Dr John Quin. Royal Sussex County Hospital, Brighton. BHIVA AUTUMN CONFERENCE 2013 Including CHIVA Parallel Sessions. None
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1 BHIVA AUTUMN CONFERENCE 2013 Including CHIVA Parallel Sessions Dr John Quin Royal Sussex County Hospital, Brighton COMPETING INTEREST OF FINANCIAL VALUE > 1,000: Speaker Name Statement Dr John Quin None Date November November 2013, Queen Elizabeth II Conference Centre, London
2 CLINICAL CASES AND QUESTIONS FROM A JOINT HIV ENDOCRINE CLINIC Dr Debbie Williams, Consultant GUM/HIV Dr John Quin, Consultant Endocrinologist
3 1 Background Pre HAART era Early HAART era Endocrine problems in HIV Advanced disease Opportunistic infections Tumours Metabolic complications of ARV s Late HAART era Lipodystrophy, Insulin resistance Age related Drug interactions IRIS
4 Slide 3 1 deborah williams, 08/11/2013
5 Case 1 45 yr MSM HIV+ 10 yrs VL<40 CD4 450 On Truvada, darunavir/ritonavir Lipodystrophy c/o fatigue, tired all the time (TATT), poor libido, erectile dysfunction, low mood
6 Question 1: What do you do with a tired all the time? 1. Tell him his CD4 count and VL are fine and you ll see you in 4/12 2. Tell him his HIV is well controlled and to go and see his GP about his tiredness 3. Check his testosterone 4. Check his vitamin D 5. Check his growth hormone 6. Do a glucose tolerance test 7. Refer to an endocrinologist
7 Question 1: What do you do with a tired all the time? 1. Tell him his CD4 count and VL are fine and you'll see him in 4/12 8% 2. Tell him his HIV is well controlled and to go and see his GP about his tiredness 18% 3. Check his testosterone 46% 4. Check his vitamin D 9% 5. Check his growth hormone 0% 6. Do a glucose tolerance test 9% 7. Refer to an endocrinologist 10%
8 TATT screen Male Female Testosterone Cortisol Thyroid function Fasting glucose Cortisol Thyroid function Fasting glucose Female hormones if amenorrhea Vitamin D, Vitamin B12 & folate, Fe studies
9 Case: Results Testosterone - random Total testosterone: 9.5 ( nmol/l) SHBG: 88 (21-77nmol/l) Thyroid function T4: 10 (12-22 pmol/l) TSH: 2.4 ( ) Cortisol: 470 ( ) Glucose: 5.0
10 Question 2: Is he hypogonadal and /or hypothyroid? 1. Hypogonadal 2. Hypothyroid 3. Both 4. Neither 5. Not sure
11 Question 2: Is he hypogonadal and /or hypothyroid? 1. Hypogonadal 17% 2. Hypothyroid 2% 3. Both 13% 4. Neither 23% 5. Not sure 45%
12 Case: Results Testosterone Total testosterone: 9.5 ( nmol/l) SHBG: 88 (21-77nmol/l) Free testosterone: 163 ( pmol/l) Thyroid function T4: 10 (12-22 pmol/l) TSH: 2.4 ( ) Cortisol: 470 ( ) Glucose: 5.0
13 What next? Repeat Testosterone Plus: LH FSH Prolactin
14 Case: Results Total testosterone: 10.0 ( nmol/l) SHBG: 88 (21-77 nmol/l) Free testosterone: 165 ( pmol/l) LH : 1.9 ( iu/l) FSH: 4.9 ( iu/l) Prolactin: 110 ( miu/ml)
15 7 Management Who? Threshold, age What with? Injectables vs gel/patches Monitoring? What Whose job is it What should improve? Duration Risks?
16 Slide 14 7? new slide of which therapeutic options? include nil.. slide on monitoring and other investigations - PSA, DEXA, therapeutic goal - clinical? hormonal? - is it forever? whose job is it? does everyone need to see an endocrinologist? whats the role of the GP? Martin Mortgage, 08/11/2013
17 What about his thyroid function? T4: 10 (12-22 pmol/l) TSH: 2.4 ( )
18 Sick euthyroidism? Repeat TFT s plus thyroid autoantibodies T3 Cortisol No indication for T4 Monitor
19 Case 2 52 yr MSM HIV+ 15 yrs Long ARV history VL<40 on Truvada/darunavir/ritonavir Impaired glucose tolerance Hyperlipidaemia c/o Fatigue TATT screen : normal Has seen adverts for growth hormone on the internet and wants to take it
20 Question 3: How many patients have you tested for growth hormone deficiency in the last year? >10 4. None
21 Question 3: How many patients have you tested for growth hormone deficiency in the last year? % % 3. >10 0% 4. None 95%
22 8 Symptoms & signs of GH deficiency Fatigue Changes in memory and concentration Depression, Anxiety Insomnia Fibromyalgia syndrome Central adiposity, decreased muscle mass & bone density Decreased insulin sensitivity Accelerated atherogenesis, increased LDL Prothrombotic state Decreased sweating and thermoregulation
23 Slide 20 8? Question sfirst - how many have you screened for HGH deficiency? Show this slide Then repeat the question! Martin Mortgage, 08/11/2013
24 Question 4: How many patients do you think you will test for growth hormone deficiency in the next year? >10 4. None
25 Question 4: How many patients do you think you will test for growth hormone deficiency in the next year? % % 3. >10 19% 4. None 29%
26 Growth hormone GH Released in pulses Breaks down fat Gluconeogenesis Stimulates insulin like GF from liver Muscle building Bone growth
27 Growth hormone Who should we test? Only those with documented evidence of pituitary dysfunction Only those already optimally treated with other hormones How to test? IGF1 Arginine stimulation Insulin stress test
28 Case: Results Arginine stimulation test Time (minutes) Growth hormone (ug/l) 0 < Normal: increase to >9 ug/l IGF (7.0-25) Endocrine screen FSH 5.0 (1.5-12) LH 6.0 ( ) prolactin 300 (86-324) TSH 2.0 ( ) T4 10 (12-22) Cortisol 420 ( ) Glucose 9
29 Management Who to consider treating GH therapy practical issues? Monitoring Risks
30 Case 3 35 yr HIV+ woman On Truvada/Atazanavir/Ritonavir VL<40 CD4 600 Fibromyalgia/seronegative spondyloarthropathy c/o 4/52 history fatigue, proximal myopathy, polydypsia and polyuria, weight gain Given Kenalog intra articularly 6/52 ago
31 9 Examination & investigations Cushingoid appearance Central obesity Proximal myopathy BP : 130/90 results glucose FBC K LFT TFT 20 mmol/l normal low normal normal
32 Slide 28 9 Question of what test - clinical diagnosis is iatrogenic Cushings - what test to prove? what to test to decide whether intervention necessary? Martin Mortgage, 08/11/2013
33 Question 5: What test would you do to confirm the diagnosis? 1. Random cortisol cortisol hr urinary cortisol +/- dexamethasone suppression test cortisol plus Synacthen test 5. ACTH 6. None of the above 7. Don t know
34 Question 5: What test would you do to confirm the diagnosis? 1. Random cortisol 0% cortisol 14% hr urinary cortisol +/- dexamethasone suppression test 35% cortisol plus Synacthen test 34% 5. ACTH 5% 6. None of the above 3% 7. Don't know 9%
35 10 Case: Results Random cortisol: 14 ( nmol/l) Synacthen test Time (minutes) Cortisol nmol/l Normal: Rise of >200nmol between 0-30 min. >550nmol/l at 30 min
36 Slide drop the HbA1c; give nomral ranges Martin Mortgage, 08/11/2013
37 Iatrogenic cushings with secondary adreno-cortical suppression
38 Corticosteroid drug interactions with ritonavir Steroid Trade names notes Inhaled steroids Fluticasone Flixotide flixonase Seretide Mometasone Nasonex Budesonide Pulmicort Symbicort Rhinocort Triamcinolone Nasocort Beclamethasone Becotide Oral Steroids Prednisolone Injectable steroids Intrarticular, im, epidural Dexamethasone Triamcinolone Kenalog Depomedrone
39 11 Iatrogenic adreno-cortical suppression When is steroid replacement needed? For how long? When is it safe to stop? Any other investigations needed? DEXA HbA1c/GTT
40 Slide whats the role of the HIV physician? when safe to stop? when is steroid replacement needed? for how long? Martin Mortgage, 08/11/2013
41 12 Case: outcome Remained on replacement steroids for 9 months Insulin discontinued after 6 months Proximal myopathy and osteoporosis persists Compensation settlement?
42 Slide what other things to test for? HbAIc/OGTT DEXA etc Martin Mortgage, 08/11/2013
43 Learning points TATT screen Hypogonadism Consider growth hormone deficiency Performance enhancing/recreational drugs Serious drug drug interactions with corticosteroids and ritonavir Education of patients and non HIV prescribers Co-manage complex patients with endocrinology
44 Acknowledgements The patients Prof Martin Fisher & Dr Daniel Richardson
45 Question In a population at risk of Diabetes what is the best method of screening? Random glucose or annual HbA1c?
46 Ritonavir drug interactions Highly potent inhibitor of Cytochrome P450 3A4 Inhaled fluticasone: Bioavailability 0.51% Metabolised by CYP 3A4 in gut mucosa µg nasally produces plasma levels of <50 pg/ml 3 patients on ritonavir and fluticasone Levels 604, 299, 77 pg/ml
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