Should all patients with hyperparathyroidism be screened for a CDC73 mutation?

Primary hyperparathyroidism (PH) is a common endocrine abnormality and may occur as part of a genetic syndrome. Inactivating mutations of the tumour suppressor gene CDC73 have been identified as accounting for a large percentage of hyperparathyroidism-jaw tumour syndrome (HPT-JT) cases and to a lesser degree account for familial isolated hyperparathyroidism (FIHP) cases. Reports of CDC73 whole gene deletions are exceedingly rare. We report the case of a 39 year-old woman with PH secondary to a parathyroid adenoma associated with a large chromosomal deletion (2.5 Mb) encompassing the entire CDC73 gene detected years after parathyroidectomy. This case highlights the necessity to screen young patients with hyperparathyroidism for an underlying genetic aetiology. It also demonstrates that molecular testing for this disorder should contain techniques that can detect large deletions

Succinate dehydrogenase subunit B mutation presenting with spermatic cord and neck paraganglioma

Objective: Paragangliomas (PGLs) are rare neuroendocrine tumors often associated with hypersecretion of catecholamines, and are found along the sympathetic chains or parasympathetic paraganglia. PGLs can occur in the context of hereditary syndromes and commonly with succinate dehydrogenase (SDH) complex gene mutations. PGLs of the spermatic cord or testes are extremely rare and reports of synchronous spermatic cord and neck PGLs have not been reported before. In previous cases of spermatic cord PGLs, screening for an underlying genetic cause was not performed apart from 1 case where the patient was positive for a SDH subunit D mutation. Methods: We present a case report and a review of the literature using the PubMed, Medline, and Google Scholar databases. Results: We report the case of a 55-year-old man with a 1-year history of dysphonia resulting in radiological diagnosis of a right vagal PGL treated with radiation. Laboratory investigations excluded a secretory PGL. Simultaneously he was diagnosed with a positron emission tomography-avid testicular mass. An orchidectomy histologically confirmed a spermatic cord PGL. Genetic testing was positive for a heterozygous germline variant c.380T>G, p.(IIe127Ser) within exon 4 of the SDH subunit B gene which has not been reported with spermatic cord PGL before. Conclusion: This case reports the synchronous occurrence of spermatic cord and neck PGLs with SDH subunit B mutation. It highlights the necessity for clinicians to screen patients with PGLs for an underlying genetic etiology, even if found in unusual locations, as this has significant implications for future treatment, screening, and family planning

Retrospective, semi-automised examination of psychopharmacological drug-drug interactions for preparation of a computerized physician order entry system

Hintergrund und Ziele Die Anforderungen an die Medizin im Allgemeinen und an die Psychiatrie im Speziellen steigen stetig durch zum Beispiel Qualitätsmanagement, Leitlinien und vor allem durch eine häufigere Verordnung von Psychopharmaka und den wachsenden Anteil älterer, multimorbider Patienten mit chronischen Erkrankungen, welche in der Regel mit mehreren Medikamenten behandelt werden. Mit der Anzahl eingenommener Wirkstoffe nimmt einerseits das Risiko von Arzneimittel-bedingten Nebenwirkungen zu, andererseits auch das Risiko unerwünschter Nebenwirkungen durch Interaktionen von Medikamenten untereinander. Im folgenden Projekt wurden die Entlassungsmedikationen stationärer Patienten des Psychiatrischen Klinikums der Universität Erlangen-Nürnberg erfasst und die möglichen Kombinationen der verschriebenen Psychopharmaka mittels PsiacOnline, einer Internet-basierten Datenbank, auf Interaktionsrisiken untersucht. Vor diesem Hintergrund wurde auch die Implementierung von Systemen wie PsiacOnline in Krankenhausinformationssysteme diskutiert. Methoden Die Studie wurde retrospektiv geplant mit dem Ziel, die Entlassungsmedikation einer zufällig ausgewählten Population stationär in der Psychiatrischen und Psychotherapeutischen Klinik des Universitätsklinikums Erlangen behandelter Patienten hinsichtlich möglicher psychopharmakologischer Interaktionen zu untersuchen. Die erhobenen Daten stammen aus stationären Aufhalten von Patienten der Psychiatrischen und Psychotherapeutischen Klinik des Universitätsklinikums Erlangen. Es wurde die Entlassungsmedikation von 342 zufällig ausgewählten Fällen, die sich zwischen 2004 - 2009 in stationärer Behandlung befanden, dokumentiert und in einem zweiten Schritt mittels PsiacOnline, einer Internet-basierten Wissensdatenbank für die Psychopharmakotherapie, semiautomatisch auf Wechselwirkungen und daraus resultierenden Nebenwirkungen analysiert. Ergebnisse und Beobachtungen Insgesamt analysierten wir 342 Datensätze wobei das Durchschnittsalter 46,3 Jahre betrug und 53 % der untersuchten Fälle Frauen waren. Bei 86 Fällen lag eine einzelne psychiatrische Diagnose vor, alle anderen Fälle hatten zwei oder mehr psychiatrische Diagnosen. Knapp 60 % der psychiatrischen Diagnosen betraf die ICD-Diagnosegruppe F2 und F3. Durchschnittlich nahm die untersuchte Population 2,88 verschiedene Psychopharmaka ein (Maximum: acht Medikamente). Nur 47 der 342 Fälle wurden mit einer Monotherapie entlassen. Die Entlassungsmedikation bestand aus insgesamt 80 unterschiedlichen Medikamenten, die in sechs verschiedene Gruppen eingeteilt wurden (19 Antidepressiva, 20 Antipsychotika, 9 Mood-Stabilizer inkl. Antiepileptika, 14 Anxiolytika/ Hypnotika, 9 Antidementiva/ Antiparkinsonmittel und 9 Medikamente, die untere „weitere Medikamente“ subsummiert wurden). Die meisten Entlassungsmedikationen betrafen die Gruppe der Antipsychotika, gefolgt von Antidepressiva und der Gruppe der Mood-Stabilizer inklusive Antiepileptika. Die Prüfung der Kombinationsbehandlungen ergab 564 Interaktionsfälle. Die möglichen Interaktionen wurden in verschiedene Risikostufen eingeteilt: In 7 Fällen (1,3 %) ging die Kombination mit einem hohen Risiko oder einem Risiko für schwerwiegende Interaktionsnebenwirkungen einher. In 40 Fällen (7,1 %) ergab sich bei Kombinationen ein erhöhtes Risiko für Interaktionsnebenwirkungen. Bei 73 Fällen (12,9 %) waren die Kombinationen kritisch für bestimmte Risikopatienten (Epilepsie, Herzkreislaufkranke, Morbus Parkinson). In 232 Fällen (41,4 %) war eine Interaktion aus in vitro-Studien oder aus Tierversuchen zu erwarten, es lagen aber bislang keine evidenzbasierten Daten zur klinischen Relevanz vor. In 86 Fällen (15,3 %) kam es zu einer Kombination mit theoretisch möglichem, in der Praxis aber nicht nachgewiesenem Interaktionsrisiko. In 126 Fällen (22,3 %) wurden die Kombinationen als unbedenklich oder ohne Interaktionsrisiko eingestuft. Praktische Schlussfolgerungen Auch wenn die Mehrzahl der Medikamentenkombinationen bezüglich Interaktionsrisiken als unbedenklich oder gering eingeschätzt wurde, weisen 7,1 % der Entlassungsmedikation ein erhöhtes Risiko und 1,3 % das Risiko einer schweren unerwünschten Arzneimittelwirkung auf. Eine Überprüfung der Entlassungsmedikation auf potenzielle Wechselwirkungen und eine Integration von Wissensdatenbanken wie PsiacOnline in Krankenhausinformationssysteme wird deshalb für sinnvoll erachtet. Dies sollte in einer adäquat geplanten, prospektiven, klinischen Studie geprüft werden.Background and Objectives Medicine and especially psychiatry are confronted with ever increasing demands. Quality management, changing guidelines, the trend of psychiatric drugs being prescribed more frequently and above all an increase of elderly patients suffering from chronic psychiatric disorders result in enormous challenges to psychiatric treatment. With the number of drugs prescribed rising, the risks of adverse drug effects including those resulting from drug-drug interactions are growing. The following study analyzed possible interactions of psychopharmacological drugs and their possibly resulting side effects using the discharge medication of inpatients treated at the psychiatric university hospital of Erlangen-Nürnberg. To detect such interactions an internet database called PsiacOnline was used. Moreover, the idea of integrating software like PsiacOnline into every day work at hospital was part of this thesis. Methods This study was planned retrospectively and aimed towards analyzing psychiatric inpatients’ discharge medication. Inpatients included in this study were these treated at the psychiatric university hospital of Erlangen during 2004 until 2009. After selecting 342 inpatients randomly off the hospital’s database, their discharge medication was documented. Possible drug-drug interactions of psychopharmacological drugs taken by selected inpatients were examined using an internet database called PsiacOnline. Results and Observations The mean age of 342 cases selected was 46.3 years with 53 % of all cases being women. While the majority of patients suffered from two or more psychiatric diagnoses, a single psychiatric diagnosis was found only 86 times. Nearly 60 % of the psychiatric diagnoses were part of the ICD F2- or F3-group. On average patients took 2.88 different psychopharmacological drugs with the maximum of drugs taken being eight. Only 47 out of 342 cases were treated with just one single drug. Discharge medications comprised 80 different drugs, which were categorized into six different groups (19 antidepressants, 20 antipsychotics, 9 mood-stabilizers including antiepileptic drugs, 14 anxiolytic and hypnotic drugs, 9 drugs for dementia and Parkinson’s disease and finally another 9 drugs that were summarized in a group denominated “others”). Most prescribed drugs were antipsychotics followed by antidepressants and mood-stabilizers including antiepileptic drugs. Using PsiacOnline we examined possible pharmacological drug-drug interactions and their adverse drug effects which resulted in 564 cases of possible interactions. 7 cases (1.3 %) were considered to be interactions with a high risk of adverse drug effects or with a risk of severe adverse drug effects. Another 40 cases (7.1 %) showed an increased risk of drug-drug interactions related adverse drug effects. In 73 cases (12.9 %) risk patients (patients suffering from epilepsy, Parkinson’s disease or having a heart condition) faced a risk of drug-drug interactions- based adverse drug effects. In 232 cases (41.4 %) a drug-drug interaction resulting in adverse drug effects can be expected from in-vitro studies or animal experiments, yet there is no evidence-based data suggesting this. 86 cases (15.3 %) resulted in a theoretically possible adverse drug effect resulting from drug-drug interactions. 126 cases (22.3 %) didn’t show any drug-drug interactions or solely interactions that were deemed harmless. Conclusions Despite the fact that the majority of pharmacological drugs prescribed did not result in drug-drug interactions related adverse drug effects, it needs to be emphasized that 7.1 % of all cases analyzed faced an increased risk of side effects based on drug-drug interactions and 1.3 % might suffer from severe side effects caused by the combinations of pharmacological drugs. Taking this into account, it seems reasonable to use databases like PsiacOnline in everyday clinical settings to uncover possible drug-drug interactions and to prevent their negative effects on patients. To undermine this a prospective, clinical study should be realized

Rare case of meningococcal sepsis-induced testicular failure, primary hypothyroidism and hypoadrenalism: is there a link?

Severe illness can lead to multiple transient endocrinopathies. In adult patients, neuroendocrine alterations include sick euthyroid syndrome, an increase in corticosteroid levels, increase in prolactin levels, decreased insulin growth factor 1 levels and hypogonadism. We report the case of a 24-year-old man with meningococcal sepsis with multiple end-organ complications who developed persistent non-autoimmune hypothyroidism, adrenal insufficiency and primary hypogonadism all requiring hormone replacement. While adrenal insufficiency as part of the Waterhouse-Friderichsen syndrome is well described, reports of primary hypothyroidism and persistent primary hypogonadism in severe illness are exceedingly rare. Multiple combined endocrinopathies as in this case have not been reported previously. This case highlights the necessity of screening for endocrine abnormalities in severe illness and the need for treatment if persistent. It also raises a novel concept of meningococcal sepsis causing multiple endocrinopathies possibly via disseminated intravascular coagulopathy-related ischaemic damage

Man with epigastric pain and persistently elevated serum lipase

Serum lipase and amylase are commonly requested in individuals presenting with abdominal pain for investigation of acute pancreatitis. Pancreatic hyperenzymaemia is not specific for acute pancreatitis, occurring in many other pancreatic and non-pancreatic conditions. Where persistent elevation of serum lipase and amylase occurs in the absence of a diagnosed cause or evidence of laboratory assay interference, ongoing radiological assessment for pancreatic disease is required for 24 months before a diagnosis of benign pancreatic hyperenzymaemia can be made. We report a case of a 71-year-old man with epigastric pain and elevated serum lipase levels. He was extensively investigated, but no pancreatic disease was detected. He is asymptomatic, but serum lipase levels remain elevated 18 months after his initial presentation

Visual loss in pregnancy

Visual loss in pregnancy may be caused by a variety of reasons including pituitary adenomas. Prolactinomas (PRLs) are the most common hormone-secreting tumours in pregnant women. As most PRLs present with menstrual abnormalities, infertility or galactorrhoea, they are most commonly diagnosed before pregnancy. We present the case of a 30-year-old primigravida who presented at 36 weeks gestation with headaches and left-sided visual loss. MRI of the pituitary gland confirmed a 10×11 mm left suprasellar mass. Results of her anterior pituitary function were unremarkable for her gestational age. Postpartum, she underwent an endoscopic endonasal resection of the pituitary tumour. The histology was consistent with a PRL. Literature review reveals only one possible case of a new diagnosis of a PRL during pregnancy. It highlights the importance to consider a wide range of differential diagnoses when assessing visual loss in pregnancy

Antimicrobial stewardship in diabetic ketoacidosis: a single centre experience

Background: Diabetic ketoacidosis (DKA) is a common and serious complication arising predominantly in patients with type 1 diabetes mellitus (T1DM). International data demonstrate that infection is one of the most common precipitating causes of DKA. Currently there is limited data regarding the role of antimicrobial stewardship (AMS) in this setting. Aim: The aim of this study is to provide epidemiologic data regarding infections precipitating DKA, microbiological aetiology, and antimicrobial prescribing practices, in order to inform AMS interventions. Methods: Retrospective chart review of all T1DM DKA presentations from May 2015 – June 2018. Results: In total 249 DKA presentations occurred in 111 patients. Suspected infection accounted for 100/249 (40%) presentations. Only 36/249 (14.5%) were proven or probable infections on review. Of 80 antimicrobial prescriptions, 75% were inappropriate based on guideline management of suspected infection. Neutrophilia was not a statistically significant indicator of infection (p = 0.78). Presence of elevated CRP had the greatest association with infection, OR: 10.1 (95% CI, 1.05 to 97.0). Lymphopenia demonstrated increased likelihood of infection, OR: 3.1 (95% CI, 1.14 to 8.2). Interestingly, thrombocytosis appeared to be associated with a decreased likelihood of infection, OR: 0.31 (95% CI, 0.105 to 0.903). Conclusion: This study demonstrates a lower incidence of infection compared to most previous publications, and suggests that infection‐precipitated DKA may be over reported. Furthermore, our findings provide support for the role of AMS in the management of DKA

Diabetes care: addressing psychosocial well-being in young adults with a newly developed assessment tool

Background: Psychosocial assessment should be part of clinic visits for people with diabetes mellitus (DM). Aims: To assess the usage and acceptance of a diabetes psychosocial assessment tool (DPAT) and to profile the clinical and psychosocial characteristics of young people with diabetes. Methods: Over a 12-month period, young adults (18–25 years) attending diabetes clinic were offered DPAT. The tool embeds validated screening tools including the Problem Areas in Diabetes 20 (PAID-20) questionnaire, the Patient Health Questionnaire-4 (PHQ-4) and the World Health Organization Well-Being Index-5 (WHO-5). Baseline clinical data were collected and questions regarding social support, body image, eating concerns, hypoglycaemia and finances were included. Results: Over the 12 month, the form was offered to 155 participants (64.6% of eligible attendees). The majority (96.1%) had type 1 DM with a mean duration of 10.5 (±5.3 SD) years. Average glycated haemoglobin (HbA1c) was 8.7% (±1.5 SD) (or 71.2 mmol/mol ±16.5 SD). Severe diabetes-related distress (PAID-20 ≥ 40) was found in 19.4%. Low WHO-5 scores (28–50 points) were seen in 14.8%. PHQ-4 identified 25.8% with anxiety and 16.1% with depression. Significant weight, shape and eating concerns were identified in 27.1, 26.6 and 28.4%, respectively. Serious hypoglycaemia concerns were raised by 4.5%. Conclusion: DPAT revealed a high prevalence of psychosocial stress among young adults with DM. The tool was easy to use and accepted by patients and may aid streamlining referrals to relevant members of a multidisciplinary team