Progesterone Receptor Antagonists – A Novel Treatment for Severe Hyponatremia from the Endocrine Paraneoplastic Syndrome

Hyponatremia related to ectopic secretion of cancer cells of argininevasopressin (AVP) or atrial natriuretic peptide (ANP) is most commonlycaused by small cell lung cancer. The ideal treatment would be one thatnot only corrects the hyponatremia, especially if it is life threatening, butat the same time causes regression of the cancer, and thus improves bothquality and length of life. As one is waiting for chemotherapy, surgery,or radiotherapy to decrease the cancer burden, tolvaptan has been usedto correct the hyponatremia to improve symptoms or prevent death.Mifepristone, a progesterone receptor modulator/antagonist has been usedto treat various cancers. The oral 200mg tablet was given to an 80-year-oldwoman who developed sudden extensive lung cancer with a serum sodiumof 118 mmol/L. She refused chemotherapy but agreed to take mifepristone.The hyponatremia was completely corrected (145 mmol/L) within onemonth of treatment. She was in complete remission for 5 years and diednot from lung cancer, but an acute myocardial infarction. Mifepristonemay serve the purpose to not only quickly correct hyponatremia when itis related to an endocrine paraneoplastic syndrome, but also to provideimproved quality and length of life.

Phosphaturic mesenchymal tumors: radiological aspects and suggested imaging pathway

Phosphaturic mesenchymal tumors (PMTs) are rare mesenchymal neoplasms of soft tissue or bone origin that can give rise to a challenge in diagnostic imaging. These tumors are frequently associated with tumor-induced osteomalacia, also called oncogenic osteomalacia, which is a rare paraneoplastic syndrome characterized by ectopic secretion of fibroblast growth factor 23, a hormone that regulates serum phosphate level. PMTs show polymorphic features on both radiological findings and histological examination, causing problems in diagnosis owing to their similarity with other mesenchymal tumors. Thus, this paper aims to describe radiological aspects of PMTs and suggest an imaging pathway for accurate diagnosis throughout the evidence from the literature review.

An urological cause of hypoglycaemia: A case report of the Doege-Potter syndrome

The Doege-Potter syndrome is a rare paraneoplastic syndrome presenting with hypoglycaemia due to ectopic secretion of insulin-like growth factor II (IGF-II) from a solitary fibrous tumor. The underlying tumor can be benign or malignant and rarely present in extrapleural sites. We describe the case of a 83-year-old male diagnosed with a Doege-Potter syndrome due to a kidney tumor.

A Case of Von Hippel–Lindau Disease with Bilateral Pheochromocytoma and Ectopic Hypersecretion of Intact Parathyroid Hormone in an Adolescent Girl

Von Hippel–Lindau disease is an autosomal dominant inherited syndrome predisposing to a variety of highly vascularised tumors in different organs. Although bilateral pheochromocytoma was reported in patients with von Hippel–Lindau disease, the coexistence of primary hyperparathyroidism is not a common condition. We report an observation of a primary hyperparathyroidism secondary to an ectopic secretion of intact parathyroid hormone in a 17-year-old girl with von Hippel–Lindau disease and bilateral pheochromocytoma. She presented with a newly diagnosed diabetes mellitus and a severe arterial hypertension. Blood tests disclosed hypercalcemia with increased intact PTH level. Cervical ultrasound and sestamibi scintigraphy were normal. Twenty-four-hour urinary normetanephrine level was highly elevated pointing to a catecholamine-secreting tumor. The abdominal computed tomography showed bilateral adrenal masses. MIBG scintigraphy exhibited a high accumulation of the tracer in both adrenal tumors. Genetic testing revealed a mutation of the VHL gene. The patient underwent a bilateral adrenalectomy. The postoperative outcome was marked by normalization of blood pressure, blood glucose, calcium, and PTH levels. In our case, the elevation of intact PTH and its spontaneous normalization after surgical treatment of pheochromocytomas confirms its ectopic secretion.

MON-294 T2 MRI Signal Analysis of The Pituitary Gland Is Efficient in the Diagnosis of Acromegaly Due to GHRH Ectopic Secretion

Less than 1% of cases of acromegaly are secondary to ectopic secretion of Growth Hormone Releasing Hormone (GHRH), usually from a neuroendocrine tumor. Symptoms of ectopic acromegaly did not differ from classical acromegaly from pituitary origin. GH and IGF 1 values are in the same range. GHRH measurement only could make the correct diagnosis but is not routinely proposed in acromegaly. MRI of the pituitary gland is considered not very effective in ectopic acromegaly. In the literature (1), different patterns are described: pituitary enlargement (46%), adenoma (30%), empty sella (2%) or normal (20%). But T2MRI signal of the pituitary is never mentioned nor illustrated. Finally, in about 30 % of published cases, pituitary surgery, of course inefficient, was performed. These data enhance the poor contribution of imaging studies in the published cases of ectopic acromegaly. We have been able to obtain and read MRIs and particularly T2WI of 27 acromegalic patients- 20 female, 7 male- due to GHRH hypersecretion from a neuroendocrine tumor –principally bronchial carcinoid and pancreatic NET- which have been published or not. Remarquably, T2 sequences were available in only 27/61 cases we have collected. In all these 27 cases but two, the T2 signal was clearly hypointense if compared with the brain cortex, as it has been described in densely granulomated somatotropinomas (2). In one case with T2 hyperintensity, the pituitary mass presented the same imaging characters as multiple brain metastases from a bronchial carcinoïd. In one case, T2 signal was isointense. In 3 cases, tiny millimetric T2 hyperintense images were disseminated within pituitary hyperplasia. In several cases where pituitary MRI was considered as normal, correlation of the patient’age with pituitary size could make suspect an enlarged gland. In a case labeled empty sella, T2MRI signal of the pituitary remnant was hypointense. When coupling T2 and T1 gadolinium enhanced sequences, no pituitary adenoma was visualized and normal pituitary tissue was never identified along with pituitary hyperplasia. In conclusion, T2 MRI hypointense signal of the pituitary gland is a better hallmark than pituitary hyperplasia for the diagnosis of acromegaly due to GHRH ectopic secretion. Analysis of T2 MR signal in these cases is essential to avoid unnecessary interventions to the pituitary. References 1 Ghazi A Endocrine 2013 2 Potorac J Endocr Relat Cancer 2015

Diagnostic accuracy of Bilateral Inferior Petrosal Sinus Sampling: The Experience of a Tertiary Centre

Purpose To assess the accuracy of bilateral inferior petrosal sinus sampling both in the differential diagnosis of adrenocorticotrophic hormone dependent Cushing’s syndrome and predicting the localization on the pituitary. Methods The authors evaluated all patients that undergone bilateral inferior petrosal sinus sampling in a tertiary centre, between January 1995 and March 2018. The probable diagnosis of Cushing’s disease was made when the basal central/peripheral gradient was>2 and/or>3 after stimulation with corticotrophin releasing hormone. The localization was suggested when the inter-sinus gradient was>1.4. The results obtained were compared with the post operatory results: compatible histology and positive immunohistochemistry to adrenocorticotrophic hormone and/or the presence of criteria of cure. Sensitivity, specificity and predictive positive value were calculated. Results A total of 49 patients were evaluated (75.5% female; mean age 45.4±16.3 years old). Bilateral inferior petrosal sinus sampling was compatible with Cushing’s disease in 27 out of 28 confirmed cases in histology or by criteria of cure, and was compatible with ectopic secretion in the 2 cases confirmed as ectopic secretion of adrenocorticotrophic hormone (sensitivity 96.4%; specificity 100%). The lateralization calculated was concordant with the results after surgery in 17 out of 27 patients with Cushing’s disease – predictive positive value of 63%. Magnetic resonance had a higher predictive value to lateralization – 70.0%. Conclusions Bilateral inferior petrosal sinus sampling is a safe and reliable procedure to diagnose Cushing’s disease, with great sensitivity and specificity. Nevertheless, the capacity of this procedure to lateralize the lesion inside the pituitary is limited.

Malignant Pheochromocytomas/Paragangliomas and Ectopic Hormonal Secretion: A Case Series and Review of the Literature

Malignant pheochromocytomas (PCs) and paragangliomas (PGLs) are rare neuroendocrine neoplasms defined by the presence of distant metastases. There is currently a relatively paucity of data regarding the natural history of PCs/PGLs and the optimal approach to their treatment. We retrospectively analyzed the clinical, biochemical, imaging, genetic and histopathological characteristics of fourteen patients with metastatic PCs/PGLs diagnosed over 15 years, along with their response to treatment. Patients were followed-up for a median of six years (range: 1–14 years). Six patients had synchronous metastases and the remaining developed metastases after a median of four years (range 2–10 years). Genetic analysis of seven patients revealed that three harbored succinate dehydrogenase subunit B/D gene (SDHB/D) mutations. Hormonal hypersecretion occurred in 70% of patients; normetanephrine, either alone or with other concomitant hormones, was the most frequent secretory component. Patients were administered multiple first and subsequent treatments including surgery (n = 12), chemotherapy (n = 7), radionuclide therapy (n = 2) and radiopeptides (n = 5). Seven patients had stable disease, four had progressive disease and three died. Ectopic hormonal secretion is rare and commonly encountered in benign PCs. Ectopic secretion of interleukin-6 in one of our patients, prompted a literature review of ectopic hormonal secretion, particularly from metastatic PCs/PGLs. Only four cases of metastatic PC/PGLs with confirmed ectopic secretion of hormones or peptides have been described so far.