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Dynamic function tests and protocols All endocrine dynamic function testing should be performed under medical supervision, by appropriately qualified staff with experience of performing the tests being undertaken. Last updated 21/04/2011 Name Protocol 24hr urine collection protocol Creatinine clearance protocol Oral Glucose Tolerance test (OGTT) Gestational OGTT See below See below See below See below Synacthen test Adults See below Paediatric protocol Contact SHSCT Endocrinologists Diabetes Insipidus investigation (water deprivation test) Cortisol Diurnal Investigation of Rhythm Cushing syndrome 24hr urine cortisol See below Contact Regional Endocrine Laboratory 028 90 633798 Dexamethone Contact SHSCT Endocrinologists suppression test. Investigation of insulinoma Contact SHSCT Endocrinologists Investigation of Urine Contact Regional Endocrine Laboratory Phaeochromocytoma Catacholamines 028 90 633798 Forearm Non-ischaemic Exercise Test Pituitary Function Test (Combined) Paediatric Endocrine Test Protocols http://www.metbio.net/docs/MetBioGuideline-KEGA290980-21-03-2010.pdf Contact Regional Endocrine Laboratory 028 90 633798 Paediatric Endocrinologist 02890 633598 Local Guidelines Disturbance Hyponatraemia Guidelines location Hyponatraemia guidance http://shsctintranet.hpss.ni.nhs.uk/HTML/documents/hyponatraemia .pdf Calculated example Click Here Crest Guidelines Click Here Crest wall chart Click Here Hyperkalaemia Click Here Hypokalaemia Hypophosphataemia Click Here Click Here Hypomagnesaemia Click Here Hypocalcaemia Hypercalcaemia See BNF Guidance See BNF Guidance Oral Glucose Tolerance test (OGTT) protocol (a) ADULT ORAL GLUCOSE TOLERANCE TEST Indication Used for diagnosis when blood glucose levels are equivocal. Technique After at least 3 days of unrestricted diet (>150g of carbohydrate daily) and usual physical activity. Test should be preceded by an overnight fast of 8 -14 hrs, during which water may be drunk. Smoking not permitted during test. Collect fasting blood sample Patient should drink 75g of anhydrous glucose or 82.5g of glucose monohydrate in 250 - 300 ml of water over 5 minutes. Collect 2 hr blood sample. Values for diagnosis of diabetes mellitus and other categories of hyperglycaemia according to the WHO. Serum/plasma glucose (mmol/L) DIABETES MELLITUS Fasting or 2hrs after glucose load 7.0 11.1 IMPAIRED GLUCOSE TOLERANCE (IGT) Fasting and < 7.0 2hrs after glucose load 7.8 - < 11.1 IMPAIRED FASTING GLYCAEMIA (IFG) Fasting and 2hrs after glucose load 6.1 - < 7.0 < 7.8 (b) ORAL GLUCOSE TOLERANCE TEST IN PREGNANCY Indication Used for diagnosis when blood glucose levels are equivocal. Technique After at least 3 days of unrestricted diet (>150g of carbohydrate daily) and usual physical activity. Test should be preceded by an overnight fast of 8 -14 hrs, during which water may be drunk. Smoking not permitted during test. Collect fasting blood sample Patient should drink 75g of anhydrous glucose or 82.5g of glucose monohydrate in 250 - 300 ml of water over 5 minutes. Collect.1 & 2 hr blood sample Values for the diagnosis of gestational diabetes mellitus according to International Association of Diabetes and pregnancy Study Groups Consensus panel Fasting plasma glucose 5.1 mmo/L 1hr plasma glucose 10.0mmo/L 2 hr plasma glucose 8.5 mmo/L Investigation of suspected adrenal insufficiency (A) 09:00 AM CORTISOL A 08:00–09:00 cortisol value of Intact adrenocortical reserve can usually be confirmed with basal morning cortisol concentrations of .500 nmol/L. The exclusion of adrenal insufficiency for those with intermediate serum cortisol concentrations (100–500 nmol/L) often requires further dynamic testing. Note basal morning cortisol value are variable and may be affected by stress, exercise and food intake. it is advisable to discontinue oestrogen therapy for a period of at least six weeks prior to assessing the HPA axis. Low serum albumin concentrations, as found in hypoproteinaemic states such as hepatic or renal failure, may lead to misleadingly reduced total serum cortisol concentrations despite normal biologically active free cortisol concentrations (B) Short Synacthen test for suspected adrenal failure Indication This is performed for the investigation of adrenal insufficiency and the diagnosis of congenital adrenal hyperplasia. There is no evidence to support the use of this test in the management of steroid replacement or withdrawal. Principle Adrenal glucocorticoid secretion is controlled by adrenocorticotrophic hormone (ACTH) released by the anterior pituitary. This test evaluates the ability of the adrenal cortex to produce cortisol after stimulation by synthetic ACTH (tetracosactide; Synacthen ®). It does not test the whole pituitaryadrenal axis. Side effects There are rare reports of hypersensitivity reactions to ‘Synacthen’ particularly in children with history of allergic disorders. Preparation There are no dietary restrictions for this test. This test should be ideally performed in the morning but may be done at any time of the day. If there is an inadequate response in the afternoon refer to endocrinology and consider repeating the test in the morning. Requirements 2 clotted gel tubes 250 microgram Synacthen (1 vial) the dose for children is 36 microgram/kg body weight up to a maximum of 250 micrograms Procedure 09:00h take 3 mL blood for cortisol inject Synacthen iv or im 09:30h take further sample for cortisol Interpretation 1. Adrenal insufficiency is excluded by a 30 min value > 550 nmol/L (Roche method). The incremental rise or 60 minute value does not provide additional useful information. 2. An abnormal result should prompt referral to an endocrinologist. 3. Interpretation of basal and stimulated cortisol in the ICU setting is controversial. 4. If the patient is taking steroids discuss with the laboratory or an endocrinologist before the synacthen test is performed. 5. In ACTH deficiency the response to the short test may be normal or reduced. Care should be taken when interpreting synacthen tests in pituitary disease. 6. Baseline and incremental cortisol values do NOT apply to women taking oral contraceptives or to pregnant women. Omit oestrogen replacement for 6 weeks prior to the test (as increased CBG will make cortisol results difficult to interpret) and discuss with an endocrinologist. Cortisol Diurnal Rhythm Indications The investigation of patients with suspected Cushing's Syndrome. Preparation The patient should not be taking steroids or ACTH. The contraceptive pill can also produce an increase in cortisol. Minimise undue distress to the patient due to Repeated venepuncture, the procedure of admission and other factors which may render accurate interpretation more difficult. Procedure 09.00 hours: Take 2 mL blood (plain tube) for serum cortisol. 20.00 hours: Take 2 mL blood for serum cortisol. Reference ranges 7-10am 171-536nmol/L 4-8pm 64-327nmol/L Estimation of Creatinine Clearance as a Guide to Glomerular Filtration Rate Introduction Creatinine is a by-product of muscular metabolism. It is filtered at the glomerulae and excreted in the urine without further reabsorption or excretion by the tubules. For this reason, it is a valuable monitoring analyte for glomeruli filtration rate. This is of value in the diagnosis and monitoring of renal disease. Note: An estimated GFR result is now reported on all electrolyte profiles. It is calculated from the serum creatinine and patients’ age and reported as part of the electrolyte profile. A 24hr urine collection for GFR is not now normally required for adults. Creatinine clearance Creatinine clearance is defined as the volume of blood in mls containing the amount of creatinine which appears in the glomerular filtrate produced in one minute. The classical formula is:UxV P Where U = Urinary creatinine in micromol / litre V = Volume of urine produced in 1 minute (24 hr volume / 1440) P = Serum creatinine in micromol / litre Creatinine Clearance gives results comparable to inulin clearance Sample requirements An accurately timed 24 hr urine taken into thymol is required although an acidified 24 hr urine specimen is also acceptable. A clotted blood sample for serum creatinine should be taken at some time during the 24hr urine collection. For unusually large or small patients, the clearance rate obtained is referred to the mean body surface area (BSA) of 1.73 m2. The BSA can be determined from nomograms for height and weight hence:Corrected creatinine clearance = 1.73 x calculated creatinine clearance/ surface area in m2 Under-estimation of creatinine clearance can occur with increased tubular creatinine reabsorption, such as exists in congestive cardiac failure; while over-estimation occurs in advanced renal failure, due to increased tubular excretion of creatinine. Reference Ranges 70 – 150 mls/minute 24hr collection protocol Introduction The accuracy and usefulness of investigations which require a timed collection of urine depends largely on obtaining a full and complete collection. The bladder should be emptied at the start of the collection (conveniently 8 am) whether or not the patient feels the need and this urine discarded. Note the start time (i.e. exact time the bladder was emptied) on the bottle label. Collect all urine passed for the next 24 hours. Exactly 24 hours later the bladder should be emptied completely, whether or not the patient feels the need. Add this final specimen to complete the 24hr collection. Screw the lid on securely. Note the End time (i.e. when bladder emptied) on the bottle label. Send the completed collection and request form with the times and date clearly noted to the laboratory without delay.