Browse
Search for other papers by Evangelos Karvounis in
Google Scholar
PubMed
Search for other papers by Ioannis Zoupas in
Google Scholar
PubMed
Search for other papers by Dimitra Bantouna in
Google Scholar
PubMed
Center for Diabetes and Endocrine Research, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio, USA
Search for other papers by Rodis D Paparodis in
Google Scholar
PubMed
Search for other papers by Roxani Efthymiadou in
Google Scholar
PubMed
Search for other papers by Christina Ioakimidou in
Google Scholar
PubMed
Search for other papers by Christos Panopoulos in
Google Scholar
PubMed
Summary
Large-cell neuroendocrine carcinoma (LCNEC) is a rare neuroendocrine prostatic malignancy. It usually arises after androgen deprivation therapy (ADT), while de novo cases are even more infrequent, with only six cases described. The patient was a 78-year-old man with no history of ADT who presented with cervical lymphadenopathy. Diagnostic approaches included PET/CT, MRI, CT scans, ultrasonography, biopsies, and cytological and immunohistochemical evaluations. Results showed a poorly differentiated carcinoma in the thyroid gland accompanied by cervical lymph node enlargement. Thyroid surgery revealed LCNEC metastasis to the thyroid gland. Additional metastases were identified in both the adrenal glands. Despite appropriate treatment, the patient died of the disease. De novo LCNEC of the prostate is a rare, highly aggressive tumor with a poor prognosis. It is resistant to most therapeutic agents, has a high metastatic potential, and is usually diagnosed at an advanced stage. Further studies are required to characterize this tumor.
Learning points
-
De novo LCNECs of the prostate gland can metastasize almost anywhere in the body, including the thyroid and adrenal glands.
-
LCNECs of the prostate are usually associated with androgen-depriving therapy, but de novo cases are also notable and should be accounted for.
-
Further studies are required to fully understand and treat LCNECs more effectively.
Search for other papers by Omayma Elshafie in
Google Scholar
PubMed
Search for other papers by Samir Hussein in
Google Scholar
PubMed
Search for other papers by Moza Al Kalbani in
Google Scholar
PubMed
Search for other papers by Aisha Al Hamadani in
Google Scholar
PubMed
Search for other papers by Abir Bou Khalil in
Google Scholar
PubMed
Search for other papers by Nicholas Woodhouse in
Google Scholar
PubMed
Summary
A 33-year-old female presented in 2013 with left flank pain. Ultrasound and MRI pelvis showed a complex mass 9 × 7 cm arising from the left ovary suggestive of ovarian torsion. She underwent a laparoscopic cystectomy, but the patient was lost to follow-up. Three years later, she presented with abdominal distension. Ultrasound and CT scan revealed a solid left ovarian mass with ascites and multiple peritoneal metastasis. Investigations showed elevated CA 125, CA 19-9. Ovarian malignancy was suspected. She underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy on November 2016. The histopathology confirmed a well-differentiated thyroid cancer of ovarian origin with features of a papillary follicular variant without evidence of ovarian cancer and the thyroglobulin (Tg) level was elevated, more than 400 consistent with the diagnosis of malignant struma ovarii. The follow-up post-surgery showed normalization of CA 125, CA 19-9 and Tg. The patient underwent total thyroidectomy on January 2017. The histology was benign excluding thyroid cancer metastases to the ovary. She was started on thyroxine suppression, following which she received two ablation doses 131iodine (131I) each 5.3 GBq. The Tg remains slightly elevated at less than 10. 131I WBS showed no residual neck uptake and no distant avid metastasis. She was planned for molecular analysis which may indicate disease severity. We describe a case of malignant struma ovarii with widespread metastatic dissemination and a good response to surgery and 131I treatment without recurrence after 5 years of follow-up. The Tg remains slightly elevated indicating minimal stable residual disease.
Learning points
-
Malignant struma ovarii is a rare disease; diagnosis is difficult and management is not well defined.
-
Presentation may mimic advanced carcinoma of the ovary.
-
Predominant sites of metastasis are adjacent pelvic structures.
-
Thyroidectomy and 131iodine therapy should be considered. The management should be similar to that of metastatic thyroid cancer.
Search for other papers by Jenny S W Yun in
Google Scholar
PubMed
Search for other papers by Chris McCormack in
Google Scholar
PubMed
Search for other papers by Michelle Goh in
Google Scholar
PubMed
University of Melbourne, Parkville, Victoria, Australia
Search for other papers by Cherie Chiang in
Google Scholar
PubMed
Summary
Acanthosis nigricans (AN) is a common dermatosis associated with hyperinsulinemia and insulin resistance. However, AN has been rarely reported in patients with insulinoma, a state of persistent hyperinsulinemia. We present a case of metastatic insulinoma, in whom AN manifested after the first cycle of peptide receptor radionuclide therapy (PRRT). A 40-year-old man was diagnosed with metastatic insulinoma after 5 months of symptomatic hypoglycemia. Within 1 month post PRRT, the patient became euglycemic but developed a pigmented, pruritic rash which was confirmed on biopsy as AN. We discuss the rare manifestation of AN in subjects with insulinoma, the role of insulin in the pathogenesis of AN, malignant AN in non-insulin-secreting malignancies and association with other insulin-resistant endocrinopathies such as acromegaly.
Learning points
-
Acanthosis nigricans (AN) is a common dermatosis which is typically asymptomatic and associated with the hyperinsulinemic state.
-
Malignant AN can rapidly spread, cause pruritus and affect mucosa and the oral cavity.
-
AN is extremely rare in patients with insulinoma despite marked hyperinsulinemia.
-
Peptide receptor radionuclide therapy might have triggered TGF-α secretion in this subject which led to malignant AN.
-
Rapid spread or unusual distribution of pruritic AN warrants further investigation to exclude underlying malignancy.
The Faculty of Medicine, Technion, Haifa, Israel
Search for other papers by Said Darawshi in
Google Scholar
PubMed
Search for other papers by Mahmoud Darawshi in
Google Scholar
PubMed
The Faculty of Medicine, Technion, Haifa, Israel
Search for other papers by Deeb Daoud Naccache in
Google Scholar
PubMed
Severe hypocalcaemia in breast cancer with bone metastasis is a rare finding usually associated with an advanced stage of the disease. We report a case of a 45-year-old woman with a history of local ductal carcinoma in situ (DCIS) of the breast, who presented with muscle tremors and general weakness. Hypocalcaemia was evident, with a positive Chvostek sign and a serum calcium level of 5.9 mg/dL (1.47 mmol/L), phosphorus 5.9 mg/dL (normal range: 2.3–4.7 mg/dL) with normal levels of albumin, magnesium and parathyroid hormone. High oral doses of alpha calcitriol and calcium with i.v. infusion of high calcium doses were instituted, altogether sufficient to maintain only mild hypocalcaemia. A whole-body CT revealed bone lesions along the axial skeleton. A biopsy from a bone lesion revealed a metastasis of breast carcinoma. With this pathological finding, leuprolide (GNRH analogue) and chlorambucil (alkylating agent) were initiated, followed by prompt tapering of infused calcium down to full discontinuation. Serum calcium was kept stable close to the low normal range by high doses of oral alpha calcitriol and calcium. This course raises suspicion that breast metastases to the skeleton caused tumour-induced hypocalcaemia by a unique mechanism. We assume that hypocalcaemia in this case was promoted by a combination of hypoparathyroidism and bone metastasis.
Learning points
-
Severe hypocalcaemia can a presenting symptom for breast cancer relapse.
Search for other papers by Vinaya Srirangam Nadhamuni in
Google Scholar
PubMed
Search for other papers by Donato Iacovazzo in
Google Scholar
PubMed
Search for other papers by Jane Evanson in
Google Scholar
PubMed
Search for other papers by Anju Sahdev in
Google Scholar
PubMed
Search for other papers by Jacqueline Trouillas in
Google Scholar
PubMed
Search for other papers by Lorraine McAndrew in
Google Scholar
PubMed
Search for other papers by Tom R Kurzawinski in
Google Scholar
PubMed
Search for other papers by David Bryant in
Google Scholar
PubMed
Search for other papers by Khalid Hussain in
Google Scholar
PubMed
Search for other papers by Satya Bhattacharya in
Google Scholar
PubMed
Search for other papers by Márta Korbonits in
Google Scholar
PubMed
Summary
A male patient with a germline mutation in MEN1 presented at the age of 18 with classical features of gigantism. Previously, he had undergone resection of an insulin-secreting pancreatic neuroendocrine tumour (pNET) at the age of 10 years and had subtotal parathyroidectomy due to primary hyperparathyroidism at the age of 15 years. He was found to have significantly elevated serum IGF-1, GH, GHRH and calcitonin levels. Pituitary MRI showed an overall bulky gland with a 3 mm hypoechoic area. Abdominal MRI showed a 27 mm mass in the head of the pancreas and a 6 mm lesion in the tail. Lanreotide-Autogel 120 mg/month reduced GHRH by 45% and IGF-1 by 20%. Following pancreaticoduodenectomy, four NETs were identified with positive GHRH and calcitonin staining and Ki-67 index of 2% in the largest lesion. The pancreas tail lesion was not removed. Post-operatively, GHRH and calcitonin levels were undetectable, IGF-1 levels normalised and GH suppressed normally on glucose challenge. Post-operative fasting glucose and HbA1c levels have remained normal at the last check-up. While adolescent-onset cases of GHRH-secreting pNETs have been described, to the best of our knowledge, this is the first reported case of ectopic GHRH in a paediatric setting leading to gigantism in a patient with MEN1. Our case highlights the importance of distinguishing between pituitary and ectopic causes of gigantism, especially in the setting of MEN1, where paediatric somatotroph adenomas causing gigantism are extremely rare.
Learning points
-
It is important to diagnose gigantism and its underlying cause (pituitary vs ectopic) early in order to prevent further growth and avoid unnecessary pituitary surgery. The most common primary tumour sites in ectopic acromegaly include the lung (53%) and the pancreas (34%) (1): 76% of patients with a pNET secreting GHRH showed a MEN1 mutation (1).
-
Plasma GHRH testing is readily available in international laboratories and can be a useful diagnostic tool in distinguishing between pituitary acromegaly mediated by GH and ectopic acromegaly mediated by GHRH. Positive GHRH immunostaining in the NET tissue confirms the diagnosis.
-
Distinguishing between pituitary (somatotroph) hyperplasia secondary to ectopic GHRH and pituitary adenoma is difficult and requires specialist neuroradiology input and consideration, especially in the MEN1 setting. It is important to note that the vast majority of GHRH-secreting tumours (lung, pancreas, phaeochromocytoma) are expected to be visible on cross-sectional imaging (median diameter 55 mm) (1). Therefore, we suggest that a chest X-ray and an abdominal ultrasound checking the adrenal glands and the pancreas should be included in the routine work-up of newly diagnosed acromegaly patients.
Search for other papers by Ziadoon Faisal in
Google Scholar
PubMed
Search for other papers by Miguel Debono in
Google Scholar
PubMed
Summary
In this case report, we describe the management of a patient who was admitted with an ectopic ACTH syndrome during the COVID pandemic with new-onset type 2 diabetes, neutrophilia and unexplained hypokalaemia. These three findings when combined should alert physicians to the potential presence of Cushing’s syndrome (CS). On admission, a quick diagnosis of CS was made based on clinical and biochemical features and the patient was treated urgently using high dose oral metyrapone thus allowing delays in surgery and rapidly improving the patient’s clinical condition. This resulted in the treatment of hyperglycaemia, hypokalaemia and hypertension reducing cardiovascular risk and likely risk for infection. Observing COVID-19 pandemic international guidelines to treat patients with CS has shown to be effective and offers endocrinologists an option to manage these patients adequately in difficult times.
Learning points
-
This case report highlights the importance of having a low threshold for suspicion and investigation for Cushing’s syndrome in a patient with neutrophilia and hypokalaemia, recently diagnosed with type 2 diabetes especially in someone with catabolic features of the disease irrespective of losing weight.
-
It also supports the use of alternative methods of approaching the diagnosis and treatment of Cushing’s syndrome during a pandemic as indicated by international protocols designed specifically for managing this condition during Covid-19.
Faculty of Medicine, The University of Queensland, Brisbane, Australia
Search for other papers by Matthew Seymour in
Google Scholar
PubMed
Faculty of Medicine, The University of Queensland, Brisbane, Australia
Search for other papers by Thomas Robertson in
Google Scholar
PubMed
Search for other papers by Jason Papacostas in
Google Scholar
PubMed
Search for other papers by Kirk Morris in
Google Scholar
PubMed
Department of Radiology, Royal Brisbane and Women’s Hospital, Brisbane, Australia
Search for other papers by Jennifer Gillespie in
Google Scholar
PubMed
Search for other papers by Debra Norris in
Google Scholar
PubMed
Faculty of Medicine, The University of Queensland, Brisbane, Australia
Institute of Health and Biomedical Innovation, Faculty of Health, Queensland University of Technology, Translational Research Institute, Princess Alexandra Hospital, Brisbane Australia
Search for other papers by Emma L Duncan in
Google Scholar
PubMed
Summary
A 34-year-old woman presented 18 months post-partum with blurred vision, polyuria, amenorrhoea, headache and general malaise. Comprehensive clinical examination showed left superior temporal visual loss only. Initial investigations revealed panhypopituitarism and MRI demonstrated a sellar mass involving the infundibulum and hypothalamus. Lymphocytic hypophysitis was suspected and high dose glucocorticoids were commenced along with desmopressin and thyroxine. However, her vision rapidly deteriorated. At surgical biopsy, an irresectable grey amorphous mass involving the optic chiasm was identified. Histopathology was initially reported as granulomatous hypophysitis. Despite the ongoing treatment with glucocorticoids, her vision worsened to light detection only. Histopathological review revised the diagnosis to partially treated lymphoma. A PET scan demonstrated avid uptake in the pituitary gland in addition to splenic involvement, lymphadenopathy above and below the diaphragm, and a bone lesion. Excisional node biopsy of an impalpable infraclavicular lymph node confirmed nodular lymphocyte-predominant Hodgkin lymphoma. Hyper-CVAD chemotherapy was commenced, along with rituximab; fluid-balance management during chemotherapy (with its requisite large fluid volumes) was extremely complex given her diabetes insipidus. The patient is now in clinical remission. Panhypopituitarism persists; however, her vision has recovered sufficiently for reading large print and driving. To the best of our knowledge, this is the first reported case of Hodgkin lymphoma presenting initially as hypopituitarism.
Learning points
-
Lymphoma involving the pituitary is exceedingly rare and, to the best of our knowledge, this is the first reported case of nodular lymphocyte-predominant Hodgkin lymphoma presenting as hypopituitarism.
-
There are myriad causes of a sellar mass and this case highlights the importance of reconsidering the diagnosis when patients fail to respond as expected to appropriate therapeutic intervention.
-
This case highlights the difficulties associated with managing panhypopituitary patients receiving chemotherapy, particularly when this involves large volumes of i.v. hydration fluid.
Search for other papers by Seong Keat Cheah in
Google Scholar
PubMed
Search for other papers by Chad Ramese Bisambar in
Google Scholar
PubMed
Search for other papers by Deborah Pitfield in
Google Scholar
PubMed
Search for other papers by Olivier Giger in
Google Scholar
PubMed
Search for other papers by Rogier ten Hoopen in
Google Scholar
PubMed
Search for other papers by Jose-Ezequiel Martin in
Google Scholar
PubMed
Search for other papers by Graeme R Clark in
Google Scholar
PubMed
Search for other papers by Soo-Mi Park in
Google Scholar
PubMed
Search for other papers by Craig Parkinson in
Google Scholar
PubMed
Search for other papers by Benjamin G Challis in
Google Scholar
PubMed
Medical Genetics, Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK
Search for other papers by Ruth T Casey in
Google Scholar
PubMed
Summary
A 38-year-old female was identified as carrying a heterozygous pathogenic MEN1 variant (c.1304delG) through predictive genetic testing, following a diagnosis of familial hyperparathyroidism. Routine screening for parathyroid and pituitary disease was negative. However, cross-sectional imaging by CT revealed a 41 mm pancreatic tail mass. Biopsy via endoscopic ultrasound confirmed the lesion to be a well-differentiated (grade 1) pancreatic neuroendocrine tumour (pNET) with MIB1<1%. Biochemically, hyperinsulinaemic hypoglycaemia was confirmed following an overnight fast, which was subsequently managed by diet alone prior to definitive surgery. Pre-operative work-up with octreotide SPECT CT demonstrated avid tracer uptake in the pancreatic lesion and, unexpectedly, a focal area of uptake in the left breast. Further investigation, and subsequent mastectomy, confirmed ductal carcinoma in situ pT2 (23 mm) grade 1, N0 (ER positive; HER2 negative). Following mastectomy, our patient underwent a successful distal pancreatectomy to resect the pNET. Loss of heterozygosity (LOH) at the MEN1 locus was found in both the breast tumour and pNET, thereby in keeping with a 'two-hit' hypothesis of oncogenesis, a suggestive but non-definitive clue for causation. To obtain further support for a causative relationship between MEN1 and breast cancer, we undertook a detailed review of the published literature which overall supports the notion that breast cancer is a MEN1-related malignancy that presents at a younger age and histologically, is typically of ductal subtype. Currently, clinical guidance regarding breast cancer surveillance in MEN1 does not exist and further research is required to establish a clinical and cost-effective surveillance strategy).
Learning points
-
We describe a case of pNET and breast cancer diagnosed at a young age of 38 years in a patient who is heterozygous for a pathogenic MEN1 variant. Loss of the wild-type allele was seen in both breast tissue and pNET specimen.
-
Breast cancer may be an under-recognised MEN1-associated malignancy that presents at a younger age than in the general population with a relative risk of 2–3.
-
Further research is required to determine the cost-effectiveness of breast cancer surveillance approach at a younger age in MEN1 patients relative to the general population .
Search for other papers by Michal Barabas in
Google Scholar
PubMed
Search for other papers by Isabel Huang-Doran in
Google Scholar
PubMed
Search for other papers by Debbie Pitfield in
Google Scholar
PubMed
Search for other papers by Hazel Philips in
Google Scholar
PubMed
Search for other papers by Manoj Goonewardene in
Google Scholar
PubMed
Search for other papers by Ruth T Casey in
Google Scholar
PubMed
IMED Biotech Unit, Clinical Discovery Unit, AstraZeneca, Cambridge, UK
Search for other papers by Benjamin G Challis in
Google Scholar
PubMed
Summary
A 67-year-old woman presented with a generalised rash associated with weight loss and resting tachycardia. She had a recent diagnosis of diabetes mellitus. Biochemical evaluation revealed elevated levels of circulating glucagon and chromogranin B. Cross-sectional imaging demonstrated a pancreatic lesion and liver metastases, which were octreotide-avid. Biopsy of the liver lesion confirmed a diagnosis of well-differentiated grade 2 pancreatic neuroendocrine tumour, consistent with metastatic glucagonoma. Serial echocardiography commenced 4 years before this diagnosis demonstrated a progressive left ventricular dilatation and dysfunction in the absence of ischaemia, suggestive of glucagonoma-associated dilated cardiomyopathy. Given the severity of the cardiac impairment, surgical management was considered inappropriate and somatostatin analogue therapy was initiated, affecting clinical and biochemical improvement. Serial cross-sectional imaging demonstrated stable disease 2 years after diagnosis. Left ventricular dysfunction persisted, however, despite somatostatin analogue therapy and optimal medical management of cardiac failure. In contrast to previous reports, the case we describe demonstrates that chronic hyperglucagonaemia may lead to irreversible left ventricular compromise. Management of glucagonoma therefore requires careful and serial evaluation of cardiac status.
Learning points:
-
In rare cases, glucagonoma may present with cardiac failure as the dominant feature. Significant cardiac impairment may occur in the absence of other features of glucagonoma syndrome due to subclinical chronic hyperglucagonaemia.
-
A diagnosis of glucagonoma should be considered in patients with non-ischaemic cardiomyopathy, particularly those with other features of glucagonoma syndrome.
-
Cardiac impairment due to glucagonoma may not respond to somatostatin analogue therapy, even in the context of biochemical improvement.
-
All patients with a new diagnosis of glucagonoma should be assessed clinically for evidence of cardiac failure and, if present, a baseline transthoracic echocardiogram should be performed. In the presence of cardiac impairment these patients should be managed by an experienced cardiologist.
Search for other papers by Sarah Y Qian in
Google Scholar
PubMed
Search for other papers by Matthew J L Hare in
Google Scholar
PubMed
Search for other papers by Alan Pham in
Google Scholar
PubMed
Department of Medicine, Monash University, Melbourne, Australia
Search for other papers by Duncan J Topliss in
Google Scholar
PubMed
Summary
Insulinomas are rare neuroendocrine tumours that classically present with fasting hypoglycaemia. This case report discusses an uncommon and challenging case of insulinoma soon after upper gastrointestinal surgery. A 63-year-old man presented with 6 months of post-prandial hypoglycaemia beginning after a laparoscopic revision of Toupet fundoplication. Hyperinsulinaemic hypoglycaemia was confirmed during a spontaneous episode and in a mixed-meal test. Localisation studies including magnetic resonance imaging (MRI), endoscopic ultrasound (EUS) and gallium dotatate positron emission tomography (68Ga Dotatate PET) were consistent with a small insulinoma in the mid-body of the pancreas. The lesion was excised and histopathology was confirmed a localised well-differentiated neuroendocrine pancreatic neoplasm. There have been no significant episodes of hypoglycaemia since. This case highlights several key points. Insulinoma should be sought in proven post-prandial hyperinsulinaemic hypoglycaemia – even in the absence of fasting hypoglycaemia. The use of nuclear imaging targeting somatostatin and GLP1 receptors has improved accuracy of localisation. Despite these advances, accurate surgical resection can remain challenging.
Learning points:
-
Hypoglycaemia is defined by Whipple’s triad and can be provoked by fasting or mixed-meal tests.
-
Although uncommon, insulinomas can present with post-prandial hypoglycaemia.
-
In hypoglycaemia following gastrointestinal surgery (i.e. bariatric surgery or less commonly Nissen fundoplication) dumping syndrome or non-insulinoma pancreatogenous hypoglycaemia syndrome (NIPHS) should be considered.
-
Improved imaging techniques including MRI, endoscopic ultrasound and functional nuclear medicine scans aid localisation of insulinomas.
-
Despite advances in imaging and surgical techniques, accurate resection of insulinomas remains challenging.
