Central serous chorioretinopathy secondary to intramuscular testosterone therapy.

Summary: A patient treated with intramuscular testosterone replacement therapy for primary hypogonadism developed blurred vision shortly after receiving his testosterone injection. The symptom resolved over subsequent weeks and recurred after his next injection. A diagnosis of central serous chorioretinopathy (CSR) was confirmed following ophthalmology review. A decision was made to change the patient's testosterone regime from this 12-weekly intramuscular injection to a daily topical testosterone gel, given the possibility that peak blood levels of testosterone following intramuscular injection were causing his ocular complaint. His CSR did not recur after this change in treatment. CSR secondary to testosterone therapy is a rare finding but has been reported previously in the literature. Learning Points: Blurred vision in patients treated with testosterone replacement therapy (TRT) should prompt an ophthalmology review. The potential for reduced risk of central serous chorioretinopathy (CSR) with daily transdermal testosterone remains a matter of conjecture. CSR is a rare potential side effect of TRT.

Serum OPG/TRAIL ratio predicts the presence of cardiovascular disease in people with type 2 diabetes mellitus.

AIMS: Cardiovascular disease (CVD) is the leading cause of mortality in type 2 diabetes mellitus (T2DM). Epidemiological studies suggest serum Osteoprotegrin (OPG)/Tumour-necrosis-factor-related-apoptosis-inducing- ligand (TRAIL) ratio may be a useful marker of cardiovascular risk. This study aimed to compare serum levels of TRAIL, OPG and OPG/TRAIL ratio in people with T2DM, with and without a history of CVD, and controls; and to determine which of these indices, if any, predict cardiovascular risk. METHODS: In this single centre observational study of 133 participants, people with T2DM, with and without a history of a cardiovascular event in the last 5 years, were recruited along with a control cohort without T2DM or CVD. Demographic information and anthropometric measurements were recorded. Blood samples were taken and OPG and TRAIL were measured using ELISA. RESULTS: People with T2DM and CVD had higher OPG/TRAIL ratios compared to controls or those with a new diagnosis of T2DM. After adjustment for potential confounding factors, OPG/TRAIL ratio was significantly associated with the presence of CVD in people with T2DM and an OPG/TRAIL ratio cut-off > 38.6 predicted the presence of CVD in this cohort with a sensitivity of 80% and specificity of 82%. CONCLUSION: This study suggests that OPG/TRAIL ratio may have a role as a biomarker of CVD in people with T2DM.

Pituitary tuberculoma: a rare cause of sellar mass.

INTRODUCTION: Pituitary tuberculosis is an uncommon cause of sellar mass [1]; the estimated prevalence worldwide is not known, and there have been no reports of the condition occurring in Ireland. Tuberculosis of the pituitary gland may present as a sellar mass or with symptoms of hypopituitarism. CASE PRESENTATION: A 41-year-old woman, with a short prodromal history without endocrine symptoms, was found to have pituitary tuberculosis after the demonstration of a sellar mass on MRI, and lumbar puncture findings consistent with lymphocytic meningitis. CONCLUSION: To our knowledge, this is the first published case of pituitary tuberculoma in Ireland.

The incidence of anterior pituitary hormone deficiencies in patients with microprolactinoma and idiopathic hyperprolactinaemia.

INTRODUCTION: Patients with microprolactinoma and idiopathic hyperprolactinaemia are not generally considered to be at risk of hypopituitarism and are therefore not routinely screened for this abnormality. In our clinical practice, we have observed a number of patients with nonmacroadenomatous hyperprolactinaemia to have anterior pituitary hormone deficits. AIMS: We aimed to establish the frequency and clinical significance of anterior pituitary hormone deficiencies, comparing patients with radiologically proven microprolactinomas and patients with idiopathic hyperprolactinaemia. STUDY DESIGN: We retrospectively examined the casenotes of 206 patients with hyperprolactinaemia from our centre. Patients who did not fit the profile of surgically naïve microprolactinoma or idiopathic hyperprolactinaemia or who had incomplete data were excluded, resulting in a study group of 56 patients. RESULTS: A total of 35 patients with MRI evidence of microprolactinoma were identified, three (8.57%) of whom had one or more anterior pituitary hormone deficiencies. A total of 21 patients with MRI-negative idiopathic hyperprolactinaemia were identified, nine (42%) of whom had one or more anterior pituitary hormone deficiencies (P<.01). Only one patient in the MRI-positive group had deficiency that required hormone replacement, in contrast six patients in the MRI-negative group had deficiencies that were of clinical significance and which required hormone replacement. SUMMARY: This study shows a clinically significant incidence of anterior pituitary hormone deficiency in patients with idiopathic hyperprolactinaemia. The authors recommend that dynamic pituitary assessment should be considered routinely in this patient group. A prospective study would be required to assess the underlying cause for these abnormalities, as they suggest a nontumour pan-pituitary process.

Heterogenous patterns of recovery of thirst in adult patients with adipsic diabetes insipidus.

BACKGROUND: The natural history of adipsic diabetes insipidus (ADI) is not well described, and reports of recovery of thirst are rare. DESIGN AND METHODS: Case histories presentation. ADI was identified by demonstrating absent thirst and arginine vasopressin (AVP) responses to hypertonic saline infusion. RESULTS: Twelve patients with ADI were identified (craniopharyngioma 5, anterior communicating artery aneurysm (ACOM) repair 4, congenital 1, neurosarcoidosis 1, prolactinoma 1). Three patients died. Six patients had permanent ADI. Three patients had recovery of thirst, with a heterogenous pattern of recovery. In the first case, ADI had developed after clipping of an ACOM aneurysm. Ten years after surgery; he sensed the return of thirst; repeated hypertonic saline infusion showed recovery of thirst and AVP secretion. In the second case, a 41-year-old female with an intrasellar craniopharyngioma developed post-operative ADI with persistent hypernatremia. Two years post-operatively, she complained of thirst, and hypertonic saline infusion showed normalization of thirst but absent AVP responses, confirming recovery of thirst, but with persistent diabetes insipidus (DI). In the third case, a 29-year-old Caucasian had craniotomy and radiotherapy for craniopharyngioma and developed ADI post-operatively. Eight years post-op, she presented with thirst, seizures and pNa of 112 mmol/l. Hypertonic saline infusion showed persistent DI but thirst responses typical of compulsive water drinking; she has had recurrent hyponatraemia since then. CONCLUSIONS: We report that 3/12 patients with ADI recovered thirst after longstanding adipsia with heterogenous pattern of recovery. Both the mortality of 25% and the recovery rate of 25% should be considered when planning long-term surveillance.

Musculoskeletal Health, Kidney and Liver Function in Retired Jockeys.

The long-term implications of making-weight daily on musculoskeletal health and functioning of the kidney and liver remain unknown. This study aimed to investigate musculoskeletal health and kidney and liver function in a group of retired jockeys. 28 retired male jockeys (age 50-70 years) provided fasting blood samples for markers of bone metabolism and kidney and liver function. A dual-energy x-ray absorptiometry (DXA) scan was performed for the assessment of bone mineral density (BMD). Established reference ranges were used for interpretation of results. Comparisons were made between retired jockeys based on the professional racing licence held: Flat, National Hunt or Dual. Mean whole-body osteopenia was reported, with no differences between groups. Bone markers, micronutrients, electrolytes and associated hormones, and markers for kidney and liver function were within clinical normative ranges. No differences existed between groups. Results indicate the retired jockeys in this study do not demonstrate compromised bone health or kidney and liver function. However, the retired jockeys may not have undergone chronic weight cycling in the extreme manner evident in present-day jockeys, indicating the next generation of jockeys may face more of a problem. Jockeys should be tracked longitudinally throughout their racing career and beyond.

Abnormal plasma sodium concentrations in patients treated with desmopressin for cranial diabetes insipidus: results of a long-term retrospective study.

CONTEXT AND OBJECTIVE: Patients with cranial diabetes insipidus (CDI) are at risk of developing both hypernatraemia and hyponatraemia, due to the condition itself or secondary to treatment with vasopressin-analogues or during administration of i.v. fluids. We aimed to assess the frequency and impact of dysnatraemias in the inpatient (INPT) and outpatient (OPT) setting in desmopressin-treated CDI, comparing those with normal thirst with those with abnormal thirst. DESIGN: The study included 192 patients with cranial diabetes, who were identified from the Beaumont Pituitary Database, a tertiary referral centre. Retrospective case note audit was performed and the clinical and biochemical information of 147 patients with CDI were available for analysis. RESULTS: A total of 4142 plasma sodium measurements for 137 patients with normal thirst, and 385 plasma sodium measurements for ten patients with abnormal thirst were analysed. In those with normal thirst, the most common OPT abnormality was mild hyponatraemia (pNa(+) 131-134  mmol/l) in 27%, while 14.6% had more significant hyponatraemia (pNa(+) ≤130  mmol/l). Of those patients with normal thirst, 5.8% were admitted due to complications directly related to hyponatraemia. Compared with patients with normal thirst, those with abnormal thirst were more likely to develop significant OPT hypernatraemia (20% vs 1.4%, P=0.02) and significant INPT hyponatraemia (50% vs 11.1%, P 0.02). CONCLUSION: OPT management of CDI is complicated by a significant incidence of hyponatraemia. In contrast, OPT hypernatraemia is almost exclusively a complication seen in adipsic CDI, who also had more frequent INPT hyponatraemia. CDI associated with thirst disorder requires increased physician attention and patient awareness of potential complications.

Education, learning and assessment: current trends and best practice for medical educators.

INTRODUCTION: Methods of teaching and assessment in medical schools have transformed over the recent past. Accreditation of medical schools through national licensing bodies and removal of bias at examinations is the norm. This review is intended to inform senior doctors who are peripherally involved in training at speciality or general professional level. MATERIALS AND METHODS: From the summative assessment of learning, the uses of assessment for learning and formative assessment have transformed the process of education. Student feedback has moved centre stage. The criteria used to rate questions and abilities are made explicit and there is accountability for student and examiner performances. Standard setting for medical professional examinations is formalised through norm or criteria referencing. Objective methods to determine the pass/fail border including Angoff, Ebel, Nedelsky, Bookmark, Hofstee, borderline group and contrast by group are described. There is some evidence for grade inflation over time at universities. Blueprinting by setting test questions to learning objectives is now standard. The Objective Structured Clinical Examination uses a wide variety of case tasks at different stations. Miller's pyramid is the road map for professional competence indication where 'doing' becomes the benchmark standard. Item response theory and computer adaptive testing are available through the Concerto testing platform which is an open resource. CONCLUSION: Examining the performance of examiners as well as that of students is a necessary part of good examination practice. The World Federation for Medical Education with the World Health Organisation has developed nine standards with two categories of basic and quality for the accreditation of medical education.

Chronic hypopituitarism is uncommon in survivors of aneurysmal subarachnoid haemorrhage.

OBJECTIVE: The incidence of hypopituitarism after aneurysmal subarachnoid haemorrhage (SAH) is unclear from the conflicting reports in the literature. As routine neuroendocrine screening for hypopituitarism for all patients would be costly and logistically difficult, there is a need for precise data on the frequency of hypopituitarism and on factors which might predict the later development of pituitary dysfunction. We aimed to: (i) Establish the incidence of long-term hypopituitarism in patients with aneurysmal SAH. (ii) Determine whether data from patients' acute admission with SAH could predict the occurrence of long-term hypopituitarism. DESIGN: One hundred patients were studied prospectively from the time of presentation with acute SAH. Plasma cortisol, plasma sodium and a variety of clinical and haemodynamic parameters were sequentially measured for the first 12 days of their acute admission. Forty-one patients then underwent dynamic pituitary testing at median 15 months following SAH (range 7-30 months), with insulin tolerance test (ITT) or, if contraindicated, a glucagon stimulation test (GST) plus short synacthen test (SST). If symptoms of cranial diabetes insipidus (CDI) were present, a water deprivation test was also performed. RESULTS: Forty-one patients attended for follow-up dynamic pituitary testing. Although 14 of 100 had acute glucocorticoid deficiency immediately following SAH, only two of 41 had long-term adrenocorticotrophic hormone (ACTH) deficiency and four of 41 had growth hormone (GH) deficiency. None were hypothyroid or gonadotrophin deficient. None had chronic CDI or hyponatraemia. There was no association between acute glucocorticoid deficiency, acute CDI or acute hyponatraemia and long-term pituitary dysfunction. CONCLUSION: Both anterior and posterior hypopituitarism are very uncommon following SAH and are not predicted by acute clinical, haemodynamic or endocrinological parameters. Routine neuroendocrine screening is not justified in SAH patients.

Hyponatremia following mild/moderate subarachnoid hemorrhage is due to SIAD and glucocorticoid deficiency and not cerebral salt wasting.

CONTEXT: Hyponatremia is common after acute subarachnoid hemorrhage (SAH) but the etiology is unclear and there is a paucity of prospective data in the field. The cause of hyponatremia is variously attributed to the syndrome of inappropriate antidiuresis (SIAD), acute glucocorticoid insufficiency, and the cerebral salt wasting syndrome (CSWS). OBJECTIVE: The objective was to prospectively determine the etiology of hyponatremia after SAH using sequential clinical examination and biochemical measurement of plasma cortisol, arginine vasopressin (AVP), and brain natriuretic peptide (BNP). DESIGN: This was a prospective cohort study. SETTING: The setting was the National Neurosurgery Centre in a tertiary referral centre in Dublin, Ireland. PATIENTS: One hundred patients with acute nontraumatic aneurysmal SAH were recruited on presentation. INTERVENTIONS: Clinical examination and basic biochemical evaluation were performed daily. Plasma cortisol at 0900 hours, AVP, and BNP concentrations were measured on days 1, 2, 3, 4, 6, 8, 10, and 12 following SAH. Those with 0900 hours plasma cortisol<300 nmol/L were empirically treated with iv hydrocortisone. MAIN OUTCOME MEASURES: Plasma sodium concentration was recorded daily along with a variety of clinical and biochemical criteria. The cause of hyponatremia was determined clinically. Later measurement of plasma AVP and BNP concentrations enabled a firm biochemical diagnosis of the cause of hyponatremia to be made. RESULTS: Forty-nine of 100 developed hyponatremia<135 mmol/L, including 14/100<130 mmol/L. The cause of hyponatremia, and determined by both clinical examination and biochemical hormone measurement, was SIAD in 36/49 (71.4%), acute glucocorticoid insufficiency in 4/49 (8.2%), incorrect iv fluids in 5/49 (10.2%), and hypovolemia in 5/49 (10.2%). There were no cases of CSWS. CONCLUSIONS: The most common cause of hyponatremia after acute nontraumatic aneurysmal SAH is SIAD. Acute glucocorticoid insufficiency accounts for a small but significant number of cases. We found no cases of CSWS.

Acute glucocorticoid deficiency and diabetes insipidus are common after acute traumatic brain injury and predict mortality.

CONTEXT: Published data demonstrates that hypopituitarism is common after traumatic brain injury (TBI). Hormone deficiencies are transient in many, but the natural history of the acute changes after TBI has not been documented. In addition, it is not clear whether there are any early parameters that accurately predict the development of permanent hypopituitarism. OBJECTIVES: There were 3 main objectives of this study: 1) to describe the natural history of plasma cortisol (PC) changes and sodium balance after TBI; 2) to identify whether acute hypocortisolemia or cranial diabetes insipidus (CDI) predict mortality; and 3) to identify whether the acute pituitary dysfunction predicts the development of chronic anterior hypopituitarism. DESIGN: Each TBI patient underwent sequential measurement of PC, plasma sodium, urine osmolality, and fluid balance after TBI. All other anterior pituitary hormones were measured on day 10 after TBI. The results from 15 surgical comparisons defined a PC less than 300 nmol/L as inappropriately low for an acutely ill patient. CDI was diagnosed according to standard criteria. Surviving TBI patients underwent dynamic anterior pituitary testing at least 6 months after TBI. SETTING: The patients were recruited from the Irish National Neurosurgery Centre. PATIENTS: One hundred sequential TBI patients were recruited. Fifteen patients admitted to Intensive Therapy Unit (ITU) after major surgery were recruited as comparison patients. MAIN OUTCOME MEASURES: PC in TBI patients was compared with that of comparison patients. The mortality rate was compared between TBI patients with and without acute hypocortisolemia. Results of follow-up dynamic pituitary testing were compared between those with and without acute hypocortisolemia. RESULTS: Most of the TBI patients (78%) developed inappropriately low PC after TBI. Low PC and CDI were predictive of mortality. Thirty-nine percent of the patients who had follow-up testing had at least 1 pituitary hormone deficit, all of whom had had previous acute hypocortisolemia or CDI. CONCLUSIONS: Acute hypocortisolemia and CDI are predictive of mortality and long-term pituitary deficits in TBI.

Poisonings and clinical toxicology: a template for Ireland.

BACKGROUND: Poisons information is accessed around the clock in the British Isles from six centres of which two are in Ireland at Dublin and Belfast accompanied by consultant toxicologist advisory service. The numbers of calls in Ireland are down to about 40 per day due to easy access to online data bases. Access to Toxbase, the clinical toxicology database of the National Poisons Information Service is available to National Health Service (NHS) health professionals and to Emergency Departments and Intensive Care units in the Republic of Ireland. There are 59 Toxbase users in the Republic of Ireland and 99 % of activity originates in Emergency Departments. All United States Poison Control Centres primarily use Poisindex which is a commercial database from Thomson Reuters. RESULTS: Information on paracetamol, diazepam, analgesics and psycho-active compounds are the commonest queries. Data from telephone and computer accesses provide an indicator of future trends in both licit and illicit drug poisons which may direct laboratory analytical service developments. Data from National Drug-Related Deaths Index is the most accurate information on toxicological deaths in Ireland. Laboratory toxicology requirements to support emergency departments are listed. CONCLUSIONS: Recommendations are made for a web-based open access Toxbase or equivalent; for a co-location of poisons information and laboratory clinical toxicology; for the establishment of a National Clinical Toxicology Institute for Ireland; for a list of accredited medical advisors in clinical toxicology; for multidisciplinary case conferences in complex toxicology cases for coroners; for the establishment of a national clinical toxicology referral out-patients service in Ireland.