Clinical Characteristics and Pituitary Dysfunction in Patients with Metastatic Cancer to the sella

ObjectiveMetastatic disease to the sella is uncommon and there are limited available data regarding the clinical aspects of this disease. We therefore sought to characterize the clinical demographics of sellar metastases.MethodsRetrospective chart review of adults treated at Stanford University Medical Center from 1980 to 2011 with metastatic disease to the sella.ResultsA total of 13 subjects were identified (9 females). The mean age at diagnosis was 55 years (range, 25 to 73 years). A total of 6 patients (46%) had breast car-cinoma, 3 (23%) had renal cell carcinoma, 2 (15%) had squamous cell carcinoma of the head and neck, 1 had bronchoalveolar carcinoma of the lung, and 1 had nodular sclerosing Hodgkin’s lymphoma. The most common presenting signs and symptoms were headache (58%), followed by fatigue (50%), polyuria (50%), visual field defects (42%), and ophthalmoplegia (42%). Seventy-five percent of patients presented with at least one pituitary hormone insufficiency, which included 6 patients (50%) with diabetes insipidus (DI). Eight (67%) subjects had secondary hypothyroidism and 5 (45%) had secondary adrenal insufficiency. Of the patients with stalk involvement, 86% had DI. All patients had a prior diagnosis of malignancy, with a mean duration of 95 months.ConclusionThe most common neoplastic sources to the sella were breast and renal cell carcinomas. Secondary hypothyroidism was the most common endocrine abnormality, followed by DI and adrenal insufficiency. Newonset central hypothyroidism and DI along with known malignancy in a patient with a sellar lesion should raise the suspicion of a metastatic source. (Endocr Pract. 2013; 19:914-919)     

Endocrine manifestations of chromosome 22q11.2 microdeletion syndrome

BACKGROUND: Endocrine abnormalities, including hypocalcemia, thyroid dysfunction, and short stature, are associated with chromosome 22q11.2 microdeletion syndrome. This study was undertaken to examine the frequencies and clinical features of endocrine abnormalities in patients with 22q11.2 microdeletion syndrome. METHODS: We analyzed 61 patients with 22q11.2 microdeletion syndrome diagnosed based on the verification of microdeletion by fluorescent in situ hybridization (FISH) using a probe of the DiGeorge syndrome critical region (TUPLE1) at 22q11.2 and a control probe, ARSA at 22q13. Serum total calcium, phosphorus, and intact parathyroid hormone (PTH) levels were measured, thyroid function test was performed, and serum IGF-1 and IGFBP-3 levels were also estimated. Height and weight of patients were compared with individual chronological ages. RESULTS: Hypocalcemia was found in 20 patients (32.8%), and overt hypoparathyroidism in 8 (13.1%). Two patients (3.3%) showed autoimmune thyroid diseases, 1 each with Graves' disease and Hashimoto thyroiditis. Ten patients (16.4%) were below the third percentile in height, but the serum IGF-1 level was normal in 9 out of these 10 patients. CONCLUSION: Our findings show that patients with chromosome 22q11.2 microdeletion syndrome present with variable endocrine manifestations and variable clinical phenotypes. In addition to FISH analysis, careful endocrine evaluations are required in patients with this microdeletion syndrome, particularly for those with hypoparathyroidism or thyroid dysfunction.     

The prevalence of familial hyperaldosteronism in apparently sporadic primary aldosteronism in Germany: a single center experience

Primary aldosteronism (PA) is the most frequent cause of secondary arterial hypertension. To date 3 forms of familial hyperaldosteronism (FH) have been described accounting for a small percentage of all PA cases. In Germany, the prevalence of FH is currently unknown. Our aim was to determine the prevalence of familiarity in a large cohort of patients with PA. A total of 166 patients with apparently sporadic PA in Munich were investigated. FH types I, II, and III were identified using established clinical, biochemical, and molecular criteria. Among the 166 patients with PA, 2 patients (1.2%) reported a family history suggestive of FH. None of the 166 patients showed clinical, endocrine, or genetic evidence of FH type I. The 2 families had characteristic features of FH type II. Family A had 3 subjects affected out of 11 evaluated family members. Family B had 3 out of 4. Bilateral adrenal hyperplasia and unilateral adrenal adenoma were found within the same family. FH type I and FH type III are rare in Germany. With a prevalence of 1.2%, FH type II seems to be more common in apparently sporadic PA than had been assumed so far.     

Primary hyperparathyroidism in patients with multiple endocrine neoplasia type 1: comparison with sporadic parathyroid adenomas.

A prospective study on the natural course of primary hyperparathyroidism has recently been reported. Since hyperparathyroidism in multiple endocrine neoplasia type 1 (MEN 1) is genetically distinct from most forms of sporadic hyperparathyroidism, it is important to know the natural course of hyperparathyroidism in MEN 1 for better clinical management. For this purpose, we retrospectively reviewed clinical parameters of patients with MEN 1 when they were diagnosed as having hyperparathyroidism, and compared them with those of patients with sporadic primary hyperparathyroidism. In patients with MEN 1: 1) levels of intact PTH (i-PTH) gradually increased with age, which accelerated over 40 years; 2) compared to the steep rise in i-PTH levels in aged patients, increase in serum calcium or decrease of serum inorganic phosphate concentration was relatively mild, and 3) the high concentrations of i-PTH in aged patients were not due to renal insufficiency. These features were not observed in patients with sporadic primary parathyroid adenomas. Clinical features of untreated hyperparathyroidism in MEN 1 may be significantly affected by the age of the patient. The effect, if any, of age-dependent deterioration on recurrence rate after subtotal or total parathyroidectomy requires further elucidation.     

A large family with hereditary MTC: role of RET genetic analysis in differential diagnosis between MEN 2A and FMTC.

Germline mutations of the RET proto-oncogene cause three different cancer syndromes: multiple endocrine neoplasia type 2A (MEN 2A), multiple endocrine neoplasia type 2B (MEN 2B) and familial medullary thyroid carcinoma (FMTC). In the absence of biochemical and/or clinical evidence of pheochromocytoma and hyperparathyroidism, patients with MEN 2A disease display the same phenotype of FMTC disease, although prognosis and clinical management in both affected and unaffected familial members are quite different. We studied a family with hereditary MTC, whose proband was referred to us because of enlarged cervical nodes and increased calcitonin serum levels 28 years after the total thyroidectomy for MTC. Cervical node dissection was carried out and subsequently the presence of MTC metastasis was histologically confirmed. A RET genomic mutation at codon 634 (TGC-->TTC) was identified in the proband and in seven out of 19 familial members studied. Accordingly, a hereditary disease was suggested. However, the strong association of RET mutation at codon 634 with the presence of pheochromocytoma in MEN 2 disease suggested a more rigorous management in all gene carriers. Indeed, during the follow-up pheochromocytoma was subsequently identified in the proband. This finding suggests that all families with a pedigree suggestive of FMTC should be regarded at risk from MEN 2A disease, at least when a critical mutation in the RET cysteine domain is detected.     

Injection of methylprednisolone directly into the extraocular muscles of eyes with disturbed motility secondary to Graves' ophthalmopathy. Preliminary report

Aim of the study was to estimate the efficacy of 6-alpha-methylprednisolone injection into involved extraocular muscles in eyes with motility disturbances caused by endocrine ophthalmopathy. MATERIAL AND METHODS: For further evaluation we qualified 4 patients, 1 female and 3 males, aged: 60, 43, 42 and 64 years, with clinical activity score equal 4, with duration of Graves' ophthalmopathy of mean 2.1 years (0.16 - 5.5). Included were patients with movement restrictions in vertical plane and echographic findings of isolated extraocular muscle involvement (inferior rectus). Each of the patients received 20 mg 6-alpha-methylprednisolone into the muscle belly of inferior rectus, in one case injection was done in both eyes. RESULTS: In all cases we were able to archive lessening of the intraocular pressure in secondary position, with slight improvement in ocular motility and bigger range of duction free of diplopia. CONCLUSIONS: Visual function improvement found by the patients is the best evidence for application of 6-alpha-methylprednisolone into the extraocular muscles of patients with motility disturbances secondary to endocrine ophthalmopathy.     

Calcium and vitamin D metabolism in hypocalcemic vitamin D-resistant rickets carriers

BACKGROUND/AIMS: Hypocalcemic vitamin D-resistant rickets (HVDRR) is a rare monogenic autosomal recessive disorder associated with mutations in the gene of the vitamin D receptor (VDR), the mediator of 1,25(OH)2D3 action. Although many investigations have discussed the clinical manifestations and molecular etiology of this disease, only a few have investigated the biochemical and hormonal status of heterozygous HVDRR. The aim of the current work was to investigate the profile of selected biochemical and hormonal parameters related to the vitamin D endocrine system in a large number of HVDRR heterozygotes. METHODS: 67 relatives of 2 HVDRR patients, all members of an extended Greek kindred of five generations with a common ancestor, were included in the study. Direct sequencing was used to identify VDR gene mutations. Serum Ca, P, 25(OH)D, iPTH, and 1,25(OH)2D levels were determined in all members of the kindred. RESULTS: DNA analysis of the participants led to the design of two study groups: the HVDRR carriers (24) and the control subjects (43). Our results showed elevated circulating serum levels of 1,25(OH)2D3 and lower levels of PTH than their age- and sex-matched controls. No hypocalcemia or hypophosphatemia were detected in HVDRR carriers. CONCLUSIONS: Our findings suggest that HVDRR carriers may have compensatory elevated serum levels of 1,25(OH)2D3 through which they restrain PTH secretion. The study of HVDRR carriers could be a useful tool for the investigation of the vitamin D endocrine system.     

TNF-alpha levels and TNF-alpha gene polymorphism in type I Gaucher disease

The objective of this pilot study was to determine the levels of Tumor Necrosis Factor (TNF)-alpha and TNF-alpha gene polymorphism as a marker of inflammation among patients with type I Gaucher disease as well as to ascertain the relationship between this cytokine and parameters of disease severity and other measures of inflammation. Levels of TNF-alpha and genotyping for the -308 G-->A polymorphism in the promoter of the TNF-alpha gene were performed in 17 patients with type I Gaucher disease. TNF-alpha levels were compared with the promoter gene polymorphism, and with hematological and other clinical parameters of Gaucher disease. Eight patients (47.1%) were homozygotes (A/A) for the TNF-alpha polymorphism, six patients (35.3%) had the wild type (G/G), and three patients (17.6%) were heterozygotes (G/A). A significant correlation was found between serum TNF-alpha levels and TNF-alpha genotypes for homozygotes versus heterozygotes patients (p = 0.02), with patients homozygous for the polymorphism having the lower levels of serum TNF-alpha relative to heterozygotes with the highest levels. No correlation was found between TNF-alpha genotypes and chitotriosidase levels, a putative biochemical marker for Gaucher disease severity. Because a significant correlation was found between homozygosity for a common promoter polymorphism of TNF-alpha and milder expression i.e. non-neuronopathic form, of Gaucher disease (versus the neuronopathic forms), this may be suggestive of an association between genetic variability in TNF-alpha and phenotypic expression in Gaucher disease. Larger studies will be required.     

Celiac Disease and the Endocrinologist: a Diagnostic Opportunity

ObjectiveTo review the association of celiac disease and various endocrine disorders and present the related clinical experience of a 3-physician adult endocrinology practice.MethodsWe provide an overview of the pertinent literature, discuss the clinical manifestations, genetics, and pathogenesis of celiac disease, and describe our clinical experience during a 5-year period.ResultsCeliac disease has been associated with numerous disorders, including several conditions treated by endocrinologists—type 1 diabetes mellitus, autoimmune thyroid disease, Addison disease, osteomalacia, secondary hyperparathyroidism, vitamin D or iron deficiency, fertility problems, hypogonadism in men, and autoimmune hypopituitarism. After our clinical awareness was raised about these potential comorbidities, 18 patients were newly diagnosed with celiac disease in our clinical practice during a 5-year interval. All patients had been referred for endocrine evaluation or were undergoing follow- up for ongoing management of endocrine disorders. When a “celiac-associated” endocrine disorder coexists with other factors associated with celiac disease, we recommend performance of IgA class antibody testing, and either antiendomysial or anti-tissue transglutaminase antibodies provide high specificity and sensitivity for the diagnosis of celiac disease.ConclusionEndocrinologists have an opportunity to diagnose celiac disease, a relatively common disorder with profound clinical implications that can often be associated with various endocrinopathies. (Endocr Pract. 2008;14: 381-388)     

Avidity of IgG antibodies distinguishes primary from non-primary cytomegalovirus infection in pregnant women

Background: Human cytomegalovirus (HCMV) is the most common cause of viral intrauterine infection. Fetal damage is mostly linked to maternal primary infection. It is therefore important to differentiate primary from non-primary infection in pregnant females. IgM tests often used for this purpose are not reliable enough.Objective: To evaluate an HCMV–IgG urea-elution assay for its ability to distinguish primary from non-primary infection. In this assay, soaking the antigen–antibody complex with an urea containing solution frees antibodies with low avidity but has no influence on those with high avidity. An avidity index (AI) was calculated: AI=(OD with urea/OD without urea)×100.Study design: HCMV–IgG avidity was measured on a single serum of 79 patients with past infection (pregnant women, graft recipients and blood donors) and of 63 patients (78 sera) with documented seroconversion (pregnant women and graft recipients). Sixty-one pregnant women positive or equivocal for HCMV–IgM but without a documented seroconversion were included in this study.Results: Most (72/79) of the patients with past infection had an AI>65% and all but one had an AI>50%. In pregnant women, in the case of a primary infection within the past 3 months, AI are usually (51/53)<50% and never>65%. Among the IgM positive pregnant women who lack a seroconversion history, 38 had AI>65% suggestive of an infection that had occured at least 3 months earlier, 11 had an AI in a grey area between 50 and 65% and 12 had an AI<50%, suggestive of a recent primary infection.Conclusions: In pregnant women, measurement of the IgG avidity may help to date a HCMV infection, an AI >65% highly suggests a past infection while an AI <50% corresponds to a recent primary infection.     

Lipopolysaccharide O1 antigen contributes to the virulence in Klebsiella pneumoniae causing pyogenic liver abscess

Klebsiella pneumoniae is the common cause of a global emerging infectious disease, community-acquired pyogenic liver abscess (PLA). Capsular polysaccharide (CPS) and lipopolysaccharide (LPS) are critical for this microorganism's ability to spread through the blood and to cause sepsis. While CPS type K1 is an important virulence factor in K. pneumoniae causing PLA, the role of LPS in PLA is not clear. Here, we characterize the role of LPS O antigen in the pathogenesis of K. pneumoniae causing PLA. NTUH-K2044 is a LPS O1 clinical strain; the presence of the O antigen was shown via the presence of 1,3-galactan in the LPS, and of sequences that align with the wb gene cluster, known to produce O-antigen. Serologic analysis of K. pneumoniae clinical isolates demonstrated that the O1 serotype was more prevalent in PLA strains than that in non-tissue-invasive strains (38/42 vs. 9/32, P<0.0001). O1 serotype isolates had a higher frequency of serum resistance, and mutation of the O1 antigen changed serum resistance in K. pneumoniae. A PLA-causing strain of CPS capsular type K2 and LPS serotype O1 (i.e., O1:K2 PLA strain) deleted for the O1 synthesizing genes was profoundly attenuated in virulence, as demonstrated in separate mouse models of septicemia and liver abscess. Immunization of mice with the K2044 magA-mutant (K(1) (-) O(1)) against LPS O1 provided protection against infection with an O1:K2 PLA strain, but not against infection with an O1:K1 PLA strain. Our findings indicate that the O1 antigen of PLA-associated K. pneumoniae contributes to virulence by conveying resistance to serum killing, promoting bacterial dissemination to and colonization of internal organs after the onset of bacteremia, and could be a useful vaccine candidate against infection by an O1:K2 PLA strain.     

Correlation between tumor burden and anticomplementary activity in sera from cancer patients

Summary A total of 739 sera from cancer patients, noncancer patients and normal donors were analyzed for anticomplementary (AC) activity by the complement consumption method. The results were correlated with clinical stage and tumor burden. The incidence of AC activity in cancer and noncancer patients' sera was 53% (233/439) and 67% (100/150), respectively, as against 14% (20/140) in normal donors' sera. Among cancer patients, this incidence was lowest (42%) for melanoma sera and highest (65%) for lung carcinoma sera. With the exception of sarcoma sera, the incidence of AC activity did not differ significantly with clinical Stages I, II, or III. Sera from Stages II and III sarcoma patients had a significantly higher incidence of AC activity (73% and 63%, respectively) than Stage I (38%). There appeared to be a higher incidence of AC activity in sera of cancer patients with 1–100 g tumor burden than in those from patients with tumors greater than 100 g or less than 1 g. Follow-up of cancer patients with no evidence of disease or minimal tumor burden revealed that 42% (18/43) whose sera were AC-positive had tumor recurrence within 3 months and 90% (57/63) whose sera were AC-negative had no detectable tumor recurrence up to at least 6 months after the serum analysis.     

Prevalence of polycystic ovaries in women with anovulation and idiopathic hirsutism.

Polycystic ovaries were defined with ultrasound imaging in a series of 173 women who presented to a gynaecological endocrine clinic with anovulation or hirsutism. Polycystic ovaries were found in 26% of women with amenorrhoea, 87% with oligomenorrhoea, and 92% with idiopathic hirsutism--that is, hirsutism but with regular menstrual cycles. Fewer than half the anovulatory patients with polycystic ovaries were hirsute, but in 93% of cases there was at least one endocrine abnormality to support the diagnosis of polycystic ovaries--that is, raised serum concentrations of luteinising hormone, raised luteinising hormone: follicle stimulating hormone ratio, or raised serum concentrations of testosterone or androstenedione. This study shows that polycystic ovaries, as defined by pelvic ultrasound, are very common in anovulatory women (57% of cases) and are not necessarily associated with hirsutism or a raised serum luteinising hormone concentration. Most women with hirsutism and regular menses have polycystic ovaries so that the term "idiopathic" hirsutism no longer seems appropriate.     

阿维菌素中毒患者血清C反应蛋白的浓度变化及意义

目的探讨口服阿维菌素中毒患者血清C反应蛋白浓度变化与病情严重程度及预后的关系。方法将39例口服阿维菌素中毒患者分为轻度中毒组和中重度中毒组,42例健康体检者为对照组。轻、中重度中毒组患者分别于入院时及入院第3、5天检测血清C反应蛋白浓度,并进行组间比较。结果中毒组血清CRP水平明显高于对照组,差异有统计学意义（P〈0.05）;轻度中毒组血清CRP水平在入院时及入院第3、5天变化较小,各时点血清CRP水平比较无显著统计学意义（P〉0.05）;中重度中毒组血清CRP水平在入院时即显著升高,入院第3天达最高值,各时点血清CRP水平比较差异有统计学意义（P〈0.05）。结论血清C反应蛋白浓度可作为判断口服阿维菌素中毒患者病情严重程度及预后的敏感指标。     

Xanthogranuloma as an Unsuspected Cause of Idiopathic Central Diabetes Insipidus

ObjectiveTo demonstrate that xanthogranuloma is a rare cause of idiopathic central diabetes insipidus in the early phase of the disease and that it presents as a suprasellar mass at a later stage. In addition, we emphasize the importance of identifying the cause of idiopathic central diabetes insipidus and review the literature concerning endocrine disturbance in central xanthogranuloma.MethodsReview of recently published case reports of central xanthogranuloma with endocrine disorders. The case of a 35-year-old man who presented with a very large suprasellar mass is also reported. The patient was diagnosed with idiopathic central diabetes insipidus 20 years ago with normal brain magnetic resonance imaging.ResultMost cases of this disease present as supra-or parasellar masses with endocrine involvement, the most common of which (in approximately 75% of patients) is sex hormone deficiency. Diabetes insipidus was found in 65% of patients.ConclusionXanthogranuloma should be in the differential diagnosis of idiopathic central diabetes insipidus and sellar and parasellar masses. A detailed skin examination is very important in making the diagnosis of central diabetes insipidus. (Endocr Pract. 2014;20:e42-e46)     

Primary Hyperparathyroidism During Pregnancy: A Case Series of 8 Patients

Objective: Due to a lack of typical clinical manifestations and physiologic changes in calcium metabolism during pregnancy, primary hyperparathyroidism (PHPT) during pregnancy is commonly underdiagnosed, and treatment during this unique period presents a clinical challenge. Hence, the aim of the present study was to summarize the cases of 8 pregnant patients with PHPT who were treated at our center to provide better clinical insight into this condition.Methods: Our study comprised a retrospective analysis of 8 pregnant PHPT patients and a control group of 22 age-matched, nonpregnant PHPT patients during the same period. Clinical manifestations, biochemical indices, pathologic types, therapeutic strategies, and pregnancy outcomes were compiled, and 25 patients were screened for germline mutations in the MEN1, CDC73, and CaSR genes.Results: The most-common symptoms in the pregnancy group involved the gastrointestinal tract (GIT) in 7/8 cases (87.5%), followed by urinary system involvement (50%) and joint pain (50%). In contrast, GIT symptoms in the control group were significantly less common (31.82%; P = .012). There was a trend of more-severe elevation of serum parathyroid hormone levels in the control group compared to that in the pregnancy group (P = .053). No differences were found in blood-ionized calcium, phosphate, or alkaline phosphatase levels between the two groups. In the pregnancy group, the serum albumin-corrected calcium level was reduced from 3.42 ± 0.66 mmol/L to 2.89 ± 0.46 mmol/L (P = .025) after hydration and medical treatment. Six patients, three of whom were in the second trimester of pregnancy, underwent parathyroidectomy, and 3 patients were after childbirth or had induced labor. Postoperative serum calcium levels were reduced to within the normal range. Fetal/neonatal complications were observed in 4 of 5 patients who had not received surgical treatment during pregnancy. In addition, 2 of 5 pregnant PHPT patients were found to carry MEN1 mutations, whereas no mutations were detected in any of the 20 nonpregnant patients.Conclusion: In this case series of PHPT during pregnancy, the most-common complaint of GIT symptoms may be easily confused with pregnancy reactions, which might contribute to the under- or misdiagnosis of this clinical entity. Patients who did not receive surgical treatment during pregnancy had high incidences of fetal/neonatal complications and worse pregnancy outcomes.Abbreviations: CaSR = calcium-sensing receptor; CDC73 = cell division cycle 73; GIT = gastrointestinal tract; MEN = multiple endocrine neoplasia; PHPT = primary hyperparathyroidism; PTH = parathyroid hormone; SCa = serum calcium     

Efficacy of empirical cardiac pacing in syncope of unknown cause.

Cardiac pacing is often considered in patients with recurrent syncope after repeated attempts to document the cause have failed. To assess the results of this tactic we reviewed the records of 104 patients who had received pacemakers for known or suspected bradycardia between September 1973 and March 1985. The patients were classified retrospectively into three groups: group 1 (31 patients with a mean age of 73 years) had unequivocal documentation of bradycardia during syncope, group 2 (42 patients with a mean age of 71 years) had electrocardiographic or electrophysiologic evidence of potential bradycardia but no documentation during spontaneous syncope, and group 3 (31 patients with a mean age of 69 years) had a history "suggestive of" bradycardia-related syncope but no other evidence to support the diagnosis. The rates of recurrence of syncope during follow-up were 6.3%, 7.3% and 32.2% in groups 1, 2 and 3 respectively (p less than 0.01). In group 3 recurrence was more probable in patients with loss of consciousness for more than 2 minutes than in those who were unconscious for 2 minutes or less (p less than 0.05). The results suggest that pacemaker implantation is justified for recurrent syncope after extensive attempts to document a spell have failed if abnormal diagnostic test results suggest bradycardia as a possible cause. Empirical pacing is less satisfactory in patients with normal results of evaluation but may arguably be justified when patients have recurrent syncope with injury.     

Mitochondrial diseases mimicking neurotransmitter defects

OBJECTIVES: Mitochondrial disorders are clinically heterogeneous. We aimed to describe 5 patients who presented with a clinical picture suggestive of primary neurotransmitter defects but who finally fulfilled diagnostic criteria for mitochondrial disease. METHODS: We report detailed clinical features, brain magnetic resonance findings and biochemical studies, including cerebrospinal fluid (CSF) biogenic amine and pterin measurements, respiratory chain enzyme activity, and molecular studies. RESULTS: The 5 patients had a very early onset age (from 1 day to 3 months) and a severe clinical course. They all showed a clinical picture suggestive of infantile hypokinetic-rigid syndrome (hypokinesia, hypomimia, slowness of reactions, tremor), other abnormal movements (myoclonus, dystonia), axial hypotonia, limb hypertonia, feeding difficulties, and psychomotor delay. Abnormal CSF findings among the 4 patients without treatment included low levels of homovanillic acid (HVA) in 3 patients, with associated low 5-hydroxyindoleacetic acid (5-HIAA) concentrations in two of them. Absent or mild and transitory improvement was observed after treatment with L-dopa. A diagnosis of mitochondrial disorder was finally made due to the appearance of hyperlactacidemia, diverse respiratory chain defects, and multisystemic involvement. CONCLUSIONS: Secondary neurotransmitter disturbances may occur in mitochondrial diseases. Differential diagnosis of hypokinetic-rigid syndrome presenting in infancy could also include paediatric mitochondrial disorders.     

Classification et aspects anatomopathologiques des tumeurs endocrines digestives

Gastrointestinal and pancreatic endocrine tumors GIPET are rare and represent only 2 % of malignant tumors. Beyond their common features, endocrine tumors are characterized by a marked diversity, which results from the large functional, structural and embryological heterogeneity of normal endocrine cells. Despite the rational basis for predicting prognosis provided by the WHO classification, there is no reliable means of predicting the clinical course of patients with gastrointestinal and pancreatic endocrine tumors. The current criteria used for the definition of the tumor grade remain unsatisfactory. According to the WHO classification system, pathologists vary significantly in their reporting of endocrine tumors. Recently, the European Neuroendocrine Tumour Society (ENETS) has proposed a TNM (tumor–node–metastasis) classification for gastrointestinal and pancreatic endocrine tumors. The use of this classification is considered simple and valuable. It is hoped that the combination of WHO classification, with anatomical staging systems TNM, and possibly incorporating molecular features of gastrointestinal and pancreatic endocrine tumors will provide clinicians with effective means of classification and prognostication of patients with these tumors.     

Effect of Rapid Intravenous Infusion on Serum Concentrations of Amphotericin B

The magnitude of the concentrations of amphotericin B produced in serum of patients with systemic mycoses may significantly influence the outcome of therapy with this drug. Since amphotericin B is conventionally administered in intravenous infusions lasting 4 to 6 hr, we asked whether faster infusions of this drug might yield higher serum concentrations without an increase in dose. This question was studied in three patients who received 16 infusions of this drug: eight infusions administered slowly (5 hr) and eight administered rapidly (45 min). Serum concentrations after each rapid infusion were compared with those after a slow infusion administered to the same patient. The mean serum concentration of amphotericin B 1 hr after the rapid infusions (2.02 mug/ml) was significantly higher (P < 0.001) than the mean serum concentration of amphotericin B 1 hr after the slow infusions of this drug (1.18 mug/ml). Mean serum concentrations 18 and 42 hr after rapid infusion remained slightly but not significantly higher than respective mean concentrations after slow infusions. By yielding higher initial serum concentration, rapid intravenous infusion may be therapeutically more effective than slow infusion of amphotericin B. Although rapid infusions caused no more toxicity than did slow infusions, the lack of greater toxicity with rapid infusion of amphotericin B should be further documented prior to extensive clinical application of this procedure.