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Jai Madhok Department of Anesthesiology, Perioperative and Pain Medicine

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Amy Kloosterboer Department of Anesthesiology, Perioperative and Pain Medicine

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Chitra Venkatasubramanian Department of Neurology & Neurological Sciences, Stanford University Medical Center, Stanford, California, USA

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Frederick G Mihm Department of Anesthesiology, Perioperative and Pain Medicine

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Summary

We report the case of a 76-year-old male with a remote history of papillary thyroid cancer who developed severe paroxysmal headaches in the setting of episodic hypertension. Brain imaging revealed multiple lesions, initially of inconclusive etiology, but suspicious for metastatic foci. A search for the primary malignancy revealed an adrenal tumor, and biochemical testing confirmed the diagnosis of a norepinephrine-secreting pheochromocytoma. Serial imaging demonstrated multiple cerebral infarctions of varying ages, evidence of vessel narrowing and irregularities in the anterior and posterior circulations, and hypoperfusion in watershed areas. An exhaustive work-up for other etiologies of stroke including thromboembolic causes or vasculitis was unremarkable. There was resolution of symptoms, absence of new infarctions, and improvement in vessel caliber after adequate alpha-adrenergic receptor blockade for the management of pheochromocytoma. This clinicoradiologic constellation of findings suggested that the etiology of the multiple infarctions was reversible cerebral vasoconstriction syndrome (RCVS). Pheochromocytoma remains a poorly recognized cause of RCVS. Unexplained multifocal cerebral infarctions in the setting of severe hypertension should prompt the consideration of a vasoactive tumor as the driver of cerebrovascular dysfunction. A missed or delayed diagnosis has the potential for serious neurologic morbidity for an otherwise treatable condition.

Learning points:

  • The constellation of multifocal watershed cerebral infarctions of uncertain etiology in a patient with malignant hypertension should trigger the consideration of undiagnosed catecholamine secreting tumors, such as pheochromocytomas and paragangliomas.

  • Reversible cerebral vasoconstriction syndrome is a serious but reversible cerebrovascular manifestation of pheochromocytomas that may lead to strokes (ischemic and hemorrhagic), seizures, and cerebral edema.

  • Alpha-adrenergic receptor blockade can reverse cerebral vasoconstriction and prevent further cerebral ischemia and infarctions.

  • Early diagnosis of catecholamine secreting tumors has the potential for reducing neurologic morbidity and mortality in patients presenting with cerebrovascular complications.

Open access
Tu Vinh Luong The Department of Cellular Pathology, Royal Free London NHS Foundation Trust, London, UK
Neuroendocrine Tumour Unit, ENETS Center of Excellence, Royal Free London NHS Foundation Trust, London, UK

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Zaibun Nisa The Department of Cellular Pathology, Royal Free London NHS Foundation Trust, London, UK

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Jennifer Watkins The Department of Cellular Pathology, Royal Free London NHS Foundation Trust, London, UK
Neuroendocrine Tumour Unit, ENETS Center of Excellence, Royal Free London NHS Foundation Trust, London, UK

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Aimee R Hayes Neuroendocrine Tumour Unit, ENETS Center of Excellence, Royal Free London NHS Foundation Trust, London, UK
Department of Medical Oncology, Royal Free London NHS Foundation Trust, London, UK

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Summary

Colorectal poorly differentiated neuroendocrine carcinomas (NECs) are typically associated with poor outcomes. The mechanisms of their aggressiveness are still being investigated. Microsatellite instability (MSI) has recently been found in colorectal NECs showing aberrant methylation of the MLH1 gene and is associated with improved prognosis. We present a 76-year-old lady with an ascending colon tumour showing features of a pT3 N0 R0, large cell NEC (LCNEC) following right hemicolectomy. The adjacent mucosa showed a sessile serrated lesion (SSL) with low-grade dysplasia. Immunohistochemistry showed loss of expression for MLH1 and PMS2 in both the LCNEC and dysplastic SSL. Molecular analysis indicated the sporadic nature of the MLH1 mismatch repair (MMR) protein-deficient status. Our patient did not receive adjuvant therapy and she is alive and disease-free after 34 months follow-up. This finding, similar to early-stage MMR-deficient colorectal adenocarcinoma, is likely practice-changing and will be critical in guiding the appropriate treatment pathway for these patients. We propose that testing of MMR status become routine for early-stage colorectal NECs.

Learning points:

  • Colorectal poorly differentiated neuroendocrine carcinomas (NECs) are known to be aggressive and typically associated with poor outcomes.

  • A subset of colorectal NECs can display microsatellite instability (MSI) with mismatch repair (MMR) protein-deficient status.

  • MMR-deficient colorectal NECs have been found to have a better prognosis compared with MMR-proficient NECs.

  • MMR status can be detected using immunohistochemistry.

  • Immunohistochemistry for MMR status is routinely performed for colorectal adenocarcinomas.

  • Immunohistochemical expression of MMR protein and MSI analysis should be performed routinely for early-stage colorectal NECs in order to identify a subgroup of MMR-deficient NECs which are associated with a significantly more favourable prognosis.

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J Pedro Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitário de São João, Porto, Portugal
Faculty of Medicine of Universidade do Porto, Porto, Portugal

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F M Cunha Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar do Tâmega e Sousa, Penafiel, Portugal

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V Neto Department of Pneumology, Centro Hospitalar Universitário de São João, Porto, Portugal

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V Hespanhol Faculty of Medicine of Universidade do Porto, Porto, Portugal
Department of Pneumology, Centro Hospitalar Universitário de São João, Porto, Portugal
Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal

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D F Martins Faculty of Medicine of Universidade do Porto, Porto, Portugal
Department of Pathology, Centro Hospitalar Universitário de São João, Porto, Portugal

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S Guimarães Department of Pathology, Centro Hospitalar Universitário de São João, Porto, Portugal

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A Varela Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitário de São João, Porto, Portugal
Faculty of Medicine of Universidade do Porto, Porto, Portugal
Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal

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D Carvalho Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitário de São João, Porto, Portugal
Faculty of Medicine of Universidade do Porto, Porto, Portugal
Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal

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Summary

We describe the case of a 56 year-old woman with the almost simultaneous appearance of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) and a carotid body paraganglioma. Of interest, 6 years earlier, the patient underwent total thyroidectomy due to papillary thyroid carcinoma and, in the meantime, she was submitted to mastectomy to treat an invasive ductal carcinoma of the breast. In order to explain these lesions, an extensive genetic study was performed. Results showed positivity for the presence of the tumor suppressor gene PALB2, whose presence had already been detected in a niece with breast cancer. The patient underwent different procedures to treat the lesions and currently she is symptom-free over 2 years of follow-up.

Learning points:

  • The presence of two rare neoplasms in a single person should raise the suspicion of a common etiology.

  • To the best of our knowledge, this is the first case that shows the coexistence of DIPNECH and paraganglioma.

  • The contribution of the PALB2 gene in the etiology of these rare neoplasms is a possibility.

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Aisha A Tepede Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)

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James Welch Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)

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Maya Lee Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)

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Adel Mandl Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)

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Sunita K Agarwal Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)

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Naris Nilubol National Cancer Institute (NCI), National Institutes of Health, Bethesda, Maryland, USA

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Dhaval Patel National Cancer Institute (NCI), National Institutes of Health, Bethesda, Maryland, USA

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Craig Cochran Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)

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William F Simonds Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)

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Lee S Weinstein Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)

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Abhishek Jha Eunice Kennedy Shriver National Institute of Child Health and Development (NICHD), National Institutes of Health, Bethesda, Maryland, USA

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Corina Millo Clinical Center PET Department (CC PET), National Institutes of Health, Bethesda, Maryland, USA

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Karel Pacak Eunice Kennedy Shriver National Institute of Child Health and Development (NICHD), National Institutes of Health, Bethesda, Maryland, USA

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Jenny E Blau Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)

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Summary

Pheochromocytoma (PHEO) in multiple endocrine neoplasia type 1 (MEN1) is extremely rare. The incidence is reported as less than 2%. We report a case of a 76-year-old male with familial MEN1 who was found to have unilateral PHEO. Although the patient was normotensive and asymptomatic, routine screening imaging with CT demonstrated bilateral adrenal masses. The left adrenal mass grew from 2.5 to 3.9 cm over 4 years with attenuation values of 9 Hounsfield units (HU) pre-contrast and 15 HU post-contrast washout. Laboratory evaluation demonstrated an adrenergic biochemical phenotype. Both 18F-fluorodeoxyglucose (18F-FDG) PET/CT and 123I-metaiodobenzylguanidine (123I-mIBG) scintigraphy demonstrated bilateral adrenal uptake. In contrast, 18F-fluorodihydroxyphenylalanine (18F-FDOPA) PET/CT demonstrated unilateral left adrenal uptake (28.7 standardized uptake value (SUV)) and physiologic right adrenal uptake. The patient underwent an uneventful left adrenalectomy with pathology consistent for PHEO. Post-operatively, he had biochemical normalization. A review of the literature suggests that adrenal tumors >2 cm may be at higher risk for pheochromocytoma in patients with MEN1. Despite a lack of symptoms related to catecholamine excess, enlarging adrenal nodules should be biochemically screened for PHEO. 18F-FDOPA PET/CT may be beneficial for localization in these patients.

Learning points:

  • 18F-FDOPA PET/CT is a beneficial imaging modality for identifying pheochromocytoma in MEN1 patients.

  • Adrenal adenomas should undergo routine biochemical workup for PHEO in MEN1 and can have serious peri-operative complications if not recognized, given that MEN1 patients undergo frequent surgical interventions.

  • MEN1 is implicated in the tumorigenesis of PHEO in this patient.

Open access
C Greco Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria di Modena, Ospedale Civile di Baggiovara, Modena, Italy

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G Brigante Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria di Modena, Ospedale Civile di Baggiovara, Modena, Italy

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E Taliani Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria di Modena, Ospedale Civile di Baggiovara, Modena, Italy

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S Corrado Department of Diagnostic, Clinical Medicine and Public Health, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy

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M Simoni Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy
Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria di Modena, Ospedale Civile di Baggiovara, Modena, Italy

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B Madeo Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria di Modena, Ospedale Civile di Baggiovara, Modena, Italy

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Summary

A 74-year-old man was referred to the Endocrinology Unit because of multinodular goiter. The dominant nodule (1.7 × 1.9 × 2.4 cm), at the medium-superior third of the left lobe, was inhomogeneously hypoechoic, with irregular margins, macrocalcifications and intranodular vascularization. Fine-needle aspiration biopsy (FNAB) was performed. The cytological diagnosis was TIR 2, benign, according to the 2013 Italian thyroid cytology classification system. Moderately high serum calcitonin (s-Ct) (61.5 pg/mL, n.r. 0–7.5) and normal CEA were detected. The Ct level in FNAB wash-out fluid (Ct-FNAB) was 1450 pg/mL. Based on s-Ct and Ct-FNAB levels, patient underwent total thyroidectomy. Macroscopically, a dominant circumscribed nodule of 2 ecm was described; the histological and immunohistochemical features identified medullary thyroid carcinoma (MTC) with paraganglioma (PG)-like pattern positive for Ct, CEA and chromogranin and negative for S-100 sustentacular cells (SC). Moreover, papillary carcinoma of 3 mm in the right lobe was also associated. No areas of hyperaccumulation of the tracer were documented at Ga68 PET/CT. No RET-proto-oncogene mutations were found. Post-surgery s-Ct levels were within normal range (4 pg/mL). Two years after thyroidectomy, the patient is still disease-free. We reported a case of sporadic and rare variant of MTC: this is the ninth described case of PG-like MTC. In this case, cytologically benign, the clinical suspicion arose from high Ct values at FNAB wash-out fluid. Even if clinical behavior of this variant seems indolent, additional studies are necessary to understand prognoses and predictive factors.

Learning points:

  • Several unusual histological variants of medullary thyroid carcinoma (MTC) have been described such as spindle cell, giant cell, clear cell, melanotic, squamous, angiosarcoma-like variants; even rarer is the paraganglioma (PG)-like pattern.

  • We here describe a case of medullary PG-like thyroid carcinoma in a 74-year-old man. This is a rare histological variant of MTC hardly diagnosed by cytology, since immunohistochemical investigations are necessary.

  • Measurement of calcitonin both in serum and in wash-out fluid from fine-needle aspiration could be an additional tool for an early and non-invasive identification of these variants.

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Alessandro Rossini Endocrinology and Diabetes Unit, ASST Papa Giovanni XXIII, Bergamo, Italy

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Francesca Perticone Endocrine Unit, Department of Internal Medicine

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Laura Frosio Endocrine Unit, Department of Internal Medicine

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Marco Schiavo Lena Department of Pathology, San Raffaele Hospital, Milan, Italy

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Roberto Lanzi Endocrine Unit, Department of Internal Medicine

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Summary

ACTH-secreting pheochromocytoma is a very rare cause of Cushing’s syndrome, with a high morbidity and mortality risk due to both cortisol and catecholamines excess. We report the case of a 45-year-old female patient with a 3 cm, high-density, left adrenal mass, diagnosed as an ACTH-secreting pheochromocytoma. The biochemical sensitivity of the tumor to somatostatin analogues was tested by a 100 μg s.c. octreotide administration, which led to an ACTH and cortisol reduction of 50 and 25% respectively. In addition to alpha and beta blockers, preoperative approach to laparoscopic adrenalectomy included octreotide, a somatostatin analogue, together with ketoconazole, in order to achieve an adequate pre-surgical control of cortisol release. Histopathological assessment confirmed an ACTH-secreting pheochromocytoma expressing type 2 and 5 somatostatin receptors (SSTR-2 and -5).

Learning points:

  • ACTH-secreting pheochromocytomas represent a rare and severe condition, characterized by high morbidity and mortality risk.

  • Surgical removal of the adrenal mass is the gold standard treatment, but adequate medical therapy is required preoperatively to improve the surgical outcome and to avoid major complications.

  • Somatostatin analogs, in addition to other medications, may represent a useful therapeutic option for the presurgical management of selected patients.

  • In this sense, the octreotide challenge test is a useful tool to predict favorable therapeutic response to the treatment.

Open access
Karen Decaestecker Department of Diabetology-Endocrinology, AZ Nikolaas, Sint-Niklaas, Belgium

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Veerle Wijtvliet Department of Diabetology-Endocrinology, AZ Nikolaas, Sint-Niklaas, Belgium

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Peter Coremans Department of Diabetology-Endocrinology, AZ Nikolaas, Sint-Niklaas, Belgium

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Nike Van Doninck Department of Diabetology-Endocrinology, AZ Nikolaas, Sint-Niklaas, Belgium

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Summary

ACTH-dependent hypercortisolism is caused by an ectopic ACTH syndrome (EAS) in 20% of cases. We report a rare cause of EAS in a 41-year-old woman, presenting with clinical features of Cushing’s syndrome which developed over several months. Biochemical tests revealed hypokalemic metabolic alkalosis and high morning cortisol and ACTH levels. Further testing, including 24-hour urine analysis, late-night saliva and low-dose dexamethasone suppression test, confirmed hypercortisolism. An MRI of the pituitary gland was normal. Inferior petrosal sinus sampling (IPSS) revealed inconsistent results, with a raised basal gradient but no rise after CRH stimulation. Additional PET-CT showed intense metabolic activity in the left nasal vault. Biopsy of this lesion revealed an unsuspected cause of Cushing’s syndrome: an olfactory neuroblastoma (ONB) with positive immunostaining for ACTH. Our patient underwent transnasal resection of the tumour mass, followed by adjuvant radiotherapy. Normalisation of cortisol and ACTH levels was seen immediately after surgery. Hydrocortisone substitution was started to prevent withdrawal symptoms. As the hypothalamic–pituitary–axis slowly recovered, daily hydrocortisone doses were tapered and stopped 4 months after surgery. Clinical Cushing’s stigmata improved gradually.

Learning points:

  • Ectopic ACTH syndrome can originate from tumours outside the thoracoabdominal region, like the sinonasal cavity.

  • The diagnostic accuracy of IPSS is not 100%: both false positives and false negatives may occur and might be due to a sinonasal tumour with ectopic ACTH secretion.

  • Olfactory neuroblastoma (syn. esthesioneuroblastoma), named because of its sensory (olfactory) and neuroectodermal origin in the upper nasal cavity, is a rare malignant neoplasm. It should not be confused with neuroblastoma, a tumour of the sympathetic nervous system typically occurring in children.

  • If one criticises MRI of the pituitary gland because of ACTH-dependent hypercortisolism, one should take a close look at the sinonasal field as well.

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Haruyuki Ohsugi Department of Urology and Andrology, Kansai Medical University, Hirakata, Japan

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Nae Takizawa Department of Urology and Andrology, Kansai Medical University, Hirakata, Japan

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Hidefumi Kinoshita Department of Urology and Andrology, Kansai Medical University, Hirakata, Japan

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Tadashi Matsuda Department of Urology and Andrology, Kansai Medical University, Hirakata, Japan

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Summary

A 21-year-old woman was referred to our hospital to treat bilateral pheochromocytomas (PCCs) after a diagnosis of multiple endocrine neoplasia type 2A (MEN2A). We performed bilateral laparoscopic adrenalectomy. One year after the operation, urinary fractionated metanephrines in 24-h urine increased. MRI showed a 30 mm tumor on the interaortocaval region and 123I-MIBG concentrated in this area. We excised the tumor and performed para-aortic lymphadenectomy. Histopathologic examination confirmed a PCC arising from ectopic adrenal tissue. Urinary fractionated metanephrines in 24-h urine declined to basal levels immediately after the operation. We detected no recurrence of paraganglioma or PCC for 5 years after the treatment.

Learning points:

  • Most ectopic adrenal tissue is associated with no symptoms and contains only the adrenal cortex.

  • Adrenocortical tumors sometimes arise from ectopic adrenal tissues similarly to in the normal adrenal gland.

  • PCC arising from ectopic adrenal tissue occurs infrequently.

  • MEN2-related PCC is accompanied by adrenal medullary hyperplasia, which might be part of tumorigenesis.

Open access
Sakshi Jhawar Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA

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Rahul Lakhotia Medical Oncology Service, Center for Cancer Research, National Cancer Institute, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA

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Mari Suzuki Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA

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James Welch Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA

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Sunita K Agarwal Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA

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John Sharretts Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA

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Maria Merino Laboratory of Pathology, National Cancer Institute, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA

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Mark Ahlman Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA

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Jenny E Blau Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA

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William F Simonds Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA

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Jaydira Del Rivero Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA

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Summary

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant condition characterized by parathyroid, anterior pituitary and enteropancreatic endocrine cell tumors. Neuroendocrine tumors occur in approximately in 5–15% of MEN1 patients. Very few cases of ovarian NETs have been reported in association with clinical MEN1 and without genetic testing confirmation. Thirty-three-year-old woman with MEN1 was found to have right adnexal mass on computed tomography (CT). Attempt at laparoscopic removal was unsuccessful, and mass was removed via a minilaparotomy in piecemeal fashion. Pathology showed ovarian NET arising from a teratoma. Four years later, patient presented with recurrence involving the pelvis and anterior abdominal wall. She was treated with debulking surgery and somatostatin analogs (SSAs). Targeted DNA sequencing analysis on the primary adnexal mass as well as the recurrent abdominal wall tumor confirmed loss of heterozygosity (LOH) at the MEN1 gene locus. This case represents to our knowledge, the first genetically confirmed case of ovarian NET arising by a MEN1 mechanism in a patient with MEN1. Extreme caution should be exercised during surgery as failure to remove an ovarian NET en masse can result in peritoneal seeding and recurrence. For patients with advanced ovarian NETs, systemic therapy options include SSAs, peptide receptor radioligand therapy (PRRT) and novel agents targeting mammalian target of rapamycin (mTOR) and vascular endothelial growth factor (VEGF).

Learning points:

  • Ovarian NET can arise from a MEN1 mechanism, and any adnexal mass in a MEN1 patient can be considered as a possible malignant NET.

  • Given the rarity of this disease, limited data are available on prognostication and treatment. Management strategies are extrapolated from evidence available in NETs from primaries of other origins.

  • Care should be exercised to remove ovarian NETs en bloc as failure to do so may result in peritoneal seeding and recurrence.

  • Treatment options for advanced disease include debulking surgery, SSAs, TKIs, mTOR inhibitors, PRRT and chemotherapy.

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Wei Yang Division of Endocrinology, Department of Internal Medicine

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David Pham Department of Radiology, University of California Davis School of Medicine, Sacramento, California, USA

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Aren T Vierra Division of Endocrinology, Department of Internal Medicine

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Sarah Azam Division of Endocrinology, Department of Internal Medicine

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Dorina Gui Department of Pathology, University of California Davis School of Medicine, Sacramento, California, USA

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John C Yoon Division of Endocrinology, Department of Internal Medicine

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Summary

Ectopic ACTH-secreting pulmonary neuroendocrine tumors are rare and account for less than 5% of endogenous Cushing’s syndrome cases. We describe an unusual case of metastatic bronchial carcinoid tumor in a young woman presenting with unprovoked pulmonary emboli, which initially prevented the detection of the primary tumor on imaging. The source of ectopic ACTH was ultimately localized by a Gallium-DOTATATE scan, which demonstrated increased tracer uptake in a right middle lobe lung nodule and multiple liver nodules. The histological diagnosis was established based on a core biopsy of a hepatic lesion and the patient was started on a glucocorticoid receptor antagonist and a somatostatin analog. This case illustrates that hypercogulability can further aggravate the diagnostic challenges in ectopic ACTH syndrome. We discuss the literature on the current diagnosis and management strategies for ectopic ACTH syndrome.

Learning points:

  • In a young patient with concurrent hypokalemia and uncontrolled hypertension on multiple antihypertensive agents, secondary causes of hypertension should be evaluated.

  • Patients with Cushing’s syndrome can develop an acquired hypercoagulable state leading to spontaneous and postoperative venous thromboembolism.

  • Pulmonary emboli may complicate the imaging of the bronchial carcinoid tumor in ectopic ACTH syndrome.

  • Imaging with Gallium-68 DOTATATE PET/CT scan has the highest sensitivity and specificity in detecting ectopic ACTH-secreting tumors.

  • A combination of various noninvasive biochemical tests can enhance the diagnostic accuracy in differentiating Cushing’s disease from ectopic ACTH syndrome provided they have concordant results. Bilateral inferior petrosal sinus sampling remains the gold standard.

Open access