thyroid surgery at a tertiary hospital between January 2010 and December 2021. Results A total of 14 patients underwent 15 surgeries. The main reason for referral to pediatric endocrinology was thyroid nodules (n=10). Thirteen fine needle aspirations (FNAs) were performed, with follicular tumor (n=6) being the most common finding. The median age of patients at surgery was 15.9 years [interquartile range(IQR): 14.0-16.8]. The most common surgical indications were the presence of a follicular tumor on FNA (n=5) and thyroid nodule size causing symptoms (n=5). There was one case of prophylactic thyroidectomy due to the identification of a multiple endocrine neoplasia type 2A (MEN2A) mutation. The most frequently described histopathology results were follicular adenoma (n=6) and colloid nodular goiter (n=6). Three postoperative complications were observed in three different patients: bilateral lesion of the recurrent laryngeal nerve, cervical hematoma, and transient hypoparathyroidism with hypocalcemia. Conclusion In our study, the most frequent surgical indication was a follicular tumor. A good correlation was found between FNA cytology and final histopathology results, which is in accordance with previous studies. This reinforces the importance of FNA in diagnosis and surgical planning. The rate of complications in our study is comparable to that in larger single-center series in the literature.

Overview of thyroid gland involvement and its prognostic value on advanced laryngeal cancer

Laryngeal cancer is the second most common malignancy in the head and neck region. The guidelines recommend prophylactic thyroidectomy for patients with advanced laryngeal cancer, but its prognostic value remains elusive. In this review, the incidence, risk factors, prognostic value of thyroid invasion in patients with laryngeal cancer were reviewed. The effect of prophylactic thyroidectomy on the outcome of advanced laryngeal cancer patients was also discussed.

Prophylactic and Early Thyroidectomy in RET Germline Mutation Carriers in Pediatric and Adult Population: Long-Term Outcomes of a Series of 63 Patients

Prophylactic and early thyroidectomy in RET germline mutation carriers allows the removal of the thyroid before medullary thyroid carcinoma (MTC) develops, or while it is still confined to the gland. This study was aimed to assess the clinicopathological features in RET carriers according to the age at surgery and the long-term outcomes after prophylactic and early thyroidectomy. A retrospective analysis of 63 operated asymptomatic RET carriers diagnosed after familial genetic screening was performed. Twenty-one RET carriers were operated at pediatric (<18 yrs) and 42 at adult (≥18 yrs) age. Serum preoperative calcitonin levels were significantly lower in pediatric compared to adult patients (p = 0.04); moreover, adult RET carriers had a greater frequency of microMTC at pathology (p = 0.009). Permanent postoperative morbidity occurred in 9.5% of patients, without differences between the two groups. Biochemical postoperative cure was achieved in all patients. At a median follow-up of 14 years, all C-cell hyperplasia patients are disease-free; conversely, biochemical, and structural recurrence of disease occurred in three adults and one pediatric patient with microMTC. The independent predictive factors of MTC were the age at surgery, the preoperative calcitonin level and the RET mutational risk profile (p < 0.02). In conclusion, prophylactic and early thyroidectomy are safe and effective procedures in achieving definitive cure in most RET carriers. However, since recurrences may occur at long-term in case of microMTC, thyroidectomy should be possibly performed earlier to prevent microMTC development.

Features of the diagnosis of primary hyperparathyroidism in children

Background. Primary hyperparathyroidism (PHPT) is a rare pathology in pediatric and adolescent patients. Collection, analysis and generalization of the literature data and experience of the leading clinics allow to develop unified, statistically substantiated approaches to diagnostics and surgical treatment of this group of patients.Material and methods. The article presents a retrospective analysis of 17 cases of PHPT in children and adolescents aged from 6 to 18 years operated on in the department of Surgery of St.-Petersburg State Pediatric Medical University in the period from 1973 till 2021. Among those operated there were 10 girls and 7 boys, the M:F ratio was 1:1.4. The mean age of the patients was 12,9±0,71 years.Results and discussion. The main criteria of the disease diagnosis were elevated blood calcium and parathormone levels, excessive urinary calcium secretion. Manifest forms of the disease were diagnosed in 10 (58,8%) of 17 children. In 3 (17,6%) cases the parathyroid neoplasms were accompanied neither by clinical, nor laboratory manifestations of the disease and were regarded as incidentalomas. Another 4 (23.5%) patients had only laboratory changes (hypercalcemia and hyperparathyrinaemia) that manifested themselves preoperatively. These observations were referred to the asymptomatic form of PHPT.In 7 (41.2%) cases parathyroid adenomas were found and removed during surgeries for various thyroid diseases (thyroid cancer in 5 cases, diffuse toxic goiter in 1 case). An incidental finding of parathyroid adenoma was during prophylactic thyroidectomy for Sipple syndrome.A radioisotope method proved to be the most informative way to localize parathyroid tumors.Conclusion. The diagnosis of the disease in manifest sporadic cases does not differ from that in adults. Genetic study is indicated in the presence of a family history of multiple involvement of the parathyroid glands. Surgical treatment with removal of parathyroid tumor is the main method, which allows to achieve complete recovery.

ODP493 Malignant Struma Ovarii with Papillary Thyroid Carcinoma and concomitant High Risk Thyroid Nodule

Abstract Introduction Struma ovarii is a rare teratoma consisting of &amp;gt;50% thyroid tissue. Malignant transformation very seldomly occurs; most pathology shows papillary thyroid carcinoma. The risk and prevalence of concurrent thyroid gland neoplasm is unclear. Thyroid cancer surveillance post-oophorectomy in these patients may be pertinent but has not yet been established. Case Report A nulliparous 54 year-old woman with one year of menopause without HRT had pelvic and back pain. Imaging detected bilateral ovarian teratomas. Pathology from laparoscopic bilateral salpingo-oophorectomy revealed a 10.7×9.9×10.9cm noninvasive struma ovarii with focal papillary thyroid carcinoma of the left ovary and a benign teratoma of the right ovary. Importantly, the patient had a known thyroid nodule. Two years prior, a FNA of the 1.4cm hypoechoic, hypervascular nodule in the left lower pole yielded benign (Bethesda 2) cytology. After struma ovarii resection, thyroid ultrasound showed highly suspicious TIRAD5. She denied symptoms of hyper- or hypothyroidism and had a normal TSH. She consequently underwent two FNA biopsies, both of which were non-diagnostic. The patient deferred further attempts. History of an initial benign biopsy and stability of the nodule size provide some reassurance. With the patient's reluctance for surgery, serial thyroglobulin (Tg) and ultrasounds will be followed. Post-operative Tg was normal with negative Tg antibody. If Tg becomes markedly elevated, a thyroidectomy will be indicated. Discussion Given the TIRAD5 nodule, this patient's risk of thyroid malignancy is 60-70%. This is compounded with her setting of malignant struma ovarii, which may imply genetic predisposition for thyroid carcinogenesis. Since cytology could not be obtained on the two recent biopsies, definitive pathology by diagnostic lobectomy or thyroidectomy may be considered. A total thyroidectomy would provide the advantage of following Tg for cancer surveillance of both thyroid and ovarian malignancies. There is scant evidence on the treatment of malignant struma ovarii. A few small case series and a pooled review of 57 cases of low-risk (confined to the ovary) malignant struma ovarii in which 50 patients did not undergo thyroidectomy/I-131 ablation showed only a 7.5% recurrence rate at 25 years (Marti et al Thyroid 2012 Apr; 22 (4): 400-406). Hence, this study recommends reserving prophylactic thyroidectomy for patients with extra-ovarian extension or metastases. Treatment of malignant struma ovarii may be extrapolated from those used in differentiated thyroid cancer; high-risk lesions would be those measuring &amp;gt;4cm, have local or distant invasion, or have a BRAF mutation (indicating an aggressive tumor). In conclusion, conservative measures of the thyroid gland with a suspicious nodule may be acceptable in patients with noninvasive malignant struma ovarii, provided strict adherence to cancer surveillance of Tg with both thyroid and pelvic sonography. Presentation: No date and time listed

PSUN378 A Turducken Phenomenon: A Case of Papillary Thyroid Carcinoma Arising Within Struma Ovarii Associated With a Large Mucinous Cystadenoma

Abstract Introduction Struma Ovarii (SO) is one of the types of mature teratoma accounting for up to 3% of all ovarian tumors, with predominant thyroid tissue (&amp;gt;50%). Most cases are reported in middle-aged women. We are presenting a case of asymptomatic papillary thyroid cancer (PTC) presented in SO that was incidentally found and treated successfully Case presentation A 72-year-old Hispanic female with a history of hysterectomy, tobacco smoking was found to have a suspicious lung nodule on screening with CT scan of Chest. A subsequent PET/CT Scan revealed incidental findings of left adnexal lesion of 12×12 cm with no FDG uptake and had a minimal uptake in lung nodule favoring a hamartoma. At the gynecology clinic, patient denied having vaginal bleeding, bowel dysfunction, abdominal pain or weight loss. She did report urinary incontinence. Pelvic exam demonstrated a mobile left adnexal mass without tenderness. MRI of Pelvis revealed a 15 cm multi-cystic, left ovarian mass compressing the urinary bladder without any lymphadenopathy. Tumor markers of CEA and CA-125 were normal. The patient underwent bilateral salpingo-oophorectomy with extensive adhesolysis. Entire ovarian mass was removed intact. Surgical Pathology revealed a 1.2 cm Unifocal PTC arising in 3 cm SO associated with mucinous cystadenoma without lympho-vascular invasion and extra-ovarian extension. No malignant cells were identified in peritoneal washing. This was staged according to AJCC 8th edition as pT1aNxMna. Immunostaining of TTF-1 and TG were positive, which additionally supported above diagnosis. Mutational testing of BRAF, K-RAS and N-RAS were negative. Post-operatively, at the Endocrine clinic, her TSH and Free T4 were normal. No nodules were detected on the thyroid ultrasound. She was deemed low risk for recurrence and no further treatment was advised except serial monitoring of Thyroglobulin levels and goal TSH &amp;lt; 2.5 mIU/L. Discussion In general, SO can be diagnosed only on a histopathological specimen and no specific radiological or biomarkers are available. Most patients are euthyroid and remain asymptomatic like our patient. Thyrotoxicosis occurs in only 5–15% of patients. SO is mostly benign. Its malignant transformation occurs in only 5% of all cases. The most widespread malignant forms of SO are papillary and follicular carcinomas. There are no well-established guidelines for optimal management of malignant SO. After undergoing oophorectomy, the decision to perform a prophylactic thyroidectomy and administration of 131I-Radioiodine is typically reserved for presence of metastatic disease or high risk of recurrence (&amp;gt;4 cm tumor size, gross extra-ovarian extension, BRAF positivity or histology other than papillary type). Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Management of malignant struma ovarii: is aggressive therapy justified? Case report and literature review

BackgroundStruma ovarii (SO) is a rare ovarian teratoma containing predominantly thyroid tissue. In rare situations SO may develop malignancy. Most cases of malignant struma ovarii (MSO) are diagnosed after surgical removal, based on histopathological examination. There are still controversies regarding the extent of surgery and postoperative management in MSO, due to its unpredictable behavior, possible risk of metastasis and relatively high rate of recurrence. Case PresentationWe present the case of a patient diagnosed with a right ovarian cyst discovered incidentally during routine ultrasound examination. Its rapid growth and pelvic MRI raised the suspicion of a neoplastic process. She underwent total hysterectomy and bilateral adnexectomy. The anatomopathological diagnosis was MSO with follicular variant of papillary thyroid carcinoma. Prophylactic total thyroidectomy was performed, followed by radioactive iodine ablation (RAI), and suppressive therapy with levothyroxine. At 1 year follow-up, the patient was disease free.ConclusionsEven if latest literature reports consider that completion of local surgery with total thyroidectomy and RAI might be too aggressive in cases of MSO without extraovarian extension, in our case it was decided to follow the protocol for primary thyroid carcinoma, in order to reduce the recurrence risk.