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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.

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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.

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Inês Henriques Vieira Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar e Universitario de Coimbra EPE, Coimbra, Portugal

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Nádia Mourinho Bala Department of Endocrinology, Diabetes and Metabolism, Hospital Beatriz Ângelo, Loures, Portugal

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Fabiana Ramos Department of Medical Genetics, Diabetes and Growth, Centro Hospitalar e Universitario de Coimbra EPE, Coimbra, Portugal

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Isabel Dinis Department of Endocrinology, Diabetes and Growth, Centro Hospitalar e Universitario de Coimbra EPE, Coimbra, Portugal

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Rita Cardoso Department of Endocrinology, Diabetes and Growth, Centro Hospitalar e Universitario de Coimbra EPE, Coimbra, Portugal

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Joana Serra Caetano Department of Endocrinology, Diabetes and Growth, Centro Hospitalar e Universitario de Coimbra EPE, Coimbra, Portugal

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Dírcea Rodrigues Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar e Universitario de Coimbra EPE, Coimbra, Portugal

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Isabel Paiva Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar e Universitario de Coimbra EPE, Coimbra, Portugal

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Alice Mirante Department of Endocrinology, Diabetes and Growth, Centro Hospitalar e Universitario de Coimbra EPE, Coimbra, Portugal

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Summary

Congenital isolated adrenocorticotrophic hormone (ACTH) deficiency due to T-box transcription factor-19 (TBX19 mutation) (MIM 201400; ORPHA 199296) usually presents in the neonatal period with severe hypoglycemia, seizures, and sometimes prolonged cholestatic jaundice. We report a case with an unusual presentation that delayed the diagnosis. A 9-month-old female patient with no relevant personal history was admitted to the emergency department due to a hypoglycemic seizure in the context of acute gastroenteritis. There was rapid recovery after glucose administration. At age 4, she presented with tonic-clonic seizures, fever, and gastrointestinal symptoms and came to need support in an intensive care unit. Low serum cortisol was documented and hydrocortisone was initiated. After normalization of inflammatory parameters, the patient was discharged with hydrocortisone. The genetic investigation was requested and compound heterozygous mutations in TBX19 were detected. This is a rare case of presentation of TBX19 mutation outside the neonatal period and in the setting of acute disease, which presented a diagnostic challenge.

Learning points

  • Congenital isolated adrenocorticotrophic hormone deficiency due to TBX19 mutation usually presents with neonatal hypoglycemia and prolonged cholestatic jaundice.

  • An uneventful neonatal period, however, does not exclude the diagnosis as the disease may be asymptomatic at this stage.

  • In the context of idiopathic hypoglycemia, even in the context of acute disease, hypocortisolism must always be excluded.

  • Genetic evaluation should be performed in cases of congenital central hypocortisolism to allow proper counselling.