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Background: Adrenal vein sampling (AVS) is crucial for differentiating between unilateral and bilateral causes of primary aldosteronism (PA) [1]. However, there is a lack of uniform agreement regarding use of adrenocorticotropic hormone (ACTH) stimulation during AVS [2]. At Monash Health, AVS has been performed both pre- and post-ACTH stimulation since 2010. Aim(s): We reviewed the impact of ACTH stimulation on AVS success rates and outcomes including selectivity index (SI = cortisoladrenal vein: cortisolperipheral vein), lateralization index (LI = aldosterone-cortisol ratiodominant adrenal vein: aldosterone-cortisol rationon-dominant adrenal vein) and contralateral suppression index (CSI = aldosterone-cortisol rationon-dominant adrenal vein: aldosterone-cortisol ratioperipheral vein). Method(s): An audit was conducted on AVS procedures performed at Monash Health between January 2010 and March 2015 inclusive. Clinical information was collected on screening aldosterone and renin concentration, AVS aldosterone and cortisol levels pre- and post-ACTH stimulation, adrenal imaging, blood pressure and antihypertensive medication. Successful cannulation was defined as SI >2 pre-ACTH and >3 post- ACTH; successful lateralisation was defined as LI >3 pre-ACTH and >4 post-ACTH, and supported by CSI <1. Result(s): Out of 28 AVS cases with pre-and post-ACTH data, cannulation success of the left adrenal vein was 81% (22/27) pre-ACTH and 96% (26/27) post-ACTH; and of the right adrenal vein was 60% (17/28) both pre-and post-ACTH. The improved cannulation rate was not associated with the timing of AVS. However, ACTH stimulation significantly lowered the LI and incorrectly obscured lateralization in five cases. These patients were diagnosed with unilateral aldosterone excess based on their pre-ACTH LI and CSI. ACTH did not significantly affect the CSI. Four of these patients have had successful surgery with one awaiting surgery. Conclusion(s): The rate of successful cannulation in AVS

Objective: Retrospective study of FT4 & FT3 distribution in children on thyroxine therapy to guide optimal monitoring for all children on thyroxine, including those with central hypothyroidism. Method(s): FT4 & FT3 results (Beckman Coulter DxI 800) over a 9- year period from patients aged 30 days to 19 years with TSH in the normal range (0.4-4.0 mU/l) were extracted from the Monash Pathology database. Patients with primary hypothyroidism were identified by treating physicians or medical records (thyroxinetreated group). Patients with a single record of thyroid function testing, not known to have thyroid disease or thyroxine therapy were analysed separately (control group). The FT4 & FT3 ranges (median, 2.5th-97.5th) were calculated. Results of thyroxine-treated group were compared to the manufacturer's reference intervals (RI) (FT4: 7.9-14.4 pmol/l; FT3: 3.8-6.0 pmol/l) & the control group. Result(s): In the control group, FT4 (n = 3128) was 11.1 pmol/l (7.9- 16.4) & FT3 (n = 660) was 5.6 pmol/l (3.7-7.3). In the thyroxinetreated group (congenital hypothyroidism (n = 89) & autoimmune hypothyroidism (n = 33)), FT4 (n = 747) was 14.5 pmol/l (9.2-22.6) & FT3 (n = 146) was 5.6 pmol/l (4.3-7.6) respectively. Conclusion(s): In thyroxine-treated hypothyroidism with normal TSH, FT4 upper limit was 38% higher than the control group & 57% higher than the RI. The corresponding FT3 limit was no different compared to the control group but were 27% higher than the RI. This study suggests target FT4 in children on thyroxine should be set well above the Beckman's RI & our in-house control interval. In addition, FT3 intervals for both thyroxine-treated & untreated should be higher than the RI. Further studies are required to establish similar ranges for other methods. These results reflect the understanding that higher FT4 level is required when FT3 is entirely dependent on peripheral conversion of administered T4.

Background: Adrenal vein sampling (AVS) is useful for distinguishing unilateral versus bilateral hypersecretion in primary aldosteronism (PA), but is technically challenging. Furthermore, the use of adrenocorticotropic hormone (ACTH)-stimulation in AVS is controversial. We implemented a Monash Health-specific AVS protocol in 2010. Aim(s): The audit aimed to: (i) examine the impact of a dedicated protocol on success rates of AVS at a tertiary referral centre; (ii) evaluate the impact of AVS on sub-typing of PA; and (iii) assess the utility of ACTH stimulation in AVS. Method(s): AVS was performed on patients with PA confirmed by positive saline suppression testing (aldosterone level >140pmol/L post-saline infusion), with sequential sampling of adrenal and peripheral veins, pre- and post-ACTH infusion. Patients with unilateral aldosterone-producing adenoma diagnosed on successful AVS were referred for adrenalectomy. Result(s): Between 2010 and 2014 inclusive, a total of 28 AVS procedures was performed, with complete pre- and post-ACTH data for 19 procedures. Bilateral successful cannulation rates improved post-implementation of our protocol (61% vs 41%). Of the patients, 32% had discordant imaging and AVS results: four patients with unilateral adenomas did not lateralise on AVS and were managed medically; four patients with bilateral or no adenomas on imaging, lateralised on AVS and had surgery. Overall, use of ACTH did not increase successful cannulation and tended to mask lateralisation. Conclusion(s): AVS is crucial in subtype classification of PA and should be performed by a dedicated radiologist with a standardised protocol. AVS outcomes were not improved with the use of ACTH stimulation.Copyright © 2015 Royal Australasian College of Physicians.

Background: Multiple myeloma prognostication is largely defined by the International Staging System (ISS)1 using serum beta-2 microglobulin (beta2M) and albumin results. Local external quality assurance data showed substantial, method-dependant variations in beta2M results. Aim(s): We determined the variability of different beta2M methods using patient samples, and whether this influences ISS prognostic scores. Method(s): beta2M stability after freeze-thawing was established first. Specimens (n=21) were then sent frozen to four laboratories using different methods/instruments for beta2M: Lab1, nephelometric (Beckman Coulter Immage); Lab2, chemiluminescent (Immulite 2000); Lab3, turbidimetric (Roche Cobas c502) and Lab 4 turbidimetric (Abbott Architect c16200). All laboratories use the same albumin method (bromocresol purple). Result(s): Lab1 produced beta2M results consistently higher than other laboratories (Figure 1): mean difference +1.55 mg/L (28.5%) (95%CI: 1.02 - 2.09, p<0.0001) compared to Lab2; +1.09 mg/L (20.1%) (95% CI: 0.78 - 1.41, p<0.0001) to Lab3; and +0.51 mg/L (9.3%) (95% CI: 0.29 - 0.73, p<0.0001) to Lab4. Compared to Lab1, ISS scores were classified one stage lower in 7, 5 and 3 patients by Lab2, Lab3 and Lab4, respectively. One patient could have been classified either stage I, II or III depending on which laboratory performed the tests. Albumin methods aligned well and had minimal impact on ISS score. Summary and Conclusion(s): Results from different beta2M methods are highly variable and harmonisation is required. This study has important implications on the validity of ISS staging for myeloma.

BACKGROUND: For over 50 years, the gold standard to assess abnormal glucocorticoid production has been the insulin tolerance test. However, for reasons of risk, patient convenience and overall practicality the short Synacthen test (SST) is now the almost universal first line procedure to rapidly assess adrenal function. Some centres measure cortisol at baseline and 30 minutes while several recent studies have argued the necessity and sufficiency of the 60-minute cortisol and that the 60-minute is equally effective as combined 30-and 60-minute sampling to identify adrenal insufficiency. METHOD(S): We have reviewed over 1100 SSTs over past 15 years. Over this period we have changed our protocol from sampling at 0, 30 and 60 minutes to 0 and 60 minutes. Cortisol was measured by Beckman Access. There is no universal consensus for either protocol but we will present justification for the latter protocol based on our data and other recent publications. RESULT(S): * Cortisol response at 60 minutes invariably exceeded the 30 min response. * Even in this well controlled study phlebotomy can be delayed due to venous access difficulty by up to 5 minutes. As cortisol level is rising much less rapidly at 60 minutes compared to 30 minutes it follows that any given delay in phlebotomy will have less impact at 60 minutes than at 30 minutes. * If a normal cortisol peak level is taken as 550 nmol/L then a 30 min sample only, will misclassify 38% of people who show a normal response at 60 minutes. * Deleting the 30 minute sample will also significantly reduce cost and patient stress. * The 60 minute cortisol response in women is approximately 6% greater than in men. CONCLUSION(S): * We recommend, in harmony with other recent reports, that Synacthen testing be harmonised to a baseline ACTH and cortisol plus a single cortisol measurement 60 minutes after Synacthen injection. Further harmonisation of Synacthen testing requires * Harmonisation of different cortisol assays. * Consensus on