Browse

You are looking at 1 - 10 of 22 items for :

  • Gland/Organ x
  • Endocrine-related cancer x
Clear All
Sandra Martens Ghent University Hospital, Ghent, Belgium

Search for other papers by Sandra Martens in
Google Scholar
PubMed
Close
and
Bruno Lapauw Ghent University Hospital, Ghent, Belgium
Ghent University, Ghent, Belgium

Search for other papers by Bruno Lapauw in
Google Scholar
PubMed
Close

Summary

Mitotane is used for treatment of advanced adrenocortical carcinoma. It is administered when the carcinoma is unresectable, metastasized, or at high-risk of recurrence after resection. In addition, mitotane is considered to have direct adrenolytic effects. Because of its narrow therapeutic–toxic range, therapeutic drug monitoring (TDM) is warranted. In 2020, a left-sided adrenal gland tumor was found (5.8 cm) in a 38-year-old man. Considering the size of this lesion and inability to exclude an adrenocortical carcinoma on imaging, a laparoscopic adrenalectomy was performed. Histopathologic examination determined presence of an adrenocortical carcinoma (pT2N0M0 ENSAT stadium II; ki67 10–15%). There was no evidence for residual or metastatic disease but given the high risk of recurrence, adjuvant therapy with mitotane was initiated. During TDM, a sudden and spuriously high level of mitotane was observed but without signs or symptoms of toxicity. After exploration, it was found that this high concentration was completely due to uncontrolled hypertriglyceridemia. After correction thereof, mitotane levels were again in the therapeutic range. This observation underscores the importance of TDM sampling in a fasting state with concurrent control of prevalent or incident dyslipidemia.

Learning points

  • TDM of mitotane is advocated to achieve therapeutic levels while avoiding toxicity. For correct TDM, sampling should be done at least 12 h after last intake of mitotane.

  • Although sampling in fasting conditions in not explicitly mentioned in the guidelines, fasting state should be considered as elevated serum triglyceride levels might cause spuriously high mitotane levels.

  • In patients undergoing treatment with mitotane and presenting with too high or unexplained fluctuating mitotane levels without signs or symptoms of toxicity, hypertriglyceridemia as a possible cause should be investigated.

  • If dyslipidemia occurs in patients under mitotane treatment, other causes than mitotane (e.g. alcohol abuse and diabetes) should be considered and appropriate treatment should be initiated.

Open access
Rikako Nakajima Department of Endocrinology and Metabolism, Tsukuba University Hospital Mito Clinical Education and Training Center, Mito Kyodo General Hospital, Miyamachi, Mito, Ibaraki, Japan

Search for other papers by Rikako Nakajima in
Google Scholar
PubMed
Close
,
Hiroto Idesawa Department of Endocrinology and Metabolism, Tsukuba University Hospital Mito Clinical Education and Training Center, Mito Kyodo General Hospital, Miyamachi, Mito, Ibaraki, Japan

Search for other papers by Hiroto Idesawa in
Google Scholar
PubMed
Close
,
Daisuke Sato Department of Endocrinology and Metabolism, Tsukuba University Hospital Mito Clinical Education and Training Center, Mito Kyodo General Hospital, Miyamachi, Mito, Ibaraki, Japan

Search for other papers by Daisuke Sato in
Google Scholar
PubMed
Close
,
Jun Ito Department of Endocrinology and Metabolism, Tsukuba University Hospital Mito Clinical Education and Training Center, Mito Kyodo General Hospital, Miyamachi, Mito, Ibaraki, Japan

Search for other papers by Jun Ito in
Google Scholar
PubMed
Close
,
Kei Ito Department of Endocrinology and Metabolism, Tsukuba University Hospital Mito Clinical Education and Training Center, Mito Kyodo General Hospital, Miyamachi, Mito, Ibaraki, Japan

Search for other papers by Kei Ito in
Google Scholar
PubMed
Close
,
Masanao Fujii Department of Endocrinology and Metabolism, Tsukuba University Hospital Mito Clinical Education and Training Center, Mito Kyodo General Hospital, Miyamachi, Mito, Ibaraki, Japan

Search for other papers by Masanao Fujii in
Google Scholar
PubMed
Close
,
Takamichi Suzuki Department of Gastrointestinal Surgery, Tsukuba University Hospital Mito Clinical Education and Training Center, Mito Kyodo General Hospital, Miyamachi, Mito, Ibaraki, Japan

Search for other papers by Takamichi Suzuki in
Google Scholar
PubMed
Close
,
Tomoaki Furuta Department of Gastrointestinal Surgery, Tsukuba University Hospital Mito Clinical Education and Training Center, Mito Kyodo General Hospital, Miyamachi, Mito, Ibaraki, Japan

Search for other papers by Tomoaki Furuta in
Google Scholar
PubMed
Close
,
Hitomi Kawai Department of Pathology, Tsukuba University Hospital Mito Clinical Education and Training Center, Mito Kyodo General Hospital, Miyamachi, Mito, Ibaraki, Japan

Search for other papers by Hitomi Kawai in
Google Scholar
PubMed
Close
,
Norio Takayashiki Department of Pathology, Tsukuba University Hospital Mito Clinical Education and Training Center, Mito Kyodo General Hospital, Miyamachi, Mito, Ibaraki, Japan

Search for other papers by Norio Takayashiki in
Google Scholar
PubMed
Close
,
Masanao Kurata Department of Gastrointestinal Surgery, Tsukuba University Hospital Mito Clinical Education and Training Center, Mito Kyodo General Hospital, Miyamachi, Mito, Ibaraki, Japan

Search for other papers by Masanao Kurata in
Google Scholar
PubMed
Close
, and
Hiroaki Yagyu Department of Endocrinology and Metabolism, Tsukuba University Hospital Mito Clinical Education and Training Center, Mito Kyodo General Hospital, Miyamachi, Mito, Ibaraki, Japan

Search for other papers by Hiroaki Yagyu in
Google Scholar
PubMed
Close

Summary

Unawareness of postprandial hypoglycemia for 5 years was identified in a 66-year-old man at a local clinic. The patient was referred to our hospital because of this first awareness of hypoglycemia (i.e. lightheadedness and impaired consciousness) developing after lunch. In a 75 g oral glucose tolerance test, the plasma glucose concentration was decreased to 32 mg/dL (1.8 mmol/L) at 150 min with relatively high concentrations of insulin (8.1 μU/mL), proinsulin (70.3 pmol/L), and C-peptide (4.63 ng/mL). In a prolonged fasting test, the plasma glucose concentration was decreased to 43 mg/dL (2.4 mmol/L) at 66 h with an insulin concentration of 1.4 μU/mL and a C-peptide concentration of 0.49 ng/mL. Computed tomography showed an 18 mm hyperenhancing tumor in the uncinate process of the pancreas. A selective arterial calcium stimulation test showed an elevated serum insulin concentration in the superior mesenteric artery. The patient was then diagnosed with insulinoma and received pancreaticoduodenectomy. Continuous glucose monitoring (CGM) using the Dexcom G6 system showed unawareness of hypoglycemia mainly during the daytime before surgery. When the sensor glucose value was reduced to 55 mg/dL (3.1 mmol/L), the Dexcom G6 system emitted an urgent low glucose alarm to the patient four times for 10 days. Two months after surgery, an overall increase in daily blood glucose concentrations and resolution of hypoglycemia were shown by CGM. We report a case of insulinoma with unawareness of postprandial hypoglycemia in the patient. The Dexcom G6 system was helpful for assessing preoperative hypoglycemia and for evaluating outcomes of treatment by surgery.

Learning points

  • Insulinoma occasionally leads to postprandial hypoglycemia.

  • The CGM system is useful for revealing the presence of unnoticed hypoglycemia and for evaluating treatment outcomes after surgical resection.

  • The Dexcom G6 system has an urgent low glucose alarm, making it particularly suitable for patients who are unaware of hypoglycemia.

Open access
Hessa Boharoon Neuroendocrine Tumour Unit, ENETS Centre of Excellence, London, UK

Search for other papers by Hessa Boharoon in
Google Scholar
PubMed
Close
,
Shaunak Navalkissoor Department of Nuclear Medicine, ENETS Centre of Excellence, London, UK

Search for other papers by Shaunak Navalkissoor in
Google Scholar
PubMed
Close
,
Tu Vinh Luong Department of Pathology, Royal Free Hospital, London, UK

Search for other papers by Tu Vinh Luong in
Google Scholar
PubMed
Close
,
Martyn Caplin Neuroendocrine Tumour Unit, ENETS Centre of Excellence, London, UK

Search for other papers by Martyn Caplin in
Google Scholar
PubMed
Close
, and
Ashley Grossman Neuroendocrine Tumour Unit, ENETS Centre of Excellence, London, UK

Search for other papers by Ashley Grossman in
Google Scholar
PubMed
Close

Summary

Insulinomas are rare pancreatic neuroendocrine neoplasms (NENs) that are typically sporadic and solitary, with the majority being <2 cm in diameter at diagnosis. The median duration of symptoms before diagnosis is variable; however, this is usually in the region of 12–18 months. We report on an insulinoma diagnosed some 25 years following initial symptoms, having by that stage attained a diameter of 4 cm. We present a 50-year-old man who was reported with hypoglycaemic symptoms on his wedding 25 years prior to eventual confirmation of an insulinoma. He had since learned to live with the symptoms by eating frequently to manage his hypoglycaemia. However, over recent months, he reported a substantial deterioration in his symptoms, and indeed, had collapsed on two occasions. He had a fasting glucose of 2.9 mmol/L with grossly inappropriate elevated insulin and C-peptide levels. MRI demonstrated a 4.1 cm lesion at the body of pancreas and an indeterminate 9-mm liver lesion with a negative 68Gallium-DOTATATE PET scan. Accordingly, he was initiated on diazoxide and referred to the surgical team for distal pancreatectomy: histology confirmed a 4.4-cm well-differentiated pancreatic NEN of intermediate grade (NEN G2, Grade 2, 2017 World Health Organization (WHO) pancreatic-NEN classification), with positive immunohistochemistry for insulin. His hypoglycaemia episodes have ceased, and he remains under active surveillance. Our case demonstrates the possibility of dietary control of insulinoma-induced hypoglycaemia, and the likelihood that such a prolonged delay in diagnosis has led to the uncommonly large size of the apparently benign tumour which is usually ‘small and indolent’.

Learning points

  • Most patients with insulinomas have lesions that are 1–2 cm in size, with 96% being less than 3 cm.

  • The mean tumour size of insulinomas found in 3 of the largest reported series was 1.5 cm, with a range of 0.1–7.0 cm.

  • It is not uncommon for patients to have symptoms for several months to years before diagnosis; however, no reported cases had the symptoms such long for 25 years, and the large size of the tumour in this case may reflect the very long history.

Open access
George Brown Department of Hepatobiliary & Pancreatic Surgery, University Hospital Southampton, Southampton, UK

Search for other papers by George Brown in
Google Scholar
PubMed
Close
,
Anthony Mark Monaghan Department of Hepatobiliary & Pancreatic Surgery, University Hospital Southampton, Southampton, UK

Search for other papers by Anthony Mark Monaghan in
Google Scholar
PubMed
Close
,
Richard Fristedt Department of Hepatobiliary & Pancreatic Surgery, University Hospital Southampton, Southampton, UK

Search for other papers by Richard Fristedt in
Google Scholar
PubMed
Close
,
Emma Ramsey Department of Hepatobiliary & Pancreatic Surgery, University Hospital Southampton, Southampton, UK

Search for other papers by Emma Ramsey in
Google Scholar
PubMed
Close
,
Ma’en Al-Mrayat Department of Endocrinology, University Hospital Southampton, Southampton, UK

Search for other papers by Ma’en Al-Mrayat in
Google Scholar
PubMed
Close
,
Rushda Rajak Department of Cellular Pathology, University Hospital Southampton, Southampton, UK

Search for other papers by Rushda Rajak in
Google Scholar
PubMed
Close
,
Thomas Armstrong Department of Hepatobiliary & Pancreatic Surgery, University Hospital Southampton, Southampton, UK

Search for other papers by Thomas Armstrong in
Google Scholar
PubMed
Close
, and
Arjun Takhar Department of Hepatobiliary & Pancreatic Surgery, University Hospital Southampton, Southampton, UK

Search for other papers by Arjun Takhar in
Google Scholar
PubMed
Close

Summary

Vasoactive intestinal peptide-secreting tumours (VIPomas) are an extremely rare form of functional pancreatic neuroendocrine tumour with an estimated annual incidence of 1 in 10 million. Associated tumour hypersecretion of other peptides, including pancreatic polypeptide (PPomas), may also be seen. These malignancies classically present with a defined triad of refractory diarrhoea, hypokalaemia and metabolic acidosis known as Verner–Morrison syndrome. Diagnosis is frequently delayed, and the majority of patients will have metastatic disease at presentation. Symptoms are usually well controlled with somatostatin analogue administration. Here we report a case of metastatic mixed VIPoma/PPoma-induced diarrhoea causing renal failure so severe that ultrafiltration was required to recover adequate renal function.

Learning points

  • Profuse, watery diarrhoea is a common presenting complaint with a multitude of aetiologies. This, combined with the rarity of these tumours, makes diagnosis difficult and frequently delayed. A functional neuroendocrine tumour should be suspected when diarrhoea is unusually extreme, prolonged and common causes have been promptly excluded.

  • These patients are likely to be profoundly unwell on presentation. They are extremely hypovolaemic with dangerous electrolyte and metabolic abnormalities. Aggressive initial rehydration and electrolyte replacement are imperative. A somatostatin analogue should be commenced as soon as the diagnosis is suspected.

  • This is an extreme example of Verner–Morrison syndrome. We are unaware of another case where renal failure secondary to diarrhoea and dehydration was so severe that renal replacement therapy was required to restore adequate renal function, further emphasising how critically unwell these patients can be.

  • Both the primary tumour and metastases showed a remarkably good and rapid response to somatostatin analogue administration. Cystic change and involution were noted on repeat imaging within days.

  • Prior to his illness, this patient was extremely high functioning with no medical history. His diagnosis was an enormous psychological shock, and the consideration and care for his psychological well-being were a crucial part of his overall management. It highlights the importance of a holistic approach to cancer care and the role of the clinical nurse specialist within the cancer multidisciplinary team.

Open access
Jenny S W Yun Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

Search for other papers by Jenny S W Yun in
Google Scholar
PubMed
Close
,
Chris McCormack Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

Search for other papers by Chris McCormack in
Google Scholar
PubMed
Close
,
Michelle Goh Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

Search for other papers by Michelle Goh in
Google Scholar
PubMed
Close
, and
Cherie Chiang Department of Internal Medicine, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
University of Melbourne, Parkville, Victoria, Australia

Search for other papers by Cherie Chiang in
Google Scholar
PubMed
Close

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.

Open access
Pranav Gupta Division of Endocrinology, Department of Pediatrics, Children’s Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia, USA

Search for other papers by Pranav Gupta in
Google Scholar
PubMed
Close
,
Karen Loechner Division of Endocrinology, Department of Pediatrics, Children’s Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia, USA
Division of Endocrinology, Department of Pediatrics, Connecticut Childrens Medical Center, Farmington, Connecticut, USA

Search for other papers by Karen Loechner in
Google Scholar
PubMed
Close
,
Briana C Patterson Division of Endocrinology, Department of Pediatrics, Children’s Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia, USA
Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta, Atlanta, Georgia, USA

Search for other papers by Briana C Patterson in
Google Scholar
PubMed
Close
, and
Eric Felner Division of Endocrinology, Department of Pediatrics, Children’s Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia, USA

Search for other papers by Eric Felner in
Google Scholar
PubMed
Close

Summary

Insulinomas are a rare cause of persistent hypoglycemia in a previously healthy child. In addition to symptoms of hypoglycemia, individuals with insulinomas usually present with a history of incessant caloric intake and weight gain due to a constant need to counter hypoglycemia. In addition to an extensive review of the literature, we report the first case of an insulinoma coexisting with reduced appetite secondary to anorexia nervosa in an adolescent female.

Learning points

  • Eliciting a detailed family history is important in hypoglycemia cases.

  • Obtaining a thorough dietary intake, weight history, and menstrual cycles (in females) and considering a psychiatric consultation for an eating disorder when indicated.

  • Although rare in the pediatric population, multiple endocrine neoplasia type 1 syndrome should be considered in the evaluation of children and adolescents with hypoglycemia who also have a family history of pituitary, pancreatic, and/or parathyroid endocrinopathies.

Open access
Vinaya Srirangam Nadhamuni Department of Endocrinology, Barts and the London School of Medicine and Dentistry, William Harvey Research Institute, Queen Mary University of London, London, UK

Search for other papers by Vinaya Srirangam Nadhamuni in
Google Scholar
PubMed
Close
,
Donato Iacovazzo Department of Endocrinology, Barts and the London School of Medicine and Dentistry, William Harvey Research Institute, Queen Mary University of London, London, UK

Search for other papers by Donato Iacovazzo in
Google Scholar
PubMed
Close
,
Jane Evanson St. Bartholomew’s Hospital, Barts and the London NHS Trust, London, UK

Search for other papers by Jane Evanson in
Google Scholar
PubMed
Close
,
Anju Sahdev St. Bartholomew’s Hospital, Barts and the London NHS Trust, London, UK

Search for other papers by Anju Sahdev in
Google Scholar
PubMed
Close
,
Jacqueline Trouillas Department of Pathology, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, France

Search for other papers by Jacqueline Trouillas in
Google Scholar
PubMed
Close
,
Lorraine McAndrew St. Bartholomew’s Hospital, Barts and the London NHS Trust, London, UK

Search for other papers by Lorraine McAndrew in
Google Scholar
PubMed
Close
,
Tom R Kurzawinski Division of Endocrine Surgery, University College Hospital, London, UK

Search for other papers by Tom R Kurzawinski in
Google Scholar
PubMed
Close
,
David Bryant Sunderland Royal Hospital, South Tyneside and Sunderland NHS Foundation Trust, South Shields, Tyne and Wear, UK

Search for other papers by David Bryant in
Google Scholar
PubMed
Close
,
Khalid Hussain Division of Endocrinology, Sidra Medicine, Doha, Ad Dawhah, Qatar

Search for other papers by Khalid Hussain in
Google Scholar
PubMed
Close
,
Satya Bhattacharya St. Bartholomew’s Hospital, Barts and the London NHS Trust, London, UK

Search for other papers by Satya Bhattacharya in
Google Scholar
PubMed
Close
, and
Márta Korbonits Department of Endocrinology, Barts and the London School of Medicine and Dentistry, William Harvey Research Institute, Queen Mary University of London, London, UK

Search for other papers by Márta Korbonits in
Google Scholar
PubMed
Close

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%) (): 76% of patients with a pNET secreting GHRH showed a MEN1 mutation ().

  • 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) (). 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.

Open access
Kieran Palmer King’s College Hospital National Health Service Foundation Trust, London, UK

Search for other papers by Kieran Palmer in
Google Scholar
PubMed
Close
,
Scott Weerasuriya King’s College Hospital National Health Service Foundation Trust, London, UK

Search for other papers by Scott Weerasuriya in
Google Scholar
PubMed
Close
,
Benjamin Whitelaw King’s College Hospital National Health Service Foundation Trust, London, UK

Search for other papers by Benjamin Whitelaw in
Google Scholar
PubMed
Close
, and
Rajaventhan Srirajaskanthan King’s College Hospital National Health Service Foundation Trust, London, UK

Search for other papers by Rajaventhan Srirajaskanthan in
Google Scholar
PubMed
Close

Summary

We report a rare case of posterior reversible encephalopathy syndrome (PRES), precipitated by ectopic Cushing’s syndrome, in a patient with a metastatic pancreatic neuroendocrine tumour. A 55-year-old female presented as a hypertensive emergency with seizures and severe biochemical disturbance, including alkalosis, hypokalaemia and hyperglycaemia. MRI showed vasogenic oedema in the parieto-occipital region, consistent with a diagnosis of PRES. She had a significantly raised serum cortisol (>6000 nmol/L) which did not suppress with dexamethasone. Plasma adrenocorticotropic hormone (ACTH) concentrations were neither suppressed nor raised but were consistently within the normal reference range. The unexpected finding of a normal ACTH may be explained by either tumour secretion of unmeasured ACTH-related peptides, immunoassay antibody interference or episodic ACTH secretion. PRES is usually reversible with prompt and appropriate treatment. Hypercortisolism associated PRES is rare and may be associated with a worse outcome.

Learning points

  • PRES secondary to ectopic Cushing’s syndrome is very rare.

  • PRES in this context may indicate a worse prognosis.

  • In ectopic Cushing’s syndrome, if the serum ACTH level is normal, consider testing for ACTH-related peptides or interfering antibodies.

  • Further research is required to establish the best treatment approach and to improve patients’ outcomes.

Open access
Seong Keat Cheah Endocrinology, Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK

Search for other papers by Seong Keat Cheah in
Google Scholar
PubMed
Close
,
Chad Ramese Bisambar Endocrinology, Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK

Search for other papers by Chad Ramese Bisambar in
Google Scholar
PubMed
Close
,
Deborah Pitfield Endocrinology, Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK

Search for other papers by Deborah Pitfield in
Google Scholar
PubMed
Close
,
Olivier Giger Pathology, Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK

Search for other papers by Olivier Giger in
Google Scholar
PubMed
Close
,
Rogier ten Hoopen Pathology, Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK

Search for other papers by Rogier ten Hoopen in
Google Scholar
PubMed
Close
,
Jose-Ezequiel Martin Medical Genetics, Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK

Search for other papers by Jose-Ezequiel Martin in
Google Scholar
PubMed
Close
,
Graeme R Clark Medical Genetics, Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK

Search for other papers by Graeme R Clark in
Google Scholar
PubMed
Close
,
Soo-Mi Park Medical Genetics, Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK

Search for other papers by Soo-Mi Park in
Google Scholar
PubMed
Close
,
Craig Parkinson Endocrinology, East Suffolk and North Essex NHS Foundation Trust, Colchester, Essex, UK

Search for other papers by Craig Parkinson in
Google Scholar
PubMed
Close
,
Benjamin G Challis Endocrinology, Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK

Search for other papers by Benjamin G Challis in
Google Scholar
PubMed
Close
, and
Ruth T Casey Endocrinology, Addenbrookes Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK
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
Close

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 .

Open access
F Keen Department of Diabetes and Endocrinology, Royal Glamorgan Hospital, Llantrisant, UK

Search for other papers by F Keen in
Google Scholar
PubMed
Close
,
F Iqbal Morriston Hospital, Swansea, UK

Search for other papers by F Iqbal in
Google Scholar
PubMed
Close
,
P Owen Department of Diabetes and Endocrinology, Royal Glamorgan Hospital, Llantrisant, UK

Search for other papers by P Owen in
Google Scholar
PubMed
Close
,
A Christian University Hospital of Wales, Cardiff, UK

Search for other papers by A Christian in
Google Scholar
PubMed
Close
,
N Kumar University Hospital of Wales, Cardiff, UK

Search for other papers by N Kumar in
Google Scholar
PubMed
Close
, and
A Kalhan Department of Diabetes and Endocrinology, Royal Glamorgan Hospital, Llantrisant, UK

Search for other papers by A Kalhan in
Google Scholar
PubMed
Close

Summary

We present a 60-year-old woman who underwent successful surgical resection (partial pancreatectomy) for a low grade non-functioning pancreatic neuroendocrine tumour (pNET), with no biochemical or radiological features of recurrence on follow-up visits for 5 years. Fourteen years after the initial surgery, she developed spontaneous severe hypoglycaemic episodes which required hospitalisation, with subsequent investigations confirming the diagnosis of a metastatic insulin-secreting pNET (insulinoma). Medical management of her severe spontaneous hypoglycaemic episodes remained challenging, despite optimum use of diazoxide and somatostatin analogue therapy. Based on a discussion at the regional neuroendocrine tumour multidisciplinary team meeting, she underwent an elective hepatic trans-arterial embolization which was unfortunately unsuccessful. She ended up requiring an emergency right hemihepatectomy and left retroperitoneal mass resection which finally stabilised her clinical condition.

Learning points:

  • Ours is only the seventh case report of a previously benign pNET presenting as a functional insulin secreting metastatic tumour. However, it is the first case report, in which the metastatic functional pNET presented after such a long hiatus (14 years).

  • There is currently no clear consensus regarding the length of follow-up of non-functional pNET which are deemed cured post-surgical resection, with most guidelines advocating a median follow up of 5 years (). The delayed presentation in our case suggests additional considerations should be made regarding optimal post-operative surveillance duration based on the age of the patient, location of the tumour, lymph node spread and Ki-67 index.

  • Hepatic artery embolization and/or partial hepatectomy remains a treatment option for pNET patients with significant hepatic metastasis.

Open access