Utilidad diagnóstica de citopatología para diagnóstico de nódulos tiroideos malignos en un hospital peruano / Diagnostic utility of cytopathology for the diagnosis of malignant thyroid nodules in a Peruvian hospital

RESUMEN Objetivos: determinar el rendimiento diagnóstico de la biopsia por punción aspiración con aguja fina (PAAF) para el diagnóstico de nódulos tiroideos malignos. Materiales y métodos: estudio retrospectivo que evaluó las PAAF de tiroides realizadas en el Hospital Nacional Guillermo Almenara Irigoyen en Lima, Perú, durante un período de tres años. Se categorizó el diagnóstico citopatológico de las biopsias usando el sistema de Bethesda, se consideró las categorías V y VI como malignas y la categoría II como benigna. Se obtuvo solo una biopsia por paciente y se consideró el resultado con la categoría de Bethesda más alta. Todos los pacientes fueron sometidos a tiroidectomía y los resultados histopatológicos se categorizaron como malignos o benignos. Resultados: se incluyó a 173 pacientes con resultados citopatológicos de Bethesda II al VI. El diagnóstico citológico mostró que el 47,4% de los pacientes tenían Bethesda VI. El 59,5% de los nódulos tiroideos fueron malignos en la histopatología, siendo el carcinoma papilar el tipo más frecuente. El rendimiento diagnóstico de la PAAF fue alta cuando considera Bethesda V y VI como malignos, con una sensibilidad 91,92%, especificidad 71,67%, valor predictivo positivo 84,26%, valor predictivo negativo 84,31% y precisión de 84,28%, razón de verosimilitud positiva 3,39; pero mejoró significativamente cuando se consideró solo Bethesda VI como maligno, con sensibilidad del 90,7%, especificidad del 89,58%, precisión 90,3% y razón de verosimilitud positiva 8,71. Conclusiones : la PAAF tiene buen rendimiento. Este estudio demostró ser de gran utilidad en nuestro centro de salud para detectar errores y promover mejoras, así también como modelo para próximas investigaciones en diferentes establecimientos de salud.

ABSTRACT Objectives: To determine the diagnostic performance of fine needle aspiration biopsy (FNAB) for diagnosing malignant thyroid nodules. Methods: This is a retrospective study that assessed thyroid FNABs in Guillermo Almenara-Irigoyen National Hospital in Lima, Peru, during a three-year period. Cytopathologic diagnosis of biopsies was categorized using the Bethesda System, considering categories V and VI as malignant, and category II as benign. A single biopsy per patient was obtained, and results with the highest value in the Bethesda System were considered. All patients underwent thyroidectomy and histopathological results were characterized as malignant or benign. Results: One hundred and seventy-three patients were included in the study. Their cytopathology results were Bethesda II to VI. Cytological diagnosis showed that 47.4% of all patients were Bethesda VI. Nearly sixty percent (59.5%) of thyroid nodules were malignant in histopathology, and papillary carcinoma was the most frequent neoplasm. Diagnostic performance of FNAB was high when considering Bethesda V and VI as malignant, with 91.92% sensitivity, 71.67% specificity, 84.26 positive predictive value, 84.31% negative predictive value, and 84.28% precision. Positive verisimilitude rate was 3.39; but this significantly improved when only Bethesda VI was considered as malignant, with 90.7% sensitivity, 89.58% specificity, 90.3% precision, and 8.71 positive verisimilitude rate. Conclusion: FNAB showed good performance. This study proved to be quite useful in our healthcare facility for detecting errors and promote improvement, as well as a model for future research in different healthcare instances.

[Clinical-epidemiological profile of patients with thyrotoxic periodic paralysis in two peruvian hospitals]. / Perfil clínico-epidemiológico de pacientes con parálisis periódica tirotóxica en dos hospitales peruanos.

Background: Thyrotoxic Periodic Paralysis (PPT) is an uncommon complication of hyperthyroidism, it is the most frequent cause of acute flaccid paralysis in adults. Material and methods: A retrospective observational study was carried out in 2 reference hospitals of the social security in Lima-Peru, which included 22 patients diagnosed with PPT during the period 2014-2021. Results: the average age at diagnosis was 35.77 ± 9.6 years, all of mixed race, in 82% of the patients the diagnosis of hyperthyroidism was established from this entity, the etiology in 95% was autoimmune (Graves-Basedow) except for one whose etiology was toxic multinodular goiter. The triggering event reported in 54% of patients was the intake of copious food high in carbohydrates, followed by exercise (27%), the most frequent presentation time was during the morning (41% of the cases), the main weakness pattern compromised lower limbs (45% paraplegia, 18% paraparesis), only 36% were diagnosed with PPT in their first episode of motor weakness. Conclusions: We consider that this condition should be suspected in any young male patient of any ethnicity with acute muscle weakness, associated with low serum potassium levels and symptoms of thyrotoxicosis, although its absence should not rule out the diagnosis. The precipitating factor should be identified as much as possible and initial therapy with propanolol with or without intravenous or oral potassium replacement should be established, with adequate subsequent monitoring to minimize the risk of rebound hyperkalemia.

Introducción: la paralisis periodica tirotóxica (PPT) es una complicación poco común del hipertiroidismo, corresponde la causa más frecuente de parálisis aguda flácida del adulto. Material y métodos: se realizó un estudio observacional retrospectivo en 2 hospitales referenciales del seguro social en Lima-Perú, que incluyo a 22 pacientes (21 hombres, 1 mujer) diagnosticados con PPT durante el periodo 2014-2021. Resultados: la edad promedio al diagnóstico fue de 35.77 ± 9.6 años, todos de raza mestiza, en 82% de los pacientes el diagnostico de hipertiroidismo fue establecido a partir de esta entidad, la etiología en el 95% fue autoinmune (enfermedad de Graves-Basedow) excepto uno cuya etiología fue bocio multinodular tóxico. El evento desencadenante reportado en 54% de pacientes fue la ingesta de comida copiosa alta en carbohidratos, seguido del ejercicio (27%), el horario más frecuente de presentación fue durante la mañana ( 41% de los casos), el patrón de debilidad principal comprometió miembros inferiores(45% paraplejia, 18% paraparesia), solo 36% fue diagnosticado de PPT en su primer episodio de debilidad motora. Conclusiones: consideramos que se debe sospechar esta condición en cualquier paciente varón joven de cualquier etnia con debilidad muscular aguda, asociado a niveles séricos bajos de potasio y síntomas de tirotoxicosis, aunque su ausencia no debe descartar el diagnostico. Se debe identificar en lo posible el factor precipitante e instaurar terapia inicial con propanolol con o sin reemplazo de potasio endovenoso u oral, con monitoreo posterior adecuado que minimice el riesgo de hiperpotasemia de rebote.

Liothyronine use in primary hypothyroidism - current concepts.

Hypothyroidism is an endocrine disorder whose management raises many challenges in clinical practice. Its standard treatment is levothyroxine (LT4). The goal of the treatment is to normalize signs and symptoms, as well as to achieve thyroid-stimulating hormone (TSH) concentrations within the reference range, on an individual basis. It is known that 5-10% of hypothyroid patients remain symptomatic, despite achieving the target TSH levels, which, in turn, affects their quality of life. After ruling out other causes of non-thyroid origin for this persistence, it is suggested that these patients could benefit from the use of liothyronine (LT3), added to LT4, especially if polymorphism of the deiodinase 2 (D2) genes is documented. There exist a variety of LT3 preparations, whose concentrations vary from 5 to 50 ug, with the recommended LT4/LT3 ratio of 13:1-20:1. The goals of combination therapy should be to achieve a physiological ratio of free triiodothyronine/free thyroxine (FT3/FT4) and non-suppression of TSH. Because there is currently no guide that makes evidence-based recommendations on the use of LT3 in primary hypothyroidism, more clinical studies are needed to be able to identify hypothyroid patients who may benefit from the use of LT3, by identifying new biomarkers.

New-onset thyrotoxicosis in a patient with anaplastic thyroid carcinoma: a diagnostic challenge.

SUMMARY: Anaplastic thyroid cancer (ATC) is the type of thyroid cancer that has the worst prognosis. It usually presents as a rapidly growing cervical mass that generates compressive symptoms. Its association with thyrotoxicosis is rare. A 76-year-old woman, with no contributory history, presented with a 3-month course of fast-growing cervical tumor, associated with tenderness, cough, and weight loss. Physical examination revealed goiter, localized erythema, and a painful and stone tumor dependent on the right thyroid lobe. Due to the malignant findings of the thyroid ultrasound, the patient underwent a thyroid core needle biopsy, which indicated ATC. Laboratory tests revealed leukocytosis, decreased thyroid-stimulating hormone, elevated free thyroxine (fT4), and increased thyroperoxidase (TPO) antibodies. At the beginning, we considered that the etiology of thyrotoxicosis was secondary to subacute thyroiditis (SAT) after SARS-CoV-2 infection, due to the immunochromatography result and chest tomography findings. The result of markedly elevated TPO antibodies left this etiology more remote. Therefore, we suspected Graves' disease as an etiology; however, thyroid histopathology and ultrasound did not show compatible findings. Therefore, we suspect that the main etiology of thyrotoxicosis in the patient was the destruction of the thyroid follicles caused by a rapid invasion of malignant cells, which is responsible for the consequent release of preformed thyroid hormone. ATC is a rare endocrine neoplasm with high mortality; it may be associated with thyrotoxicosis, whose etiology can be varied; therefore, differential diagnosis is important for proper management. LEARNING POINTS: Anaplastic thyroid cancer is the thyroid cancer with the worst prognosis and the highest mortality. The association of anaplastic thyroid cancer with thyrotoxicosis is rare, and a differential diagnosis is necessary to provide adequate treatment. Due to the current pandemic, in patients with thyrotoxicosis, it is important to rule out SARS-CoV-2 as an etiology. Anaplastic thyroid cancer, due to its aggressive behavior and rapid growth, can destroy thyroid follicular cells, generating preformed thyroid hormone release, being responsible for thyrotoxicosis.

Surgical Remission of Diabetes in a Patient With Mutation of RET Proto-Oncogene.

OBJECTIVE: In pheochromocytomas, accelerated catecholamine production can cause secondary diabetes. The gene responsible for multiple endocrine neoplasia type 2 (MEN2)-related pheochromocytomas is the RET proto-oncogene. The objective of this report is to describe a unique case of surgical remission of misdiagnosed type 2 diabetes mellitus (T2DM) in a woman with bilateral pheochromocytoma and RET proto-oncogene mutation. METHODS: Clinical examination, urinary metanephrine level, triple-phase abdominal computed tomography (CT) with adrenal protocol, positron emission tomography with 18F-fluorodeoxyglucose integrated with CT, surgical pathology, and genetic testing were performed. RESULTS: A 46-year-old woman with a 5-year history of apparent T2DM complicated by neuropathy, without a contributory family history, presented with occasional headaches, weight loss, and abdominal pain. A 24-hour urinary metanephrine of 5 mg (reference range, 0.05-1 mg) was found. Abdominal CT showed bilateral adrenal masses with <60% washout. Positron emission tomography with 18F-fluorodeoxyglucose integrated with CT showed a left solid-cystic lesion with low metabolic activity and a right nodular lesion with a higher metabolic activity, which was conclusive of bilateral pheochromocytoma. The remission of diabetes was achieved 1 year after a bilateral adrenalectomy. In addition, a multinodular goiter was found, and a fine-needle aspiration biopsy confirmed that it was a medullary thyroid carcinoma. A heterozygous pathogenic variant of the RET proto-oncogene was found and MEN2A was confirmed. CONCLUSION: This is the first report of a patient with a RET proto-oncogene mutation experiencing remission of diabetes after surgical resection of bilateral pheochromocytomas. Timely recognition and treatment of the underlying condition are important to potentially achieve diabetes remission and prevent its long-term complications.

Pregnancy during the course of Cushing's syndrome: a case report and literature review.

SUMMARY: Cushing's syndrome is an endocrine disorder that causes anovulatory infertility secondary to hypercortisolism; therefore, pregnancy rarely occurs during its course. We present the case of a 24-year-old, 16-week pregnant female with a 10-month history of unintentional weight gain, dorsal gibbus, nonpruritic comedones, hirsutism and hair loss. Initial biochemical, hormonal and ultrasound investigations revealed hypokalemia, increased nocturnal cortisolemia and a right adrenal mass. The patient had persistent high blood pressure, hyperglycemia and hypercortisolemia. She was initially treated with antihypertensive medications and insulin therapy. Endogenous Cushing's syndrome was confirmed by an abdominal MRI that demonstrated a right adrenal adenoma. The patient underwent right laparoscopic adrenalectomy and anatomopathological examination revealed an adrenal adenoma with areas of oncocytic changes. Finally, antihypertensive medication was progressively reduced and glycemic control and hypokalemia reversal were achieved. Long-term therapy consisted of low-dose daily prednisone. During follow-up, despite favorable outcomes regarding the patient's Cushing's syndrome, stillbirth was confirmed at 28 weeks of pregnancy. We discuss the importance of early diagnosis and treatment of Cushing's syndrome to prevent severe maternal and fetal complications. LEARNING POINTS: Pregnancy can occur, though rarely, during the course of Cushing's syndrome. Pregnancy is a transient physiological state of hypercortisolism and it must be differentiated from Cushing's syndrome based on clinical manifestations and laboratory tests. The diagnosis of Cushing's syndrome during pregnancy may be challenging, particularly in the second and third trimesters because of the changes in the maternal hypothalamic-pituitary-adrenal axis. Pregnancy during the course of Cushing's syndrome is associated with severe maternal and fetal complications; therefore, its early diagnosis and treatment is critical.

Successful remission of type B insulin resistance syndrome without rituximab in an elderly male.

SUMMARY: Type B insulin resistance syndrome (TBIR) is a rare autoimmune disease caused by antibodies against the insulin receptor. It should be considered in patients with dysglycaemia and severe insulin resistance when other more common causes have been ruled out. We report a case of a 72-year-old male with a 4-year history of type 2 diabetes who presented with hypercatabolism, vitiligo, acanthosis nigricans, and hyperglycaemia resistant to massive doses of insulin (up to 1000 U/day). Detection of anti-insulin receptor antibodies confirmed TBIR. The patient received six pulses of methylprednisolone and daily treatment with cyclophosphamide for 6 months. Response to treatment was evident after the fourth pulse of methylprednisolone, as indicated by weight gain, decreased glycosylated haemoglobin and decreased requirement of exogenous insulin that was later discontinued due to episodes of hypoglycaemia. Remission was eventually achieved and the patient is currently asymptomatic, does not require insulin therapy, has normal glycaemia and is awaiting initiation of maintenance therapy with azathioprine. Thus, TBIR remitted without the use of rituximab. This case highlights the importance of diagnosis and treatment in a timely fashion, as well as the significance of clinical features, available laboratory findings and medication. Large controlled studies are required to standardise a therapeutic protocol, particularly in resource-constrained settings where access to rituximab is limited. LEARNING POINTS: Type B insulin resistance syndrome is a rare autoimmune disorder that should be considered in patients with dysglycaemia, severe insulin resistance and a concomitant autoimmune disease. Serological confirmation of antibodies against the insulin receptor is not necessary in all cases due to the high associated mortality without timely treatment. Although there is no standardised immunosuppressive treatment, a protocol containing rituximab, cyclophosphamide and steroids has shown a significant reduction in previously reported mortality rates. The present case, reports successful remission in an atypical patient using cyclophosphamide and methylprednisolone, which is an effective therapy in countries in which rituximab is not covered by health insurance. When there is improvement in the hypercatabolic phase, the insulin dose should be reduced and/or discontinued to prevent hypoglycaemia; a mild postprandial hyperglycaemic state should be acceptable.