Clinical investigation unit tests
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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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Clinical investigation unit tests

CLINICAL INVESTIGATION UNIT TESTS

Presented by:

ALAA MONJED

Endocrinology fellow


Outline

OUTLINE

  • Background- Provocative endocrine tests

  • CIU tests

  • Indications

  • Side effects / Contraindications


Background

Background

  • What can we measure?

    • basal hormone levels

    • stimulated or suppressed hormone levels

  • Why do we do dynamic endocrine testing?

    • test of secretory reserve


Clinical investigation unit tests

  • INSUFFICIENCY/DEFICIENCY

    Stimulate!

  • OVERPRODUCTION

    Suppress!


Clinical investigation unit ciu

Clinical Investigation Unit - CIU

  • Liz Froats, RN

  • Room B5-502

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


Clinical investigation unit tests

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


Available ciu tests

Available CIU Tests


Examples

Examples


Evaluation of growth hormone deficiency

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


  • Itt 14 units of insulin given

    ITT 14 units of insulin given


    Clinical investigation unit tests

    • Interpretation:

      • abnormal

  • Why?

    • Glucose fell to <2.2 mm

    • Normally GH should rise over 10


  • Clinical investigation unit tests

    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


    Clinical investigation unit tests

    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


    Evaluation of gh hypersecretion acromegaly

    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


    Clinical investigation unit tests

    Interpretation?


    Evaluation of lh fsh deficiency

    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


  • Evaluation of tsh secondary hypothyroidism

    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


    Evaluation of hypopituitarism

    EVALUATION OF HYPOPITUITARISM

    • Components:

      • Insulin Tolerance Test

        • GH deficiency, adrenal insufficiency

      • GnRH stimulation test

        • hypogonadotropichypogonadism

      • TRH stimulation test

        • central hypothyroidism, hypoprolactinemia


    Clinical investigation unit tests

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


    Acth and cortisol secretion

    ACTH and Cortisol Secretion

    Kronenberg HM et al.Williams Textbook of Endocrinology. 11th edition. 2008 Saunders Elsevier.


    Acth and cortisol secretion1

    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.


    Pituitary adrenal reserve dynamic tests

    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


    Adrenal insufficiency diagnosis

    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


    Adrenal insufficiency diagnosis1

    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


    Adrenal insufficiency diagnosis2

    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


    Clinical investigation unit tests

    • 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


  • Adrenal insufficiency diagnosis3

    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


    Adrenal insufficiency diagnosis4

    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


    Adrenal insufficiency diagnosis5

    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


    Posterior pituitary

    Posterior Pituitary


    Diabetes insipidus

    Diabetes Insipidus

    • Central

      • Antidiuretic hormone deficiency

      • Responds to Desmopressin

      • Diagnosis:

        • Water Restriction Test


    Water restriction test

    Water Restriction Test


    Water deprivation test

    Water Deprivation Test


    Clinical investigation unit tests

    • 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]


    Refrences

    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


    Thank you

    THANK YOU


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