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Alessandra Mangone Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
Endocrinology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
Institute of Metabolism and System Research, University of Birmingham, Birmingham, UK

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Quratulain Yousuf University Hospitals of North Midlands NHS Trust, Stoke-on-Trent, UK

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Wiebke Arlt Institute of Metabolism and System Research, University of Birmingham, Birmingham, UK
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK

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Alessandro Prete Institute of Metabolism and System Research, University of Birmingham, Birmingham, UK
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK

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Fozia Shaheen Institute of Metabolism and System Research, University of Birmingham, Birmingham, UK

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Senthil-kumar Krishnasamy Walsall Healthcare NHS Trust, Walsall, UK

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Yasir S Elhassan Institute of Metabolism and System Research, University of Birmingham, Birmingham, UK
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK

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Cristina L Ronchi Institute of Metabolism and System Research, University of Birmingham, Birmingham, UK
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK
Department of Endocrinology and Diabetes, University Hospital of Wurzburg, Wurzburg, Germany

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Summary

The spectrum of endocrine-related complications of COVID-19 infection is expanding; one of the most concerning of which is adrenal haemorrhage due to the risk of catastrophic adrenal crisis. In this study, we present a case that highlights the challenging management of a large, indeterminate unilateral adrenal mass during pregnancy and draws attention to a rare yet probably underestimated complication of COVID-19. During hospitalization for severe COVID-19 pneumonia, a 26-year-old woman was incidentally found to have a 12.5 cm heterogeneous left adrenal mass. Soon after the discovery, she became pregnant and upon referral, she was in the seventh week of gestation, without clinical or biochemical features of hormonal excess. The uncertainty of the diagnosis and the risks of malignancy and surgical intervention were discussed with the patient, and a period of radiological surveillance was agreed upon. An MRI scan performed 3 months later showed a size reduction of the adrenal lesion to 7.9 cm, which was against malignancy. A Doppler ultrasound showed a non-vascular, well-defined round lesion consistent with an adrenal haematoma, likely a complication of the recent COVID-19 infection. The multidisciplinary team recommended further radiological follow-up. The patient then spontaneously had miscarriage at 12 weeks gestation. Subsequent radiological surveillance showed a further size reduction of the adrenal lesion to 5.5 cm. The patient conceived again during follow-up, and the repeated Doppler ultrasound showed stable appearances of the adrenal mass, and thus, it was agreed to continue radiological monitoring after delivery. The pregnancy was uneventful, and the patient delivered a healthy baby. An MRI scan performed after delivery showed a stable but persistent lesion consistent with a likely underlying adrenal lesion.

Learning points

  • Unilateral adrenal haemorrhage can occur as a complication of COVID-19 and should be considered in the differential diagnosis of heterogeneous adrenal masses if there is a history of recent infection.

  • Management of large indeterminate adrenal masses during pregnancy poses several challenges and should be led by an experienced multidisciplinary team.

  • Underlying adrenal tumours may trigger non-traumatic haemorrhages, especially if exacerbated by stressful illness.

Open access
Evangelos Karvounis Department of Endocrine Surgery, ‘Euroclinic’ Hospital, Athens, Greece

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Ioannis Zoupas Department of Endocrine Surgery, ‘Euroclinic’ Hospital, Athens, Greece

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Dimitra Bantouna Private Practice, Patras, Greece

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Rodis D Paparodis Private Practice, Patras, Greece
Center for Diabetes and Endocrine Research, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio, USA

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Roxani Efthymiadou PET-CT Department, Hygeia Hospital, Athens, Greece

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Christina Ioakimidou Department of Pathology

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Christos Panopoulos Department of Medical Oncology, ‘Euroclinic’ Hospital, Athens, Greece

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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.

Open access
Omayma Elshafie Department of Endocrinology, Sultan Qaboos Comprehensive Cancer Care and Research Centre, Muscat, Sultanate of Oman

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Samir Hussein Department of Radiology, Sultan Qaboos University Hospital, Muscat, Sultanate of Oman

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Moza Al Kalbani Department of Gynaecology, Sultan Qaboos Comprehensive Cancer Care and Research Centre, Muscat, Sultanate of Oman

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Aisha Al Hamadani Department of Pathology

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Abir Bou Khalil Department of Endocrinology, Sultan Qaboos Comprehensive Cancer Care and Research Centre, Muscat, Sultanate of Oman

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Nicholas Woodhouse Department of Endocrinology, Sultan Qaboos University Hospital, Muscat, Sultanate of Oman

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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.

Open access
Iris Dirven Department of Endocrinology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium

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Bert Bravenboer Department of Endocrinology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium

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Steven Raeymaeckers Department of Radiology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium

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Corina E Andreescu Department of Endocrinology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium

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Summary

The Covid-19 vaccination has been rapidly implemented among patients with cancer. We present two cases of patients with endocrine tumours who developed lymphadenopathy following a Covid-19 vaccination. In the case of a patient with multiple endocrine neoplasia (MEN) 1 syndrome, an 18-fluorodeoxyglucose (18FDG)-PET/CT showed positive axillary lymph nodes. Further work-up with fine needle aspiration showed a reactive pattern following a Covid-19 vaccination in the ipsilateral arm shortly before the 18FDG-PET/CT. A second patient, in follow-up for thyroid cancer, developed clinical supraclavicular lymphadenopathy after a Covid-19 vaccination. Follow-up ultrasound proved the lesion to be transient. These cases demonstrate lymphadenopathy in response to a Covid-19 vaccination in two patients susceptible to endocrine tumours and metastatic disease. With growing evidence about the pattern and occurrence of lymphadenopathy after mRNA Covid-19 vaccination, recommendations for scheduling and interpretation of imaging among cancer patients should be implemented to reduce equivocal findings, overdiagnosis, and overtreatment, while maintaining a good standard of care in oncological follow-up.

Learning points

  • Reactive lymphadenopathy is very common after an mRNA vaccination against Covid-19 and should be part of the differential diagnosis in patients with endocrine tumours who recently received a Covid-19 mRNA vaccination and present with an ipsilateral lymphadenopathy.

  • A good vaccine history is essential in assessing the risk for lymphadenopathy and if possible, screening imaging in patients with endocrine tumours should be postponed at least 6 weeks after the previous vaccination.

  • For now, a multidisciplinary care approach is recommended to determine the necessary steps in the diagnostic evaluation of lymphadenopathy in the proximity of a Covid-19 vaccination.

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

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Chris McCormack Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

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Michelle Goh Department of Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

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Cherie Chiang Department of Internal Medicine, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
University of Melbourne, Parkville, Victoria, Australia

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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.

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Eugénie Van Mieghem Department of Internal Medicine, GZA Hospitals, Antwerpen, Belgium

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Valent Intan-Goey Department of Internal Medicine, GZA Hospitals, Antwerpen, Belgium

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Wendi Buffet Department of Pathological Anatomy, GZA Hospitals, Antwerpen, Belgium
Department of Pathological Anatomy, ZNA Hospitals, Antwerpen, Belgium

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Martin Lammens Department of Pathological Anatomy, University Hospital of Antwerp, Edegem, Belgium

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Pieter Van Loo Department of Neurosurgery, GZA Hospitals, Antwerpen, Belgium

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Pascale Abrams Department of Endocrinology, GZA Hospitals, Antwerpen, Belgium

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Summary

Pituitary carcinoma is a rare type of malignancy and only accounts for 0.1–0.2% of all pituitary tumours. Most pituitary carcinomas are hormonally active and they are mostly represented by corticotroph and lactotroph carcinomas. Corticotroph carcinoma can present as symptomatic Cushing’s disease or can evolve from silent corticotroph adenoma which is not associated with clinical or biochemical evidence of hypercortisolism. We hereby present a case of a bone-metastasized corticotroph pituitary carcinoma masquerading as an ectopic adrenocorticotropic hormone (ACTH) syndrome in a patient with a history of a non-functioning pituitary macro-adenoma. Our patient underwent two transsphenoidal resections of the primary pituitary tumour followed by external beam radiation therapy. Under hydrocortisone substitution therapy she developed ACTH-dependent hypercortisolism without arguments for recurrence on pituitary MRI and without central-to-peripheral ACTH-gradient on inferior petrosal sinus sampling, both suggesting ectopic production. Ultimately, she was diagnosed with an ACTH-secreting vertebral metastasis originating from the primary pituitary tumour. This case report demonstrates the complex pathophysiology of pituitary carcinoma and the long diagnostic work-up. Certain features in pituitary adenoma should raise the suspicion of malignancy.

Learning points

  • The diagnosis of pituitary carcinoma can only be made based on documented metastasis, therefore, due to the often long latency period between the detection of the primary tumour and the occurrence of metastasis, the diagnostic work-up most often spans over multiple years.

  • Pituitary carcinoma including corticotroph carcinoma is very rare in contrast to pituitary adenoma and only accounts for 0.1–0.2% of all pituitary tumours.

  • Histopathology in pituitary adenoma should certainly accomplish the following goals: accurate tumour subtyping and assessment of tumoural proliferative potential.

  • Repeated recurrence of pituitary adenoma after surgical resection, a discrepancy between biochemical and radiological findings, resistance to medical and radiation therapy, and silent tumours becoming functional are all hallmarks of pituitary carcinoma.

  • Silent corticotroph adenomas are non-functioning pituitary adenomas that arise from T-PIT lineage adenohypophyseal cells and that can express adrenocorticotropic hormone on immunohistochemistry, but are not associated with biochemical or clinical evidence of hypercortisolism. Silent corticotroph adenomas exhibit a more aggressive clinical behaviour than other non-functioning adenomas.

  • Treatment options for corticotroph carcinoma include primary tumour resection, radiation therapy, medical therapy, and chemotherapy. Sometimes bilateral adrenalectomy is necessary to achieve sufficient control of the cortisol excess.

Open access
David Kishlyansky Division of Internal Medicine, Department of Medicine, University of Calgary, Calgary, Alberta, Canada

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Gregory Kline Divison of Endocrinology and Metabolism, Department of Medicine, University of Calgary, Calgary, Alberta, Canada

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Amita Mahajan Divison of Endocrinology and Metabolism, Department of Medicine, University of Calgary, Calgary, Alberta, Canada

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Konstantin Koro Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada

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Janice L Pasieka Divison of Endocrine surgery, Surgical Oncology and Endocrinology, Department of Surgery, University of Calgary, Calgary, Alberta, Canada

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Patrick Champagne Department of Cardiac Sciences, University of Calgary, Calgary, Alberta, Canada

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Summary

An adrenocorticotropic hormone (ACTH)-producing pheochromocytoma (PCC)/paraganglioma is the cause of ectopic Cushing’s syndrome (CS) in 5.2% of cases reported in the literature. We present a previously healthy 43-year-old woman admitted to our hospital with cushingoid features and hypertensive urgency (blood pressure = 200/120 mmHg). Her 24-h urinary free cortisol was >4270 nmol/day (reference range (RR) = 100–380 nmol/day) with a plasma ACTH of 91.5 pmol/L (RR: 2.0–11.5 pmol/L). Twenty-four-hour urinary metanephrines were increased by 30-fold. Whole-body CT demonstrated a 3.7-cm left adrenal mass with a normal-appearing right adrenal gland. Sellar MRI showed a 5-mm sellar lesion. MIBG scan revealed intense uptake only in the left adrenal mass. She was managed pre-operatively with ketoconazole and phenoxybenzamine and underwent an uneventful left laparoscopic adrenalectomy, which resulted in biochemical resolution of her hypercortisolemia and catecholamine excess. Histology demonstrated a PCC (Grading System for Adrenal Pheochromocytoma and Paraganglioma score 5) with positive ACTH staining by immunohistochemistry. A PCC gene panel showed no mutations and there has been no evidence of recurrence at 24 months. This case highlights the difficult nature of localizing the source of CS in the setting of a co-existing PCC and sellar mass.

Learning points

  • An adrenocorticotropic hormone (ACTH)-producing pheochromocytoma (PCC) is an important item to be considered in all patients presenting with ectopic Cushing’s syndrome (CS).

  • In exceptionally rare cases, patients with ectopic CS may present with multiple lesions, and a systematic approach considering all potential sources is crucial to avoid misdiagnosis.

  • CS with a large adrenal mass but lacking contralateral adrenal atrophy should raise suspicion of an ACTH-dependent process.

  • In patients with clinical suspicion of PCC, clinicians should be mindful of the use of steroids and beta-blockers without appropriate alpha blockade as they may precipitate an adrenergic crisis.

Open access
Jay Nguyen Lincoln Memorial University-DeBusk College of Osteopathic Medicine, Harrogate, Tennessee, USA

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Dennis Joseph Endocrinology Center of Lake Cumberland, Somerset, Kentucky, USA

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Summary

Autonomous thyroid adenomas are caused by activating mutations in the genes encoding the thyroid-stimulating hormone receptor (TSHR) or mutations in the Gas subunit of the TSHR. Nodules with suspicious sonographic features should be submitted to fine-needle aspiration. Additional molecular testing may be performed to characterize the thyroid nodule’s malignant potential further. We present a patient who underwent whole-transcriptome RNA-sequencing that indicated a TSHR I568T mutation after an ultrasound showed