bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Case Report on Parathyroid Carcinoma - an Extremely Rare Endocrine Malignancy
Authors: Mandal Shobha , Bethala Mary Grace , MolsKowalczewski Barbara 
Published: May 2021

Abstract
Background: Parathyroid carcinoma is an extremely rare endocrine malignancy with a prevalence of &It 1%. It is associated with hyperparathyroidism-jaw tumor syndrome (HJTS), multiple endocrine neoplasia (MEN) type 1 or 2A syndromes, secondary hyperparathyroidism, and chronic kidney disease. Incidence is equal in both men and women. Patients may present with symptoms of hypercalcemia, and should be further worked up with neck ultrasound, Tc-99m sestamibi imaging, single-photon emission computed tomography, magnetic resonance imaging, positron emission tomography combined with CT scan, and biopsy of the parathyroid mass. Parathyroid carcinoma can be treated surgically with complete resection. Patients treated with En-bloc resection with microscopically negative margins remain cancer-free for at least three years to a maximum of twenty years.
Case Report: A 50-year-old female treated with laparoscopic sleeve gastrectomy for morbid obesity, came for the follow-up visit. She denied any active complaint. Routine Lab work showed mild hypercalcemia, hypophosphatemia, elevated PTH, and alkaline phosphatase. Neck ultrasound showed a cystic lesion adjacent to the right thyroid lobe. Sestamibi (MIBI) parathyroid scintigraphy showed increased radiopharmaceutical uptake by the right superior parathyroid gland without any enlarged or suspicious lymph nodes. Dexa scan was positive for osteopenia. The patient underwent right superior parathyroidectomy along with en-bloc right thyroid lobectomy. Histological examination revealed anaplastic regions, giant cells with abundant cytoplasm, and polymorphous nuclei with a Ki-67 labeling index of 10% consistent with parathyroid carcinoma. Post-surgery imaging with ultrasound and magnetic resonance imaging of the neck computed tomography of the chest, and abdomen, whole-body MIBI scintigraphy was negative for residuals or metastatic disease. She was started on oral calcium carbonate and was monitored regularly with routine lab work. The most recent lab work was within normal limits.
Conclusion: Most of the patients with parathyroid carcinoma present in the early stage with the symptoms of hypercalcemia. Many of them do not have symptoms of mass or tumor effects. Parathyroid cancer is a rare malignancy and can be missed, therefore all patients with hypercalcemia should be further evaluated with lab work, imaging, and biopsy to rule out parathyroid carcinoma. Early diagnosis and treatment have a better outcome.
Urinary Steroid Metabolome Signature Is Associated With Pre-Frailty and Frailty Phenotype in Older Adults
Authors: Singh Sumitabh , Ebbehoj Andreas , Rivard Ann L , Thomas Melinda , Singh Ravinder J , Grebe Stefan Karl Gunther , Khosla Sundeep , LeBrasseur Nathan K , Bancos Irina 
Published: May 2021

Abstract
Background: Frailty is characterized by an increased vulnerability and a decline in physiological reserve. Frailty has been previously linked to cortisol concentrations and blunted diurnal cortisol secretion. Our objective was to determine the association of urine steroid metabolome and its diurnal variation with frailty and prefrailty in older adults. Methods: Cross-sectional study of community-dwelling adults ≥ 50 years. Participants with adrenal disorders, end-stage renal or liver disease, on exogenous steroids or drugs affecting steroid metabolism were excluded. All participants completed day and night separate urine collection. Frailty was assessed using a phenotype model (weight loss, exhaustion, grip strength, low physical activity, and slow walking pace). Participants were characterized as frail if they met at least three criteria, pre-frail if they fulfilled one or two criteria, and robust if no criteria were met. Urine samples were analyzed with the liquid-chromatography, high-resolution, accurate-mass mass spectrometry for 25 urine steroid metabolites. Results: Of 119 participants, 60 (50.4%) were women, without sex differences in age or education status. On frailty assessment, 5 (4.2%) participants were frail and 33 (27.7%) were prefrail, with equal sex distribution. Urine steroid metabolome analysis demonstrated 21/25 steroids were higher in men vs women. In an age adjusted model, presence of prefrailty or frailty was associated with a higher ratio of total cortisol metabolites/total androgen metabolites (TCM/TAM) in men (estimate 0.64, P-value= 0.0004), but not in women. In men, after adjusting for age, among cortisol metabolites, lower day to night ratio of 5α-Tetrahydrocortisol (estimate -0.36, P-value= 0.0419) and β-Cortol (estimate -0.35, P-value= 0.0238) were associated with frail or prefrail phenotype. After adjusting for age, higher ratio of TCM/TAM was associated lower gait speed in men (estimate -1.2, P-value= 0.046) and women (estimate -3.9, P-value= 0.012); and lower hand grip strength in men (estimate -0.04, P-value= 0.046) but not in women. Conclusion: We showed that a higher glucocorticoid to androgen ratio and a flattened circadian steroid variation were associated with presence of frail or prefrail phenotype in men. Further studies should examine the role of steroid metabolism and HPA axis impairment, and the associated sex differences, in the functional decline in aging population.
Utility of Urinary Ratio of Cortisol to Aldosterone as Inflammatory and Metabolic Parameters
Authors: Otsuka Yuki , Nakano Yasuhiro , Tokumasu Kazuki , Honda Hiroyuki , Obika Mikako , Hasegawa Kou , Hanayama Yoshihisa , Otsuka Fumio 
Published: May 2021

Abstract
Corticosteroids are important bioactive substances in the body that regulate inflammation, metabolism, immunity, and circulatory dynamics. Cortisol and aldosterone are two major naturally occurring steroids, which synthesized in the adrenal fasciculata and in the adrenal glomerulosa under the regulation of adrenocorticotropin (ACTH) and renin-angiotensin system (RAS), respectively. The conventional strategy for evaluating adrenocortical function has been to measure random serum cortisol or 24-hour stored levels of urine free cortisol (UFC). UFC is a more appropriate marker to avoid the effects of diurnal fluctuation of cortisol, serum cortisol-binding proteins, and cortisol clearance in the kidney. Thus, measurement of UFC has been a reliable test for diagnosis of Cushing’s disease or adrenal insufficiency. However, since the normal range of UFC varies widely, it is often difficult to evaluate whether the UFC level is optimal or not for each patient. That is because UFC is greatly affected by the amount of fluid intake or urine volume, and an immunoassay for UFC, which is the usual method for measuring UFC, is susceptible to interference from other steroid metabolites and synthetic glucocorticoids. To explore an alternative indicator, we tried to standardize the levels of UFC by the levels of urinary aldosterone concentration (UAC) in the same urinary sample. Medical records of all 246 patients in whom daily excretions of UFC and UAC had been measured between 2015 and 2018 at our department were reviewed. 142 patients (including 93 females) were included after exclusion of 104 patients because of corticosteroid replacement therapy. UFC/UAC ratio showed significant positive and negative correlations with the levels of serum cortisol (R=0.287) and aldosterone (R=-0.762), respectively. UFC/UAC ratio increased with aging in female patients, while the ratio was not altered by the levels of BMI in either gender. Markers for metabolic and inflammatory status including hemoglobin A1c (R=0.327), albumin (R=-0.331), chorine esterase (R=-0.248), C-reactive protein (R=0.317), ferritin (R=0.473), and D-dimer (R=0.569) showed correlations to the ratio of UFC/UAC that were more significant than the correlations to the serum level of cortisol or UFC alone. Of note, the UFC/UAC ratio was shown as an indicator for risks of diabetes (AUC: 0.765), hypoalbuminemia (0.839), hyper-CRPemia (0.748), and thrombophilia (0.824), in which the cut-off levels of UFC/UAC ratios were found to be around 12. These results indicate that the UFC/UAC ratio is a suitable variable for the detection of metabolic and inflammatory complications related to adrenocortical dysfunction.
Case Report: Exceptional Association of Leydig Cell Ovarian Tumor and Primary Hyperparathyroidism in a Postmenopausal Patient
Authors: Chuki Elias , Hannoush Zeina Carolina 
Published: May 2021

Abstract
Background: Leydig cell tumors account for less than 0.1% of all ovarian tumors and are usually unilateral and benign. They present mostly in postmenopausal women with symptoms of hyperandrogenism. On the other hand, primary hyperparathyroidism (PHPT) is a relatively common endocrine disorder, with a prevalence of one to seven cases per 1,000 adults. It most commonly presents as an isolated, sporadic clinical entity, but in approximately 10% of the cases, it presents with a clear hereditary pattern and sometimes in association with other hormone producing tumors. Clinical Case: a 55-year-old nulliparous postmenopausal woman with history of breast cancer, Type 2 Diabetes Mellitus, hypothyroidism, hypercalcemia and hypertension who presented with progressive hirsutism and male pattern hair loss. Total testosterone levels were found to be significantly elevated in the 800s ng/dL (normal range 14–76 ng/dL). Additionally, patient was found to have mild hypercalcemia with inappropriately normal PTH and hypercalciuria, consistent with primary hyperparathyroidism (PHPT). A hypoechoic lesion in the left ovary was evident on pelvic ultrasound after 1 year of repeat imaging studies, including MRI. Bone density was within normal limits. The patient underwent bilateral Hysterosalpingo-oophorectomy and pathology report was consistent with Ovarian Leydig cell tumor. During the postoperative period, the patient reported improvement of hyperandrogenism symptoms. Discussion: We are presenting this case because of the rare association of ovarian Leydig cell tumor and PHPT in a postmenopausal female patient with virilizing symptoms. Thus, this would be the second case reported in literature by this time. This could be a rare coincidence or part of an inherited or sporadic mutation yet to be discovered. This case restates the concept that in the presence of hirsutism, rare etiologies should be sought. Virilizing tumors of the ovary should be considered despite negative initial imaging studies. PHPT should be considered in patients with asymptomatic hypercalcemia with inappropriately normal PTH and hypercalciuria. Conclusion: Careful identification and report of cases with unusual clinical presentations is essential to better understand the pathophysiology of uncommon diseases and ultimately be able to guide their management.
Description of a SDHD c.129G&gt;A (p.W43X) Mutation With Variable Presentation in Multiple Family Members
Authors: Greenberg Samantha , Luke Buchmann , Naumer Anne , Kohlmann Wendy , Garfield Kinley , Sharma Anu 
Published: May 2021

Abstract
Approximately 40% of paragangliomas and pheochromocytomas are attributed to hereditary mutations. SDHD mutations account for 7% of inherited mutations (PGL1 syndrome), is maternally imprinted and has variable penetrance. SDHD pathogenic variants (PV) have been previously described extensively in Dutch pedigrees, with a varying lifetime risk for tumor development. Here we report a large family (Fig 1) displaying a SDHD c.129G&gt;A (p.W43X) variation in 12 family members, 10 of whom had screening or tumor history available. The presentation and age of diagnosis in family members showed variable penetrance. Age at first diagnosis of a pheochromocytoma/paraganglioma ranged from 10 - 45 years. Family members displayed bilateral pheochromocytomas, bilateral carotid body tumors, and paragangliomas of the head, neck and trunk with variable recurrence rates (none to multiple). No malignant lesions were detected to date. Pheochromocytomas were norepinephrine producing. Paragangliomas ranged from non-functional to dopamine and norepinephrine producing. Compared to previous reports of other SDHD mutations, the SDHD c.129G&gt;A (p.W43X) variation displayed an earlier age at first diagnosis with a highly variable phenotype ranging from one benign, non-secreting paraganglioma to bilateral pheochromocytomas and recurrent parganagliomas along the parasympathetic chain from head to abdomen. This report contributes to the evolving understanding of the phenotypic presentations of various genetic mutations. We propose that expert guidelines that suggest screening family members with the SDHD c.129G&gt;A (p.W43X) variation at the age of 8 for early detection of pheochromocytomas and paragangliomas is beneficial.
Gastrointestinal Stromal Tumor Mimicking an Adrenal Incidentaloma: A Case Report
Authors: Hamidi Sarah , Mercier Frédéric , Bourdeau Isabelle , Rakel Agnes 
Published: May 2021

Abstract
Background: The differential diagnosis of adrenal incidentalomas is broad and includes benign or malignant primary adrenal lesions, metastases, myelolipomas, infections or hemorrhage. We present here a patient with a gastrointestinal stromal tumor (GIST) presenting as an adrenal incidentaloma. Clinical Case: A 64-year-old man was referred to Endocrinology for the work-up of a left adrenal incidentaloma discovered on an abdominal CT scan performed for left upper quadrant abdominal pain. His past medical history included well-controlled type 2 diabetes and hypertension. On subsequent imaging, the mass was described as a solid homogenous nodule with a density of 31 HU and an absolute contrast washout of 22%. Between 2017 and 2020, the mass’ size increased from 14 x 13 to 24 x 19 millimeters. Further functional imaging revealed no 131I-MIBG uptake but moderate hypermetabolism on FDG PET-CT with a SUVmax of 4.5. There was discordance regarding the mass’ localization between the various imaging modalities used preoperatively: some showed a left adrenal lesion whereas others suggested that it was adjacent to, but distinct from, the adrenal gland. Biochemical workup included normal 1-mg dexamethasone suppression test, serum potassium levels, 24-hour urine fractionated catecholamines, as well as plasma free metanephrines and normetanephrines. Chromogranin A levels were also normal. In light of these findings, laparoscopic tumor resection, with or without left adrenalectomy, was scheduled. During surgery, it was discovered that the tumor was intraperitoneal, located next to the splenic hilum and originating from the greater curvature of the stomach; a partial gastrectomy was therefore performed, without left adrenalectomy. Pathological evaluation revealed that the mass was a small spindle cell-type GIST. Genetic analysis of the tumoral DNA showed a somatic mutation in exon 11 of the KIT gene (c.1658_1669del, p.Tyr553_Gln556del). Conclusion: We report a rare case of gastric GIST initially mimicking a left adrenal incidentaloma. Localization of GISTs in the adrenal area is rare, with very few cases reported to date in the literature. Unlike other cases described previously, our patient underwent the right procedure thanks to adequate tumor localization during surgery. However, as some patients have experienced unnecessary adrenalectomy for similar clinical presentations, gastric GISTs should be kept in mind in the differential diagnosis of non-functional atypical adrenal masses, especially in the presence of suspicious PET scan imaging. References: 1. Hexi Du, Jun Zhou, Cheng Yang, Li Zhang, Chaozhao Liang: Gastrointestinal stromal tumor masquerading as an adrenal tumor: a case report with literature review. Int J Clin Exp Med 2017;10(10):14883-14887.
Life-Threatening VIPoma Crisis in an Immunocompromised Patient
Authors: Borhan Marisa Khatijah , Sieng Tan Florence Hui 
Published: May 2021

Abstract
Background: Vasoactive intestinal peptide-secreting tumors (VIPoma) are rare neuroendocrine tumors (NETs) that present with a triad of profuse watery diarrhea, hypokalemia, and achlorhydria. The resulting renal impairment, electrolytes and acid-base imbalances pose a high risk of morbidity and mortality. We describe a case of life-threatening VIPoma crisis in an immunocompromised patient. Clinical Case: A 64-year-old man was intubated after he was brought in unconscious with tachypnea. Upon review, he had experienced persistent watery diarrhea for the past 6 months, with a weight loss of 18 kg. He had severe hypokalemia (potassium 1.9 mmol/L, n= 3.5-5.0), metabolic acidosis (blood gases pH 6.927, bicarbonate 4.8 mmol/L, base excess -25.9 mmol/L), and acute kidney injury (urea 47.9 mmol/L, creatinine 980umol/L). He continued to have electrolyte imbalances and acidosis due to persistent diarrhea, despite hydration and dialysis support. His biohazard screening results were positive for human immunodeficiency virus (HIV), with a CD4 count of 101 cells/µl. He was given courses of antibiotics for treating pathogenic infections; however, his septic workups were negative for infection, including HIV-related opportunistic infections. Later, pancreatic CT revealed a well-defined heterogeneously enhancing pancreatic head mass, size 6.8x5.2x7.5 cm. Further laboratory investigations confirmed the diagnosis of VIPoma, with elevated VIP levels (1600 pg/ml, n &lt; 75). Eventually, subcutaneous octreotide was started, with resolution of the diarrhea and normalization of his electrolytes and renal function. After a 6-week hospital stay, he was discharged well with monthly octreotide and initiated on antiretroviral therapy (ART). After 3 months of ART, his CD4 count improved, and he remained diarrhea-free with octreotide. He is scheduled for tumor debulking surgery.
Conclusion:This case highlights the importance of having a clinical suspicion of NETs, especially in immunocompromised patients. Further investigations and imaging studies to rule out noninfectious pathologies should be considered in patients who respond poorly to standard therapy. In VIPoma, somatostatin analog is an antisecretory treatment and it is highly effective for controlling diarrhea. High-dose octreotide up to 1500 µg/day has previously been studied for treatment of refractory diarrhoea in the setting of HIV infection² and it has been found to be helpful in reducing stool volume and frequency. Lastly, delays in the diagnosis and treatment of VIPoma in immunocompromised patients can be fatal. References1/ Hoffland J., Kaltsas G., de Herder W. Advances in the Diagnosis and Management of Well-Differentiated Neuroendocrine Neoplasms. Endocrine Reviews, Volume 41, Issue 2, April 2020, Pages 371-403.2/ Farthing MJ. Octreotide in the treatment of refractory diarrhoea and intestinal fistulae. Gut 1994;35:S5-10.
Metastatic Thyroid Cancer After Thyroidectomy in Patient With Neuroendocrinal Tumor
Authors: Khalifa Maram , Aftab Hassaan , Kantorovich Vitaly 
Published: May 2021

Abstract
Background: Multiple endocrine neoplasia type 2 is an autosomal dominant disorder with an estimated prevalence of 1 per 30,000 in the general population. Classical multiple endocrine neoplasia 2A is the most common variant. It is a heritable predisposition to medullary thyroid cancer, pheochromocytoma, and primary parathyroid hyperplasia. The respective frequency of these tumors in classical MEN2A is over 90 percent for MTC, approximately 10 to 50 percent for pheochromocytoma, and 10 to 20 percent for multigland parathyroid hyperplasia.
Discussion: our interesting patient is a 67-year-old patient with past medical history of prophylactic total thyroidectomy at the age of 25 years after a positive pentagastrin test (sister was diagnosed with MTC, pheochromocytoma),niece with metastatic kidney cancer.at that time, patient had benign pathology. Patient presented to the ED with a complain of shortness of breath after being referred by her PCP for evaluation of possible pneumonia. In the ED, her vitals were within normal, chest X-ray was done and didn’t show pneumonia but the patient was found to have elevated procalcitonin of 22.7 ng/mL(0.09 ng/mL) CT chest was done and showed enlarged necrotic cervical lymphadenopathy which was confirmed by obtaining CT of the neck. Patient had right cervical LN core biopsy, pathology was positive for medullary thyroid cancer with Immunohistochemical studies positive for TTF-1, chromogranin, synaptophysin and calcitonin, testing for pheochromocytoma came back within normal, CEA 70.7ng/ml (&lt;0.25 ng/ml), calcitonin 2949 pg/ml (5 pg/mL) Chromogranin was high at 453 ng/ml (25 - 140 ng/mL) had PET CT with multiple low right cervical and supraclavicular lymph nodes with internal calcifications and abnormal FDG activity, which were suspicious for medullary thyroid cancer metastases, she eventually had radical neck dissection with pathology from inferior parathyroid gland positive for medullary thyroid cancer and 12/15 regional LN positive for malignancy, after the procedure her calcitonin dropped nicely to 194pg/ml, CEA dropped to 4.0, chromogrannin to 394, she was referred to genetic testing and tested positive for pathogenic variant within RET (c.1859G&gt;T, p.Cys620Phe), which is known to be associated with multiple endocrine neoplasia type 2A, she is currently being evaluated for Lutathera treatment.
Conclusion: In contrast to MEN1, in which the long-term benefit of early diagnosis by genetic screening is not well established, early diagnosis by screening of “at-risk” family members in MEN2 with positive RET mutation kindreds is essential because MTC is a life-threatening disease that can be cured or prevented by early thyroidectomy. Total thyroidectomy has been recommended for patients as young as 3 years for MEN2A if they contain the genetic mutation.
Neurofibromatosis Type 1 Presenting With Adrenal Pheochromocytoma
Authors: ElEbrashy Shady Ibrahim , ElShimy Lina Adel 
Published: May 2021

Abstract
Background: Pheochromocytomas & Paragangliomas (PCC/PGL) are amongst the rare endocrine tumours, occurring with an incidence of 0.8 per 100,0001. Though most of them have a benign nature, they are usually hormonally active causing significant cardiovascular morbidity due to the catecholamine secretion. Approximately a third of PCC/PGL have underlying germline mutations including Neurofibromatosis type 1 (NF1). Clinical Case: A 49 year old man was reviewed for symptoms of palpitation, headache, sweating, and blurred vision. physical examination revealed signs of NF1. He had multiple neurofibromas over the skin of the back, chest and neck, café-au-lait spots on the trunk and limbs. Ophthalmology assessment revealed multiple Lisch nodules bilaterally. Urinary catecholamines were significantly elevated. His initial systolic blood pressure was 190/148 mmHg. The patient’s medical history included hypertension that used to be well-controlled with Amlodipine 10 mg and Bisoprolol 5mg. however his blood pressure was harder to control during the past year. Laboratory investigations testing included measurements of urinary fractionated metanephrines which revealed high normetanephrines with a value of 690 nmol/d (N &lt; 240). metanephrines (485 nmol/d: N &lt; 275) and norepinephrines (456 nmol/d: N &lt; 440). Plasma free normetanephrines were 3.20 nmol/L (N &lt;1.20) and free metanephrines 0.4 nmol/L (N &lt; 0.48). CT scan of the abdomen showed a 1.3 x 2.4x 3.9 mass in the left suprarenal gland which showed showed moderate uptake on A meta-iodobenzylguanidine (MIBG) scan. And no evidence of metastases. The patient underwent laparoscopic adrenalectomy of the left suprarenal gland and histopathological examination was confirmatory of pheochromocytoma postoperatively. Conclusion:This is a case demonstrating the association between the germline mutation causing neurofibromatosis type 1 with the rare catecholamine secreting tumour (pheochromocytoma). Reference:1. Lefebvre M, Foulkes WD. Pheochromocytoma and paraganglioma syndromes: genetics and management update. Curr Oncol. 2014;21(1):e8-e17. doi: 10.3747/co.21.1579. [PMC free article] [PubMed] [CrossRef] [Google Scholar]