SOCIETY FOR ENDOCRINOLOGY CLINICAL GUIDANCE: Inpatient management of cranial diabetes insipidus.

Cranial diabetes insipidus (CDI) is a treatable chronic condition that can potentially develop into a life-threatening medical emergency. CDI is due to the relative or absolute lack of the posterior pituitary hormone vasopressin (AVP), also known as anti-diuretic hormone. AVP deficiency results in uncontrolled diuresis. Complete deficiency can lead to polyuria exceeding 10 L/24 h. Given a functioning thirst mechanism and free access to water, patients with CDI can normally maintain adequate fluid balance through increased drinking. Desmopressin (DDAVP, a synthetic AVP analogue) reduces uncontrolled water excretion in CDI and is commonly used in treatment. Critically, loss of thirst perception (through primary pathology or reduced consciousness) or limited access to water (through non-availability, disability or inter-current illness) in a patient with CDI can lead to life-threatening dehydration. This position can be further exacerbated through the omission of DDAVP. Recent data have highlighted serious adverse events (including deaths) in patients with CDI. These adverse outcomes and deaths have occurred through a combination of lack of knowledge and treatment failures by health professionals. Here, with our guideline, we recommend treatment pathways for patients with known CDI admitted to hospital. Following these guidelines is essential for the safe management of patients with CDI.

Clinical characteristics of people experiencing biochemical hypoglycaemia during an oral glucose tolerance test: cross-sectional analyses from a UK multi-ethnic population.

AIMS: People who experience biochemical hypoglycaemia during an oral glucose tolerance test (OGTT) may be insulin resistant, but this has not been investigated robustly, therefore we examined this in a population-based multi-ethnic UK study. METHODS: Cross-sectional data from 6478 diabetes-free participants (849 with fasting insulin data available) who had an OGTT in the ADDITION-Leicester screening study (2005-2009) were analysed. People with biochemical hypoglycaemia (2-h glucose <3.3mmol/l) were compared with people with normal glucose tolerance (NGT) or impaired glucose regulation (IGR) using regression methods. RESULTS: 359 participants (5.5%) had biochemical hypoglycaemia, 1079 (16.7%) IGR and 5040 (77.8%) NGT. Biochemical hypoglycaemia was associated with younger age (P<0.01), white European ethnicity (P<0.001), higher HDL cholesterol (P<0.01), higher insulin sensitivity (P<0.05), and lower body mass index (P<0.001), blood pressure (P<0.01), fasting glucose (P<0.001), HbA1C (P<0.01), and triglycerides (P<0.01) compared with NGT and IGR separately in both unadjusted and adjusted (age, sex, ethnicity, body mass index, smoking status) models. CONCLUSIONS: Biochemical hypoglycaemia during an OGTT in the absence of diabetes or IGR was not associated with insulin resistance, but instead appeared to be associated with more favourable glycaemic risk profiles than IGR and NGT. Thus, clinicians may not need to intervene due to biochemical hypoglycaemia on a 2-h OGTT.

Perinatal testosterone exposure and maternal care effects on the female rat's development and sexual behaviour.

Natural variations in maternal care have profound influences on offspring behaviour, brain activity and hormone release. Measuring the amount of time that a rat dam spends licking/grooming (LG) her pups during their first week of life allows for characterisation of distinctive Low, Mid and High LG phenotypes. We have previously found that female offspring of High LG mothers are less sexually receptive, less motivated to mate and show a later onset of puberty relative to Low LG offspring. Given that High LG females are exposed to greater levels of testosterone in utero, we hypothesise that differences in sexual behaviour between High and Low LG female offspring are driven in part by differences in prenatal hormone exposure. To test this hypothesis, pregnant dams pre-characterised as Low, Mid, or High LG mothers were implanted with testosterone or placebo on gestational day (GD) 16. Offspring body weight and anogenital index were assessed at GD 21 and in adulthood. Age of vaginal opening and oestrous cyclicity were assessed to determine the timing of pubertal onset. Testosterone exposure removed the difference between LG phenotypes in pubertal onset by delaying vaginal opening and the appearance of first pro-oestrus. In adulthood, sexual behaviour in a paced mating chamber after sham surgery or ovariectomy with steroid-replacement was examined. Our findings show that Low, Mid and High LG female offspring are differentially affected by perinatal testosterone exposure, and that this exposure removes the precocial pubertal onset of Low LG offspring and increases the sexual proceptivity and receptivity of High LG offspring. These results suggest that maternal programming of the female reproductive system may be mediated, in part, through differences in perinatal testosterone exposure, instead of solely through maternal behaviour.

Cluster headache secondary to macroprolactinoma with ipsilateral cavernous sinus invasion.

We present a 25 year-old man with episodic cluster headache that was refractory to all standard pharmacological prophylactic and abortive treatments. Because of the lack of response, an MRI brain was performed which showed a large pituitary tumour with ipsilateral cavernous sinus invasion. The serum prolactin was significantly elevated at 54,700 miU/L (50-400) confirming a macro-prolactinoma. Within a few days of cabergoline therapy the headache resolved. He continues to be headache free several years after starting the dopamine agonist. This case highlights the importance of imaging the pituitary fossa in patients with refractory cluster headache, It also raises the potential anatomical importance of the cavernous sinus in pituitary-associated headache.

The challenges with NOTES retroperitoneal access in humans.

BACKGROUND: Animal studies have supported natural orifice transluminal endoscopic surgery (NOTES) retroperitoneal access. NOTES also may offer unique retroperitoneal access in humans. OBJECTIVES: This study was designed to assess the feasibility of endoscopic transgastric and transrectal retroperitoneal access in a cadaver model using prone and supine positioning, and to compare NOTES retroperitoneal examination with endoscopic ultrasound. METHODS: Using a multidisciplinary team, this institutional review board-approved study evaluated transgastric and transrectal retroperitoneal examination in six cadavers (3 male, 3 female; body mass index range, 25-37 kg/m(2)). Endoscopic ultrasound retroperitoneal examination preceded NOTES access. Transgastric Access: Using a prototype dual channel endoscope, a needle knife gastrotomy was created on the preantral posterior gastric wall. Retroperitoneal examination specifically targeted the pancreas and surrounding structures with the cadaver supine and prone. Transrectal Access: Using the same endoscope, a posterior needle knife rectotomy distal to the upper valve of Houston provided extraluminal access. Retroperitoneal examination proceeded with the cadaver prone and supine. Open dissection followed procedure completion. RESULTS: Access into the retroperitoneum succeeded at all sites. Significant challenges locating identifiable landmarks were faced-mostly transrectal and improved transgastric prone. All cadavers, despite body mass index or sex, had significant retroperitoneal adipose tissue limiting the endoscopic view. CONCLUSIONS: Although porcine studies have highlighted successful NOTES retroperitoneal procedures, the abundant human retroperitoneal adipose tissue challenged the translation of porcine research to humans. Additionally, although access to the retroperitoneal space and dissection within this space were accomplished easily, the appearance of cadaveric tissue and lack of blood flow made confident landmark identification impossible. Further study should continue in this area and focus on confident landmark identification for directed dissection. In a cadaveric model, this would best be improved by pre-NOTES anatomic marking or active perfusion of vasculature along with consideration of direct entry into the retroperitoneum from a targeted intraperitoneal site in clinical patients.

Endoscopic retrograde cholangiopancreatography using a single-balloon enteroscope in patients with altered Roux-en-Y anatomy.

BACKGROUND AND STUDY AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) is challenging to perform in patients with postsurgical gastrointestinal anatomy. We assessed the diagnostic and therapeutic success rates using single-balloon enteroscopy in patients with Roux-en-Y anastomosis. PATIENTS AND METHODS: Patients who underwent single-balloon ERCP between April 2008 and February 2010 were retrospectively identified using a computerized endoscopy database. Diagnostic success was defined as successful duct cannulation or securing the diagnosis, and therapeutic success was defined as the ability to successfully carry out endoscopic therapy. Complications of ERCP were defined according to standard criteria. RESULTS: A total of 50 patients (34-male, mean age 57 years, range 19 - 85 years) with Roux-en-Y anastomosis underwent ERCP using a single-balloon enteroscope on 56 occasions. Indications for ERCP were cholestasis, acute cholangitis, recurrent primary sclerosing cholangitis with strictures, and choledocholithiasis. Overall diagnostic success was achieved in 39 / 56 cases (70 %). Therapeutic success was achieved in 21/23 cases (91 %). In 16 cases therapeutic intervention was not required. Therapeutic interventions included balloon dilation of strictures (n = 14), retrieval of retained biliopancreatic stents (n = 5), biliary stone extraction (n = 2), insertion of biliopancreatic stents (n = 4), and biliary and pancreatic sphincterotomy (n = 5). No major complications occurred. Importantly, in 22 / 56 procedures (39 %) a prior attempt at ERCP failed using conventional colonoscopes; single-balloon ERCP was successful in 15 / 22 (68 %) of these cases. CONCLUSIONS: Single-balloon ERCP is feasible in patients with complex postsurgical Roux-en-Y anastomosis, allows diagnostic evaluation and therapeutic intervention in patients with pancreaticobiliary disease, and is a useful salvage technique in the majority of patients in whom ERCP using colonoscopies has failed.

The role of endoscopic ultrasound for loco-regional staging of rectal cancer.

Rectal cancer is projected to have the 10th highest incidence of cancer in the United States in 2009, with 40 870 estimated new cases this year. The prognosis for patients with rectal cancer is directly related to several factors, with the most important, based on current data, the extent of primary tumor invasion, the number of lymph nodes involved, involvement of the circumferential resection margin, and the presence of metastases. Contemporary therapy is dependent upon pre-surgical diagnostic imaging modalities, which influence the indication for neoadjuvant therapy and the decision process concerning the appropriate surgical approach. A comprehensive overview based on the currently available evidence of endoscopic ultrasound imaging in the loco-regional assessment of primary de novo rectal cancer evaluation following neoadjuvant therapy and post operative disease surveillance is presented. Relevant ano-rectal anatomy, staging systems for rectal cancer and alternative radiological staging strategies are also presented.

Endoscopic transpapillary gallbladder drainage: 10-year single center experience.

AIM: A subset of patients with acute cholecystitis is severely ill and extremely high-risk to undergo cholecystectomy. Data on the use of endoscopic transpapillary gallbladder drainage (ETGBD) in the treatment of acute cholecystitis are limited. This article reviews the 10-year experience of ETGBD at Mayo Clinic and evaluated patient and procedure characteristics. METHODS: A retrospective review of the endoscopy database from 1998-2007 was performed to identify patients who had undergone ETGBD. Clinical information and procedure details were abstracted from the electronic medical record. RESULTS: Fifty one patients underwent ETGBD for acute cholecystitis between 1998 to July 2007. The mean age was 62+/-19 years and 67% of patients were males. The median number of comorbid medical conditions was two (range 0-5) and 27% had underlying diabetes mellitus. Acute calculous cholecystitis was the predominant indication for ETGBD (78%). A gallbladder stent was used in 33 (65%) patients, nasocholecystic drain in 14 (27%) patients, and both in four patients (8%). Bleeding (4%) and sedation-related complications (4%) were the most common complications noted. Among patients who underwent cholecystectomy, the majority (76%) needed an open procedure. The median time to cholecystectomy was 15 days (range 1-352 days). Four patients (8%) succumbed to septic shock during their hospitalization. CONCLUSIONS: ETGBD is a valuable alternative therapeutic modality for the treatment of patients with acute cholecystitis who are at high-risk for early cholecystectomy, and/or those who have contraindications to percutaneous gallbladder drainage.

Endoscopic ultrasound (EUS) guided access and therapy of pancreatico-biliary disorders.

Endoscopic ultrasound (EUS) has evolved from a purely diagnostic imaging modality to one that allows therapeutic intervention. It now serves as a viable alternative, and at times is preferred, to percutaneous and surgical techniques for obtaining biliary and pancreatic duct access and for providing drainage. EUS guided intervention is usually performed following failed endoscopic retrograde cholangiopancreatography (ERCP) or as an option for patients who decline surgical intervention or in poor operative candidates. Published data demonstrate overall technical success in 83% of patients with 12% experiencing a procedure related complication. New techniques and equipment must be developed to simplify and abbreviate the procedures, to limit complications, and improve outcomes. In addition, longitudinal data are needed to determine the long-term outcomes and role of EUS guided pancreaticobiliary intervention.