Polyneuropathy in Australian outpatients with type II diabetes mellitus

In order to determine the local prevalence of polyneuropathy among adult outpatients with type II (non-insulin-dependent) diabetes mellitus, we applied a series of standardised measures to patients attending a multidisciplinary diabetes clinic. The study group comprised 94 men and 15 women; mean age, 70.6 +/- 7.8 years; mean duration of diabetes, 11.7 +/- 10.1 years; and mean HbA(1C), 8.3% +/- 1.7%. Neuropathy Symptom Scores greater than or equal to 1 were present in 97% of patients (mean, 3 +/- 2; range, 0-12), and 95% had Neuropathy Disability Scores greater than or equal to 2 (mean, 27 +/- 19; range, 0-87). 52% of men reported impotence. Autonomic dysfunction on cardiovascular reflex testing was present in 46% of patients (39/84). Finger and toe vibration perception thresholds were greater than 3SD higher than mean thresholds measured in control subjects without diabetes in 43% and 58% of patients, respectively Polyneuropathy, defined as lower limb sensory and motor nerve conduction velocity or latency outside mean +/- 2SD of that measured in age-matched controls, was present in 49% of patients (53/109). These results suggest that there is a high prevalence of polyneuropathy in Australian out-patients with type II diabetes mellitus, In this study, clinical assessment using Neuropathy Disability Stores was not diagnostically useful since only five patients had a normal score. Using nerve-conduction studies as the gold standard diagnostic criteria the best alternative test for the presence of polyneuropathy was toe vibration perception threshold (sensitivity 74%, specificity 56%). In view of the emerging evidence that intensive glycaemic control reduces the rate of progression of polyneuropathy, we recommend that patients with type II diabetes mellitus have nerve-conduction studies performed for early detection of this important complication. (C) 1999 Elsevier Science Inc

Multiple Endocrine Tumors Associated with Germline MAX Mutations:Multiple Endocrine Neoplasia Type 5?

Context: Pathogenic germline MAX variants are associated with pheochromocytoma and paraganglioma (PPGL), pituitary neuroendocrine tumors and, possibly, other endocrine and nonendocrine tumors. Objective: To report 2 families with germline MAX variants, pheochromocytomas (PCs) and multiple other tumors. Methods: Clinical, genetic, immunohistochemical, and functional studies at University hospitals in Australia on 2 families with germline MAX variants undergoing usual clinical care. The main outcome measures were phenotyping; germline and tumor sequencing; immunohistochemistry of PC and other tumors; functional studies of MAX variants. Results: Family A has multiple individuals with PC (including bilateral and metastatic disease) and 2 children (to date, without PC) with neuroendocrine tumors (paravertebral ganglioneuroma and abdominal neuroblastoma, respectively). One individual has acromegaly; immunohistochemistry of PC tissue showed positive growth hormone-releasing hormone staining. Another individual with previously resected PCs has pituitary enlargement and elevated insulin-like growth factor (IGF-1). A germline MAX variant (c.200C>A, p.Ala67Asp) was identified in all individuals with PC and both children, with loss of heterozygosity in PC tissue. Immunohistochemistry showed loss of MAX staining in PCs and other neural crest tumors. In vitro studies confirmed the variant as loss of function. In Family B, the proband has bilateral and metastatic PC, prolactin-producing pituitary tumor, multigland parathyroid adenomas, chondrosarcoma, and multifocal pulmonary adenocarcinomas. A truncating germline MAX variant (c.22G>T, p.Glu8∗) was identified. Conclusion: Germline MAX mutations are associated with PCs, ganglioneuromas, neuroblastomas, pituitary neuroendocrine tumors, and, possibly, parathyroid adenomas, as well as nonendocrine tumors of chondrosarcoma and lung adenocarcinoma, suggesting MAX is a novel multiple endocrine neoplasia gene.</p

Inhibition of naloxone-stimulated adrenocorticotropin release by alprazolam in myotonic dystrophy patients

Myotonic dystrophy (DM) is an autosomal dominant disorder causing myotonia, progressive muscle weakness, and endocrine abnormalities including hypothalamic-pituitary-adrenal (HPA) axis hyperresponsiveness to CRH-mediated stimuli. This ACTH hyperresponsiveness appears directly related to the underlying genetic abnormality, Naloxone (Nal)-mediated CRH release causes ACTH release in normal humans and an ACTH hyperresponse in DM. Alprazolam (APZ) attenuates the ACTH release in response to Nal in normal individuals, probably by inhibiting CRH release, This study investigates the effects of APZ on Nal-induced HPA axis stimulation in DM, The ACTH response to Nal in DM subjects was significantly reduced by APZ, Despite this DM patients have a relative resistance to APZ inhibition of Nal-induced ACTH/cortisol release. APZ caused a smaller percentage reduction in AUC for ACTH in DM compared with controls. These findings provide further insight into the mechanism(s) of the HPA axis abnormalities in DM, In DM, there may be an increase in tonic opioid inhibition to CRH release with compensatory increases in stimulatory pathways, Alternatively, these patients may have a basal increase in pituitary vasopressin levels or an enhanced AVP/CRH synergistic mechanism at the level of the corticotroph