Nursing care during management of recurrent pheochromocytoma: A case study.

BACKGROUND: Pheochromocytoma can occur in patients with multiple endocrine neoplasia type 2, placing them at increased risk of tumour recurrence after surgical resection. Therefore, management of pheochromocytoma in these patients is a clinical challenge. AIMS: We aim to present and discuss the nursing management of patient with recurrent pheochromocytoma. STUDY DESIGN: Case studies. We reviewed and retrieved the necessary information from the medical records. RESULTS: A 34-year-old female with a history of medullary thyroid carcinoma and pheochromocytoma complicated by cardiomyopathy, who had undergone surgical resections 6 years ago, presented with abdominal pain for 1 day and was diagnosed with recurrent bilateral pheochromocytoma, hypertensive crisis, acute heart failure, and acute renal failure. Eight hours after hospital admission, she experienced sudden cardiac arrest and received cardiopulmonary resuscitations. She was then supported under extracorporeal membrane oxygenation and continuous renal replacement therapy (CRRT). The adrenal tumour was successfully treated with absolute ethanol ablation followed by gelatin sponge particle embolization, a management approach which has not been reported previously. She had a satisfactory recovery. CONCLUSIONS: A comprehensive nursing management approach, including prone ventilation; safe transportation; close cardiopulmonary monitoring; pre-, intra- and post-procedure care; individualized early rehabilitation; and psychological supports, should be applied to improve the prognoses in patients with similar medical conditions. RELEVANCE TO CLINICAL PRACTICE: Bilateral adrenal pheochromocytoma can be managed by absolute ethanol ablation followed by gelatin sponge particle embolization. Comprehensive nursing management, including a team effort regarding patient positioning, transportation, close monitoring, early rehabilitation and psychological support, should be provided during the peri-procedure period.

Multiple endocrine neoplasia type 2B (MEN2B) diagnosis: a case report.

Background: Multiple endocrine neoplasia type 2B (MEN2B) is a rare autosomal dominant syndrome characterized by medullary carcinoma of the early thyroid, pheochromocytoma, and non-endocrine manifestations, such as marfanoid habits and other skeletal abnormalities as well as mucosal neuromas and ganglioneuromatosis of the gastrointestinal tract. Case Description: A 10-year-old male began follow-up at our service at 3 years of age through pediatric gastroenterology due to intestinal constipation. The mother also reported that the child had painless lesions on the tip of the tongue since birth with progressive worsening. The patient simultaneously began follow-up with pediatric endocrinology due to low gains in weight and height, between which only isolated low weight was found, and the onset of follow-up with the pediatric neurology team due to longstanding headache combined with vomiting, photophobia, and phonophobia as well as a specific reading and writing disorder. The patient was sent to clinical genetics. The child's karyotype was 46, XY (normal). Through a physical examination, the pediatric neurology team identified joint hypermobility, important muscle hypotrophy, gingival hypertrophy, and lipodystrophy. The patient was sent to neurogenetics, initiating a set of general laboratory exams for the investigation of the lipodystrophy and a panel of exams for lipodystrophy, neuropathy, and muscle hypotrophy as well as electroneuromyography. MEN2B due to genetic mutation was confirmed and the patient was sent to the pediatric endocrinology clinic for follow-up. Currently 10 years of age and again with the pediatric endocrinology team for the diagnosis of MEN2B, the investigation of pheochromocytoma and medullary thyroid cancer was initiated. Conclusions: An additional mutation occurs in most cases of MEN2B. The diagnosis is only established when the child or, in most cases, adolescent presents with medullary thyroid cancer in an advanced and even metastatic stage. However, non-endocrine manifestations, can lead to an early diagnosis and timely intervention. The diagnosis of MEN2B is made with the confirmation of the autosomal dominant genetic mutation or a mutation of the RET gene. In the absence of these mutations, the majority of clinical manifestations should be present.

Case report: Novel germline c.587delA pathogenic variant in familial multiple endocrine neoplasia type 1.

Multiple Endocrine Neoplasia type 1 (MEN1) is a rare genetic disease, characterized by co-occurrence of several lesions of the endocrine system. In MEN1, the pathogenic MEN1 gene mutations lead to the Abnormal expression of menin, a critical tumor suppressor protein. We here reported a case of a 14-year-old male with insulinoma and primary hyperparathyroidism. Genetic testing demonstrated a novel heterozygote variant c.587delA of MEN1, resulting in the substitution of the 196th amino acid, changing from glutamic acid to glycine, followed by a frameshift translation of 33 amino acids. An identical variant was identified in the proband's father, who was further diagnosed with hyperparathyroidism. To the best of our knowledge, this is the first report of MEN1 syndrome caused by the c.587delA MEN1 variant. Observations indicated that, despite sharing the same MEN1 gene change, family members exhibited diverse clinical phenotypes. This underscored the presence of genetic anticipation within the familial context.

Diagnosis and management of pituitary adenomas in children and adolescents.

BACKGROUND: Pituitary adenomas (PA) - also now called pituitary neuroendocrine tumours or Pit-NETS - are rare in children and adolescents, and exceptional below the age of 10. Most evidence-based high-quality data are derived from larger studies in adult patients. AIMS: We will review recent knowledge on the epidemiology, clinical features, diagnosis and treatment modalities of the different types of pituitary adenomas diagnosed in children and adolescents, emphasizing the many reasons why these cases should be discussed within pituitary-specific multidisciplinary teams with experts from both paediatric and adult practice. CONCLUSIONS: Paediatric PA present multiple peculiarities that may challenge their adequate management. They are overall proportionally larger and more aggressive than in adults, with potential mass effects including hypopituitarism. Hormonal hypersecretion is frequent, resulting in clinical syndromes affecting normal growth and pubertal development. Prolactinomas represent the most frequent subtype of PA found during childhood, followed by adrenocorticotropin (ACTH) and growth hormone (GH)-secreting adenomas, while clinically non-functioning adenomas are exceptionally diagnosed before the age of 16. The occurrence of a pituitary tumour in a young individual should also prompt genetic testing in each case, searching for either germline mutations in one of the known genes that may drive inherited/familial PA (such as the multiple endocrine neoplasia type 1 or MEN1 gene, or the aryl hydrocarbon receptor Interacting protein or AIP gene), or for a mosaic activating mutation of GNAS as found in the McCune-Albright syndrome.

Genotype and clinical phenotype characteristics of MAX germline mutation-associated pheochromocytoma/paraganglioma syndrome.

Objective: The aim of this study was to investigate the genotypic and clinical phenotypic characteristics of MAX germline mutation-associated pheochromocytoma (PCC) and paraganglioma (PGL). Methods: We retrospectively analyzed the family investigation data and clinical genetic characteristics of six individuals from three independent families with PCC carrying MAX germline mutations from December 2005 to March 2024. A literature review was then conducted of the six carriers and another 103 carriers from the other 84 families with MAX germline mutations reported previously. Results: There were 109 patients in 87 families with all five exons and 53 types of MAX germline mutations. p.R33* (c.97C>T; 21.1%), p.R75* (c.223C>T; 13.8%), and p.A67D (c.200C>A; 7.3%), which accounted for 42.2% of mutations detected, were the most common mutations. Moreover, 101 (92.7%) patients developed PCCs, including 59 bilateral PCCs and 42 unilateral PCCs, and 19 (18.8%) patients showed metastasis. The mean age at diagnosis was 32.8 ± 12.6 (13-80) years. The male-to-female ratio was 1.3:1. In 11 (10.9%) patients, the PCC was accompanied by chest or abdominal PGL, and one other patient had sole head and neck PGL. Nine (8.3%) patients also had functional pituitary adenomas, 11 (10.9%) developed other neuroendocrine tumors (NETs), and 7 (6.4%) presented with concomitant non-NET. Meanwhile, MAX-p.Q82Tfs*89 and p.E158A mutations are reported for the first time in this study. Conclusion: MAX germline mutations may cause new types of multiple endocrine neoplasia. A comprehensive baseline assessment of neural crest cell-derived diseases is recommended for all individuals with MAX germline mutations. The risk of bilateral and metastatic PCCs should also be considered.

Thyroid Malignancy and Cutaneous Lichen Amyloidosis: Key Points Amid RET Pathogenic Variants in Medullary Thyroid Cancer/Multiple Endocrine Neoplasia Type 2 (MEN2).

We aimed to provide an updated narrative review with respect to the RET pathogenic variants and their implications at the clinical and molecular level in the diagnosis of medullary thyroid cancer (MTC)/multiple endocrine neoplasia (MEN) type 2, particularly with respect to the presence of cutaneous lichen amyloidosis (CLA). We searched English-language, in extenso original articles with no timeline nor study design restriction that were published on PubMed. A traditional interplay stands for CLA and MTC in MEN2 (not MEN3) confirmation. While the connection has been reported for more than three decades, there is still a large gap in understanding and addressing it. The majority of patients with MEN2A-CLA have RET pathogenic variants at codon 634; hence, it suggests an involvement of this specific cysteine residue in both disorders (most data agree that one-third of C634-positive subjects have CLA, but the ranges are between 9% and 50%). Females seem more prone to MEN2-CLA than males. Non-C634 germline RET pathogenic variants included (at a low level of statistical evidence) the following: RET V804M mutation in exon 14 for MTC-CLA (CLA at upper back); RET S891A mutation in exon 15 binding OSMR variant G513D (familial MTC and CLA comprising the lower legs to thighs, upper back, shoulders, arms, and forearms); and C611Y (CLA at interscapular region), respectively. Typically, CLA is detected at an early age (from childhood until young adulthood) before the actual MTC identification unless RET screening protocols are already applied. The time frame between CLA diagnosis and the identification of RET pathogenic variants was between 5 and 60 years according to one study. The same RET mutation in one family is not necessarily associated with the same CLA presentation. In MTC/MEN2 subjects, the most affected CLA area was the scapular region of the upper back. Alternatively, another hypothesis highlighted the fact that CLA is secondary to long-term prurit/notalgia paresthetica (NP) in MTC/MEN2. OSMR p. G513D may play a role in modifying the evolutionary processes of CLA in subjects co-harboring RET mutations (further studies are necessary to sustain this aspect). Awareness in CLA-positive patients is essential, including the decision of RET testing in selected cases.

Prospective Genetic Screening in Multiple Endocrine Neoplasia Syndromes.

Multiple endocrine neoplasia syndromes are a rare but potentially fatal pathology due to the lack of early diagnosis. We have performed a narrative review of the medical literature, summarizing the main clinical concepts useful in current clinical practice, showing the importance of screening and early diagnosis during childhood.

68Ga-DOTATATE PET/CT: How is it reliable in imaging of cases having clinical suspicion of insulinomas?

PURPOSE: This retrospective study evaluates the value of 68Ga-DOTATATE PET/CT in the diagnosis and localization of insulinomas, whether sporadic, malignant or MEN-1 associated insulinoma. METHOD: The study included 43 patients, having clinical (symptomatic hypoglycemia) and/or laboratory suspicion of having insulinoma (72 h fasting test with serum insulin ≥18 pmol/L), with available pre-operative 68Ga-DOTATATE PET/CT and CE-CT, and diagnosed with insulinoma confirmed by post-operative histopathology. Preoperative imaging was retrospectively analyzed by two radiologists who were blinded to the final diagnosis and to the results of other imaging modalities. Histopathology of specimen was considered the reference standard, and head-to-head comparison of preoperative CE-CT and PET imaging findings. Findings were classified as true positive (TP), true negative (TN), false positive (FP), and false negative (FN) for each modality. Based on these results, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of CE-CT, and 68Ga-DOTATATE PET/CT for the detection of insulinoma were calculated. RESULTS: 43 patients (N = 43 patients, L = 56 lesions), out of these, 37 patients had benign sporadic insulinoma (N = 37, L = 42), only 3 patients had malignant sporadic insulinoma (N = 2, L = 9), and 3 patients had MEN-1 syndrome associated insulinoma (N = 3, L = 5). There was no significant statistical difference in sensitivity (P = 0.3058) and PPV (P = 0.5533) for insulinoma localization in the overall cohort with 68Ga-DOTATATE PET/CT (87.5 %, 90.74 %) compared to CE-CT (80.36 %, 93.75 %). CONCLUSION: 68Ga-DOTATATE PET/CT is a non-invasive imaging modality that can identify most insulinomas. Still, it offers limited additional information when the tumor is localized by other anatomic imaging studies, so should be used as an adjunct when imaging studies fail to localize the tumor in insulinoma patients, especially when minimally invasive surgical is intended.

Pituitary Neuroendocrine Tumors in Multiple Endocrine Neoplasia.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal-dominant disorder characterized by tumors of the pituitary, parathyroid, and endocrine-gastrointestinal tract. Pituitary neuroendocrine tumors (PitNETs) occur in about 40% of MEN1 cases, with 10% being the first manifestation. Recent studies show a slight female predominance, with microPitNETs (<1 cm) being more common than macroPitNETs (>1 cm). Functional PitNETs (FPitNETs) are more frequent than non-functional ones (36% to 48%), with prolactinomas being the most common FPitNETs. MEN1-associated PitNETs are often plurihormonal, larger, and more invasive compared to sporadic types, though patient age and FPitNET proportions are similar. MEN1 mutation-negative patients tend to have larger, symptomatic PitNETs at diagnosis. Six patients with MEN1 have been reported to have pituitary carcinomas, including a mutation- negative patient. Treatment approach between PitNETs in MEN1 and sporadic types appears to be similar. PitNETs also occur in MEN4, but their epidemiology is less understood. In patients with a MEN1-like phenotype and negative genetic testing, MEN4 should be considered.

Case report: Comprehensive follow-up of a Colombian family carrying a novel MEN1 variant linked to a rare ACTH-producing pancreatic neuroendocrine carcinoma.

Background: Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant disorder marked by pathogenic variants in the MEN1 tumor suppressor gene, leading to tumors in the parathyroid glands, pancreas, and pituitary. The occurrence of ACTH-producing pancreatic neuroendocrine carcinoma is exceedingly rare in MEN1. Case presentation: This report details a Colombian family harboring a novel MEN1 variant identified through genetic screening initiated by the index case. Affected family members exhibited primary hyperparathyroidism (PHPT) symptoms from their 20s to 50s. Uniquely, the index case developed an ACTH-secreting pancreatic neuroendocrine carcinoma, a rarity in MEN1 syndromes. Proactive screening enabled the early detection of pituitary neuroendocrine tumors (PitNETs) as microadenomas in two carriers, with subsequent surgical or pharmacological intervention based on the clinical presentation. Conclusion: Our findings underscore the significance of cascade screening in facilitating the early diagnosis and individualized treatment of MEN1, contributing to better patient outcomes. Additionally, this study brings to light a novel presentation of ACTH-producing pancreatic neuroendocrine carcinoma within the MEN1 spectrum, expanding our understanding of the disease's manifestations.

Early detection of multiple endocrine neoplasia type 1: A case report.

BACKGROUND: Multiple endocrine neoplasias (MENs) are a group of hereditary diseases involving multiple endocrine glands, and their prevalence is low. MEN type 1 (MEN1) has diverse clinical manifestations, mainly involving the parathyroid glands, gastrointestinal tract, pancreas and pituitary gland, making it easy to miss the clinical diagnosis. CASE SUMMARY: We present the case of a patient in whom MEN1 was detected early. A middle-aged male with recurrent abdominal pain and diarrhea was admitted to the hospital. Blood tests at admission revealed hypercalcemia and hypophosphatemia, and emission computed tomography of the parathyroid glands revealed a hyperfunctioning parathyroid lesion. Gastroscopy findings suggested a duodenal bulge and ulceration. Ultrasound endoscopy revealed a hypoechoic lesion in the duodenal bulb. Further blood tests revealed elevated levels of serum gastrin. Surgery was performed, and pathological analysis of the surgical specimens revealed a parathyroid adenoma after parathyroidectomy and a neuroendocrine tumor after duodenal bulbectomy. The time from onset to the definitive diagnosis of MEN1 was only approximately 1 year. CONCLUSION: For patients who present with gastrointestinal symptoms accompanied by hypercalcemia and hypophosphatemia, clinicians need to be alert to the possibility of MEN1.

Menin signaling and therapeutic targeting in breast cancer.

To date, mounting evidence have shown that patients with multiple endocrine neoplasia type 1 (MEN1) may face an increased risk for breast carcinogenesis. The product of the MEN1 gene, menin, was also indicated to be an important regulator in breast cancer signaling network. Menin directly interacts with MLL, EZH2, JunD, NF-κB, PPARγ, VDR, Smad3, ß-catenin and ERα to modulate gene transcriptions leading to cell proliferation inhibition. Moreover, interaction of menin-FANCD2 contributes to the enhancement of BRCA1-mediated DNA repair mechanism. Ectopic expression of menin causes Bax-, Bak- and Caspase-8-dependent apoptosis. However, despite numbers of menin inhibitors were exploited in other cancers, data on the usage of menin inhibitors in breast cancer treatment remain limited. In this review, we focused on the menin associated signaling pathways and gene transcription regulations, with the aim of elucidating its molecular mechanisms and of guiding the development of novel menin targeted drugs in breast cancer therapy.

Incidental detection of multiple endocrine neoplasia and medullary thyroid carcinoma before starting GLP-1 agonist: A case report.

A man, in his 30s, with a history of obesity and hypothyroidism planned to begin taking a new Glucagon-like peptide-1 (GLP-1) agonist for weight loss. As these medications have been associated with C-cell hyperplasia, a calcitonin level was checked as evaluation prior to starting the drug. This returned at 131 pg/mL (upper limit of normal<10 pg/mL), and a subsequent carcinoembryonic antigen was 5.2 ng/mL (ref<3 ng/mL). Thyroid ultrasound was performed and demonstrated bilateral subcentimeter nodules. After total thyroidectomy, final pathology demonstrated bilateral 0.8 cm medullary thyroid carcinoma. Genetic testing revealed a NM_020975.6: c.1826G > A; p.Cys609Tyr. germline RET mutation, confirming the diagnosis of multiple endocrine neoplasia 2 syndrome. The patient recovered well from treatment. His first-degree relatives also underwent genetic testing. This case represents a surprising diagnosis of familial multiple endocrine neoplasia 2A prior to starting a Glucagon-like peptide-1 agonist.

Multiple endocrine neoplasia type 1 with MEN1 variant of unknown significance, in a patient after the diagnosed of pancreatic neuroendocrine neoplasia.

Duodenopancreatic neuroendocrine neoplasia (DP-NEN) is in approximately 10% of cases of multiple endocrine neoplasia type 1 (MEN1). We encountered a case in which the onset of NEN led to suspicion and diagnosis of MEN1. Although genetic testing showed MEN1 variant of uncertain significance (VUS), we considered it pathological from the clinical course, promoting the provision of genetic counseling and screening for relatives. MEN1 has a variety of clinical manifestations, and DP-NENs are the second-most common manifestation after primary hyperparathyroidism (pHPT). It is important to assume that MEN1 is an underlying cause of NEN.

Sweet Saboteur: Insulinoma Presenting As Recurrent Hypoglycemic Seizures.

Insulinoma, a rare neuroendocrine tumor of the pancreas, often presents diagnostic challenges due to its diverse clinical manifestations. We present the case of a 25-year-old female with recurrent hypoglycemic seizures and neuroglycopenic symptoms, ultimately diagnosed with insulinoma. Despite an initial asymptomatic period, the patient experienced progressively worsening symptoms over three years, culminating in eight episodes of generalized tonic-clonic seizures per week. Biochemical investigations during hypoglycemic episodes revealed elevated C-peptide and insulin levels, consistent with endogenous hyperinsulinemia. Imaging studies, including contrast-enhanced computed tomography (CECT) and Ga-DOTATATE scan, confirmed a hyper-enhancing lesion in the distal body of the pancreas, indicative of insulinoma. Histopathological examination (HPE) further corroborated the diagnosis. Prompt recognition and surgical excision led to the complete resolution of symptoms and improved long-term prognosis. This case underscores the importance of considering insulinoma in young individuals presenting with recurrent hypoglycemic episodes and highlights the significance of early diagnosis and intervention in preventing morbidity and mortality associated with this condition.

Multiple Endocrine Neoplasia Type 1, Type 2A, and Type 2B.

Multiple endocrine neoplasia type 1 is a rare genetic neuroendocrine syndrome caused by over 1500 different germline mutations. It can cause 20 different endocrine tumors affecting primarily the parathyroid glands, gastroenteropancreatic tract, and the anterior pituitary gland. Multiple endocrine neoplasia type 2A (MEN2A) and Multiple endocrine neoplasia type 2B (MEN2B) are autosomal dominant genetic syndromes because of a germline variant in the 'rearranged during transfection' (RET) proto-oncogene. There are common RET mutations causing receptor hyperactivation and induction of downstream signals that cause oncogenesis. Common conditions with MEN2A are medullary thyroid cancer (MTC), pheochromocytoma, and primary hyperparathyroidism. Common conditions with MEN2B include MTC, pheochromocytomas, and benign ganglioneuromas.

Management of Pancreatic Neuroendocrine Tumors: Surgical Strategies and Controversies.

OBJECTIVE: Pancreatic neuroendocrine tumors (PNETs) are uncommon tumors which are increasing in incidence. The management of these tumors continues to evolve. This review examines the current role of surgery in the treatment of these tumors. METHODS: Studies published over the past 10 years were identified using several databases including PubMed, MEDLINE, and Science Direct. Search terms included PNETs, treatment, and surgery. Clinical practice guidelines and updates from several major groups were reviewed. RESULTS: Surgery continues to have a major role in the treatment of sporadic functional and nonfunctional PNETs. Pancreas-sparing approaches are increasingly accepted as alternatives to formal pancreatic resection in selected patients. Options such as watch and wait or endoscopic ablation may be reasonable alternatives to surgery for non-functional PNETs < 2 cm in size. Surgical decision-making in multiple endocrine neoplasia type 1 patients remains complex and in some situations such as gastrinoma quite controversial. The role of surgery has significantly diminished in patients with advanced disease due to the advent of more effective systemic and liver-directed therapies. However, the optimal treatments and sequencing in advanced disease remain poorly defined, and it has been suggested that surgery is underutilized in these patients. CONCLUSIONS: Surgery remains a major treatment modality for PNETs. Given the plethora of available treatments, ongoing controversies and the changing landscape, management has become increasingly complex. An experienced multidisciplinary team which includes surgery is essential to manage these patients.

Neoplasia endócrina múltiple y enfermedad inflamatoria intestinal de inicio muy temprano. Una asociación inesperada / Multiple endocrine neoplasia and very early onset in flammatory bowel disease. An unexpected association

Resumen La enfermedad inflamatoria intestinal de inicio muy temprano (VEOIBD) es una entidad rara en pediatría. Es conocida su asociación con inmunodeficiencias prima rias de origen monogénico. Presentamos el caso de una paciente con diagnóstico de VEOIBD a quien se le realizó una secuenciación masiva del exoma. El resultado del estudio permitió identificar una variante patogénica en el proto oncogen RET, asociada con enfermedad neoplasia endocrina múltiple tipo 2A. No hay reportes de asociación de variantes en el proto oncogen RET con VEOIBD. No se puede adjudicar la presencia de estas dos entidades clínicas a una única causa genética.

Abstract Very early onset inflammatory bowel disease (VEOI BD) is a rare entity in pediatrics. Its association with pri mary immunodeficiencies of monogenic origin is known. We present the case of a patient diagnosed with VEOIBD who underwent massive paralleled exome sequencing. The result of the study showed a pathogenic variant in the RET proto-oncogene, associated with multiple endo crine neoplasia type 2A disease. There are no previous reports of association of RET proto-oncogene variants with VEOIBD. The presence of these two clinical entities cannot be attributed to a single genetic cause.