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GROWTH HORMONE DEFICIENCY

GROWTH HORMONE DEFICIENCY. Brig Waqar Azim MBBS, MCPS, Dip Family Medicine, FCPS, OJT Endocrinology Prof & HOD Pathology CMH Lahore. Childhood Growth Hormone Deficiency. Short stature Small for age. Reduce bone age. Pituitary & Hypothalamic disease. Adult Growth Hormone Deficiency.

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GROWTH HORMONE DEFICIENCY

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  1. GROWTH HORMONE DEFICIENCY Brig Waqar AzimMBBS, MCPS, Dip Family Medicine, FCPS, OJT EndocrinologyProf & HOD Pathology CMH Lahore

  2. Childhood Growth Hormone Deficiency • Short stature • Small for age. • Reduce bone age. • Pituitary & Hypothalamic disease

  3. Adult Growth Hormone Deficiency • Clinical features include • alterations in body composition • reduced lean body mass & bone mineral density • increase in fat mass, particularly abdominal • dry skin with reduced sweating • reduced muscle strength & exercise performance • impaired sense of well-being and other psychological complaints

  4. Indication for Growth Hormone Assesment • Stunted growth in children • Those with evidence of hypothalamic or pituitary disease or cranial irradiation • likelihood of deficiency increases with number of pituitary hormone deficits • approaches 100% if 3-4 pituitary hormone deficits exist • Childhood-onset growth hormone deficiency • all patients should be re-tested as adults before continuing treatment with GH

  5. GROWTH HORMONE ASSESSMENT Assessment suspected GH deficiency after clinical and radiological assessment • Detailed history and thorough physical examination •  Exact chronological age of the child • Determination of percentile of height and weight according to the standard height and weight chart • Parental height and weight • bone age of the patient - x- ray of the non dominant wrist

  6. GROWTH HORMONE ASSESSMENT Assessment suspected GH deficiency after clinical and radiological assessment • Detailed history and thorough physical examination • Exact chronological age of the child • Determination of percentile of height and weight according to the standard height and weight chart • Parental height and weight • bone age of the patient -x- ray of the non dominant wrist

  7. GROWTH HORMONE STIMULATION TEST Stimulation test: GH stimulation includes • Exercise stimulation test • L-Dopa stimulation test • Clonidine stimulation test • Insulin stress test • Arginine stimulation test • Sleep Test

  8. Biochemical Diagnosis of Adult GH Deficiency (GHD) • Dynamic tests of GH secretion • patients should be on stable & adequate replacement of other hormonal deficits before testing • the insulin tolerance test is the diagnostic test of choice • providing adequate hypoglycaemia is achieved, this test distinguishes GH deficiency from the reduced GH secretion with ageing & obesity

  9. GROWTH HORMONE STIMULATION TEST(CONTD) Diagnosis of GH related Growth Failure • For establishing GH deficiency • Two provocative tests (GH levels < 10 mIU/L) • Partial GH deficiency • Borderline response between 10- 20 mIU/L in one or two provocative tests • Rule Out other Causes of Dwarfism • Chromosomal analysis • X-Ray skull • Thyroid function tests.

  10. The Insulin Tolerance Test in GHD • Should be performed in experienced endocrine units where the test is performed frequently • Contraindicated in those with ECG evidence of ischaemic heart disease and in those with seizure disorders • in these people, alternative tests should be used

  11. Insulin Tolerance Test Principle Hypoglycaemia induced by IV insulin is a potent stimules for GH secretion. Procedure Basal Growth hormone levels IV insulin (0.15 U/kg) is given Hypoglycaemia 2.2 mmol/L should ge obtained. GH levels are measured at 30, 60, 90 &180 min Interpertation > 20mIU/L means adequate stimulation

  12. GROWTH HORMONE STIMULATION TEST(CONTD) • EXERCISE STIMULATION TEST • Principle: • Strenuous physical exercise causes GH secretion in normal subjects • Preparation: • Fasting over night • Early in the morning (0800 hours) • Procedure: • Basal blood specimen for GH • Rigorous exercise on a tread mill for 15-20 minutes • Pulse is monitored during the test • Blood specimen taken 10 minutes after the cessation of exercise

  13. GROWTH HORMONE STIMULATION TEST(CONTD) • L- DOPA STIMULATION TEST • Principle • L- Dopa stimulates growth hormone (GH) secretion from the anterior pituitary gland measurements of which (GH) serve as a test of anterior pituitary function • Preparation • Overnight fast • At 0800 hrs • Procedure • Basal sample for GH • L- Dopa is administered orally preferably with food and milk • Patient > 30 Kg: 500 mg • Patient between 15 - 30 Kg: 250 mg • Patient < 15 Kg: 125 mg

  14. GROWTH HORMONE STIMULATION TEST(CONTD) • Sampling • 5 ml venous blood is collected at 0 (basal) • 60 minutes after L- Dopa administration • Interpretation • GH level > 20 mIU/L Normal response • GH level between 10 - 20 mIU/L -suggestive of partial GH deficiency • GH levels < 10 mIU/L - GH deficiency

  15. GROWTH HORMONE STIMULATION TEST(CONTD) • Arginine Test • Prepration NPO atleast 8 hrs prior to the test • Procedure 1. Base line serum GH and somatomedin-C levels 2. Inject 0.5 g/kg (maximum 30 g) arginine over 30 min IV 3. Serum GH levels at 30,60,90, 120 mins

  16. GROWTH HORMONE STIMULATION TEST(CONTD) • Glucagon stimulation test • Indications Particularly useful when insulin induced hypoglycaemia is contraindicated. • Contraindication Hypothyroidism Marked adrenal failure Diabetes millitus • Principle Glucagon stimulates release of GH and ACTH by Hypothalamic stimulation and therefore indirectly stimulates cortisol.

  17. GROWTH HORMONE STIMULATION TEST(CONTD) • GHRH -ARGININE STIMULATION TEST • Indication • To confirm persistence of childhood GH deficiency in early adulthood if ITT is contraindicated, pt is over weight or has DM. • Procedure Baseline GH and IGF-1 level Inject GHRH 1meg/kg (maximum dose 100 meg) as bolus. Infuse 0.5 g/kg arginine as a 10% solution in normal saline over 30 min. Take sample for GH (but not for IGF-1) at 30,60,90, 120 & 150 min after start of arginine infusion. Monitor pule and blood pressure every 15 min Interpertaion GH level > 20 mU/L

  18. GROWTH HORMONE STIMULATION TEST(CONTD) • Sleep Test • Take advantage of known rise in GH conc. occuring with deep sleep. • Sample is obtained 60 – 90 mins after on set of sleep. • Patient must be in the hospital or a clinical research centre for testing. • Interpertation: • GH ≥ 15 mU/L ---- normal

  19. Number of Provocative Tests Needed to Establish Diagnosis of GHD • One test in reconfirmation of childhood-onset GHD • One test only in adults with hypothalamic or pituitary disease and one or more pituitary hormonal deficits • Two test in adults with isolated GHD

  20. Biochemical Diagnosis of Adult GH Deficiency (GHD) • B.Biochemical Markers of GH Action • Serum IGF-I • only of value with age-adjusted normal ranges • a normal serum IGF-I does not exclude GHD • a serum IGF-I below the normal range is suggestive of GHD (in absence of confounding conditions e.g. malnutrition, liver disease, hypothyroidism) • of greater value in presence of 2 or more hormonal deficiencies

  21. B. TREATMENT of GROWTH HORMONE DEFICIENCY in ADULTS

  22. Treatment of Growth Hormone Deficiency • Patients who should be treated: • all patients with documented severe growth hormone deficiency • Goal of therapy: • to correct abnormalities associated with severe growth hormone deficiency

  23. Dose Selection • Objective: • To maximise benefit and minimise side effects In practice, optimum dose varies greatly • sensitivity increase with age • men more sensitive than women

  24. Starting GH Replacement • Start with a low dose • 0.15 - 0.30 mg / day (0.45 - 0.90 U / day) • subcutaneously at bedtime • Monitor response carefully • clinically and biochemically • Increase dose slowly • no more frequently than at monthly intervals

  25. Target Dose of GH • Women aged 30 - 50 secrete on average 0.2 mg / day and men 0.1 mg / day • Sensitivity varies considerably between patients and probably between the sexes • The daily dose rarely exceeds 1 mg (3 U) • Doses used now are lower than previously and are no longer based on body weight or surface area

  26. Monitoring Treatment Efficacy - Clinical & Safety Issues • Good clinical practice requires regular imaging of any residual pituitary disease • GH replacement does not impose any need to intensify this • A baseline MRI or CT scan is to be recommended before GH replacement is started

  27. Conclusions • Growth hormone stimulation tests should confirm GH deficiency • Those receiving GH replacement should remain under supervision of an endocrinologist specialising in pituitary disorders • Monthly GH monitoring initially but once stabilised can usually be reduced to one or two times a year

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