Critical illness and endocrinology. ICU Fellowship Training Radboudumc

Transcription

1 Critical illness and endocrinology ICU Fellowship Training Radboudumc

2 Critical illness Ultimate form of severe physical stress Generates an orchestrated endocrine response to provide the energy for fight and flight response Lipolysis, proteolysis and gluconeogenesis

3 Thyroid metabolism T3 TSH _ T3 Bound to: TBG TB pre-albumin Transthyretin Albumin Protein mrna T3 T3R RxR T3 and T4 T3 (10%) T4 (90%) FT4 0.03% FT3 0.3% T3 T4 D3,D1 T3 T4 D1,D2 T3 rt3 D1,D2 T2 D3,D1

4 Non-thyroidal illness syndrome Low T3, low T4 and normal or slightly decreased TSH Serum T3 decreases within hours after the onset of acute stress (amount varies with severity of stress and predicts outcome)

5 Considerations Acute changes probably adaptive (compare fasting) Potentially maladaptive during prolonged critical illness Four small trials show no benefit from thyroid hormone replacement

6 Pathogenesis Central downregulation of HPT axis (decreased TRH) Changes in liver metabolism of thyroid hormone

7 Acute Chronic Acute low T3-syndrome Euthyroid sick syndrome Non thyroidal illness TRH 7 TSH TSH (miu/l) No nocturnal TSH surge h h h h Acute Chronic T4 Plasma T3 rt3 Liver activity D1 D3 Muscle activity D2

8 NTIS often combined with low food intake

9 Drugs interfering with thyroid hormones

10 Thyroid storm < 10% of patients hospitalized for thyrotoxicosis More common in women (age years) Usually precipitating event Diverse symptoms and signs

11

12 Myxedema coma End stage of untreated hypothyroidism Usually precipitating event Extremely rare (estimated 0.22/ year) Usually hospitalized elderly women

13 Treatment

14 Critical Illness-Related Corticosteroid Insufficiency Inadequate cellular corticosteroid activity for the severity of the patient s critical illness Stress system HPA-axis & Locus ceruleus/ne sympathetic NS Acute phase reaction Systemic inflammation Vital organs tissue defense response

15 HPA axis dysfunction during critical illness 10-20% in critically ill medical patients up to 60% in septic shock

16 Dissociation between ACTH and cortisol

17 Circadian rhythm Daily production of cortisol is μmol

18 Cortisol metabolism during critical illness Cortisol levels are high during acute physical stress Attributed to stress-induced HPA axis activation Reduced cortisol metabolism could be another explanation Bile acids may suppress activity of cortisol metabolising hormones Boonen E. N Engl J Med 2013

19 Cortisol metabolism Kidney Liver

20 Cortisol levels increase during critical illness Boonen E. N Engl J Med 2013

21 ACTH levels are low during critical illness Boonen E. N Engl J Med 2013

22 Boonen E. N Engl J Med 2013

23 Boonen E. N Engl J Med 2013

24 Plasma cortisol 80-90% tightly bound to corticosteroid-binding globulin 10-15% bound with low affinity to albumin or free

25

26 Impairment of adrenal cortisol synthesis Damage to neuroendocrine cells (W-F syndrome) Suppressed ACTH synthesis (feedback by elevated free cortisol and medications) Diminished adrenal steroidogenesis (60%) also by medications (etomidate, opioids) Tissue resistance to glucocorticoids

27

28 Symptoms General Fever, asthenia Neurological Cardiovascular Digestive Respiratory Laboratory Imaging Confusion, delirium, coma Hypotension refractory to fluid loading Decreased sensitivity to catecholamines Huh cardiac index Nausea, vomiting, intolerance to enteral feeding Persistent hypoxia Hypoglycemia, hyponatremia, hyperkalemia, metabolic acidosis, hypereosinophilia Hemorrhage or necrosis in hypothalamus, pituitary gland or adrenal gland

29 Diagnosis Either delta cortisol < 9 μg/dl after 250 μg cosyntropin or random plasma cortisol < 10 μg/dl Use plasma total cortisol and not salivary free cortisol Do not use the hemodynamic response to hydrocortisone for the diagnosis of CIRCI Do not use plasma corticotropin levels for the diagnosis of CIRCI

30 Recommendations for corticosteroids in critical care Do not use corticosteroids in septic patients without shock Only use corticosteroids in patients with septic shock resistant to fluid and moderate- to high vasopressor therapy Use < 400 mg hydrocortison for 3 days In patients with ARDS and P/F < 200 mmhg corticosteroids may be administered within 14 D

31 Recommendations for corticosteroids in critical care Hydrocortison < 400 mg/day for 5-7 days may be considered for severe CAP Do not use corticosteroids in severe influenza Strong recommendation for the use of corticosteroids in meningitis Consider the use of corticosteroids in comatose patients after cardiac arrest

32 Growth hormone secretion Sleep Growth hormone (μg/l) 8 AM 8 PM Midnight 8 AM Pulsatile secretion stimulated by GHRH/ghrelin and inhibited by somatostatin

33 In acute critical illness peripheral GH resistance develops with low IGF-1 levels

34 GH and critical illness Health Acute critical illness Prolonged critical illness In prolonged critical illness during feeding pulsatility is lost and GH resistance decreases

35 GH secretion can be reactivated