Insulin Autoimmune Syndrome: a rare case of hypoglycaemia resolving with immunosuppression.

We report a case of a 58-year-old male presenting with confusion and hypoglycaemia. There had been no prior exposure to oral hypoglycaemic agents or insulin. He was found to have inappropriate endogenous hyperinsulinaemia. Insulinoma was excluded by detailed endocrine assessment. Insulin antibodies were positive in keeping with a diagnosis of insulin autoimmune syndrome (IAS). He was treated with prednisolone 5mg once daily and nutritional supplements leading to resolution of acute confusion and hypoglycaemic episodes. The patient also had severe psoriasis and following discharge was treated with a variety of immunosuppressant therapies. This was associated with disappearance of insulin antibodies after twelve months of follow up. While it is possible that there was spontaneous resolution of insulin antibodies, we speculate that his prednisolone and immunosuppressant therapy may have suppressed insulin antibody production. There are several well recognised associations with IAS and autoimmune conditions, including Grave's disease, systemic lupus erythematous and rheumatoid arthritis. To our knowledge this is the first reported case of insulin autoimmune syndrome, resolving with immunosuppressant treatment of psoriasis.

HbA1c for Diabetes Screening in Acute Coronary Syndrome: time for a reappraisal of the guidelines?

OBJECTIVE: Diabetes is highly prevalent in individuals with acute coronary syndrome (ACS). Current NICE guidelines recommend diabetes screening of hyperglycaemic patients using a fasting plasma glucose after 4 days from admission. In 2012 the World Health Organisation (WHO) approved the use of HbA1c in the diagnosis and targeted screening for type 2 diabetes. We introduced a service improvement project using HbA1c for diabetes screening in patients with no previous diagnosis of diabetes admitted with ACS regardless of glycaemic state. METHOD: An initial retrospective audit utilised 21 months of data from the MINAP database to identify patients meeting current NICE criteria for diabetes screening. A prospective service improvement project was undertaken over a 4 month period using HbA1c as a universal screening test to categorise ACS patients based on WHO criteria. RESULTS: The retrospective audit identified 93 of 420 (22%) patients with pre-existing diabetes and 8 of the remaining 327 (2.4%) were hyperglycaemic, thus meeting NICE criteria for diabetes screening. In the service improvement project 2/49 patients (4%) met NICE criteria for diabetes screening. Twenty six of these 49 patients had a HbA1c test on admission and 17/26 (65.4%) were classified as probable diabetes or high risk. CONCLUSION: A significant proportion of ACS patients have diabetes, which may be undetected by current NICE criteria. Universal HbA1c testing offers utility as a simple and effective screening test for diabetes in the ACS population.

Treatment of adrenocorticotropin-dependent Cushing's syndrome: a consensus statement.

OBJECTIVE: Our objective was to evaluate the published literature and reach a consensus on the treatment of patients with ACTH-dependent Cushing's syndrome, because there is no recent consensus on the management of this rare disorder. PARTICIPANTS: Thirty-two leading endocrinologists, clinicians, and neurosurgeons with specific expertise in the management of ACTH-dependent Cushing's syndrome representing nine countries were chosen to address 1) criteria for cure and remission of this disorder, 2) surgical treatment of Cushing's disease, 3) therapeutic options in the event of persistent disease after transsphenoidal surgery, 4) medical therapy of Cushing's disease, and 5) management of ectopic ACTH syndrome, Nelson's syndrome, and special patient populations. EVIDENCE: Participants presented published scientific data, which formed the basis of the recommendations. Opinion shared by a majority of experts was used where strong evidence was lacking. CONSENSUS PROCESS: Participants met for 2 d, during which there were four chaired sessions of presentations, followed by general discussion where a consensus was reached. The consensus statement was prepared by a steering committee and was then reviewed by all authors, with suggestions incorporated if agreed upon by the majority. CONCLUSIONS: ACTH-dependent Cushing's syndrome is a heterogeneous disorder requiring a multidisciplinary and individualized approach to patient management. Generally, the treatment of choice for ACTH-dependent Cushing's syndrome is curative surgery with selective pituitary or ectopic corticotroph tumor resection. Second-line treatments include more radical surgery, radiation therapy (for Cushing's disease), medical therapy, and bilateral adrenalectomy. Because of the significant morbidity of Cushing's syndrome, early diagnosis and prompt therapy are warranted.

Inhibition of dipeptidyl peptidase IV activity by oral metformin in Type 2 diabetes.

AIMS: Glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) are important insulinotropic hormones that enhance the insulin secretory response to feeding. Their potential for treating Type 2 diabetes is limited by short biological half-life owing to degradation by dipeptidyl peptidase IV (DPP IV). We investigated the acute effects of metformin on DPP IV activity in Type 2 diabetes to elucidate inhibition of DPP IV as a possible mechanism of action. METHODS: Eight fasting subjects with Type 2 diabetes (5M/3F, age 53.1+/-4.2 years, BMI 36.8+/-1.8 kg/m2, glucose 8.9+/-1.2 mmol/l, HbA1c 7.8+/-0.6%) received placebo or metformin 1 g orally 1 week apart in a random, crossover design. RESULTS: Following metformin, DPP IV activity was suppressed compared with placebo (AUC0-6 h 3230+/-373 vs. 5764+/-504 nmol ml/l, respectively, P=0.001). Circulating glucose, insulin and total GLP-1 were unchanged. Metformin also concentration-dependently inhibited endogenous DPP IV activity in vitro in plasma from Type 2 diabetic subjects. CONCLUSION: Oral metformin effectively inhibits DPP IV activity in Type 2 diabetic patients, suggesting that the drug may have potential for future combination therapy with incretin hormones.

Poor responses to a test dose of subcutaneous octreotide predict the need for adjuvant therapy to achieve 'safe' growth hormone levels.

OBJECTIVE: Somatostatin analogues are an established treatment in acromegaly. This study was designed to evaluate whether the acute serum growth hormone (GH) response to a test dose of octreotide in acromegaly predicts longer-term response to the drug at 3 years. DESIGN AND METHODS: In 23 patients, GH responses across 8 h to a subcutaneous test dose (50 microg) of octreotide were compared with GH levels after 3 years of therapy. The majority had pituitary surgery as primary therapy and at 3 years were receiving at least 600 microg octreotide daily subcutaneously or 20 mg LAR monthly intramuscularly. RESULTS: Seven had a test day GH Nadir of 5 mU/l or less of whom 4 achieved GH < 5 mU/l at 3 years. Sixteen had a test day nadir GH of 10 mU/l or less and of these 8 achieved GH < 5 mU/l at 3 years. Seven of the 23 had a GH Nadir >10 mU/l and of these 3 had achieved GH <5 mU/l at 3 years. However all of these 3 had received external pituitary irradiation within 4 years of the 3 year assessment, as compared with 3 of the <5 mU/l nadir group and 5 of the <10 mU/l nadir group. CONCLUSIONS: In patients on optimal long-term doses of octreotide for acromegaly, absence of a nadir GH <10 mU/l in the 8 h after a test dose was associated with failure to achieve GH levels associated with a normal life expectancy (5 mU/l or less) unless adjunctive external pituitary irradiation was given. As well as testing tolerability a test dose of octreotide may help in determining which patients should be offered early external pituitary irradiation or therapy with a GH receptor antagonist if surgery has failed to achieve 'safe' GH levels.

Excimer laser coronary angioplasty and intracoronary radiation for in-stent restenosis: six-month angiographic and clinical outcomes.

BACKGROUND: The purpose of this study was to evaluate 6-month clinical and angiographic outcomes in patients treated with excimer laser coronary angioplasty (ELCA) and intracoronary radiation (ICR) for in-stent restenosis (ISR). METHODS: A consecutive series of 175 patients with ISR treated with ELCA+ICR (gamma and beta emitters) were compared to 33 patients with ISR treated with ELCA alone. Baseline characteristics were similar between groups. ELCA+ICR and ELCA-alone patients had similar lesion lengths (25.0+/-12.0 vs. 24.0+/-16.8 mm, P=NS) in predominantly saphenous vein grafts (SVG, 38% vs. 42%, P=NS). RESULTS: Procedural success was high (ELCA+ICR, 97.0% vs. ELCA alone, 98.5%, P=NS), with no perforations or acute vessel closures. ELCA+ICR therapy reduced target vessel revascularization (TVR; 27% vs. 64%, P<.0001) and major adverse cardiac events [MACE: death, myocardial infarction (MI), or TVR; 30% vs. 64%, P<.0001] compared to ELCA alone. Late loss was 0.66+/-0.90 mm in ELCA+ICR patients and 0.85+/-0.60 mm in ELCA-alone patients (P=NS). Angiographic binary restenosis (>50%) was significantly reduced with adjunctive ICR (28% vs. 54%, P=.014). CONCLUSION: Radiation therapy with ELCA significantly reduces angiographic binary restenosis at 6 months in patients with diffuse ISR, driven predominantly by reduced percutaneous TVR.

Necrotizing ("malignant") external otitis histopathologic processes.

The histologic findings in a serially sectioned temporal bone, from a patient who succumbed to brain abscess secondary to necrotizing ("malignant") external otitis, are described. The mechanism of invasion of the ear canal appears to be due to local bone necrosis. This in turn extends to the submucosal vasculature of the pneumatic spaces. The infective process extends submucosally, establishing one or several sites of bone destruction. The lumen of the pneumatic space is not involved. In this process, the periphery of the fibrous inflammatory tissue formation is the site of active bone destruction. In pneumococcal petrositis, the peripheral fibrous elements are protective. The process in malignant external otitis may extend directly to adjacent central nervous system structures inoculating the structure with Pseudomonas. Development of Pseudomonas brain abscesses can be slow, allowing for new bone closure of the site from which the infection spreads as demonstrated in this specimen. Therefore, apparent local control of the disease can be established while a central infective process progresses.

Ear anomalies associated with renal dysplasia and immunodeficiency disease. A histopathological study.

The histopathologic study of the temporal bones of a case with low-set rudimentary auricles, without preauricular pits or cervical fistula is presented. Abnormalities of the middle and inner ear, fusion of the kidneys, hydrocephalus, short-limbed dwarfism and immunodeficiency are described. An abnormally low position of the middle cranial fossa in relation to the petrous pyramid was observed. The cochlea was of normal length. The modiolus was poorly developed with apparently normal population of ganglion cells and moderate diffuse hydrops of the cochlear duct and saccule. The stria vascularis was partially degenerated in the upper apical coil. Vestibular abnormalities included bilateral absence of common crus of the vertical canals and unusually high origin of endolymphatic aqueduct with no medial dilation present, the convoluted portion of the sac located beneath the dura.

Recurrent meningitis and labyrinthine gusher, related to congenital defects of the labyrinthine capsule and stapes footplate.

A congenital defect in the bony footplate of the stapes is now known to be a point of lowered resistance to extension of bacterial middle ear suppuration to the vestibule and thence to the meninges. Tomographic demonstration of the congenital pathologic condition of the ear permits the surgeon preoperatively to chart his surgical course. Despite antibiotic and chemotherapy, recurrent meningitis remains a serious disease as manifested by the death of two of the patients reported. The capacity for surgical correction of the congenital defect is manifested by one of our patients who has been free of meningitis for more than two years after surgery. If a congenital defect is considered in each case of recurrent meningitis, it is believed the mortality of this serious disease can be reversed.

Inner ear degeneration in acoustic neurinoma.

The temporal bones of three cases of acoustic neurinoma are described to illustrate histopathological features of inner ear lesions due to chronic partial obstruction of blood circulation by the tumor in the internal auditory meatus. Degenerative changes in the inner ear due to acoustic neurinoma were evaluated and compared with changes in the opposite ear. The main pathological findings in the inner ear which were attributed to the tumor were degeneration of nerve fibers and of ganglion cells, degeneration of the stria vascularis, degeneration of the tectorial membrane, fibrosis and ossification of a semicircular canal. Fairly good preservation of sensory cells was observed in the presence of total degeneration of nerve fibers and ganglion cells and subtotal degeneration of the stria vascularis.

Sensorineural deafness due to osteitis fibrosa.

A 91-year-old woman with deafness died from renal failure. Autopsy revealed osteitis fibrosa cystica generalisata, chronic myeloid leukemia, renal atrophy, and hyperplastic parathyroid glands. The temporal bones showed senile osteoporosis, osteitis fibrosa, and chronic myeloid leukemia. The inner ears showed extensive degeneration of cochlear sensorineural elements. The perilymph showed a general increased staining reaction with hematoxylin-eosin that was most evident in localized areas, where marrow spaces of osteitis fibrosa communicated directly with perilymph. It appears that the active diseased marrow exerted a toxic effect on the sensorineural elements of the cochlea by diffusion through the perilymph.

Osteogenesis imperfecta congenita and tarda: a temporal bone report.

The temporal bone report of an operated case of osteogenesis imperfecta tarda is presented. Histological examination confirmed the presence of bilateral fixation of the footplate by otosclerosis as the cause of the conductive hearing loss. Fragility of bony septae in the mastoid and of the stapedial crura were observed. Sensorineural impairment in later years with a reduction in neural elements in the cochlea appear related to the extent and activity of the otosclerotic foci. Additional temporal bone reports of three cases of osteogenesis imperfecta congenita show lack of deposition of the skein-like bone in the endochondral layer, sparse bony septae in marrow spaces and deficiency of the perosteal layer. The stapedial crura were thin and in two cases both were deformed and fractured.

Acrocephalosyndactly (Apert's syndrome): Temporal bone findings.

The middle ear and ossicular chain were not complete in the specimen, but the remnants present appeared normally developed except for the stapediovestibular joint region. The annular ligament was incompletely developed in two areas where fixation by undedifferentiated cartilage occurred. The subarcuate fossa, normally filled with fibrous tissue and usually narrowed by a rim of newly deposited periosteal bone at birth, was unusually large. Included in this fibrous tissue were remnants of the primary cartilaginous capusule undergoing absorption, as well as islands of partially removed endochondral bone. The abnormalities in both instances indicated a disturbance in maturation or resorption of the embryonal cartilaginous capsule.