Neoplasia endocrina múltiple tipo 1 en paciente con diagnóstico de nesidioblastosis. Presentación de un caso

Las neoplasias endocrinas múltiples engloban una serie de síndromes caracterizados por su origen genético y la afectación de una o más glándulas. Se describe el caso de un paciente masculino, de 23 años, con antecedentes de salud de nesidioblastosis diagnosticado a los 16 años de edad, quien acudió al Hospital General Docente Ambato por presentar convulsiones tónico clónicas, e hipoglucemia severa con posterior estatus epiléptico. Los estudios de laboratorio mostraron hiperparatiroidismo primario, y los de imagen identificaron lesiones sugerentes de adenoma paratiroideo e insulinoma de cabeza de páncreas. Después de analizar el caso, se identificaron dos criterios para plantear una neoplasia endocrina múltiple tipo 1: presencia de insulinoma e hiperparatiroidismo primario. Además de tratamiento con bifosfonato, se planificó interconsulta con el servicio de Genética, para estudio del paciente y familiares; y con Cirugía General, para programación de resolución quirúrgica. Debido a la poca frecuencia de esta enfermedad, resulta de interés describir el caso, con el objetivo de exponer las principales manifestaciones clínicas y conducta a seguir. Constituye una prioridad el diagnóstico de su causa en cada paciente.

Multiple endocrine neoplasias encompass a series of syndromes characterized by their genetic origin and the involvement of one or more glands. A 23-years-old male patient with a health history of nesidioblastosis diagnosed at 16 years of age, who attended the Ambato General Teaching Hospital with tonic-clonic seizures and severe hypoglycemia with subsequent epileptic status, is described. Laboratory studies showed primary hyperparathyroidism, and imaging identified lesions suggestive of parathyroid adenoma and insulinoma of the head of the pancreas. After analyzing the case, two criteria were identified to suggest multiple endocrine neoplasia type 1: presence of insulinoma and primary hyperparathyroidism. In addition to treatment with bisphosphonate, consultation with the Genetics service was planned for study of the patient and family members; and with General Surgery, for scheduling surgical resolution. Due to the infrequency of this disease, it is of interest to describe the case, with the aim of exposing the main clinical manifestations and conduct to follow. Diagnosing its cause in each patient is a priority.

A Rare Case of Hyperfunctioning Lipoadenoma Presenting as a Cystic Pararthyroid Lesion.

A 58-year-old woman visited the hospital complaining of fatigue and indigestion lasting for more than 3 months. She had no medical history other than taking a calcium plus vitamin D supplement for osteopenia. The initial blood test showed a high calcium level of 14.0 mg/dL. Additional tests were performed to differentially diagnose hypercalcemia. The blood test results were as follows: serum parathyroid hormone (PTH)=247.0 pg/mL, PTH-related peptide <1.0 pg/mL, phosphorous=2.6 mg/dL, 25-hydroxy-vitamin D=14.5 pg/mL, creatinine=1.09 mg/dL, and 24 hr urine calcium=215 mg/dL. A 4.5 cm sized cystic lesion on the intra-thyroidal space was confirmed on neck sonography and 4-dimensional parathyroid computed tomography, but technetium-99m methoxyisobutylisonitrile parathyroid scintigraphy showed equivocal results. After removal of the cystic lesion, serum calcium and PTH were normalized, and parathyroid lipoadenoma was confirmed in the postoperative pathology. Clinical features of parathyroid lipoadenoma are known to be similar to common parathyroid adenoma, but imaging studies often report negative findings. Therefore, it is necessary to better understand this rare disease for the differential diagnosis. For the final diagnosis and treatment of this disease, parathyroidectomy with intraoperative PTH measurement may be required.

Postoperative longitudinal changes of serum calcium level and its influencing factors in patients with primary hyperparathyroidism / 中华普通外科杂志

Objective:To compare the changes of serum calcium level before and after surgical resection in patients with primary hyperparathyroidism.Methods:Two hundred and seventy-one patients with primary hyperparathyroidism were enrolled from Dec 1992 to Dec 2020 in Beijing Jishuitan Hospital. Serum calcium concentrations were measured before operation, 20 min during surgery, then 2 weeks 1-6 months , 7-12 months and 1 year respectively after operation. The baseline data of postoperative serum calcium such as sex, age, other genetic endocrine diseases, osteopathia and urolithiasis were calculated. The generalized estimation equation was used to analyze the changes of serum calcium in different types of patients before and after operation.Results:The most common postoperative hypocalcemia occurred within 2 weeks, and it occurred frequently half a year after surgery. There was no significant difference in blood calcium between male patients ( t=0.875, P=1.000) and patients with bone lesions ( t=0.034, P=3.049) from 1 to 6 months after surgery and 2 weeks after surgery. Blood calcium level in patients aged 15-35 years old from 1 to 6 months ( t=0.239, P=1.000) , from 7 to 12 months ( t=1.380, P=0.935) and 2 weeks after surgery was not statistically different. The change of bone mineral density was correlated with the change of blood calcium after operation ( F=6.895, P=0.004). Conclusions:The incidence of hypocalcemia was the highest in patients with hyperparathyroidism 2 weeks after surgery, and the blood calcium level was stable within the normal range 1 year later. The blood calcium value of male patients was still at a lower level than that of female patients within six months after surgery. In patients with bone disease, the blood calcium value was lower and recovered slowly 2 weeks after surgery. The blood calcium value of patients aged 15-35 was at a low level within 1 year after surgery.

Update on Preoperative Parathyroid Localization in Primary Hyperparathyroidism.

Parathyroidectomy is the treatment of choice for primary hyperparathyroidism when the clinical criteria are met. Although bilateral neck exploration is traditionally the standard method for surgery, minimally invasive parathyroidectomy (MIP), or focused parathyroidectomy, has been widely accepted with comparable curative outcomes. For successful MIP, accurate preoperative localization of parathyroid lesions is essential. However, no consensus exists on the optimal approach for localization. Currently, ultrasonography and technetium-99m-sestamibi-single photon emission computed tomography/computed tomography are widely accepted in most cases. However, exact localization cannot always be achieved, especially in cases with multiglandular disease, ectopic glands, recurrent disease, and normocalcemic primary hyperparathyroidism. Therefore, new modalities for preoperative localization have been developed and evaluated. Positron emission tomography/computed tomography and parathyroid venous sampling have demonstrated improvements in sensitivity and accuracy. Both anatomical and functional information can be obtained by combining these methods. As each approach has its advantages and disadvantages, the localization study should be deliberately chosen based on each patient's clinical profile, costs, radiation exposure, and the availability of experienced experts. In this review, we summarize various methods for the localization of hyperfunctioning parathyroid tissues in primary hyperparathyroidism.

Retropharyngeal Ectopic Parathyroid Adenoma Localized by 18F-Fluorocholine Positron Emission Tomography/Computed Tomography: A Case Report.

Ectopic parathyroid adenomas of the retropharyngeal space are relatively rare. Herein, we report a case of primary hyperparathyroidism (PHPT) secondary to a retropharyngeal parathyroid adenoma. A 22-year-old woman presented with elevated serum calcium and parathyroid hormone (PTH) levels, revealed during a medical check-up. The patient had a history of ureteral stones and a confirmed low bone mass. Neck 99mTechnetium-sestamibi singlephoton emission computed tomography (CT) and ultrasonography did not reveal any suspicious lesions. There was no evidence of hereditary PHPT based on the results of targeted gene sequencing. Surgical exploration was unsuccessful, and the PHPT persisted after the first surgery. Approximately a year after the failed operation, 18F-fluorocholine (FCH) positron emission tomography/CT (PET-CT) became available, and when performed, it revealed increased uptake in the retropharyngeal space of the right side of the neck. The results of parathyroid venous sampling were concordant with a >2-fold elevation of PTH level in the veins on the right side of the neck compared to the peripheral veins. The 1.8 cm-diameter mass was successfully removed resulting in an 87% reduction in intraoperative PTH level (198.0-26.5 pg/mL). Subsequently, normalizations of calcium and PTH levels were achieved. In summary, ectopic parathyroid adenomas, including retropharyngeal lesions, should also be suspected when investigating an elusive case of PHPT. 18F-FCH PET-CT can be a useful complementary modality for detecting culprit lesions.

Manejo quirúrgico del hiperparatiroidismo primario con pruebas de localización prequirúrgicas negativas / Surgical management of primary hyperparathyroidism with negative preoperative imaging workup

Introducción y objetivo: Una vez realizado el diagnóstico de hiperparatiroidismo primario (HPTp), el único tratamiento curativo posible es la paratiroidectomía. Puede llevarse a cabo mediante una exploración cervical bilateral o por medio de una paratiroidectomía mínimamente invasiva (MIP), en la que exclusivamente se explora el compartimento cervical en el que se encuentra la glándula paratiroides sospechosa de causar el HPTp. Los resultados de ambas técnicas son comparables, existiendo una mayor tendencia a realizar MIP cuando en las pruebas de localización de imagen se localiza correctamente la glándula afecta. En el caso de que las pruebas de localización resulten negativas o discordantes el tipo de abordaje quirúrgico es controvertido. Método: Se realizó una revisión sistemática de artículos originales, guías, y documentos de sociedades científicas dedicadas al manejo del hiperparatiroidismo primario que incluían casos con pruebas de localización contradictorias o negativas. Se localizaron 211 estudios y finalmente se seleccionaron 2 revisiones sistemáticas, 20 estudios originales y 4 guías de recomendaciones de sociedades profesionales.Discusión: La recomendación formal de las guías es realizar una BNE en los casos de pruebas de localización negativa. En el resto de la literatura revisada se observó una tendencia creciente de los cirujanos a solicitar pruebas de localización complementarias para intentar una MIP, aunque la mayoría seguían la recomendación de las guías. Algunos autores han reportado tasas de éxito de MIP con medición intraoperatoria de PTH similares a los obtenidos con BNE. Técnicas como el PET-TC con 18F-fluorocolina o 11C-colina, la cirugía radioguiada con gammacámara y la medición intraoperatoria de PTH, son de especial utilidad en el estudio prequirúrgico y como apoyo durante la cirugía de casos con pruebas de localización negativas. (AU)

Introduction and objective: Once the diagnosis of primary hyperparathyroidism (pHPT) is made, the only curative treatment available is parathyroidectomy. This can be achieved by a bilateral neck exploration or through a minimally invasive parathyroidectomy, in which the only neck compartment explored is the one suspected of having the parathyroid gland causing the pHPT. The results of both techniques are equivalent. However, there is a growing tendency to choose MIP when imaging studies correctly localize the affected gland. When imaging studies are negative or discordant, surgical management causes some controversies. Method: We performed a systematic review of original articles, guidelines and scientific socie-ties documents related to the management of primary hyperparathyroidism with contradictory or negative preoperative localization. We found 211 studies, and selected 2 systematic reviews, 20 original articles and 4 guidelines. Discussion: Guidelines recommend performing a BNE when preoperative localization fails. In the reviewed literature we observed a growing tendency of requesting further imaging studies to perform a MIP, although the majority of surgeons follow the guidelines. MIP + intraoperative PTH monitoring has been reported to have similar success rates as BNE. Some techniques like 18F-Fluorocloline or 11C-coline PET-TC, radioguided surgery with intraoperative gamma camera and intraoperative PTH monitoring, are especially useful in the preoperative workup and as support during surgery when localizing imaging tests result negative. (AU)

Clinical features and signaling effects of RET D631Y variant multiple endocrine neoplasia type 2 (MEN2).

BACKGROUND/AIMS: Germline mutations of the rearranged during transfection (RET) gene cause multiple endocrine neoplasia type 2 (MEN2). About 85% of RET mutations in MEN2 occur in codon Cys634. The RET D631Y mutation has recently been discovered, and we have studied its molecular expression and clinical consequences. METHODS: We analyzed the clinical characteristics of a total of 34 D631Y variant MEN2 individuals from seven families. We also constructed wild-type and mutant C630Y, D631Y, and C634R/W expression vectors and investigated their effects on signaling pathways and ability to correct the phenotypes of RET mutant cells. RESULTS: The median ages at diagnosis of pheochromocytoma and medullary thyroid carcinoma (MTC) were higher in patients with RET D631Y variant MEN2 than in those with the C634R/W variant (49:53.5 years vs. 33.5:27 years, respectively), and the penetration of the D631Y mutation with respect to MTC was lower than that of the C634R/W mutation (32.3% vs. 90%). The effects of the mutant vectors on phosphorylation of RET signaling molecules and focus formation were significantly different from those of wild type, but there were no significant differences between the mutants. D631Y scored significantly higher for chemotaxis and wound healing than C630Y, but lower than C634R and C634W. CONCLUSION: We suggest that the tumorigenic potential conferred by the D631Y mutation is lower than that conferred by the C634R/W mutation, but higher than that conferred by C630Y. Thus, the risk level of the RET D631Y variant appears to be higher than that of C630Y and lower than that of C634R/W.

Familial hypocalciuric hypercalcemia as a differential diagnosis of primary hyperparathyroidism with negative images / Hipercalcemia hipocalciúrica familiar como diagnóstico diferencial de hiperparatiroidismo primario con imágenes negativas / Hipercalcemia hipocalciúrica familiar como diagnóstico diferencial de hiperparatireoidismo primário com imagens negativas

Introduction. Familial hypocalciuric hypercalcemia is a rare inherited calcium metabolism disorder in which an alteration of the parathyroid hormone secretion set-point causes hypercalcemia with relative hypocalciuria. Some data suggest that its prevalence is around 74.1 per 100,000 inhabitants. Often, patients are asymptomatic. However, they can develop mild symptoms and an overactive parathyroid adenoma, its main differential diagnosis. The objective was to describe a patient's case and highlight the importance of clinical suspicion and diagnosis to avoid unnecessary surgical neck explorations for parathyroid adenomas. Case report. This is the case of a 40-year-old man with a biochemical profile compatible with primary hyperparathyroidism with anatomical and functional images negative for adenoma and a calcium/creatinine clearance ratio below 0.001, considering familial hypocalciuric hypercalcemia. Genetic studies evidence a mutation in the calcium sensor receptor gene and confirm the diagnosis. Discussion. Familial hypocalciuric hypercalcemia's main differential diagnosis is an overactive parathyroid adenoma. For both, mild or no symptoms may be present; serum calcium exceeds the upper limit, and parathormone is more than 25pg/ml. The calcium/creatinine clearance ratio should be used to differentiate one from the other and avoid unnecessary surgical neck explorations. Besides the lack of information on this topic, evidence supports the use of calcimimetics to treat symptomatic hypercalcemia. Conclusions. Patients with mild hypercalcemia with parathyroid hormone readings above 25pg/ml and a calcium/creatinine clearance ratio below 0.001, or patients with primary hyperparathyroidism with negative imaging, should not undergo surgical neck explorations. In these cases, familial hypocalciuric hypercalcemia is a reliable diagnosis; Cinacalcet may be administered in cases of symptomatic hypercalcemia.

Introducción. La hipercalcemia hipocalciúrica familiar es un trastorno hereditario poco común del metabolismo del calcio en donde una alteración del punto de ajuste de la secreción de hormona paratiroidea ocasiona hipercalcemia con hipocalciuria relativa. Algunos datos sugieren que su prevalencia es de alrededor de 74.1 por 100,000 habitantes. Los pacientes muchas veces son asintomáticos. Sin embargo, pueden desarrollar síntomas leves y un adenoma paratiroideo hiperactivo, que representa su principal diagnóstico diferencial. El objetivo fue describir el caso de un paciente y resaltar la importancia de la sospecha y el diagnóstico clínico para evitar exploraciones quirúrgicas cervicales innecesarias en búsqueda de adenomas paratiroideos. Reporte de caso. Este es el caso de un hombre de 40 años con un perfil bioquímico compatible con hiperparatiroidismo primario, con imágenes anatómicas y funcionales negativas para adenoma, además de una relación de depuración de calcio/creatinina menor a 0.001, con consideración de hipercalcemia hipocalciúrica familiar. Los estudios genéticos evidencian una mutación en el gen del receptor sensor del calcio y confirman el diagnóstico. Discusión. El principal diagnóstico diferencial de la hipercalcemia hipocalciúrica familiar es un adenoma paratiroideo hiperactivo. En ambos casos, es posible que no haya síntomas o que estos sean leves; el calcio sérico excede al límite superior, y la paratohormona es mayor de 25pg/ml. Se debe usar la relación de depuración de calcio/creatinina para diferenciar entre estas patologías y evitar exploraciones quirúrgicas cervicales innecesarias. Aparte de la falta de información sobre este tema, la evidencia apoya el uso de calciomiméticos para tratar la hipercalcemia sintomática. Conclusiones. Los pacientes con hipercalcemia leve, con valores de hormona paratiroidea mayores de 25pg/ml y con una relación de depuración de calcio/creatinina menor de 0.001, o los pacientes con hiperparatiroidismo primario con imágenes negativas, no deben ser sometidos a exploraciones quirúrgicas cervicales. En estos casos, la hipercalcemia hipocalciúrica familiar representa un diagnóstico confiable; se puede administrar Cinacalcet en casos de hipercalcemia sintomática.

Introdução. A hipercalcemia hipocalciúrica familiar é um distúrbio hereditário raro do metabolismo do cálcio, no qual uma alteração no ponto de ajuste da secreção do hormônio da paratireóide causa hipercalcemia com hipocalciúria relativa. Alguns dados sugerem que sua prevalência gira em torno de 74.1 por 100,000 habitantes. Os pacientes geralmente são assintomáticos. No entanto, eles podem desenvolver sintomas leves e um adenoma de paratireoide hiperativo, que representa seu principal diagnóstico diferencial. O objetivo foi descrever o caso de um paciente e destacar a importância da suspeita clínica e do diagnóstico para evitar exploração cirúrgica cervical desnecessária em busca de adenomas de paratireoide. Relato de caso. É o caso de um homem de 40 anos com perfil bioquímico compatível com hiperparatireoidismo primário, com imagens anatômicas e funcionais negativas para adenoma, além de relação depuração de cálcio/creatinina menor que 0.001, considerando hipercalcemia hipocalciúrica familiar. Estudos genéticos revelam uma mutação no gene receptor da sensibilidade ao cálcio e confirmam o diagnóstico. Discussão. O principal diagnóstico diferencial da hipercalcemia hipocalciúrica familiar é um adenoma de paratireoide hiperativo. Em ambos os casos, os sintomas podem estar ausentes ou leves; o cálcio sérico excede o limite superior e o hormônio da paratireóide é superior a 25pg/ml. A relação depuração de cálcio/creatinina deve ser usada para diferenciar entre essas patologias e evitar exploração cirúrgica cervical desnecessária. Além da falta de informações sobre esta questão, as evidências apoiam o uso de calcimiméticos para tratar a hipercalcemia sintomática. Conclusões. Pacientes com hipercalcemia leve, com valores de hormônio da paratireóide maiores que 25pg/ml e uma relação de depuração de cálcio/creatinina menor que 0.001, ou pacientes com hiperparatireoidismo primário com imagens negativas, não devem ser submetidos a exploração cirúrgica cervical. Nesses casos, a hipercalcemia hipocalciúrica familiar representa um diagnóstico confiável; Cinacalcet pode ser administrado em casos de hipercalcemia sintomática.

Tibial brown tumor as a presentation of primary hyperparathyroidism / [Tumor pardo tibial como forma de presentación de un hiperparatiroidismo primario]

Cystic fibrous osteitis is a complication of a very evolved hyperparathyroidism. Because the determination of calcium, parathyroid hormone and vitamin D have become routine studies, this bone complication is uncommon in western countries. However, it should be considered in the differential diagnosis of hypercalcemia and lytic bone lesions. The treatment is to suppress the excess parathyroid hormone by parathyroidectomy and osteosynthesis in pathological fracture. We present the case of a female patient with primary hyperparathyroidism and a brown tumor in the right tibia.

La osteítis fibrosa quística es la complicación de un hiperparatiroidismo muy evolucionado. Debido a que la determinación del calcio, hormona paratiroides y vitamina D han pasado a ser estudios rutinarios, esta complicación ósea es infrecuente en los países occidentales. Sin embargo, debe ser considerada en el diagnóstico diferencial de hipercalcemia y lesiones óseas líticas. El tratamiento de esta entidad va dirigido a suprimir el exceso de hormona paratiroides mediante la paratiroidectomia y osteosíntesis en los casos de fracturas patológicas. Se presenta el caso de una paciente con hiperparatiroidismo primario y un tumor pardo en la tibia derecha.

Radioactive Parathyroid Adenomas on Sestamibi Scans: Low Parathyroid Hormone Secretory Potential and Large Volume.

BACKGROUND: We investigated the clinical characteristics of parathyroid adenomas according to radioactivity on 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) single-photon emission computed tomography/computed tomography (SPECT/CT) in primary hyperparathyroidism (PHPT) patients. METHODS: The study included 217 patients diagnosed with PHPT from 2000 to 2019 at Seoul National University Hospital who underwent 99mTc-MIBI SPECT/CT scans. On SPECT/CT, the radioactivity of parathyroid adenomas was measured as the ratio of the mean radioactivity count of the parathyroid adenoma to that of the contralateral thyroid. RESULTS: Tumors were localized by MIBI scans in 190 patients (MIBI [+] group) and by ultrasound or parathyroid four-dimensional CT in 27 patients (MIBI [-] group). The mean age was 55 years, and mean body mass index was 23.4 kg/m2. Patients in the MIBI (+) group had higher parathyroid hormone (iPTH) and lower 25-hydroxy vitamin D levels than those in the MIBI (-) group (168.0 pg/mL [interquartile range, IQR, 111.0 to 250.7] vs. 134.7 pg/mL [IQR, 98.2 to 191.2], P=0.049; 15.4 ng/mL [IQR, 11.1 to 20.8] vs. 21.2 ng/mL [IQR, 13.9 to 24.8], P=0.012, respectively). Patients in the MIBI (+) group had larger tumor volumes, but lower iPTH/volume ratios than those in the MIBI (-) group (1,216.66 [IQR, 513.40 to 2,663.02], 499.82 mm3 [IQR, 167.77 to 1,229.80], P=0.002; 0.18 [IQR, 0.08 to 0.46], 0.40 pg/mL/mm3 [IQR, 0.16 to 1.29], P=0.016, respectively). Adenoma radioactivity was positively correlated with calcium, iPTH, and volume (r=0.180, P=0.020; r=0.208, P=0.006; r=0.288, P<0.001, respectively), but not with iPTH/volume. CONCLUSION: Parathyroid adenomas with positive MIBI scans had larger volumes and higher iPTH than adenomas with negative scans, but lower iPTH per unit volume.

Hiperparatiroidismo primario por adenoma gigante de paratiroides. Abordaje quirúrgico selectivo / Primary hyperparathyroidism caused by giant parathyroid adenoma. Selective surgical approach / Hiperparatireoidismo primário devido a um adenoma gigante da paratireoide. Abordagem cirúrgica seletiva

Resumen: Introducción: el hiperparatiroidismo primario por un adenoma gigante de paratiroides es infrecuente. Los adenomas de mayor tamaño reportados ocurrieron sobre paratiroides ectópicas (mediastinales). Comparte con el carcinoma su gran tamaño y elevadas cifras de calcemia y de hormona paratiroidea, hecho que dificulta el diagnóstico. Su tratamiento quirúrgico es la paratiroidectomía mediante una cervicotomía transversa centrada en la región infrahioidea. Objetivo: presentar un caso clínico de hiperparatiroidismo primario por un adenoma gigante de paratiroides tratado quirúrgicamente mediante un abordaje selectivo. Caso clínico: paciente de 53 años, sexo femenino, con antecedentes de litiasis ureteral, dolores óseos y tumoración infrahiodea de 4 cm de diámetro que imagenológicamente presentó las características de un adenoma paratiroideo inferior izquierdo. La valoración funcional confirmó hiperparatiroidismo. Con diagnóstico de hiperparatiroidismo primario por adenoma gigante se trató quirúrgicamente a través de una incisión pequeña y centrada en la tumoración, realizándose la paratiroidectomía inferior izquierda con la cual remitió la sintomatología y normalizó la funcionalidad paratiroidea. Discusión: el hiperparatiroidismo primario por adenoma gigante de paratiroides tiene indicación quirúrgica y es curativo. El caso presentado demuestra la factibilidad y seguridad de un abordaje selectivo a lo que suma una menor afectación cosmética, dejando indemne la logia tiroidea contralateral ante futuras cirugías sobre ésta.

Summary: Introduction: primary hyperparathyroidism caused by giant parathyroid adenoma is a rather unusual condition. Reported large adenomas occurred in ectopic parathyroid glands (mediastinal). Just like carcinomas, they are large, present high calcemia and parathyroid hormone values, what complicates diagnosis. Surgical treatment consists in parathyroidectomy by means of transversal cervicotomy around the infrahyoid region. Objective: the study presents the clinical case of primary hyperparathyroidism caused by giant parathyroid adenoma that was treated by selective surgery approach. Clinical case: 53 year-old female patient with a history of uretheral lithiasis, bone pain and 4-cm-diameter infrahyoid tumor. Imagenology studies revealed the characteristics of lower left parathyroid adenoma. Functional assessment confirmed hyperparathyroidism. Upon the diagnosis of primary hyperparathyroidism caused by giant parathyroid adenoma it was surgically addressed by means of a small cut around the tumour and performing a lower left parathyroidectomy, what resulted in the remission of symptoms and normalized parathyroid functionality. Discussion: primary hyperparathyroidism caused by giant parathyroid adenoma has an indication for surgery and is therapeutic. The case presented shows the feasibility and safety of a selective approach, as well as its smaller cosmetic harm, managing to keep the contralateral thyroid loggia intact, in view of future surgeries involving it.

Resumo: Introdução: o hiperparatireoidismo primário devido a adenoma de paratireoide gigante é raro. Os maiores adenomas relatados ocorreram em paratireoides ectópicas (mediastinais). Compartilha com o carcinoma seu grande tamanho e altos níveis de cálcio e hormônio da paratireoide, o que torna o diagnóstico difícil. Seu tratamento cirúrgico é a paratireoidectomia por meio de cervicotomia transversa com foco na região infra-hióidea. Objetivo: apresentar um caso clínico de hiperparatireoidismo primário por adenoma gigante da paratireoide tratado cirurgicamente por abordagem seletiva. Caso clínico: paciente do sexo feminino, 53 anos, com história de litíase ureteral, dor óssea e tumor infra-hióideo de 4 cm de diâmetro que apresentava características de imagem de adenoma de paratireoide inferior esquerdo. A avaliação funcional confirmou hiperparatireoidismo. Com diagnóstico de hiperparatireoidismo primário por adenoma gigante, foi tratada cirurgicamente por meio de pequena incisão focada no tumor, realizando paratireoidectomia inferior esquerda com remissão dos sintomas e normalização da funcionalidade da paratireoide. Discussão: o hiperparatireoidismo primário devido ao adenoma gigante da paratireoide tem indicação cirúrgica e é curativo. O caso apresentado demonstra a viabilidade e segurança de uma abordagem seletiva que apresenta um menor envolvimento estético, deixando o espaço contralateral da tireoide sem danos para futuras cirurgias.

Value of ultrasonography, radionuclide imaging and CT in preoperative location diagnosis of primary hyperparathyroidism / 中华普通外科杂志

Objectiv:To evaluate ultrasound, radionuclide imaging and CT in preoperative localization diagnosis of primary hyperparathyroidism (PHPT).Method:A total of 170 PHPT patients admitted to the hospital between Jan 1992 and Dec 2020 were analyzed retrospectively. The preoperative localization diagnostic efficacy of ultrasonography, radionuclide and CT alone and in combination was compared in groups.Results:The overall sensitivity of ultrasound, radionuclide and CT were 82.13%,80.43% and 75.74%. For normal positioned parathyroid adenoma: as for sensitivity of location diagnosis, ultrasound (86.67%) was higher than radionuclide (81.82%, P<0.05) and CT (80.59%, P<0.05), ultrasound/CT parallel test (94.70%, P<0.05) was higher than ultrasound alone. For specificity of location diagnosis, radionuclide (97.78%) was higher than ultrasound (91.62%) and CT (93.39%), both ultrasound/radionuclide series tests (99.00%, P<0.001)and ultrasound/CT series tests (96.94%, P<0.001) were higher than ultrasound alone. In case of ectopic parathyroid adenoma and parathyroid hyperplasia: the sensitivity and specificity of radionuclide seemed higher than ultrasound and CT. Conclusions:Ultrasound is the first choice for preoperative location diagnosis of PHPT. Ultrasound combined with radionuclide or CT can significantly improve the diagnostic efficiency of parathyroid lesions.

Association of Hyperparathyroidism and Papillary Thyroid Cancer: A Multicenter Retrospective Study.

BACKGROUND: Concomitant papillary thyroid cancer (PTC) and hyperparathyroidism (HPT) have been reported in several studies. Our study aimed to investigate the incidence of concomitant PTC in HPT patients upon preoperative diagnosis and present a clinical opinion on detecting thyroid malignancy in case of parathyroidectomy. METHODS: Patients who underwent parathyroidectomy between January 2009 and December 2019 in two medical centers were included. Of the 279 participants 154 were diagnosed as primary hyperparathyroidism (pHPT) and 125 as secondary hyperparathyroidism (sHPT). The incidence of concomitant PTC and its clinical characteristics were compared with 98 patients who underwent thyroidectomy and were diagnosed with classical PTC during the same period. RESULTS: Concurrent PTC was detected in 14 patients (9.1%) with pHPT and in nine patients (7.2%) with sHPT. Ten (71.4%) and seven (77.8%) PTCs were microcarcinomas in the pHPT and sHPT cases respectively. In the pHPT patients, vitamin D was lower in the pHPT+PTC group (13.0±3.7 ng/mL) than in the pHPT-only group (18.5±10.4 ng/mL; P=0.01). Vitamin D levels were also lower in the sHPT+PTC group (12.3±5.6 ng/mL) than in the sHPT-only group (18.0±10.2 ng/mL; P=0.12). In the concomitant PTC group, lymph node ratio was higher than in the classical PTC group (P=0.00). CONCLUSION: A high prevalence of concomitant PTC was seen in patients with pHPT and sHPT. Those concomitant PTCs were mostly microcarcinomas and had more aggressive features, suggesting that efforts should be made to detect concomitant malignancies in the preoperative parathyroidectomy evaluation.

[Diagnostic value of 4-dimensional computed tomography in preoperative localization in patients with primary hyperparathyroidism].

Objective: To provide more options for preoperative localization diagnosis in patients with primary hyperparathyroidism (PHPT), the diagnostic efficacy of parathyroid 4-dimensional computed tomography (4D-CT) in patients with PHPT was evaluated. Methods: This was a single-center retrospective study including 57 patients with surgical proved PHPT. All of the patients underwent 4D-CT, 99Tcm -sestamibi parathyroid imaging (MIBI), and ultrasonography (US) preoperatively. The reference standard for correct localization was based on operation reports and pathology confirmation. The patients were grouped according to the preoperative serum calcium levels, tumor diameter, or ectopic lesions (yes/no), respectively. The sensitivity, specificity, positive predictive value, negative predictive value and area under the curve (AUC) of 4D-CT, MIBI and US, alone or in combination, were analyzed in total and each subgroup patients. Results: Fifty-seven patients (39 women, 18 men; mean age of 56.5 years) were evaluated, including four cases with multi-gland disease and thirteen cases with ectopic parathyroid lesions. In all the patients, similar diagnostic efficacy was found in 4D-CT (AUC: 0.943) and MIBI (AUC: 0.927), both of which were higher than that of US (AUC: 0.847) (P = 0.01 for 4D-CT vs. US; P = 0.04 for MIBI vs. US). In a subset analysis for ectopic quadrants, the diagnostic efficacy of 4D-CT was significantly higher than that of MIBI (P = 0.04) or US (P = 0.01), with the sensitivity of 100%, 69.2%, and 61.5%, and AUC of 0.989, 0.846, and 0.808 for 4D-CT, MIBI and US, respectively. Conclusions: 4D-CT has similar diagnostic efficacy for preoperative localization to MIBI in patients with PHPT, and it is superior to MIBI and US in identifying the ectopic parathyroid gland. 4D-CT can be recommended as an alternative preoperative localization method, especially when parathyroid lesions could not be precisely located by US and MIBI.

Myositis, rhabdomyolysis and severe hypercalcaemia in a body builder.

SUMMARY: A 53-year-old man who used growth hormone (GH), anabolic steroids and testosterone (T) for over 20 years presented with severe constipation and hypercalcaemia. He had benign prostatic hyperplasia and renal stones but no significant family history. Investigations showed - (1) corrected calcium (reference range) 3.66 mmol/L (2.2-2.6), phosphate 1.39 mmol/L (0.80-1.50), and PTH 2 pmol/L (1.6-7.2); (2) urea 21.9 mmol/L (2.5-7.8), creatinine 319 mmol/L (58-110), eGFR 18 mL/min (>90), and urine analysis (protein 4+, glucose 4+, red cells 2+); (3) creatine kinase 7952 U/L (40-320), positive anti Jo-1, and Ro-52 antibodies; (4) vitamin D 46 nmol/L (30-50), vitamin D3 29 pmol/L (55-139), vitamin A 4.65 mmol/L (1.10-2.60), and normal protein electrophoresis; (5) normal CT thorax, abdomen and pelvis and MRI of muscles showed 'inflammation', myositis and calcification; (6) biopsy of thigh muscles showed active myositis, chronic myopathic changes and mineral deposition and of the kidneys showed positive CD3 and CD45, focal segmental glomerulosclerosis and hypercalcaemic tubular changes; and (7) echocardiography showed left ventricular hypertrophy (likely medications and myositis contributing), aortic stenosis and an ejection fraction of 44%, and MRI confirmed these with possible right coronary artery disease. Hypercalcaemia was possibly multifactorial - (1) calcium release following myositis, rhabdomyolysis and acute kidney injury; (2) possible primary hyperparathyroidism (a low but detectable PTH); and (3) hypervitaminosis A. He was hydrated and given pamidronate, mycophenolate and prednisolone. Following initial biochemical and clinical improvement, he had multiple subsequent admissions for hypercalcaemia and renal deterioration. He continued taking GH and T despite counselling but died suddenly of a myocardial infarction. LEARNING POINTS: The differential diagnosis of hypercalcaemia is sometimes a challenge. Diagnosis may require multidisciplinary expertise and multiple and invasive investigations. There may be several disparate causes for hypercalcaemia, although one usually predominates. Maintaining 'body image' even with the use of harmful drugs may be an overpowering emotion despite counselling about their dangers.

Brown tumor of the iliac crest initially misdiagnosed as a giant cell tumor of the bone.

SUMMARY: Brown tumors (BTs) are expansile osteolytic lesions complicating severe primary hyperparathyroidism (PHPT). Clinical, radiological and histological features of BTs share many similarities with other giant cell-containing lesions of the bone, which can make their diagnosis challenging. We report the case of a 32-year-old man in whom an aggressive osteolytic lesion of the iliac crest was initially diagnosed as a giant cell tumor by biopsy. The patient was scheduled for surgical curettage, with a course of neoadjuvant denosumab. Routine biochemical workup prior to denosumab administration incidentally revealed high serum calcium levels. The patient was diagnosed with PHPT and a parathyroid adenoma was identified. In light of these findings, histological slices of the iliac lesion were reviewed and diagnosis of a BT was confirmed. Follow-up CT-scans performed 2 and 7 months after parathyroidectomy showed regression and re-ossification of the bone lesion. The aim of this case report is to underline the importance of distinguishing BTs from other giant cell-containing lesions of the bone and to highlight the relevance of measuring serum calcium as part of the initial evaluation of osteolytic bone lesions. This can have a major impact on patients' management and can prevent unnecessary invasive surgical interventions. LEARNING POINTS: Although rare, brown tumors should always be considered in the differential diagnosis of osteolytic giant cell-containing bone lesions. Among giant cell-containing lesions of the bone, the main differential diagnoses of brown tumors are giant cell tumors and aneurysmal bone cysts. Clinical, radiological and histological characteristics can be non-discriminating between brown tumors and giant cell tumors. One of the best ways to distinguish these two diagnoses appears to be through biochemical workup. Differentiating brown tumors from giant cell tumors and aneurysmal bone cysts is crucial in order to ensure better patient care and prevent unnecessary morbid surgical interventions.

When primary hyperparathyroidism comes as good news.

SUMMARY: Brown tumors are osteoclastic, benign lesions characterized by fibrotic stroma, intense vascularization and multinucleated giant cells. They are the terminal expression of the bone remodelling process occurring in advanced hyperparathyroidism. Nowadays, due to earlier diagnosis, primary hyperparathyroidism keeps few of the classical manifestations and brown tumors are definitely unexpected. Thus, it may happen that they are misdiagnosed as primary or metastatic bone cancer. Besides bone imaging, endocrine evaluation including measurement of serum parathyroid hormone and calcium (Ca) levels supports the pathologist to address the diagnosis. Herein, a case of multiple large brown tumors misdiagnosed as a non-treatable osteosarcoma is described, with special regards to diagnostic work-up. After selective parathyroidectomy, treatment with denosumab was initiated and a regular follow-up was established. The central role of multidisciplinary approach involving pathologist, endocrinologist and oncologist in the diagnostic and therapeutic work-up is reported. In our opinion, the discussion of this case would be functional especially for clinicians and pathologists not used to the differential diagnosis in uncommon bone disorders. LEARNING POINTS: Brown tumors develop during the remodelling process of bone in advanced and long-lasting primary or secondary hyperparathyroidism. Although rare, they should be considered during the challenging diagnostic work-up of giant cell lesions. Coexistence of high parathyroid hormone levels and hypercalcemia in primary hyperparathyroidism is crucial for the diagnosis. A detailed imaging study includes bone X-ray, bone scintiscan and total body CT; to rule out bone malignancy, evaluation of bone lesion biopsy should include immunostaining for neoplastic markers as H3G34W and Ki67 index. If primary hyperparathyroidism is confirmed, selective parathyroidectomy is the first-line treatment. In advanced bone disease, treatment with denosumab should be considered, ensuring a strict control of Ca levels.

Impact of Perinatal Primary Hyperparathyroidism on Maternal and Fetal and Neonatal Outcomes: Retrospective Case Series.

OBJECTIVE: We sought to describe the maternal, fetal, and neonatal outcomes of primary hyperparathyroidism in a contemporary setting through a retrospective case series conducted in a tertiary referral centre focused on women diagnosed with primary hyperparathyroidism prior to conception, in the antepartum period, or within 6 weeks postpartum. METHODS: A retrospective chart review was conducted and data were abstracted to case report forms. Summary statistics are reported. RESULTS: From 2000 to 2017, 19 women (23 pregnancies) with primary hyperparathyroidism were identified. Most women (79%) were symptomatic at presentation, though often with non-specific manifestations. While 14% of pregnancies involved maternal/obstetric complications, fetal/neonatal complications were observed in 45%. Mild hypercalcemia was identified in 57% of women, with accompanying hypophosphatemia and hypomagnesemia in 46% and 36% of women, respectively. Surgical intervention was performed for 89% women, and no complications were encountered. Normal calcium levels achieved through treatment before conception did not fully eliminate adverse outcomes. CONCLUSION: Rates of perinatal complications in our series are more reassuring than the ubiquitously quoted rates from small and dated studies. The diagnosis of primary hyperparathyroidism may be easily missed during pregnancy, owing to its non-specific presentation. A high index of suspicion and measurement of ionized calcium levels is encouraged, especially for patients with excessive nausea and vomiting, nephrolithiasis, atypical presentations of hypertensive disorders, or isolated polyhydramnios. Mild degrees of calcium derangement do not preclude adverse perinatal outcomes. Surgery appears to be safe, even in the third trimester. The attenuated rate of complications noted in our series may have been the result of the high proportion of surgery, though this will require verification via meta-analysis or future prospective work.

18F-FDOPA PET/CT accurately identifies MEN1-associated pheochromocytoma.

SUMMARY: Pheochromocytoma (PHEO) in multiple endocrine neoplasia type 1 (MEN1) is extremely rare. The incidence is reported as less than 2%. We report a case of a 76-year-old male with familial MEN1 who was found to have unilateral PHEO. Although the patient was normotensive and asymptomatic, routine screening imaging with CT demonstrated bilateral adrenal masses. The left adrenal mass grew from 2.5 to 3.9 cm over 4 years with attenuation values of 9 Hounsfield units (HU) pre-contrast and 15 HU post-contrast washout. Laboratory evaluation demonstrated an adrenergic biochemical phenotype. Both 18F-fluorodeoxyglucose (18F-FDG) PET/CT and 123I-metaiodobenzylguanidine (123I-mIBG) scintigraphy demonstrated bilateral adrenal uptake. In contrast, 18F-fluorodihydroxyphenylalanine (18F-FDOPA) PET/CT demonstrated unilateral left adrenal uptake (28.7 standardized uptake value (SUV)) and physiologic right adrenal uptake. The patient underwent an uneventful left adrenalectomy with pathology consistent for PHEO. Post-operatively, he had biochemical normalization. A review of the literature suggests that adrenal tumors >2 cm may be at higher risk for pheochromocytoma in patients with MEN1. Despite a lack of symptoms related to catecholamine excess, enlarging adrenal nodules should be biochemically screened for PHEO. 18F-FDOPA PET/CT may be beneficial for localization in these patients. LEARNING POINTS: 18F-FDOPA PET/CT is a beneficial imaging modality for identifying pheochromocytoma in MEN1 patients. Adrenal adenomas should undergo routine biochemical workup for PHEO in MEN1 and can have serious peri-operative complications if not recognized, given that MEN1 patients undergo frequent surgical interventions. MEN1 is implicated in the tumorigenesis of PHEO in this patient.

Intraoperative Parathyroid Hormone Monitoring in the Surgical Management of Sporadic Primary Hyperparathyroidism.

Intraoperative parathyroid hormone monitoring (IPM) has been shown to be a useful adjunct during parathyroidectomy to ensure operative success at many specialized medical centers worldwide. Using the Miami or ">50% intraoperative PTH drop" criterion, IPM confirms the complete excision of all hyperfunctioning parathyroid tissue before the operation is finished, and helps guide the surgeon to identify additional hyperfunctioning parathyroid glands that may necessitate further extensive neck exploration when intraoperative parathyroid hormone (PTH) levels do not drop sufficiently. The intraoperative PTH assay is also used to differentiate parathyroid from non-parathyroid tissues during operations using fine needle aspiration samples and to lateralize the side of the neck harboring the hypersecreting parathyroid through differential jugular venous sampling when preoperative localization studies are negative or equivocal. The use of IPM underscores the recognition and understanding of sporadic primary hyperparathyroidism (SPHPT) as a disease of function rather than form, where the surgeon is better equipped to treat such patients with quantitative instead of qualitative information for durable long-term operative success. There has been a significant paradigm shift over the last 2 decades from conventional to focused parathyroidectomy guided by IPM. This approach has proven to be a safe and rapid operation requiring minimal dissection performed in an ambulatory setting for the treatment of SPHPT.