RESUMEN
Acromegaly secondary to extra-pituitary tumors secreting growth hormone releasing hormone (GHRH) is rarely encountered. We review the literature on ectopic acromegaly and present the index report of ectopic acromegaly secondary to GHRH secretion from a mediastinal paraganglioma. Clinical and pathological manifestations and therapeutic management of 99 patients with ectopic acromegaly are reviewed. Acromegaly secondary to ectopic GHRH secretion is usually caused by a neuroendocrine tumor in the lung and pancreas. We report an additional cause of ectopic acromegaly from a mediastinal paraganglioma. Diagnostic criteria of ectopic GHRH syndrome include biochemical and pathologic tumoral confirmation of GHRH secretion and expression. Management of ectopic acromegaly consists of surgical resection of the primary tumor and biochemical normalization, with possible adjuvant use of somatostatin analogs. The review demonstrates that there are several tumor types, including paragangliomas which may secrete GHRH, leading to acromegaly. Clinical and laboratory manifestations of the syndrome and challenges in diagnosis and management of these rarely encountered patients require early diagnosis and appropriate treatment to prevent long-term morbidity and mortality with ectopic acromegaly.
Asunto(s)
Acromegalia/diagnóstico , Acromegalia/etiología , Hormona Liberadora de Hormona del Crecimiento/metabolismo , Paraganglioma Extraadrenal/metabolismo , Acromegalia/tratamiento farmacológico , Adolescente , Adulto , Anciano , Terapia Combinada , Femenino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/cirugía , Masculino , Neoplasias del Mediastino/metabolismo , Neoplasias del Mediastino/cirugía , Persona de Mediana Edad , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/cirugía , Paraganglioma Extraadrenal/cirugía , Somatostatina/análogos & derivados , Somatostatina/uso terapéutico , Adulto JovenRESUMEN
OBJECTIVE: To present an Iranian patient with a nonclassic form of multiple endocrine neoplasia type 1 (MEN 1) who presented with ectopic Cushing syndrome (CS) secondary to a corticotropin (ACTH)-producing thymic neuroendocrine tumor (NET), recurrent renal stones, and a giant cell granuloma of the jaw due to primary hyperparathyroidism (PHPT) without involvement of the pituitary or pancreas. METHODS: Relevant imaging and hormonal evaluations were performed. The patient was operated on 2 occasions for a thymic NET and on 3 occasions for PHPT. DNA from a peripheral blood sample was extracted for sequencing of the MEN1 gene. RESULT: Histopathologic evaluation of the thymic tumor removed during the first surgery showed an atypical carcinoid tumor with a Ki-67 labeling index of 5%. Evaluation after the second surgery revealed an invasive carcinoid tumor with a Ki-67 labeling index of 30%. Parathyroid pathology was suggestive of glandular hyperplasia. Menin gene sequencing revealed a novel frameshift mutation c.1642_1648dup in exon 10. CONCLUSION: This case of MEN 1 is unusual because most thymic NETs in MEN 1 are nonfunctional, and secretion of ACTH or other ectopic hormones rarely occurs. In patients presenting with thymic NETs, the possibility of MEN 1 should be considered, especially in the presence of hyperparathyroidism. This case also demonstrates that the behavior of thymic NETs can change over time from slow-growing tumors to highly invasive neoplasia, and that ectopic ACTH can be produced by these tumors in the context of MEN 1.
Asunto(s)
Síndrome de Cushing/diagnóstico , Síndrome de Cushing/etiología , Neoplasia Endocrina Múltiple Tipo 1/complicaciones , Neoplasias del Timo/diagnóstico , Neoplasias del Timo/etiología , Adulto , Humanos , MasculinoRESUMEN
Parathyroid hormone-related protein producing pancreatic neuroendocrine tumors have been infrequently reported. Herein, we report a case of an Iranian woman who had such a tumor during pregnancy, and gave birth to a female neonate with esophago-tracheal fistula and imperforated anus. Hypercalcemia was diagnosed at postpartum because of elevated serum calcium levels in the neonate and neurologic deterioration of the mother. Extensive literature review revealed 42 cases with pancreatic neuroendocrine tumors and hypercalcaemia. The clinical and laboratory findings of such patients are reviewed in this manuscript.
RESUMEN
INTRODUCTION: Hypercalcemia is the major electrolyte abnormality in patients with malignant tumors. It can be due to localized osteolytic hypercalcemia or elaboration of humoral substances such as parathyroid hormone-related protein from tumoral cells. In hematological malignancies, a third mechanism of uncontrolled synthesis and secretion of 1-25(OH)2D3 from tumoral cells or neighboring macrophages may contribute to the problem. However, hypercalcemia is quite unusual in patients with B-cell non-Hodgkin's lymphoma. CASE PRESENTATION: An 85-year-old Caucasian woman presented with low grade fever, anorexia, abdominal discomfort and fullness in her left abdomen for the last six months. She was mildly anemic and complained of fatigability. She had huge splenomegaly and was hypercalcemic. After correction of her hypercalcemia, she had a splenectomy. Microscopic evaluation revealed a malignant lymphoma. Her immunohistochemistry was positive for leukocyte common antigen, CD20 and parathyroid hormone-related peptide. CONCLUSION: Immunopositivity for parathyroid hormone-related peptide clearly demonstrates that hypersecretion of a parathyroid hormone-like substance from the tumor had led to hypercalcemia in this case. High serum calcium is seen in only seven to eight percent of patients with B-cell non-Hodgkin's lymphoma, apparently due to different mechanisms. Evaluation of serum parathyroid hormone-related protein and 1-25(OH)2D3 can be helpful in diagnosis and management. It should be noted that presentation with hypercalcemia has a serious impact on prognosis and survival.