Redefining ITT cortisol thresholds on Abbott platforms to prevent misdiagnosis of adrenal insufficiency.

BACKGROUND: Adrenal insufficiency (AI) is a life-threatening condition which requires long term glucocorticoid replacement. The insulin tolerance test (ITT) is the current gold standard test for diagnosis of secondary AI, but the widely accepted cut-off value of a peak cortisol of less than 500 nmol/L assumes that anyone who does not reach this value has AI and thus requires full replacement. The cut-off used to diagnose AI is also founded on outdated assays. Use of this cut-off in an era of more specific immunoassays therefore risks misdiagnosis, subsequent unnecessary glucocorticoid exposure and associated adverse effects with increased mortality risk. DESIGN, PATIENTS AND MEASUREMENTS: This retrospective analysis assessed 300 ITT cortisol responses using the Abbott Architect and Alinity analyser platforms in patients with suspected AI over a period of 12 years (August 2010 to January 2022), at a tertiary centre. RESULTS: Patients were classified as having AI or not, based on a comprehensive clinical review of electronic patient records from the point of test to the present day by a panel of pituitary and adrenal specialists. Using the current institutional cut-off value of 500 nmol/L, receiver operating characteristic analysis identified a 100.0% sensitivity and 43.6% specificity (area under the curve 0.979). Using a lower cortisol threshold value of 416 nmol/L on the Abbott analyser platform maintained a sensitivity of 100.0% and improved the specificity to 86.7%. CONCLUSION: This data supports lowering the Abbott analyser ITT peak cortisol threshold to 416 nmol/L. Use of this improved cut-off avoids unnecessary glucocorticoid replacement therapy in 104 (34.7%) of individuals in this study. All patients remained well with at least 1 year longitudinal follow up of glucocorticoid replacement.

Fasting pancreatic polypeptide predicts incident microvascular and macrovascular complications of type 2 diabetes: An observational study.

AIMS: Pancreatic polypeptide (PP) is elevated in people with vascular risk factors such as type 2 diabetes or increased visceral fat. We investigated potential relationships between PP and microvascular and macrovascular complications of diabetes. MATERIALS AND METHODS: Animal study: Subcutaneous PP infusion for 4 weeks in high fat diet mouse model. Retinal mRNA submitted for Ingenuity Pathway Analysis. Human study: fasting PP measured in 1478 participants and vascular complications recorded over median 5.5 (IQR 4.9-5.8) years follow-up. RESULTS: Animal study: The retinal transcriptional response to PP was indicative of cellular stress and damage, and this footprint matched responses described in previously published studies of retinal disease. Of mechanistic importance the transcriptional landscape was consistent with upregulation of folliculin, a recently identified susceptibility gene for diabetic retinopathy. Human study: Adjusting for established risk factors, PP was associated with prevalent and incident clinically significant retinopathy (odds ratio (OR) 1.289 (1.107-1.501) p = 0.001; hazard ratio (HR) 1.259 (1.035-1.531) p = 0.0213), albuminuria (OR 1.277 (1.124-1.454), p = 0.0002; HR 1.608 (1.208-2.141) p = 0.0011), and macrovascular disease (OR 1.021 (1.006-1.037) p = 0.0068; HR 1.324 (1.089-1.61), p = 0.0049), in individuals with type 2 diabetes, and progression to diabetes in non-diabetic individuals (HR 1.402 (1.081-1.818), p = 0.0109). CONCLUSIONS: Elevated fasting PP is independently associated with vascular complications of diabetes and affects retinal pathways potentially influencing retinal neuronal survival. Our results suggest possible new roles for PP-fold peptides in the pathophysiology of diabetes complications and vascular risk stratification.

Pituitary hypophysitis in granulomatosis with polyangiitis (GPA): a case series.

Granulomatosis with polyangiitis (GPA) rarely involves the pituitary gland. Pituitary involvement has been reported in ~ 1% of all cases of GPA. Most commonly, pituitary swelling and inflammation results in symptoms due to pituitary mass effect and arginine vasopressin deficiency. To date, there are no pituitary-specific treatment guidelines for this rare condition. We present three patients with GPA-related hypophysitis highlighting the spectrum of pituitary involvement. All three patients were successfully treated with immunosuppressive regimens that included rituximab (RTX). Following remission induction with high-dose glucocorticoids, patients received 6 monthly RTX for remission maintenance. RTX was well tolerated without significant side effects.

Clinical characteristics of functioning gonadotroph adenoma in women presenting with ovarian hyperstimulation: Audit of UK pituitary centres.

OBJECTIVE: Functioning gonadotroph adenomas (FGAs) are rare pituitary tumours stimulating ovarian function with potential life-threatening consequences in women. However, a lack of aggregated clinical experience of FGAs impairs management in affected women. The aim of this study is to present the clinical course of FGA-induced ovarian hyperstimulation syndrome (OHSS) cases as identified by some of the largest UK pituitary endocrine tertiary centres with a view to increasing awareness and improving diagnosis and management of women with FGA. DESIGN: A retrospective observational study; audit of eight UK regional pituitary centres for cases of FGAs. SETTING: Specialist neuroendocrine centres in the United Kingdom. PATIENTS AND MEASUREMENTS: Women diagnosed with FGA-induced OHSS. Description of their clinical course. RESULTS: Seven cases of FGA were identified in women, all causing OHSS. Mean age was 33.4 years at diagnosis. Abdominal pain, irregular periods, headache, and visual disturbances were reported at presentation by 100%, 71%, 57% and 43% of women, respectively. Three of seven women underwent ovarian surgery before FGA diagnosis. Six women underwent transsphenoidal surgery (TSS) with incomplete tumour resection in five of those, but all showed improvement or resolution in symptoms and biochemistry postoperatively. CONCLUSION: FGA is a rare cause of spontaneous OHSS. TSS improves clinical and biochemical features of ovarian hyperstimulation in FGAs. Improved awareness of FGA will prevent inappropriate emergency ovarian surgery.

The Impact of Obesity on the Resolution of Hypertension Following Adrenalectomy for Primary Hyperaldosteronism.

BACKGROUND: This study aims to determine the impact of patient obesity on the resolution of hypertension and pill burden post-adrenalectomy for PA. Primary hyperaldosteronism (PA) is the most common cause of secondary hypertension that may be remedied with surgery (unilateral adrenalectomy). Obesity may independently cause hypertension through several mechanisms including activation of the renin-angiotensin-aldosterone pathway. The influence of obesity on the efficacy of adrenalectomy in PA has not been established. METHODS: This is a retrospective analysis of prospectively collected data on patients undergoing adrenalectomy for PA at a single, tertiary-care surgical centre from January 2015 to December 2020. Electronic health records of patients were screened to collect relevant data. The primary outcomes of the study include post-operative blood pressure, the reduction in the number of anti-hypertensive medications and potassium supplementation burden post-adrenalectomy. RESULTS: Fifty-three patients were included in the final analysis. There was a significant reduction in the blood pressure and the number of anti-hypertensive medications in all patients after adrenalectomy (p < 0.001). Of the 34 patients (64.2%) with pre-operative hypokalaemia, all became normokalaemic and were able to stop supplementation. However obese patients required more anti-hypertensive medications to achieve an acceptable blood pressure than overweight or normal BMI patients (p < 0.01). Multivariate logistic regression analysis showed that male gender and BMI were independent predictors of resolution of hypertension (p <0.01). CONCLUSION: Unilateral adrenalectomy improves the management of hypertension and hypokalaemia when present in patients with PA. However, obesity has an independent deleterious impact on improvement in blood pressure post-adrenalectomy for PA.

The impact of patient skin colour on diagnostic ability and confidence of medical students.

Previous literature has explored unconscious racial biases in clinical education and medicine, finding that people with darker skin tones can be underrepresented in learning resources and managed differently in a clinical setting. This study aimed to examine whether patient skin colour can affect the diagnostic ability and confidence of medical students, and their cognitive reasoning processes. We presented students with 12 different clinical presentations on both white skin (WS) and non-white skin (NWS). A think aloud (TA) study was conducted to explore students' cognitive reasoning processes (n = 8). An online quiz was also conducted where students submitted a diagnosis and confidence level for each clinical presentation (n = 185). In the TA interviews, students used similar levels of information gathering and analytical reasoning for each skin type but appeared to display increased uncertainty and reduced non-analytical reasoning methods for the NWS images compared to the WS images. In the online quiz, students were significantly more likely to accurately diagnose five of the 12 clinical presentations (shingles, cellulitis, Lyme disease, eczema and meningococcal disease) on WS compared to NWS (p < 0.01). With regards to students' confidence, they were significantly more confident diagnosing eight of the 12 clinical presentations (shingles, cellulitis, Lyme disease, eczema, meningococcal disease, urticaria, chickenpox and Kawasaki disease) on WS when compared to NWS (p < 0.01). These findings highlight the need to improve teaching resources to include a greater diversity of skin colours exhibiting clinical signs, to improve students' knowledge and confidence, and ultimately, to avoid patients being misdiagnosed due to the colour of their skin.

Understanding concepts of generalism and specialism amongst medical students at a research-intensive London medical school.

BACKGROUND: Many prominent UK medical organisations have identified a need for more generalist clinicians to address the complex requirements of an aging society. We sought to clarify attitudes towards "Specialists" and "Generalists" amongst medical students and junior doctors at Imperial College School of Medicine. METHODS: A survey exploring medical students' beliefs was followed up by qualitative analysis of focus groups of medical students and Imperial-graduate foundation year doctors. RESULTS: First year medical students associated specialists with academia and higher income, and generalists with ease of training and job availability. Senior (Years 5/6) medical students associated specialists even more firmly with broader influence and academic work, whilst generalists were assigned lower prestige but the same workload as specialists. The medical student focus group discussed concepts of Generalism pertaining only to Primary Care. In contrast, the foundation year doctor focus group revealed that Generalism was now seen to include some hospital care, and the perception that generalists sat lower in a knowledge hierarchy had been challenged. CONCLUSION: Perceptions that Generalism is associated with lower prestige in the medical profession are already present at the very start of medical school and seem to be reinforced during undergraduate training. In early postgraduate clinical practice, the perceived knowledge and prestige hierarchy lessens. These findings can help inform curriculum redesign and the promotion of Generalism as a rewarding career aspiration.

Imperial Satiety Protocol: A new non-surgical weight-loss programme, delivered in a health care setting, produces improved clinical outcomes for people with obesity.

'Imperial Satiety Protocol' (I-SatPro) is a new multifaceted approach to weight loss for people with obesity (PwO), encompassing dietary advice, time-restricted eating, physical activity and coaching to support behaviour change. Participants (n = 84) attended fortnightly I-SatPro group sessions for 30 weeks, with 70% of participants completing. On completion at 30 weeks, the mean weight loss was 15.2 ± 1.1 kg (13.2 ± 0.8% from baseline, P < .0001), which was maintained to 52 weeks (16.6 ± 1.5 kg, 14.1 ± 1.2%, P < .0001). Weight loss was not associated with reduced energy expenditure. In participants with type 2 diabetes and pre-diabetes (n = 16), glycated haemoglobin fell from 50 to 43 mmol/mol (P < .01). Systolic blood pressure fell by 12 mmHg (P < .0001). Triglycerides fell by 0.37 mmol/L (P < .01) and high-density lipoprotein rose by 0.08 mmol/L (P < .01). Short Form-36 (SF-36) functioning and wellbeing scores increased in all domains post I-SatPro intervention. For selected PwO, I-SatPro delivers clinically meaningful weight loss, and the potential for long-term health and wellbeing improvements.

Fasting with adrenal insufficiency: Practical guidance for healthcare professionals managing patients on steroids during Ramadan.

There are limited recommendations for fasting in many chronic diseases such as adrenal insufficiency (AI). Research in such situations highlights potential for complications and need for education for patients with AI undertaking fasting during Ramadan. This article aimed to provide up-to-date guidance for healthcare professionals to educate, discuss and manage patients with AI who are considering fasting in Ramadan and is religiously compatible. Latest guidance on this topic and the evidence base for steroid dosing are reviewed and discussed. Risk stratification for patients with AI and optimal strategies for management, including steroid dosing, are detailed. Our review highlights that patients with AI wishing to fast should undergo a thorough risk assessment ideally several months before Ramadan. 'High risk' and 'Very high risk' patients should be encouraged to explore alternative options to fasting discussed below. Prior to the commencement of Ramadan, all patients must receive up-to-date education on sick day rules, instructions on when to terminate their fast or abstain from fasting, carry steroid warning information and must have a valid intramuscular (IM) hydrocortisone pack and know how to administer this. Switching patients with AI desiring to fast from multiple daily hydrocortisone replacement to prednisolone 5 mg once daily at dawn (during Suhoor or Sehri) is recommended and discussed. Patients on fludrocortisone for AI should be advised to take their total dose at dawn. We provide practically relevant case-based scenarios to help with the application of this guidance. Future efforts need to focus on healthcare professional awareness and further research in this setting.

Clinical prioritisation questions: A novel assessment tool to encourage tolerance of uncertainty?

Uncertainty is a common and increasingly acknowledged problem in clinical practice. Current single best answer (SBA) style assessments test areas where there is one correct answer, and as the approach to assessment impacts on the approach to learning, these exams may poorly prepare our future doctors to handle uncertainty. We therefore, need to modify our approach to assessment to emphasize reasoning and introduce the possibility of more than one 'correct' answer. We have developed clinical prioritization questions (CPQs), a novel formative assessment tool in which students prioritize possible responses in order of likelihood. This assessment format was piloted with a group of medical students and evaluated in comparison with the more traditional SBA question format in a team-based learning setting. Students reported that they felt ongoing use would help improve their tolerance of uncertainty (p < 0.01). Furthermore, over 80% of students felt that CPQs were more reflective of real-life clinical practice. Group based discussions were significantly longer when answering CPQs (p < 0.01), suggesting they may promote richer discourse. CPQs may have a role in formative assessment to help equip students with the skills to cope with ambiguity and strengthen clinical reasoning and decision-making. Institutions may find them more practical to implement compared with other clinical reasoning assessment tools.

Improving glucocorticoid replacement profiles in adrenal insufficiency.

There is an increased mortality associated with adrenal insufficiency despite glucocorticoid replacement therapy with a standardized mortality ratio greater than two. The cause of the increased mortality is yet to be definitively elucidated, but may be due to excess steroid exposure, or replacement regimens that are uncoupled from the normal physiological cortisol profile. Cortisol secretion follows an ultradian pattern which is not possible to reproduce using oral replacement. With the advent of new pumps, it is now possible to mimic the pulsatility of the adrenal glands. While the cognitive and emotional benefits of reproducing the ultradian rhythm are known, the presence of long-term benefits is not yet clear. There is a dearth of evidence and high-quality studies to underline our current understanding of the pathophysiology of adrenal insufficiency and replacement therapy. There is a particular lack of research comparing objective outcomes between patients receiving hydrocortisone replacement (either standard therapy or new sustained release preparations), prednisolone replacement and ultradian pumps. Direct comparative studies are now warranted to understand the optimal approach.

Interpretation of Serum Gonadotropin Levels in Hyperprolactinaemia.

BACKGROUND/AIMS: Hyperprolactinaemia is a common cause of amenorrhoea due to hypogonadotropic hypogonadism. Prolactin is hypothesised to impede the reproductive axis through an inhibitory action at the hypothalamus. However, limited data exist to aid the interpretation of serum gonadotropins in the context of hyperprolactinaemia. METHODS: Serum gonadotropin values were reviewed in 243 patients with elevated serum monomeric prolactin due to discrete aetiologies at a tertiary reproductive endocrine centre between 2012 and 2015. The cause of hyperprolactinaemia was categorised by an experienced endocrinologist/pituitary multidisciplinary team, unless superseded by histology. The most frequently encountered diagnoses were microprolactinoma (n = 88), macroprolactinoma (n = 46), non-functioning pituitary adenoma (NFPA) (n = 72), drug-induced hyperprolactinaemia (n = 22) and polycystic ovarian syndrome (PCOS) (n = 15). RESULTS: In patients with prolactinoma and modestly raised serum prolactin levels (< 4,000 mU/L), increasingly FSH-predominant gonadotropin values were observed with rising prolactin level, consistent with a progressive reduction in hypothalamic gonadotropin-releasing hormone (GnRH) pulsatility. Patients with prolactinoma and higher prolactin values (> 4,000 mU/L) were more likely to have a reduction in serum levels of both FSH and LH, consistent with direct pituitary gonadotrope dysfunction. Patients with macroadenoma and extremes of serum gonadotropin values (either serum FSH or LH > 8 IU/L) were more likely to have NFPA than prolactinoma. Patients with PCOS and hyperprolactinaemia had LH-predominant secretion in keeping with increased GnRH pulsatility despite a raised prolactin level. CONCLUSION: The pattern of gonadotropin secretion in patients with hyperprolactinaemia reflects the underlying aetiology.

Very-short-answer questions: reliability, discrimination and acceptability.

CONTEXT: Single-best-answer questions (SBAQs) have been widely used to test knowledge because they are easy to mark and demonstrate high reliability. However, SBAQs have been criticised for being subject to cueing. OBJECTIVES: We used a novel assessment tool that facilitates efficient marking of open-ended very-short-answer questions (VSAQs). We compared VSAQs with SBAQs with regard to reliability, discrimination and student performance, and evaluated the acceptability of VSAQs. METHODS: Medical students were randomised to sit a 60-question assessment administered in either VSAQ and then SBAQ format (Group 1, n = 155) or the reverse (Group 2, n = 144). The VSAQs were delivered on a tablet; responses were computer-marked and subsequently reviewed by two examiners. The standard error of measurement (SEM) across the ability spectrum was estimated using item response theory. RESULTS: The review of machine-marked questions took an average of 1 minute, 36 seconds per question for all students. The VSAQs had high reliability (alpha: 0.91), a significantly lower SEM than the SBAQs (p < 0.001) and higher mean item-total point biserial correlations (p < 0.001). The VSAQ scores were significantly lower than the SBAQ scores (p < 0.001). The difference in scores between VSAQs and SBAQs was attenuated in Group 2. Although 80.4% of students found the VSAQs more difficult, 69.2% found them more authentic. CONCLUSIONS: The VSAQ format demonstrated high reliability and discrimination and items were perceived as more authentic. The SBAQ format was associated with significant cueing. The present results suggest the VSAQ format has a higher degree of validity.

Association Between Use of Sodium-Glucose Cotransporter 2 Inhibitors, Glucagon-like Peptide 1 Agonists, and Dipeptidyl Peptidase 4 Inhibitors With All-Cause Mortality in Patients With Type 2 Diabetes: A Systematic Review and Meta-analysis.

Importance: The comparative clinical efficacy of sodium-glucose cotransporter 2 (SGLT-2) inhibitors, glucagon-like peptide 1 (GLP-1) agonists, and dipeptidyl peptidase 4 (DPP-4) inhibitors for treatment of type 2 diabetes is unknown. Objective: To compare the efficacies of SGLT-2 inhibitors, GLP-1 agonists, and DPP-4 inhibitors on mortality and cardiovascular end points using network meta-analysis. Data Sources: MEDLINE, Embase, Cochrane Library Central Register of Controlled Trials, and published meta-analyses from inception through October 11, 2017. Study Selection: Randomized clinical trials enrolling participants with type 2 diabetes and a follow-up of at least 12 weeks were included, for which SGLT-2 inhibitors, GLP-1 agonists, and DPP-4 inhibitors were compared with either each other or placebo or no treatment. Data Extraction and Synthesis: Data were screened by 1 investigator and extracted in duplicate by 2 investigators. A Bayesian hierarchical network meta-analysis was performed. Main Outcomes and Measures: The primary outcome: all-cause mortality; secondary outcomes: cardiovascular (CV) mortality, heart failure (HF) events, myocardial infarction (MI), unstable angina, and stroke; safety end points: adverse events and hypoglycemia. Results: This network meta-analysis of 236 trials randomizing 176 310 participants found SGLT-2 inhibitors (absolute risk difference [RD], -1.0%; hazard ratio [HR], 0.80 [95% credible interval {CrI}, 0.71 to 0.89]) and GLP-1 agonists (absolute RD, -0.6%; HR, 0.88 [95% CrI, 0.81 to 0.94]) were associated with significantly lower all-cause mortality than the control groups. SGLT-2 inhibitors (absolute RD, -0.9%; HR, 0.78 [95% CrI, 0.68 to 0.90]) and GLP-1 agonists (absolute RD, -0.5%; HR, 0.86 [95% CrI, 0.77 to 0.96]) were associated with lower mortality than were DPP-4 inhibitors. DPP-4 inhibitors were not significantly associated with lower all-cause mortality (absolute RD, 0.1%; HR, 1.02 [95% CrI, 0.94 to 1.11]) than were the control groups. SGLT-2 inhibitors (absolute RD, -0.8%; HR, 0.79 [95% CrI, 0.69 to 0.91]) and GLP-1 agonists (absolute RD, -0.5%; HR, 0.85 [95% CrI, 0.77 to 0.94]) were significantly associated with lower CV mortality than were the control groups. SGLT-2 inhibitors were significantly associated with lower rates of HF events (absolute RD, -1.1%; HR, 0.62 [95% CrI, 0.54 to 0.72]) and MI (absolute RD, -0.6%; HR, 0.86 [95% CrI, 0.77 to 0.97]) than were the control groups. GLP-1 agonists were associated with a higher risk of adverse events leading to trial withdrawal than were SGLT-2 inhibitors (absolute RD, 5.8%; HR, 1.80 [95% CrI, 1.44 to 2.25]) and DPP-4 inhibitors (absolute RD, 3.1%; HR, 1.93 [95% CrI, 1.59 to 2.35]). Conclusions and Relevance: In this network meta-analysis, the use of SGLT-2 inhibitors or GLP-1 agonists was associated with lower mortality than DPP-4 inhibitors or placebo or no treatment. Use of DPP-4 inhibitors was not associated with lower mortality than placebo or no treatment.

Redefining the stress cortisol response to surgery.

BACKGROUND: Cortisol levels rise with the physiological stress of surgery. Previous studies have used older, less-specific assays, have not differentiated by severity or only studied procedures of a defined type. The aim of this study was to examine this phenomenon in surgeries of varying severity using a widely used cortisol immunoassay. METHODS: Euadrenal patients undergoing elective surgery were enrolled prospectively. Serum samples were taken at 8 am on surgical day, induction and 1 hour, 2 hour, 4 hour and 8 hour after. Subsequent samples were taken daily at 8 am until postoperative day 5 or hospital discharge. Total cortisol was measured using an Abbott Architect immunoassay, and cortisol-binding globulin (CBG) using a radioimmunoassay. Surgical severity was classified by POSSUM operative severity score. RESULTS: Ninety-three patients underwent surgery: Major/Major+ (n = 37), Moderate (n = 33) and Minor (n = 23). Peak cortisol positively correlated to severity: Major/Major+ median 680 [range 375-1452], Moderate 581 [270-1009] and Minor 574 [272-1066] nmol/L (Kruskal-Wallis test, P = .0031). CBG fell by 23%; the magnitude of the drop positively correlated to severity. CONCLUSIONS: The range in baseline and peak cortisol response to surgery is wide, and peak cortisol levels are lower than previously appreciated. Improvements in surgery, anaesthetic techniques and cortisol assays might explain our observed lower peak cortisols. The criteria for the dynamic testing of cortisol response may need to be reduced to take account of these factors. Our data also support a lower-dose, stratified approach to dosing of steroid replacement in hypoadrenal patients, to minimize the deleterious effects of over-replacement.

Validity of very short answer versus single best answer questions for undergraduate assessment.

BACKGROUND: Single Best Answer (SBA) questions are widely used in undergraduate and postgraduate medical examinations. Selection of the correct answer in SBA questions may be subject to cueing and therefore might not test the student's knowledge. In contrast to this artificial construct, doctors are ultimately required to perform in a real-life setting that does not offer a list of choices. This professional competence can be tested using Short Answer Questions (SAQs), where the student writes the correct answer without prompting from the question. However, SAQs cannot easily be machine marked and are therefore not feasible as an instrument for testing a representative sample of the curriculum for a large number of candidates. We hypothesised that a novel assessment instrument consisting of very short answer (VSA) questions is a superior test of knowledge than assessment by SBA. METHODS: We conducted a prospective pilot study on one cohort of 266 medical students sitting a formative examination. All students were assessed by both a novel assessment instrument consisting of VSAs and by SBA questions. Both instruments tested the same knowledge base. Using the filter function of Microsoft Excel, the range of answers provided for each VSA question was reviewed and correct answers accepted in less than two minutes. Examination results were compared between the two methods of assessment. RESULTS: Students scored more highly in all fifteen SBA questions than in the VSA question format, despite both examinations requiring the same knowledge base. CONCLUSIONS: Valid assessment of undergraduate and postgraduate knowledge can be improved by the use of VSA questions. Such an approach will test nascent physician ability rather than ability to pass exams.

Associations of coefficient of variation of serum GH with previous radiotherapy, hypopituitarism and cardiac disease in patients with treated acromegaly.

BACKGROUND: Cardiovascular complications represent the biggest cause of mortality in acromegaly. It is therefore important to optimally stratify acromegalic patients according to disease activity and complication risk. GH is secreted in a pulsatile manner from the pituitary gland, but GH pulsatility is not routinely assessed clinically. The coefficient of variation of serum GH (GHCV) during oral glucose tolerance test (OGTT) quantifies the variation of GH secretion in patients with acromegaly, but has not been reported previously. AIM: To investigate whether GHCV during OGTT is associated with clinical parameters predicted to relate with hypothalamo-pituitary dysfunction during acromegaly, such as radiotherapy treatment, pituitary deficiency and cardiac disease. METHODS: GHCV was calculated during 584 OGTTs and compared with nadir serum GH and IGF-1 in 111 acromegalic patients treated at a single centre. RESULTS: Acromegalic patients treated with radiotherapy had a 37% lower level of GHCV when compared to the nonradiotherapy group (mean GHCV: 0·298 ± 0·015, no radiotherapy; 0·189 ± 0·007, radiotherapy; P < 0·001). Neither serum IGF-1 nor nadir GH was significantly altered in the radiotherapy group. Mean GHCV was 50% lower in the acromegalic patients with cardiac failure when compared to acromegalic patients with normal echocardiogram (0·161 ± 0·034 vs 0·297 ± 0·055; P < 0·05). Neither serum IGF-1 nor nadir GH was significantly altered during cardiac failure. CONCLUSION: Our preliminary data suggest that GHCV during OGTT may be reduced during acromegaly in patients with previous radiotherapy, pituitary deficiencies and cardiac disease. Larger studies are required to determine whether GHCV could provide help to assess the morbidity status of patients with treated acromegaly.