Endocrine and metabolic assessment in adults with Langerhans cell histiocytosis.

CONTEXT: Diabetes insipidus (DI) is one of most common complications of Langerhans cell histiocytosis (LCH) but prevalence of anterior pituitary deficiencies and metabolic alterations have not been clearly defined yet. OBJECTIVES: Evaluate prevalence of endocrine and metabolic manifestations in a cohort of patients affected by Pulmonary LCH. METHODS: Observational cross-sectional study on 18 adults (7 M/11 F, 42±12years) studied for complete basal and dynamic endocrine lab tests and glucose metabolism. RESULTS: Hypothalamic-pituitary endocrine alterations were found in 9 patients: 9 had DI, 5 Growth Hormone Deficiency (GHD), 5 central hypogonadism, 3 central hypothyroidism and 1 central hypoadrenalism. Hyperprolactinemia and hypothalamic syndrome were found in 2 patients each. All these central endocrine alterations were always associated to DI. Five of the 10 MRI performed showed abnormalities. Prevalence of obesity and glucose alterations (either DM or IFG/IGT) were respectively 39% and 33%, higher than expected basing on epidemiological data on general Italian population. Multi-system-LCH without risk-organ involvement (LCH MS-RO-) seems to have slightly higher prevalence of insulin resistance, glucose alterations and metabolic syndrome than LCH with isolated lung involvement (LCH SS lung+). A papillary BRAFV600E positive thyroid carcinoma was diagnosed in one patient. CONCLUSIONS: The presence of anterior pituitary deficiencies should be systematically sought in all LCH patients with DI both at diagnosis and during the follow-up by basal and dynamic hormonal assessment. Patients with pulmonary LCH, particularly those with MS disease, have a worse metabolic profile than general population. Occurrence of papillary thyroid carcinoma has been reported.

New therapeutic options for acromegaly.

Acromegaly is a slowly developing disfiguring disease characterized by chronic growth hormone (GH) and insulin-like growth factor-I (IGF-I) excess and caused by a pituitary somatotroph adenoma. It is associated to 2- to 3 fold increased mortality, compared to normal population, mostly due to cardiovascular and cerebro-vascular diseases, and to several co-morbid systemic illnesses, such as diabetes mellitus, hypertension, severe arthropathies, a specific cardio-myopathy, goitre, sleep-apnoea, intractable headache. The morbidity and excess mortality of acromegaly are usually the consequence of the metabolic actions of excess GH and IGF-I secretion, while only in rare patients mortality is due to the mass effects of the pituitary tumour. Since, serum IGF-I concentrations within age-adjusted normal range, and a tight GH control have to be achieved to normalize life-expectancy in these patients, an aggressive, and often multi-modality treatment is required for acromegaly. In recent years, new drugs, and new formulations of old drugs, have been developed that are able to effectively inhibit GH secretion or GH action, and may represent important adjuncts or even alternatives to the traditional approaches of surgery and radiotherapy. This review briefly summarizes the therapeutic options nowadays available for acromegaly. A brief note about innovative drugs under study, is also given.

[Nodular regenerative hyperplasia and primary biliary cirrhosis]. / Hyperplasie nodulaire régénérative et cirrhose biliaire primitive.

We report two cases of nodular regenerative hyperplasia of the liver associated with primary biliary cirrhosis. Cholestasis and presence of antimitochondrial antibodies were noted in both patients. In one patient, the diagnosis of nodular regenerative hyperplasia was supported by the demonstration of disseminated small hepatic nodules without perinodular fibrosis. Twelve years later, the histopathological picture was one of primary biliary cirrhosis. The other patient presented an histological picture of regenerative hyperplasia of the liver and primary biliary cirrhosis. The association of regenerative hyperplasia of the liver and primary biliary cirrhosis is discussed.

Ultrasound-guided laser thermal ablation for parathyroid adenomas: analysis of three cases with a three-year follow-up.

BACKGROUND: In patients with primary hyperparathyroidism (pHPT) the therapeutical choice is surgery. In patients with high surgical and anesthetic risks, ultrasound-guided laser ablation (LTA) of parathyroid adenoma has been reported to reduce parathyroid hormone (PTH) hypersecretion without relevant side effects. No data are available from patients followed for >6 months. We report our 3-year follow-up experience with LTA in 3 patients affected by pHPT due to a parathyroid tumor. METHODS: LTA was performed under color-Doppler ultrasound guidance with a continuous pulse at 2 W (total treatment duration: 300 s in each session; total energy: 1,200 J in two sessions). RESULTS: In the first patient who refused to undergo the second LTA session, calcium, PTH levels and parathyroid lesion volume showed a slight reduction, returning to baseline values in a month. In the second patient, no modification of parathyroid lesion was obtained even if calcium levels temporarily normalized. In the third patient, LTA led to normalization of calcium and PTH levels and to a 99% reduction of parathyroid volume. CONCLUSION: After LTA procedures the long-term disease remission of pHPT is achievable in a minority of patients. Data from larger samples are needed to verify the usefulness of this procedure.

Hydronephrosis due to pelviureteric junction obstruction in infancy.

Thirty-one cases of hydronephrosis caused by pelviureteric obstruction have been treated during the last 12 years at the Saint-Vincent de Paul Hospital in Paris. There were only 3 bilateral cases but a significant number of contralateral anomalies. No primary nephrectomy was done but 2 children had a secondary nephrectomy. Evaluation of late results showed practically no change from the early post-operative urogram; a 197 Ce2 scintigram proved a useful adjunct for assessment of renal function. A further study will be necessary to make sure that the results remain stable in adult life.

Development of the human pancreas: variations and pathology. A tentative classification.

The pathology of the pancreas is sometimes related to the embryological development of the organ. The first part of this paper is a presentation of the embryology, morphogenesis and cytogenesis of the pancreas. A tentative classification is then proposed to group together the lesions directly related to anomalies of the position and differentiation of the pancreatic buds. Pathological processes affecting the pancreas can be divided into those related to the ducts and those related to the parenchyma of the gland. In each case anomalies arising at a given stage of development lead to different diseases of the pancreas.

Bleeding pseudocysts and pseudoaneurysms in chronic pancreatitis.

Spontaneous haemorrhage associated with chronic pancreatitis in 17 patients was related to a pseudocyst in 15 (88 per cent) patients and to pancreatic lithiasis (one patient) or to infarction-rupture of the spleen (one patient). Bleeding was massive in six patients and intermittent in 11. It resulted from erosion of the gastroduodenal or the splenic artery in four patients. Bleeding into the pancreatic duct occurred in four patients and erosion of the duodenum by a bleeding pseudocyst in five. Haemorrhage was confined to a pseudocyst in six patients and was intraperitoneal in two. Of the 15 patients with bleeding pseudocysts, ten underwent primary pancreatic resection (eight proximal and two distal pancreatectomies) with no mortality but four had early complications. Four of the five patients who underwent transcystic ligation of bleeding vessels and pseudocyst drainage had postoperative complications: one died from sepsis and liver failure and three underwent reoperation for severe postoperative bleeding. Of these, two had proximal pancreatic resection with one death. The third patient had further suture ligation and external drainage. The overall postoperative mortality rate was 12 per cent and following emergency surgery 33 per cent. Favourable results were achieved in two-thirds of patients when the primary operative strategy could be directed towards the control of bleeding and removal of the affected pancreatic segment. Primary pancreatic resection, although technically demanding in the presence of haemorrhage, is recommended whenever possible for the treatment of bleeding pancreatic pseudocysts and pseudoaneurysms associated with chronic pancreatitis.

Therapy for the syndromes of GH excess.

This short review summarizes the results of treatments now available in Italy for the management of GH and IGF-I excess due to primary pituitary somatotroph adenoma, which accounts for over 99% of cases of acromegaly. Goals of treatment of acromegaly should now include, in addition to the reduction of tumor bulk and symptomatic relief, the lowering of GH circulating concentrations to below a critical level (2.5 microg/l, "safe" GH), the normalization of serum IGF-I concentrations according to age, improvement (or at least not worsening) of co-morbidities (diabetes mellitus, hypertension, cardiomyopathy, sleep-apnea), the decrease of the risk of premature mortality. Surgery, radiation (fractionated conventional radiotherapy and radiosurgery) and medical treatments with dopamine agonists and somatostatin analogs are the available options that are discussed in detail. The treatment of acromegaly must be tailored to the needs of the individual patient. Age, tumor size and invasiveness, GH concentrations, the patient's general medical conditions, presence and severity of co-morbidities, availability of local resources such as an expert neurosurgeon or gamma-knife radiosurgery, and of course the informed wishes of the patient are all factors that must be taken into account. For most patients the treatment will be multimodal. However, despite criteria and guidelines based on continuously emerging information about the management of acromegaly, patient outcomes are still less than desirable, with 10 to 20% of patients with uncontrolled disease, despite the use of all available therapies. This underscores the need for the quick introduction in clinical practice of the new therapies.

[Early jaundice after orthotopic liver transplantation. The role of ischaemia (author's transl)]. / Ictère précoce après transplantation hépatique orthotopique. Le rôle de l'ischémie.

The purpose of this experimental study was to identify the cause of early cholestatic jaundice occurring after orthotopic liver transplantation. The role of ischaemia was investigated in dogs undergoing auto-transplantation of the liver preserved for two hours. The animals developed early cholestasis with lesions that were markedly different from the graft-rejection lesions observed in a control group, being restricted to the cells and canaliculi of the central lobular area. The results of this work have made it possible to avoid overdosage with immunosuppressive drugs in a patient who had recently undergone orthotopic liver transplantation.

Baseline and CRH-stimulated ACTH and cortisol levels after administration of the peroxisome proliferator-activated receptor-gamma ligand, rosiglitazone, in Cushing's disease.

UNLABELLED: The ability of acute rosiglitazone administration in influencing ACTH/cortisol secretion in basal conditions and after CRH stimulation was studied in patients with Cushing's disease. Ten patients (8 women and 2 men, aged 18-65 yr) with Cushing's disease were enrolled in the study: 6 of them had previously undergone unsuccessful surgery and 4 were untreated. Plasma ACTH and serum cortisol levels were evaluated at serial time points for 3 h during saline infusion and after the administration of rosiglitazone (8 mg, po) and for 1 h after the injection of CRH (1 microg/kg iv) given alone or 30 min following rosiglitazone administration. The 4 tests were performed in all subjects in randomized order on different days. No significant difference was observed between the pattern of hormone secretion during saline alone and after rosiglitazone, as evaluated by two-way analysis of variance (ANOVA). The integrated areas under the curves (AUCs) were also not significantly different (ACTH: 5683 +/- 1038 vs 6111 +/- 1007 pg/ml/180 min; cortisol: 2333 +/- 267 vs 2902 +/- 486 microg/dl/180 min). In addition, there was no difference for ACTH and cortisol responses to CRH given either alone or after rosiglitazone, when evaluated as peak, increment or AUC; the pattern of the responses analyzed by two-way ANOVA was also similar. IN CONCLUSION: 1) the administration of a single dose of rosiglitazone did not decrease ACTH/cortisol levels or blunt their response after CRH injection; 2) the activation of PPAR-gamma receptors by rosiglitazone seems unable to affect ACTH and cortisol secretion, at least in acute conditions, in patients with ACTH-secreting pituitary adenomas.