Surgery for massive splenomegaly.

BACKGROUND: Splenectomy for massive splenomegaly (spleen weight more than 1·5 kg) is commonly believed to be hazardous and to provide poor palliation. The aim of this cohort study was to investigate these issues and examine the many definitions of massive splenomegaly to see whether a better tool might be proposed for preoperative evaluation of these patients. METHODS: Morbidity and long-term outcomes were assessed in consecutive patients. Relief of pressure-volume-related symptoms and sustainable independence from transfusion in patients were used to ascertain the impact of splenectomy. RESULTS: Splenectomy was performed in 56 patients, mainly for non-Hodgkin's lymphoma and myeloproliferative diseases. Median spleen weight was 2·3 (range 1·5-6·0) kg. Mortality at 180 days was zero, and the postoperative complication rate was 25 per cent (17 complications in 14 patients). At 2 years, relief of pain was maintained in 33 of 34 patients, with sustained independence from transfusion in 15 of 19 patients with anaemia and nine of 11 with thrombocytopenia. Spleen weight correlated negatively with BMI (P = 0·036). CONCLUSION: Splenectomy for massive splenomegaly is safe and provides effective palliation. Provisional cut-off points relating to spleen size and BMI help to identify patients benefiting from a splenectomy, even those in a critical state.

Chronic necrotising aspergillosis mimicking ACTH-secreting tumour in a case of Cushing's disease.

An 18-year-old man presenting with speech and behaviour disorders was found to suffer from Cushing's syndrome. Ectopic ACTH secretion was initially suspected on the basis of very high cortisoluria and ACTH concentrations, severe hypokalemia, a lung hypermetabolic lesion and a normal pituitary on conventional magnetic resonance imaging (MRI). After lung surgery, this lesion proved to be chronic necrotising aspergillosis (CNA). Diagnostic reevaluation by bilateral inferior petrosal sinus sampling disclosed a right-sided petrosal sinus gradient consistent with Cushing's disease (CD). A new high resolution thin-section MRI demonstrated a 5 mm pituitary adenoma, which could be removed successfully. Thus, a lung mass associated with several clues in favour of ectopic ACTH secretion may hide a diagnosis of CD. Such a mass can be CNA, an opportunistic infection favoured by immunosuppression, which to our knowledge, is the first case reported in CD.

The rationale for performing MR imaging before surgery for primary hyperparathyroidism.

OBJECTIVE: The purpose of this study was to evaluate prospectively Magnetic Resonance Imaging (MRI) for the preoperative localization of hyperfunctioning parathyroid glands. DESIGN: Prospective study of 58 consecutive patients with biochemically confirmed primary hyperparathyroidism who underwent preoperative MRI. SETTING: The setting is a referral centre. PATIENTS: Fifty-six of the 58 consecutive patients (41 women, 17 men) were studied by both preoperative MRI and 99mTC MIBI scintigraphy, and two by MRI alone. The same surgeon, using the information from both MRI and 99mTC MIBI, performed surgery in 58 patients, including 19 with a history of neck surgery. Initial interpretation of each MR study was done independently by one radiologist and the surgeon and then results were compared. At surgery, the operative duration, the precise anatomical location, weight, and dimensions as well as complete histopathological evaluations of all excised glands were recorded. MAIN OUTCOME MEASURE: In addition to the prospective assessment of MRI, this study compared performance of MRI with double-phase 99mTC MIBI scintigraphy for preoperative localization of hyperfunctioning parathyroid glands. RESULTS: All patients became normocalcaemic after surgery. MRI and 99mTC MIBI imaging revealed 53 of 58 (91%) and 47 of 56 (84%) of abnormal glands, respectively. Sensitivities of MRI and 99mTC MIBI were respectively 94.3 and 88.0. Positive predictive values were 96.15 and 93.60. When MRI and 99mTC MIBI were interpreted together, the sensitivity and positive predictive values both raised to 98.10. Median operative duration was 30 minutes (ranges 20-300 minutes, mean 65). CONCLUSION: MRI has better sensitivity and positive predictive value than 99mTC MIBI scintigraphy for the detection of hyperfunctioning parathyroid glands. The combination of the two studies provides an additional increase in sensitivity and positive predictive value leading to a more precise anatomical localization of the abnormal parathyroid glands reducing both the extent of the surgical dissection and the operative duration.

Pituitary incidentaloma: to operate or not to operate?

The wide use of sophisticated imaging techniques has led to the discovery of asymptomatic pituitary lesions, which are called 'incidentalomas'. Their global prevalence averages 10% whereas that of macroadenomas (> 10 mm) is less than 1%. The most frequently encountered lesions are non-functioning adenomas followed by Rathke's cleft cysts. Physiological pituitary hypertrophy is also frequent in young women. Silent functioning adenomas especially prolactinomas can be found among incidentalomas. Hypopituitarism appears to be more frequent in larger lesions but can occur in microadenomas (< 10 mm). The incidence of tumour growth is higher in macroadenomas and solid lesions in comparison with microadenomas and cystic lesions. The baseline evaluation should include in all patients a complete history and physical examination, a screening for hormone hypersecretion and hypopituitarism and a visual field examination if the lesion abuts the optic nerves or chiasm. If there is hormone hypersecretion, an appropriate treatment is indicated (dopamine agonists for prolactinomas and surgery for tumours producing GH, ACTH or TSH). If there is hypopituitarism, adequate hormone replacement therapy is required. According to recent guidelines, the indications for surgery of non-functioning incidentalomas include a visual field deficit, other visual abnormalities such as ophtalmoplegia or a lesion abutting the optic nerves or chiasm on magnetic resonance imaging (MRI). Regarding the follow-up of incidentalomas not meeting the criteria for surgery, the following tests should be performed: MRI at 1 year for micro-incidentalomas, at 6 months for macro-incidentalomas and then less frequently if unchanged in size, visual field examination for lesions enlarging to abut or compress the optic nerves or chiasm (6 months and yearly) and endocrine testing for macro-incidentalomas (6 months and yearly). Nowadays, data are insufficient to suggest the routine use of medical therapy in non-functioning tumours. Pituitary radiotherapy may be useful as an adjunctive treatment for tumour remnants growing progressively.

Misleading diagnosis of renal artery stenosis by magnetic resonance angiography in a patient with primary aldosteronism.

A 24-year-old woman presented with severe hypertension. A diagnostic evaluation for secondary hypertension was undertaken. A duplex ultrasonography followed by a magnetic angiography suspected fibromuscular dysplasia. Unexpectedly, a contrast-enhanced angiography performed for renal angioplasty showed normal renal arteries. Primary aldosteronism was then evoked on the basis of decreased plasma renin and increased plasma aldosterone and aldosterone/renin ratio. After a CT-scan disclosed a left adrenal tumour, the patient underwent a left laparoscopic adrenalectomy. Pathological findings confirmed a benign adrenocortical adenoma. Blood pressure and aldosterone levels were normalized after surgery. Thus, clinicians should be aware of false-positive results of magnetic resonance angiography that could hide other causes of secondary hypertension.

Phaeochromocytoma: state-of-the-art.

Phaeochromocytomas are catecholamine-secreting tumours that arise from chromaffin cells of the adrenal medulla and extra-adrenal sites. Extra-adrenal phaeochromocytomas are called paragangliomas. A diagnosis of phaeochromocytoma is suspected by typical paroxysmal symptoms, unusual or refractory hypertension, discovery of an adrenal incidentaloma or a family history of phaeochromocytoma or paraganglioma, possibly associated with other genetic syndromes (multiple endocrine neoplasia type 2 A or B, neurofibromatosis type 1 and von Hippel-Lindau disease). It can be confirmed by measurements of urinary or plasma fractionated catecholamines and metanephrines. The best diagnostic performances are achieved by metanephrines. Twenty-four hour urine fractionated metanephrines are still recommended as a screening test but some experts prefer plasma measurements in high-risk patients. Increased serum chromogranin-A levels, combined with high catecholamine or metanephrine in a patient with normal renal function is also a tool, virtually diagnostic of phaeochromocytoma. Recent studies have suggested that 25% of patients with phaeochromocytoma have germline mutations of several genes (NF1, VHL, SDHD, SDHB and RET). Thus, genetic testing should be carried out according to an algorithm of risk factors and specific characteristics. Once a biochemical diagnosis of phaeochromocytoma is made, a CT scan or MRI of the abdomen and pelvis should be performed first. If these investigations remain negative, the chest and neck should be explored. After anatomical imaging, functional imaging by 123I-MIBG should be considered. If the MIBG scan is negative, other imaging modalities have recently proven to be useful (PET, Octreoscan). After localization, the treatment of phaeochromocytoma is a surgical resection, which may be laparoscopic. Preoperative preparation with alpha- and beta-adrenergic blockade and/or calcium channel blockers associated with volume expansion is essential. Malignant phaeochromocytoma is rare and its treatment still unsatisfying. Phaeochromocytoma during pregnancy is also rare and its diagnosis easily missed because of its clinical resemblance to pre-eclampsia.

Diabetes mellitus as a primary manifestation of multiple endocrine neoplasia type 2B.

A 22-year-old-man presenting with diabetes mellitus was found to suffer from multiple endocrine neoplasia type 2B (MEN B). The characteristic phenotype including mucosal neuromas, musculoskeletal abnormalities and a marfanoid habitus led us to suspect this diagnosis, which was confirmed by the genetic analysis showing the typical mutation in the RET proto-oncogene at codon 918. Subsequently, diagnoses of bilateral phaeochromocytoma and medullary thyroid carcinoma were made. The patient underwent first a laparoscopic removal of bilateral phaeochromocytoma and a radical thyroidectomy three months later. Both operations were uneventful. After operation, diabetes resolved, an effect partly explainable by an improvement of insulin sensitivity. Thus, clinicians should be aware of a diagnosis of MEN 2B in a young patient presenting with diabetes, a typical phenotype, symptoms of phaeochromocytoma or a nodule in the thyroid.

Bilateral adrenal lymphoma with Addison's disease : a surgical pitfall.

A 65 year old man presenting with abdominal and back pain was found to have bilateral adrenal masses. Phaeochromocytomas were initially suspected on the basis of increased catecholamine excretion. This diagnosis seemed unlikely in view of clinical findings and a negative 123I-metaiodobenzylguanidine scintigraphy. A biopsy of the right adrenal mass revealed a diagnosis of primary adrenal B-cell lymphoma. Hyponatraemia and subtle clinical signs of adrenal insufficiency led to a diagnosis of Addison's disease, a common complication of primary adrenal lymphoma. Thus, bilateral adrenal masses associated with Addison's disease should raise the suspicion of possible primary adrenal lymphoma.

Metabolic (glycaemic, lipidic) and blood pressure control in 101 type 2 diabetic patients on first admission to diabetes centres.

The aim of our study was to analyse the quality of metabolic and blood pressure control in a cohort of 101 patients with type 2 diabetes (54 males; 47 females), previously followed in primary care settings and admitted for the first time to the diabetes centres of Saint-Luc (n=66) or Mont-Godinne (n=35) University Hospitals. Age and (known) duration of diabetes were 64 +/-12 and 6 +/- 7 years (mean +/- SD), respectively. Body mass index was 31 +/- 7 kg/m2. Systolic and diastolic blood pressures were 140 +/-12 and 81 +/-11 mmHg. Homeostasis model assessment (HOMA) showed insulin sensitivity at 63 +/-32% and P-cell function at 49 +/- 44% (n=34). Forty-seven percent of patients received either diet alone or combined with an oral antidiabetic monotherapy. Seven-teen percent of all patients were on insulin monotherapy or associated with oral drugs. HbAlc was 9.0 +/- 2.3%, with 22% of patients within HbAlc targets of < or = 7%. Only a subset of patients reached international targets of care in terms of blood pressure and lipidic profile, despite antihypertensive and lipid-lowering agents in 62% and 36% of patients, respectively. Forty-five percent of individuals had at least one diabetes-related long-term complication. In view of this unsatisfactory control, our results suggest that "anti-diabetic" treatment should be intensified earlier in primary care settings.

Metastasis of a small cell carcinoma from undetected origin to the pituitary gland--the otolaryngologist's view.

Tumour metastasis to the anterior pituitary-hypothalamic area is rare. We present a patient who had severe headache, bitemporal quadrant hemianopsia and an expanding mass in the sella turcica as revealed by MRI. Partial resection via a transsphenoidal approach was performed and postoperative radiation therapy was initiated. Immunohistochemical investigation identified the tumour as a metastatic small cell carcinoma whose primary site remained undetected for more than 12 months despite repeated oncological evaluations. We reviewed the literature on metastatic disease of the pituitary gland.

Expression of endothelin-1 by adrenocortical carcinoma: a new target for anti-cancer therapy?

Adrenocortical carcinoma is a rare neoplasm with poor prognosis. Endothelin-1 (ET-1) has been implicated in carcinogenesis, but has never been studied in this neoplasm. A 76-year-old woman with Cushing's syndrome due adrenocortical carcinoma was operated on and the tumour removed was studied by immunohistochemistry for ET-1. Patient history illustrates the poor prognosis of this cancer that became metastatic after one year. Immunohistochemical studies disclosed a strong expression of ET-1 by adrenocortical carcinoma cells. As shown in other cancers, ET-1 expression by adrenocortical carcinoma may suggest a pathogenic role of ET-1 in tumorigenesis that possibly could be countered by ET-1 receptor antagonists. These agents could open new therapeutic perspectives to treat a carcinoma known to have a poor prognosis.

Late-onset primary hyperoxaluria triggered by hypothyroidism and presenting as rapidly progressive renal failure--description of a new mutation.

Primary hyperoxaluria type 1 (PH1) is a rare autosomal metabolic recessive disease, caused by the deficiency of the liver peroxysomal alanine:glyoxylate aminotransferase (AGT), characterized by accumulation of calcium oxalate crystals in kidneys and others organs. We present the case of an elderly woman with PH1, presenting as acute renal failure. Precipitation of calcium oxalate crystals was probably due to amiodarone-induced severe hypothyroidism. Residual AGT activity is associated with the G170R (G630A) mutation. A new mutation of AGT, called R36C, was also discovered; the role of this new mutation is actually not known.

[Increased expression of endothelin-1 and its mitogen receptor ET(A) in thyroid papillary cancer in humans]. / Expression accrue de l'endothéline-1 et de son récepteur mitogène ET(A) dans le cancer papillaire de la thyroïde chez l'homme.

Since its discovery in 1988, endothelin has initiated intense research activities, showing that it was not only a vasoconstrictor and mitogenic peptide produced by the vascular endothelium but also a ubiquitous molecule with various functions. A production of ET-1 has been evidenced in the thyroid and ET-1 receptors have been detected on thyroid cells. Produced by the vessels and the thyrocytes, ET-1 could exert paracrine and/or autocrine effects on vascular tone in the thyroid and on some functions of thyrocytes. Because of proliferative effects, its role in thyroid diseases could involve goitrogenesis and carcinogenesis. Using thyroid samples obtained at the time of surgery, we demonstrated increased expressions of ET-1 and its mitogenic receptor ET(A) in papillary carcinoma of the thyroid. Immunohistochemical studies and real-time quantitative polymerase chain reaction (RTQ-PCR) were used for this purpose. As demonstrated in other cancers, activation of endothelin axis, particularly through ET(A) receptor could contribute to cell proliferation, cell survival, angiogenesis and the development of bone metastases. ET-1 is also a proinflammatory mediator and we demonstrated an overexpression of ET-1 and of its receptor ET(A) in Hashimoto's thyroiditis. This suggests a role of ET-1 as a cytokine. In nodular goitre, ET-1 is also overexpressed but to a lesser extent than in papillary thyroid carcinoma and in Hashimoto's thyroiditis. Finally, antagonists of ET-1 receptors are currently under development and could be used in man. They could open new therapeutic perspectives in the treatment of metastatic thyroid carcinoma.

Emergency hepato-renal artery bypass using a PTFE graft.

A 51-year-old patient suffering from Buerger's disease with bilateral lower limb amputation and Leriche syndrome presented with uncontrollable hypertension and renal failure caused by right renal artery subocclusive stenosis associated with an occluded left renal artery and atrophic kidney. He underwent a right hepato-renal bypass grafting using an externally supported polytetrafluorethylene (PTFE) graft. Renal function improved markedly and hypertension could be controlled by standard antihypertensive treatment. Normal right renal function was maintained at one-year follow-up.

Decreased expression of myocardial eNOS and caveolin in dogs with hypertrophic cardiomyopathy.

Because nitric oxide (NO) regulates cardiac and vessel contraction, we compared the expression and activity of the endothelial NO synthase (eNOS) and caveolin, which tonically inhibits eNOS in normal and hypertrophic cardiomyopathic hearts. NOS activity (L-[(3)H]citrulline formation), eNOS immunostaining, and caveolin abundance were measured in heart tissue of 23 mongrel dogs before and at 3 and 7 wk of perinephritic hypertension (PHT). Hemodynamic parameters in vivo and endothelial NO-dependent relaxation of macro- and coronary microvessels in vitro were assessed in the same animals. eNOS immunostaining and total calcium-dependent NOS activity decreased at 7 wk in all four heart cavities (in left ventricle, from 17.0 +/- 1.3 to 0.2 +/- 0.2 fmol. min(-1). mg protein(-1), P < 0.001). Caveolin-1 and -3 also decreased in PHT dog hearts. Accordingly, basal vascular tone was preserved, but maximal endothelial NO-dependent relaxation was impaired in all vessels from 7-wk PHT dogs. The latter had preserved systolic function but impaired diastolic relaxation [relaxation time constant (T(1)), 25.1 +/- 0.9 vs. 22.0 +/- 1 ms in controls; P < 0.05]. Peripheral infusion of the NOS inhibitor N(G)-nitro-L-arginine methyl ester increased mean aortic pressure in both groups and reduced diastolic (T(1), 31.9 +/- 1.4 ms) and systolic function in PHT dogs (DP40, 47.5 +/- 2.5 vs. 59.4 +/- 3.8 s(-1) in control animals). In conclusion, both eNOS and caveolin proteins are decreased in the hypertrophic hearts of PHT dogs. This is associated with altered maximal (but not basal) vascular relaxation and impaired diastolic function. Further degradation of cardiac function after NOS inhibition suggests a critical role of residual NOS activity, probably supported by the concurrent downregulation of caveolin.

Antiproliferative effect of octreotide in somatotroph pituitary adenomas: discussion from a single case report.

The case of a 20-year-old man presenting with a rapidly expanding pituitary somatotrophic adenoma with a tumour volume doubling time of 426 days is reported. Preoperative octreotide therapy induced a 45% tumour shrinkage and proliferating cells were absent at the time of tumoural resection. The correlation between clinical and proliferation markers data in this single case report affords an opportunity to discuss the antitumoral effect of octreotide on somatotrophic adenomas which may result from a suppression of cell proliferation.