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CLINICAL INVESTIGATION UNIT TESTS

CLINICAL INVESTIGATION UNIT TESTS. Presented by: ALAA MONJED Endocrinology fellow. OUTLINE. Background- Provocative endocrine tests CIU tests Indications Side effects / Contraindications. Background. What can we measure? basal hormone levels stimulated or suppressed hormone levels

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CLINICAL INVESTIGATION UNIT TESTS

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  1. CLINICAL INVESTIGATION UNIT TESTS Presented by: ALAA MONJED Endocrinology fellow

  2. OUTLINE • Background- Provocative endocrine tests • CIU tests • Indications • Side effects / Contraindications

  3. Background • What can we measure? • basal hormone levels • stimulated or suppressed hormone levels • Why do we do dynamic endocrine testing? • test of secretory reserve

  4. INSUFFICIENCY/DEFICIENCY Stimulate! • OVERPRODUCTION Suppress!

  5. Clinical Investigation Unit - CIU • Liz Froats, RN • Room B5-502 http://dom.lhsc.on.ca/dom/divisions/endo/ciu.htm

  6. http://lhdomws.lhsc.on.ca/dom/divisions/endo/ciu.htm

  7. Available CIU Tests

  8. Examples

  9. EVALUATION OF GROWTH HORMONE DEFICIENCY • Screening test: low IGF-1 level • butnormal IGF-1 does not exclude it • Dynamic tests: • because basal levels of GH are usually low, which do not distinguish between normal and GH-deficient patients. • Insulin induced hypoglycemia • Most reliable stimulus to GH secretion • A subnormal increase in serumGH(<5.1 ng/mL) confirms the diagnosis of growth hormone deficiency

  10. ITT 14 units of insulin given

  11. Interpretation: • abnormal • Why? • Glucose fell to <2.2 mm • Normally GH should rise over 10

  12. 2. GHRH-Arginine test • 1mg GHRH combined with a 30-min infusion of Arginine IV to stimulate GH secretion • Possible side effects: mild flushing, metallic taste, N/V • Contraindications: severe liver or renal disease

  13. 3.Glucagon stimulation test • 1 mg Glucagon IM, followed by measurement of GH every 30 min for 3 hours • Useful when ITT is contraindicated or GHRH is not available • Side effects: nausea, vomiting and possible late hypoglycemia • Contraindications: malnourished patients • Failure of GH to rise > 3ng/ml is a positive test

  14. Evaluation Of GH Hypersecretion/Acromegaly • Screening test: high IGF-1 level • Dynamic tests: • Oral glucose tolerance test • Failure of GH suppression or paradoxical rise in GH level confirms Acromegaly • Also, seen in starvation, anorexia nervosa, and protein-calorie malnutrition • Side effects: nausea • If a radioimmunoassay method= GH level > 1mcg/L • If one of the newer, highly sensitive immunoradiometricGH assays is used= GH level >0.3 mcg/L

  15. Interpretation?

  16. Evaluation Of LH/FSH Deficiency • Measurement of gonadal steroids (estradiol, testosterone). • Measurement of LH/FSH. • Primary gonadal failure • Low gonadal steroids, High LH/FSH • Hypogonadotrophichypogonadism • Low gonadal steroids, LH,FSH • GnRH test • Assess LH/FSH secretory reserve by stimulating their secretion • Uncommonly performed

  17. Evaluation Of TSH(Secondary Hypothyroidism) • Measurement of TSH • Measurement of free T4/free T3 • If high TSH, low T4 ……. • If low/normal TSH, low T4 ……. 3. TRH stimulation test • is rarely done now because of the accurate methods of determining TSH and freeT4

  18. EVALUATION OF HYPOPITUITARISM • Components: • Insulin Tolerance Test • GH deficiency, adrenal insufficiency • GnRH stimulation test • hypogonadotropichypogonadism • TRH stimulation test • central hypothyroidism, hypoprolactinemia

  19. 1984. J Neurosurg 61(3):586-590

  20. ACTH and Cortisol Secretion Kronenberg HM et al.Williams Textbook of Endocrinology. 11th edition. 2008 Saunders Elsevier.

  21. ACTH and Cortisol Secretion • pulsatile secretion • circadian rhythm • highest in a.m. 24:00 08:00 12:00 20:00 Kronenberg HM et al.Williams Textbook of Endocrinology. 11th edition. 2008 Saunders Elsevier.

  22. Pituitary-Adrenal ReserveDynamic Tests • Used to evaluate the ability of the HPA axis to respond to stress • ACTH stimulation test: directly stimulates adrenal secretion • Metyrapone test: inhibits cortisol synthesis and stimulates pituitary ACTH secretion • Insulin-induced hypoglycemia: stimulates ACTH secretion by increasing CRH • CRH test: stimulates directly the pituitary corticotrophs to release ACTH

  23. Adrenal Insufficiency Diagnosis Steps: • To rule out adrenal insufficiency - fasting 08:00 am cortisol • if 08:00 am cortisol >524 nmol/L, adrenal insufficiency excluded • if 08:00 am cortisol <83 nmol/L, adrenal insufficiency confirmed • if 08:00 am cortisol between these values, is borderline – need further testing reviewed in Oelkers W. N Engl J Med 1996; 335(16):1206-1212

  24. Adrenal Insufficiency Diagnosis Steps: • If suspect primary adrenal insufficiency, do both 08:00 am cortisol and ACTH • low cortisol and high ACTH - primary • if cortisol normal – rules out primary, but does not exclude mild secondary adrenal insufficiency • in primary adrenal insufficiency – ACTH usually >22pmol/L • low cortisol and low/normal ACTH – secondary/tertiary

  25. Adrenal Insufficiency Diagnosis • Dynamic Tests: • To confirm adrenal insufficiency: • High dose ACTH stimulation test • Fasting is not required • 250 mg cosyntropin (Cortrosyn) IV/IM • Cortisol/ACTH at -15, 0, 30, 60 min • If peak cortisol >500 nmol/L (preferably >550 nmol/L), rules out primary adrenal insufficiency Oelkers W. N Engl J Med 1996; 335(16):1206-1212

  26. A normal response to ACTH stimulation test: • Excludes primary AI • Excludes overt secondary AI with adrenal atrophy • Dose not rule out partial ACTH deficiency • pts with sufficient basal ACTH secretion to prevent adrenocortical atrophy • Or pts with recently developed secondary AI who have not yet undergone adrenal atrophy • In such patients, other pituitary-adrenal reserve dynamic testing may be indicated

  27. Adrenal Insufficiency Diagnosis • Low dose short ACTH stimulation test • must be undertaken in the morning • 1 mg cosyntropin (Cortrosyn) IV • Cortisol/ACTH at -15, 0, 30, 60 min • Normal peak cortisol >500 nmol/L • 2 meta-analyses comparing low vs. high dose tests had conflicting results: • Dorin et al. 2003 – no difference in sensitivity or specificity • Kazlauskaite et al. 2008 – low dose test had higher sensitivity Oelkers W. N Engl J Med 1996; 335(16):1206-1212

  28. Adrenal Insufficiency Diagnosis • Insulin-induced hypoglycemia test: • It measures the integrity of the HPA axis and its ability to respond to stress • Normal plasma cortisol response: an increment >220nmol/l and a peak level >550 nmol/l • Normal ACTH response > 22pmol/l • A normal response exclude AI and decreased pituitary reserve i.e. no need to cortisol therapy during illness or stress • Contraindicated in: Elderly, CVD, CVA and seizure disorders

  29. Adrenal Insufficiency Diagnosis • To distinguish secondary vs. tertiary adrenal insufficiency: CRH stimulation test (if you can get CRH!) • 100 mg CRH IV • ACTH, cortisol at -15, 0, 30, 60, 90 min • low/absent ACTH = pituitary adrenal insufficiency (secondary) • high ACTH = hypothalamic adrenal insufficiency (tertiary) (values not as well standardized as for ITT) Oelkers W. N Engl J Med 1996; 335(16):1206-1212

  30. Posterior Pituitary

  31. Diabetes Insipidus • Central • Antidiuretic hormone deficiency • Responds to Desmopressin • Diagnosis: • Water Restriction Test

  32. Water Restriction Test

  33. Water Deprivation Test

  34. Interpretation: abnormal, consistent with central DI • Why? • Serum osmolality rose but urine osmolality remained relatively dilute still; similarly serum Na rose • [At ** time DDAVP was given and serum/urine/Na responded appropriately]

  35. REFRENCES • Kronenberg HM et al.Williams Textbook of Endocrinology. 11th edition. 2008 Saunders Elsevier. • Gardner DG & Shoback D (eds) Greenspan’s Basic & Clinical Endocrinology, 9th Edition.2011 McGraw-Hill. • www.uptodate.com • http://dom.lhsc.on.ca/dom/divisions/endo/ciu.htm

  36. THANK YOU

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