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.

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.

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.

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.

B-type natriuretic peptide in the cardiology department.

Heart Failure is one of the fastest growing cardiovascular diseases of the 21st century. Echocardiogram is considered the gold standard for diagnosis, but is costly, time consuming and not readily accessible to all patients. Our aim was to assess the diagnostic utility of BNP to risk stratify patients for ECHO. Seventy-four GP referred, non-pregnant patients of > or = 18 years with a working diagnosis of HF were recruited. Patients were given two appointments to attend the Cardiology Department and at each, were examined by the same cardiologist, had their medications recorded and blood drawn for BNP analysis. ECHO was performed at the second visit. The diagnosis of HF was confirmed in 49 of 74 patients (66%). The clinical utility of BNP to rule-in HF was evaluated using ROC curve analysis. The AUC was satisfactory at 0.691 (C.I. 0.573-0.793). The positive likelihood ratio (+LR) was 5.87, negative likelihood ratio (-LR) was 0.58, the positive predictive value was 92% and a negative predictive value was 47%. One-third of patients (n = 25) had a BNP >178 pg/mL, 23 of whom had HF confirmed. At this decision threshold BNP correctly classified 23 of 25 patients who were confirmed not to have HF (Specificity for HF of 92%). A BNP of > or = 178 pg/mL can be used to prioritise GP patients for ECHO.

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.

Incidence and pathophysiology of severe hyponatraemia in neurosurgical patients.

BACKGROUND: Hyponatraemia is a well-recognised complication of neurosurgical conditions, but the incidence and implications have not been well documented. OBJECTIVE: To define the incidence, pathophysiology and clinical implications of significant hyponatraemia in several neurosurgical conditions. METHODS: All patients admitted to the Irish National Neurosciences Centre at Beaumont Hospital, Dublin with traumatic brain injury, subarachnoid haemorrhage, intracranial neoplasm, pituitary disorders and spinal disorders who developed significant hyponatraemia (plasma sodium <130 mmol/l) from January 2002 to September 2003 were identified from computerised laboratory records. Data were collected by retrospective case note analysis. RESULTS: Hyponatraemia was more common in patients with pituitary disorders (5/81, 6.25%; p = 0.004), traumatic brain injury (44/457, 9.6%; p<0.001), intracranial neoplasm (56/355, 15.8%; p<0.001) and subarachnoid haemorrhage (62/316, 19.6%; p<0.001) than in those with spinal disorders (4/489, 0.81%). The pathophysiology of hyponatraemia was: syndrome of inappropriate antidiuretic hormone secretion (SIADH) in 116 cases (62%) (31 (16.6%) drug-associated), hypovolaemic hyponatraemia in 50 cases (26.7%) (which included patients with insufficient data to assign to the cerebral salt-wasting group (CSWS)), CSWS in nine cases (4.8%), intravenous fluids in seven cases (3.7%) and mixed SIADH/CSWS in five cases (2.7%). Hyponatraemic patients with cerebral irritation had significantly lower plasma sodium concentrations (mean (SD) 124.8 (0.34) mmol/l) than asymptomatic patients (126.6 (0.29) mmol/l) (p<0.0001). Hyponatraemic patients had a significantly longer hospital stay (median 19 days (interquartile range (IQR) 12-28)) than normonatraemic patients (median 12 days (IQR 10.5-15)) (p<0.001). CONCLUSIONS: Hyponatraemia is common in intracerebral disorders and is associated with a longer hospital stay. Cerebral irritation is associated with more severe hyponatraemia. SIADH is the most common cause of hyponatraemia and is often drug-associated.

An apparent phaeochromocytoma and abnormal thyroid function tests.

A 41-year-old lady presented with classical symptoms of a phaeochromocytoma and markedly elevated urinary adrenaline concentration. Urinary fractionated metanephrine and normetanephrine concentrations were within the normal reference range. Computed tomography of the abdomen/pelvis and I(123) meta-iodobenzylguanidine scans were negative. Factitious adrenaline use was established as the diagnosis.

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.

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.

Hypophosphatemia complicating bronchodilator therapy for acute severe asthma.

Hypophosphatemia has been recently highlighted as a reversible cause of respiratory muscle hypocontractility and reduced tissue oxygen extraction in patients with chronic obstructive lung disease and asthma. To define the prevalence and mechanism of hypophosphatemia under these circumstances, we studied phosphate homeostasis in 22 patients with chronic asthma, who had been hospitalized for emergency bronchodilator therapy. Serum phosphate concentration was normal in all patients on presentation, and fell after the initiation of bronchodilator therapy. Twelve patients (54%) developed hypophosphatemia (serum phosphate, less than 0.8 mmol/L). Urinary phosphate level fell in parallel. A negative correlation was observed between serum phosphate and serum theophylline concentrations, and a positive correlation between serum and urinary phosphate concentrations. No correlation was found between serum phosphate and serum albumin or urea concentration. These data indicate that hypophosphatemia is a common metabolic abnormality during the emergency treatment of asthma. The underlying mechanism appears to be drug-induced phosphate flux from the extra-cellular to the intracellular space. We suggest that the serum phosphate level be monitored in patients undergoing emergency treatment of bronchospasm, particularly if a prolonged period of bronchodilator therapy is required or if respiratory muscle fatigue supervenes.

Elevated plasma concentrations of atrial and brain natriuretic peptide in type 1 diabetic subjects.

BACKGROUND: The intravenous infusion of atrial (ANP) and brain (BNP) natriuretic peptides have been shown to increase urinary albumin excretion in type 1 diabetes. AIMS: To measure plasma ANP and BNP concentrations in patients with type 1 diabetes and to examine the parameters associated with elevated plasma concentrations. Methods We measured plasma ANP and BNP concentrations, UAER, HbA1C systolic blood pressure, and left ventricular mass index. Plasma ANP and BNP were also measured in non-diabetic control subjects for comparison. RESULTS: Using multivariate regression analysis plasma ANP correlated positively with HbA1C (1.9 + 0.47, p = 0.0002), UAER (0.37 + 0.05, p = 0.00001), SBP (1.26 + 0.5, p = 0.01) and LVMI (00.46 + 0.25, p = 0.07). BNP was positively related with LVMI (0.95 + 0.4, p = 0.02), and UAER (0.56 + 0.08, p = 0.001). CONCLUSIONS: Plasma concentrations of ANP and BNP are elevated in some patients with type 1 diabetes. Plasma ANP concentrations are closely related to UAER and elevated plasma concentrations are associated with poor glycaemic control and systemic hypertension. Plasma BNP concentration is related to LVMI.

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.