IL-6-producing Renal Cell Carcinoma Causing Renal and Endocrine Paraneoplastic Syndromes.

An 83-year-old man with stable chronic kidney disease (CKD) exhibited a sudden increase in urinary N-acetyl-ß-D-glucosaminidase and protein excretion, suggesting aggravated kidney damage. Simultaneously, he lost diabetic control, requiring up to 54 units of insulin daily. A detailed examination revealed the presence of renal cell carcinoma, which was surgically resected and confirmed to be interleukin-6-positive by immunohistochemistry. Postoperatively, his uni-nephrectomy necessitated hemodialysis, but the patient's insulin resistance was ameliorated; no medication was required to control diabetes, suggesting that the tumor had caused the insulin resistance. This report describes a case of a tumor secreting interleukin-6, which affects both the control of diabetes and CKD progression.

Hypoglycemia Observed on Continuous Glucose Monitoring Associated With IGF-2-Producing Solitary Fibrous Tumor.

CONTEXT: Tumors producing IGF-2 (IGF-2oma) are a major cause of spontaneous hypoglycemia. The treatment mainstay is surgical resection. Many case reports note resolution of hypoglycemia after IGF-2oma resection; however, outcomes are variable according to tumor type. We report a case of resolving hypoglycemia, observed on continuous glucose monitoring, after resection of an IGF-2-producing solitary fibrous tumor of pleura and review the current literature. CASE REPORT: A 69-year-old woman presented with impaired consciousness because of hypoglycemia. An IGF-2oma was diagnosed as the cause for hypoglycemia because of decreased serum insulin and IGF-1, the presence of a pleural tumor, and a high-molecular-weight form of serum IGF-2 detected by Western immunoblot. Surgical resection was performed; pathological examination demonstrated a solitary fibrous tumor with low-grade malignancy. Continuous glucose monitoring showed reversal of hypoglycemia after tumor resection. Approximately 2 years after resection, the patient has no signs of tumor recurrence or hypoglycemia. CONCLUSIONS: An IGF-2-producing solitary fibrous tumor of pleura in this case caused hypoglycemia. From a search of the literature of 2004-2014, 32 cases of IGF-2oma with hypoglycemia that underwent radical surgery were identified; in 19 (59%) patients, hypoglycemia was reversed, and there was no subsequent recurrence. The remaining 13 (41%) patients experienced tumor recurrence or metastasis an average of 43 months after initial tumor resection. The tumor of the present case was a low-grade malignancy. Regular follow-up with biomarker monitoring of glucose metabolism and assessment of hypoglycemic symptomatology, in conjunction with imaging tests, is important for detecting possible tumor recurrence and metastasis.

No metabolic impact of surgical normalization of hyperandrogenism in postmenopausal women with ovarian androgen-secreting tumours.

AIM: To examine the impact of surgical normalization of testosterone on body weight and on glucose and lipid metabolism and insulin sensitivity in a group of hyperandrogenic women with ovarian androgen-secreting tumours (OAST). METHODS: Five consecutive postmenopausal hyperandrogenic patients (aged 63 ± 5 years) with a diagnosis of OAST were prospectively evaluated. Clinical signs, symptoms and metabolic and hormonal parameters were collected at the time of the diagnosis and at follow-up, 12 months after surgical oophorectomy. A group of 15 age-matched and body mass index-matched postmenopausal control women served as a reference group. RESULTS: At baseline, patients with OAST had very high testosterone levels and inappropriately low gonadotrophin levels for their menopausal status. All the women were overweight or obese, and one had a history of polycystic ovary syndrome and Type 2 diabetes. Twelve months after surgical oophorectomy, testosterone and gonadotrophin levels returned to appropriate values for menopausal status in all patients; however, no change in body weight was found. Fasting glucose levels slightly increased (P < 0·05) without any significant change in other metabolic parameters. In the woman with diabetes, a moderate decrease in haemoglobin A1c occurred. Red blood cell count and haematocrit values were normalized (P < 0·05, respectively). CONCLUSION: Normalization of androgen levels achieved after surgical oophorectomy did not cause any significant change in body weight and insulin sensitivity. These findings may offer a different perspective on the impact of hyperandrogenaemia on metabolism.

"Rescue" bilateral adrenalectomy in paraneoplastic Cushing's syndrome with invasive Aspergillus fumigatus infection.

We report the case of a patient with life-threatening Aspergillosis during paraneoplastic Cushing's syndrome. Anticortisolic drug ketoconazole was unable to lower severe hypercortisolism and despite antifungal treatment available at this time (liposomal amphotericine B and terbinafine), Aspergillus fumigatus infection was uncontrolled and extensive. "Rescue" bilateral adrenalectomy was performed to control hypercortisolism, leading to rapid fungal infection cure. We emphasize surgical management of hypercortisolism to achieve rapid blunting of cortisol production in a such life-threatening situation.

Acromegaly caused by growth hormone-releasing hormone-producing tumors: long-term observational studies in three patients.

We report on three newly diagnosed patients with extracranial ectopic GHRH-associated acromegaly with long-term follow-up after surgery of the primary tumor. One patient with a pancreatic tumor and two parathyroid adenomas was the index case of a large kindred of MEN-I syndrome. The other two patients had a large bronchial carcinoid. The first patient is still in remission now almost 22 years after surgery. In the two other patients GHRH did not normalize completely after surgery and they are now treated with slow-release octreotide. IGF-I normalized in all patients. During medical treatment basal GH secretion remained (slightly) elevated and secretory regularity was decreased in 24 h blood sampling studies. We did not observe development of tachyphylaxis towards the drug or radiological evidence of (growing) metastases. We propose life-long suppressive therapy with somatostatin analogs in cases with persisting elevated serum GHRH concentrations after removal of the primary tumor. Independent parameters of residual disease are elevated basal (nonpulsatile) GH secretion and decreased GH secretory regularity.

[Recurrent operations on the adrenal glands]. / Wiederholungseingriffe an den Nebennieren.

Repeat adrenalectomy may be required due to ipsilateral recurrence of benign or malignant adrenal tumors after previous total or subtotal adrenalectomy. Even for multivisceral resection in patients with adrenocortical carcinoma, complete resection of local recurrent tumor offers results similar to those of primary resection (5-year survival 40-60%). In contrast, since no benefit on long-term survival has been shown so far by tumor debulking, palliative tumor resection should only be performed individually for control of severe endocrine symptoms. The effect of endoscopic adrenalectomy in patients with large tumors (>5 cm) or suspected malignancy has still not been well examined. Further studies are required. In any case, during open or endoscopic approach, tumor spillage must be avoided to prevent local tumor cell implantation. Following subtotal adrenalectomy, the risk of ipsilateral recurrence correlates with disease, follow-up, localization, size of the adrenal remnant, and, in case of familial pheochromocytoma, probably with genotype.

[Preoperative diagnostics in patients with adrenal tumors]. / Diagnostyka przedoperacyjna u chorych z guzami nadnerczy.

The aim of the study was analysis of preoperative diagnostics of patients who underwent laparoscopic adrenalectomy. In the preoperative diagnostics in 10 patients (22.2%) pheochromocytoma was found, in 8 (17.8%) Conn's syndrome, in 4 (8.9%) Cushing's syndrome and in 1 (2.2%) adrenal virilization. Full accordance between histopathological findings and preoperative diagnosis was achieved in 91% of cases. Four cases of discrepancy were: 1 false positive preoperative diagnosis of aldosteronoma, 1 false positive and 2 false negative diagnosis of pheochromocytoma.

Ectopic TSH-secreting pituitary adenoma of the vomerosphenoidal junction.

OBJECTIVE: We describe an unusual case of ectopic TSH-secreting pituitary adenoma arising from the vomerosphenoidal junction. CLINICAL PRESENTATION: A 52-Year-old man with a long-standing history of hyperthyroidism was referred to the University Hospital in September 2001 because of increasingly disabling symptoms of nasal obstruction. For the past 18 Years the patient had complained of palpitations, hypertension, weight loss, and nervousness. A presumptive diagnosis of Graves' disease was made. Treatment with methimazole was begun, but the patient was lost to follow-up. On admission, physical examination revealed signs of hyperthyroidism and a large diffuse goiter. Tests of thyroid function showed inappropriate secretion of TSH with hyperthyroidism. Both a TSH-secreting pituitary adenoma and resistance to thyroid hormone could be taken into account. There was no evidence of pituitary tumour by magnetic resonance imaging (MRI), but a large space-occupying lesion involving the nasal cavity and the nasopharynx was incidentally discovered. INTERVENTATION AND TECHNIQUE: Using an endoscopic endonasal approach, the tumour was removed en bloc together with the sphenoid floor, sphenoid rostrum, bony septum, and part of the soft palate mucosa. Histological features and immunophenotype were those of a TSH-secreting tumour. CONCLUSION: Although exceedingly rare, ectopic TSH-secreting pituitary tumour should be borne in mind in cases of inappropriate secretion of TSH with hyperthyroidism and no evidence of pituitary tumour by computed tomography and/or MRI when a mass located along the migration path of the Rathke's pouch is demonstrated by radiological examination. To our knowledge, this is only the second reported case in the literature.

[Pituitary adenomas: neurosurgical treatment]. / Hypophysenadenome: Neurochirurgische Therapie.

Due to their diversity, pituitary adenomas represent an interdisciplinary therapeutic challenge in regard to endocrinology, radiology and neurosurgery. Advanced radiological methods such as magnetic resonance imaging (MRI) and the possibility of three-dimensional reconstruction have profoundly improved surgical planning and intraoperative neuronavigation. With the application of modern surgical techniques like endoscope-assisted microsurgery or pure endoscopic surgery further improvements in the treatment of pituitary adenomas at difficult locations can be expected. Major prognostic factors predicting surgical outcome are extension of the adenoma and invasivity into adjacent structures. Both may be perfectly visualized by high-resolution MRI. The proliferation marker MIB-1 as a parameter of growth-rate and invasivity of pituitary adenomas provides information for postoperative management in terms of additional treatment and follow-up imaging. The current management of pituitary adenomas is discussed according to the different therapeutic options available and new developments are presented.

Primary neuroendocrine tumors of the thymus.

Primary neuroendocrine tumors of the thymus are highly aggressive tumors that rarely occur. A little more than 200 cases have been reported, many of which were single case reports. Only a few articles contained modest series from single centers for analysis. A review of 157 cases collected from the major series reported to-date show a clinical pattern with male preponderance (male:female ratio, 3:1) and a mean age of 54 years. Most patients presented with symptoms and signs of local compression. Almost 50% of these tumors were functionally active and were associated with endocrinopathies. Several histologic variants have been described, all with similar ultrastructural features. The biologic behavior of these tumors shows a direct relation to the degree of differentiation. Whenever possible, surgical resection is the treatment of choice as adjuvant therapy is controversial and has been used with variable success. Potential therapies exploit the presence of somatostatin receptors on a variety of these tumors. Use of radiolabeled Octreotide for radionuclide therapy has yielded tumor inhibition in animal models and may have clinical application. Fifty-one percent of the patients survived 3 years, 27% survived 5 years, and less than 10% survived beyond 10 years. Histologic grade, tumor extension, and early detection are the most important factors affecting survival. Other prognostic factors that impact outcome include presence of endocrinopathy, incomplete resectability, nodal status, and presence of distant metastasis.

[Laparoscopic adrenalectomy--experiences with transperitoneal approach]. / Die laparoskopische Adrenalektomie--Ergebnisse mit dem transperitonealen Zugang.

INTRODUCTION: We report our results of laparoscopic anterior transperitoneal adrenalectomy. PATIENTS: Between 4/1996 to 05/2001, a laparoscopic adrenalectomy was performed in 34 patients (median age 48 years). The adrenalectomy was performed transperitoneally (31 unilateral; 3 bilateral). The adrenaline level was measured in 7 patients with a pheochromocytoma. RESULTS: All tumors (mean size 3.5 cm; 0.4 to 8.0 cm) could be extirpated by laparoscopy. 9 pheochromocytomas; 9 cortisol producing tumors (one patient with a Carney's syndrome); 7 Conn's adenomas and 9 incidentalomas constituted these tumors. In the first third of the observation period, the surgery lasted 176 (95-270) minutes, in the last third 82 (50-130) minutes (p < 0,01). We postoperatively observed the following complications: one abdominal wall hematoma at a port-site and one edematous pancreatitis after alteration of the pancreatic tail. The adrenaline level continually rose from the beginning of surgery to the ligature of the suprarenal vein. CONCLUSION: Transperitoneal adrenalectomy in benign tumors (< 8 cm) is our method of choice. The resulting learning curve allowed the performance of adrenalectomy within an acceptable operative time and without significant blood loss. The transperitoneal technique is safe and well reproducible. The cosmetical results are convincing. We recommend an early ligature of the suprarenal vein in a pheochromocytoma.

January 2002: 59-year-old woman with an intrasellar lesion.

An intrasellar lesion resembling a hormone-inactive pituitary adenoma was resected in a 59-year-old woman. The well-differentiated benign tumor was composed of ganglion-like cells, clusters of adenohypophyseal tissue as well as a GH-expressing adenoma. In addition, small cells exhibited an intermediate neuronal and epithelial immunoreactivity. Surrounding the tumor was a spindle cell component that histologically resembled Antoni A areas of a schwannoma, but showed a mixed immunohistochemical profile. Final diagnosis was intrasellar glioneuronal hamartoma with GH-cell pituitary adenoma.

[Unifocal autonomy and carcinoma of the thyroid gland]. / Unifokale Autonomie und Karzinom der Schilddrüse.

Two cases operated upon with the clinical diagnosis of unifocal autonomous functioning thyroid nodules (AFTN) are reported where the histological diagnosis revealed a well differentiated thyroid carcinoma (follicular, papillary) without metastasis. The pathogenesis of differentiated thyroid carcinomas in cases of AFTN may be coincident. Alternatively it may evolve from thyroid epithelial cells of the hot nodule, resulting in a "hot" well differentiated thyroid carcinoma. These cases show that under the clinical diagnosis of AFTN a differentiated thyroid carcinoma can be hidden occasionally.

Functioning adrenal tumours in children and adolescents: an institutional experience.

BACKGROUND: The purpose of the present paper was to carry out an audit of clinicopathological profile and treatment outcome in 13 children with functioning adrenal tumours. METHODS: The medical records of 13 children with functioning adrenal tumours who were managed between June 1990 and January 1999 were reviewed. Demographic data, clinical features, biochemical and localization studies, operative details and follow-up records were studied. Children with neuroblastoma were excluded. RESULTS: The mean age was 7.4 +/- 5.3 years. Seven patients had Cushing's syndrome (CS), two patients had virilizing tumours, three patients had phaeochromocytoma (PCC) and one patient had Conn's syndrome. All patients (except one child with CS) were treated surgically. Two children with adrenocortical carcinoma (ACCa) died during the perioperative period. Histopathological diagnosis was adrenal cortical adenoma (ACAd) in four patients, ACCa in five patients and PCC in three patients. Two ACCa patients died of metastases at 12 and 14 months, respectively, while the third is alive and well at 30 months. Children with ACAd are alive and well at 91, 56, 32 and 27 months postoperatively. Children with PCC are free of disease (normal urinary metanephrines) at 63, 18 and 8 months after surgery but require antihypertensive drugs in low doses. CONCLUSION: The outcome of surgery is good in cases of ACAd and PCC. Although outcome is poor in ACCa, surgery remains the mainstay of treatment and offers good palliation.