A rare case of ectopic ACTH syndrome caused by primary renal neuroendocrine tumor.

SUMMARY: Ectopic adrenocorticotropic hormone (ACTH) secretion is responsible for 5-15% of Cushing's syndrome (CS). Neuroendocrine tumor (NET) is a common cause of ectopic ACTH syndrome (EAS). However, primary renal NET is exceedingly rare. Fewer than 100 cases have been reported and only a few cases presented with CS. Because of its rarity and lack of long-term follow-up data, clinical manifestations, biological behavior and prognosis are not well understood. Here, we report the case of a 51-year-old man who presented with clinical and laboratory findings compatible with EAS. CT scan revealed a lesion of uncertain nature at the lower pole of the left kidney. Octreotide scan found a filling defect at the lower pole of left kidney. It was difficult to determine if this finding was the true etiology or an incidental finding. Unfortunately, the patient's clinical status rapidly deteriorated with limited medical treatment. The patient underwent left nephrectomy and left adrenalectomy. Histopathological examination confirmed NET with oncocytic features. Immunohistochemistry staining was positive for ACTH. The patient's condition gradually improved. Additionally, glucocorticoid replacement was required only 6 months during a gradual recovery of hypothalamic pituitary adrenal axis achieved approximately three years after tumor removal. Although extremely rare, primary renal NET should be considered as a cause of EAS particularly in a patient with rapid clinical deterioration. Thorough investigation, early diagnosis and careful management are crucial to reduce morbidity and mortality. LEARNING POINTS: Primary renal NET is an extremely rare cause of ectopic ACTH syndrome. Ectopic ACTH syndrome has a rapid onset with severe clinical manifestations. In this case, the patient's condition deteriorated rapidly, resulting from severe hypercortisolism. Resection of the tumor is the most effective treatment. Localization of ectopic ACTH-secreting tumors is very challenging. Multimodality imaging including CT, MRI, octreotide scan, and positron emission tomography plays a crucial role in identifying the tumors. However, each imaging modality has limitations.

Safety of preoperative carvedilol in a patient with recent atenolol-induced pheochromocytoma crisis and cardiomyopathy: A case report.

INTRODUCTION: Beta-adrenergic blockade without adequate alpha blockade is an established trigger of pheochromocytoma crisis (PC). Carvedilol is a nonselective beta-adrenergic and alpha 1-adrenergic blocking agent, and its use for preoperative preparation of pheochromocytoma patients with prior cardiomyopathy secondary to PC resulting from unopposed beta-blocker therapy has never been reported. CASE PRESENTATION: A 48-year-old woman was admitted to the Urology Department for evaluation of a huge right upper abdominal mass. She developed hypertensive crisis with acute pulmonary edema resulting in respiratory failure after administration of atenolol to treat hypertension and tachycardia. Transthoracic echocardiogram revealed global hypokinesia. The patient was managed with intravenous nicardipine, furosemide, and prazosin because of the clinical suspicion of pheochromocytoma that was subsequently confirmed by elevated plasma and urine catecholamine levels. Within 3 days of alpha-adrenergic blockers treatment, there was rapid amelioration of hypertension and pulmonary congestion, as well as normalization of left ventricular function by echocardiography. However, tachycardia persisted after 1 month of adequate alpha-adrenergic blockade. Given the benefit of beta-adrenergic blockers in patients with systolic dysfunction, we slowly titrated carvedilol while carefully monitoring the patient's condition in the intensive care unit. Tachycardia was controlled without inducing PC. Surgical resection was successful without perioperative complications. CONCLUSION: Clinicians should be cautious when prescribing beta-adrenergic blocker in patients with hypertension and upper quadrant mass of unknown etiology. The mass may be pheochromocytoma. Preoperative use of carvedilol after sufficient alpha-adrenergic blockade for control of tachycardia in a patient with prior cardiomyopathy associated with atenolol-induced PC is safe and effective.

Diabetes insipidus and panhypopituitarism as a first presentation of silent adenocarcinoma of lung: a case report and literature review.

BACKGROUND: Pituitary metastasis is a rare condition with a poor prognosis. Very few patients with pituitary metastasis are symptomatic. It is often associated with presence of co-existing metastases to other organs. Isolated pituitary metastasis as the first presentation of primary malignancy is uncommon. CASE PRESENTATION: A 72-year-old woman presented with a 2-month history of polyuria, increasing thirst and unexplained weight loss. Esophagogastroduodenoscopy (EGD) was scheduled as part of the investigation. She was kept nil per os for 10 h prior to EGD, after which she developed alteration of consciousness. Further investigation revealed hypernatremia with sodium level of 161 mmol/L and low urine osmolality of 62 mOsm/kg. Her urine output was 300 mL per hour. Diabetes insipidus (DI) was diagnosed based on evidence of polyuria, hypernatremia, and low urine osmolality. Her urine output decreased and urine osmolality increased to 570 mOsm/kg in response to subcutaneous desmopressin acetate, confirming central DI. Pituitary magnetic resonance imaging showed a heterogeneous gadolinium enhancing lesion at the sellar and suprasellar regions, measuring 2.4 × 2.6 × 3.9 cm compressing both the hypothalamus bilaterally and the inferior aspect of optic chiasm as well as displacing the residual pituitary gland anteriorly. The posterior pituitary bright spot was absent. These MRI findings suggested pituitary macroadenoma. There were also multiple small gadolinium-enhancing lesions up to 0.7 cm in size with adjacent vasogenic brain edema at the subcortical and subpial regions of the left frontal and parietal areas, raising the concern of brain metastases. Pituitary hormonal evaluation was consistent with panhypopituitarism. Histopathological and immunohistochemical studies of the pituitary tissue revealed an adenocarcinoma, originating from the lung. Computed tomography of the chest and abdomen was subsequently performed, showing a 2.2-cm soft tissue mass at the proximal part of right bronchus. There was no evidence of distant metastases elsewhere. The final diagnosis was adenocarcinoma of the lung with pituitary metastasis manifesting as panhypopituitarism and central DI. Palliative care along with hormonal replacement therapy was offered to the patient. She died 4 months after diagnosis. CONCLUSION: Diagnosis of pituitary metastasis is challenging, especially in patients with previously undiagnosed primary cancer. It should be considered in the elderly patients presenting with new-onset central DI with or without anterior pituitary dysfunction.

Endocrine Disorders Are Prominent Clinical Features in Patients With Primary Antibody Deficiencies.

Background: Primary antibody deficiencies (PADs) and anterior pituitary dysfunction are both rare conditions. However, recent studies have remarkably reported the occurrence of anterior pituitary dysfunction in PAD patients. Methods: In this cross-sectional, single-center study we evaluated the prevalence of endocrine disorders in adult PAD patients. Our study focused on common variable immunodeficiency (CVID), immunoglobulin G (IgG) subclass deficiency (IgGSD), and specific anti-polysaccharide antibody deficiency (SPAD). We assessed hormone levels, performed provocative tests and genetic testing in a subset of patients by direct sequencing of the nuclear factor kappa beta subunit 2 (NFKB2) gene and primary immunodeficiency (PID) gene panel testing by whole exome sequencing (WES). Results: Our results demonstrated that one out of 24 IgGSD/SPAD patients had secondary hypothyroidism and three out of 9 men with IgGSD/SPAD had secondary hypogonadism. Premature ovarian failure was observed in four out of 9 women with CVID and primary testicular failure in one out of 15 men with CVID. In two out of 26 CVID patients we found partial adrenal insufficiency (AI) and in one out of 18 patients with IgGSD/SPAD secondary AI was found. Moreover, in one out of 23 patients with CVID and in two out of 17 patients with IgGSD/SPAD severe growth hormone deficiency (GHD) was found, while one patient with IgGSD/SPAD showed mild GHD. Combined endocrine disorders were detected in two women with CVID (either partial secondary AI or autoimmune thyroiditis with primary hypogonadism) and in three men with IgGSD/SPAD (two with either mild GHD or secondary hypothyroidism combined with secondary hypogonadism, and one man with secondary AI and severe GHD). Genetic testing in a subset of patients did not reveal pathogenic variants in NFKB2 or other known PID-associated genes. Conclusion: This is the first study to describe a high prevalence of both anterior pituitary and end-organ endocrine dysfunction in adult PAD patients. As these endocrine disorders may cause considerable health burden, assessment of endocrine axes should be considered in PAD patients.

Dopamine Agonists Can Reduce Cystic Prolactinomas.

CONTEXT: Cystic prolactinomas are considered resistant to volume reduction by dopamine agonists (DAs). Although several individual case reports and small case series have suggested that DAs may reduce these lesions, larger series using standardized imaging metrics are lacking. OBJECTIVE: The objectives of the study were to assess the efficacy of DAs on cyst size in patients with predominantly cystic prolactinomas and to characterize the clinical course and treatment outcomes in these patients. DESIGN: This study was a retrospective review. SETTING: The study was conducted at a tertiary referral center. SUBJECTS: The study comprised 30 adults with cystic prolactinomas treated at Massachusetts General Hospital. INTERVENTION(S): The interventions included treatment with Das and transsphenoidal surgery. MAIN OUTCOME MEASURE(S): Cyst volume calculated by a commercial software and pituitary hormone function were measured. RESULTS: Median age was 31.5 years (interquartile range [IR] 24.5-39.2), and 24 of 30 were female. Median length of follow-up was 3.05 years (IR 1.04-5.28). Twenty-three of 30 patients received initial treatment with DAs. Median cyst volume for these patients was 435 mm3 (IR 255-1785). Persistent cyst reduction occurred in 20 of 22 patients after DA treatment. Median cyst volume reduction was 83.5% (IR 48.8-96.2). Median time to cyst reduction was 24.6 weeks (range 2.6-73). Chiasm compression resolved in four of five patients, and nongonadal anterior hypopituitarism improved in five of six. Transsphenoidal surgery was ultimately performed in 15 of 30 patients. CONCLUSIONS: Significant cyst reduction occurred in the majority of patients treated with DAs, including those with larger lesions and chiasm compression. This study is the first formal analysis of cyst reduction with DAs in patients with cystic prolactinomas, and contrary to long-held assumptions, our results suggest that medical therapy may be effective in many such patients.

Tumor suppression by MEG3 lncRNA in a human pituitary tumor derived cell line.

Human clinically non-functioning pituitary adenomas (NFAs) account for approximately 40% of diagnosed pituitary tumors. Epigenetic mutations in tumor suppressive genes play an important role in NFA development. Maternally expressed gene 3 (MEG3) is a long non-coding RNA (lncRNA) and we hypothesized that it is a candidate tumor suppressor whose epigenetic silencing is specifically linked to NFA development. In this study, we introduced MEG3 expression into PDFS cells, derived from a human NFA, using both inducible and constitutively active expression systems. MEG3 expression significantly suppressed xenograft tumor growth in vivo in nude mice. When induced in culture, MEG3 caused cell cycle arrest at the G1 phase. In addition, inactivation of p53 completely abolished tumor suppression by MEG3, indicating that MEG3 tumor suppression is mediated by p53. In conclusion, our data support the hypothesis that MEG3 is a lncRNA tumor suppressor in the pituitary and its inactivation contributes to NFA development.