Brig Waqar AzimMBBS, MCPS, Dip Family

Medicine, FCPS, OJT Endocrinology

Prof & HOD Pathology CMH Lahore

Short stature Small for age. Reduce bone age. Pituitary & Hypothalamic disease

 

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

 

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

 

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 

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 

Stimulation test:GH stimulation includes◦Exercise stimulation test◦L-Dopa stimulation test◦Clonidine stimulation test◦Insulin stress test◦Arginine stimulation test◦Sleep Test

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

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.

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

Principle Hypoglycaemia induced by IV insulin is a potent

stimulesfor GH secretion. ProcedureBasal Growth hormone levelsIV 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

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

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

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

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

Glucagon stimulation test Indications

Particularly useful when insulin induced hypoglycaemia is contraindicated.

ContraindicationHypothyroidismMarked adrenal failure Diabetes millitus

PrincipleGlucagon stimulates release of GH and ACTH by Hypothalamic stimulation and therefore indirectly stimulates cortisol.

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 minInterpertaionGH level > 20 mU/L

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

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

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

B. TREATMENT of GROWTH HORMONE DEFICIENCY in

ADULTS

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

Objective:◦ To maximise benefit and minimise side effects

In practice, optimum dose varies greatly◦ sensitivity increase with age◦ men more sensitive than women

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

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

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

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