Diagnosis and Treatment > Medication > Dexamethasone

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Avital Nahmias Neuroendocrine Tumor Unit, Endocrinology and Metabolism Service, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

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Simona Grozinsky-Glasberg Neuroendocrine Tumor Unit, Endocrinology and Metabolism Service, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

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Asher Salmon Department of Oncology, Hadassah-Hebrew University Medical Center, Kiryat Hadassah, Jerusalem, POB 12000, 91120, Israel

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David J Gross Neuroendocrine Tumor Unit, Endocrinology and Metabolism Service, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

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Summary

Approximately 35% of the pancreatic neuroendocrine tumors (pNETs) are functional, the most common of which is an insulinoma. Rarely can initially nonfunctioning tumor undergo biological transformation to a hormone-secreting tumor with subsequent changes in the clinical picture. We present here three unique patients with long-standing pNETs who developed life-threatening hyperinsulinemic hypoglycemia along with tumor progression. In two of the patients, everolimus (Afinitor) was administered in an attempt to control both tumor growth and hypoglycemia. In two cases everolimus therapy resulted in the abolishment of hypoglycemia and induced significant tumor regression; however these beneficial responses were transient. These cases highlight the exceptional ability of pNETs to change biological behavior in parallel with disease progression. Our experience concurs with recently published studies demonstrating the utility of everolimus for the control of both hypoglycemia and tumor progression.

Learning points

  • Nonfunctional pNET can gain new features such as insulin secretion with related morbidity.

  • Gain of function in a previously nonfunctional pNET signifies tumor progression and is usually associated with poor prognosis.

  • Everolimus proved to be a viable treatment for hypoglycemia in insulinoma patients and was also proven highly effective in the patients presented here.

  • As disease progresses, the effect of everolimus on hypoglycemia wanes. We report for the first time the development of hypoglycemia during everolimus treatment.

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J Rajkanna Department of Endocrinology, Peterborough City Hospital Bretton Gate, Peterborough PE3 9GZ, UK

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S O Oyibo Department of Endocrinology, Peterborough City Hospital Bretton Gate, Peterborough PE3 9GZ, UK

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Summary

Testicular adrenal rest tumours (TARTs) are benign ACTH-dependent tumours that occur in males with congenital adrenal hyperplasia (CAH) and if left untreated can destroy testicular tissue. Corticosteroid suppressive treatment could result in the regression of these testicular tumours. We present a patient with bilateral large TARTs as a consequence of poor compliance to treatment and follow-up for his CAH, who consequently had to have bilateral orchidectomies and prosthesis replacement.

Learning points

  • TARTs are frequently seen in males with CAH, and can be misdiagnosed as primary testicular cancer.

  • Patient compliance to treatment and follow-up are necessary to reduce the risk of testicular damage as a result of TARTs in patients with CAH.

  • Boys with CAH should have periodic ultrasonographic screening from before adolescent age for early detection of TARTs.

  • Regular monitoring of renin, 17-hydroxyprogesterone and androgens levels is required to assess corticosteroid suppressive treatment.

  • Patients with CAH should be offered psychological support and information concerning CAH support groups.

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Sally K Abell Department of Endocrinology and Diabetes, St Vincent's Hospital, PO Box 2900, Fitzroy, Melbourne, 3065 Victoria, Australia

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Jessie Teng Department of Endocrinology and Diabetes, St Vincent's Hospital, PO Box 2900, Fitzroy, Melbourne, 3065 Victoria, Australia

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Anthony Dowling Department of Oncology, St Vincent's Hospital, PO Box 2900, Fitzroy, Melbourne, 3065 Victoria, Australia

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Michael S Hofman Department of Medicine, University of Melbourne, Parkville, Melbourne, Victoria, Australia
Molecular Imaging, Centre for Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, Melbourne, Victoria, Australia

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Richard J MacIsaac Department of Endocrinology and Diabetes, St Vincent's Hospital, PO Box 2900, Fitzroy, Melbourne, 3065 Victoria, Australia
Department of Medicine, University of Melbourne, Parkville, Melbourne, Victoria, Australia

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Nirupa Sachithanandan Department of Endocrinology and Diabetes, St Vincent's Hospital, PO Box 2900, Fitzroy, Melbourne, 3065 Victoria, Australia

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Summary

This paper details the case of a 77-year-old male with refractory hypoglycaemia due to inoperable metastatic pancreatic neuroendocrine tumour (pNET) co-secreting insulin and gastrin. Multiple medical therapies were trialled with limited success, and we describe the complications experienced by our patient. Somatostatin analogues can ameliorate hypoglycaemia and may have tumour-stabilising effects; however, in our case resulted in paradoxical worsening of hypoglycaemia. This rendered our patient hospital dependent for glycaemic support including continuous dextrose infusion. Although this is a reported adverse effect with initiation of therapy, we describe successful initiation of short-acting octreotide as an inpatient followed by commencement of long-acting octreotide. Hypoglycaemic collapse occurred only after dose titration of long-acting octreotide. We outline the pitfalls of somatostatin analogue therapy and the mechanisms that may contribute to worsening hypoglycaemia. This rare side effect cannot be reliably predicted, necessitating close supervision and glucose monitoring during therapy. Our patient achieved disease stabilisation and gradual resolution of hypoglycaemia with peptide receptor radionuclide therapy (PRRT), an emerging therapeutic option for metastatic neuroendocrine tumours with high efficacy and low toxicity. We present a brief but comprehensive discussion of currently available and novel therapies for insulin secreting pNETs.

Learning points

  • Hypoglycaemia due to malignant insulin secreting pNET is frequently severe and may be life-threatening despite supportive therapies.

  • Octreotide can ameliorate hypoglycaemia, and may have anti-proliferative and tumour-stabilising effects in malignant pNETs that are surgically unresectable.

  • Paradoxical worsening of hypoglycaemia may occur with octreotide initiation and dose titration, necessitating close supervision and glucose monitoring.

  • PRRT is emerging as a therapeutic option with high efficacy and low toxicity.

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