Handbook of Endocrine Investigations in Children -  I. A. Hughes

Handbook of Endocrine Investigations in Children (eBook)

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2013 | 1. Auflage
166 Seiten
Elsevier Science (Verlag)
978-1-4831-8352-7 (ISBN)
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Handbook of Endocrine Investigations in Children
Handbook of Endocrine Investigations in Children serves as a guide to general pediatricians in the investigation of childhood disorders. This book discusses the widespread availability of commercially prepared growth hormone by recombinant DNA technology. Organized into eight chapters, this book begins with an overview of the general principles of endocrine testing in children. This text then explores the anterior pituitary gland, which secretes several hormones, including growth hormones, thyroid stimulating hormone, adrenocorticotrophin, prolactin, luteinizing hormone, and follicle-stimulating hormone. Other chapters consider the thyroid function, which is divided into thyroid profile and definitive tests. This book discusses as well the investigations required to determine the causes of hypo-or hypercalcemia associated with either parathyroid disease or disordered vitamin D metabolism. The final chapter deals with the potential application of the methods of molecular biology to the study of endocrine diseases in children. This book is a valuable resource for general pediatricians, pediatric endocrinologists, and endocrinologists.

CHAPTER 2

The Pituitary


Publisher Summary


This chapter explains the use of growth hormone-releasing hormone (GHRH or GRF) and corticotrophin-releasing factor (CRF) hormones in diagnostic tests. It has been found that CRF has a little practical application in the investigation of pediatric endocrine disease. The chapter also explains that antidiuretic hormone (ADH) is synthesized in the hypothalamus, transported along axons in the neurohypophyseal tract, and stored in the posterior pituitary gland. As ADH secretion is controlled mainly by plasma osmolality, water deprivation is the main stimulus for testing adequate ADH secretion. Secretion from the posterior pituitary is regulated mainly by changes in osmolality of the extracellular fluid. ADH release is assessed by indirect methods. Tests of growth hormone (GH) secretion are classified into physiological and pharmacological. The former takes advantage of some normal physiological variables, such as exercise and sleep where GH secretion is enhanced.

The anterior pituitary gland secretes several hormones—GH, TSH, ACTH, PRL, LH and FSH—whose synthesis and secretion are controlled by hypothalamic releasing or inhibiting factors. Some of these factors have been isolated, characterized and synthesised and are used in the evaluation of anterior pituitary function. They include TRH and LHRH. Indirect methods of stimulation are normally used to test the secretory reserve of GH and ACTH. However, releasing factors for these two hormones, GHRH and CRF, respectively, have recently been isolated and characterized. Their use in diagnostic tests is now being evaluated but CRF appears to have little practical application in the investigation of paediatric endocrine disease.

ADH is synthesized in the hypothalamus, transported along axons in the neurohypophyseal tract and stored in the posterior pituitary gland. Secretion from the posterior pituitary is regulated mainly by changes in osmolality of the extracellular fluid. ADH release is assessed by indirect methods.

GROWTH HORMONE


Tests of GH secretion are classified into physiological and pharmacological. The former takes advantage of some normal physiological variables such as exercise and sleep where GH secretion is enhanced.

STIMULATION


Physiological

Random

Occasionally a random blood sample will detect an elevated GH level, particularly if the child is stressed or is fasted.

Such a result would exclude GH deficiency. However, the test is so unreliable that it is not recommended.

There as been a recent resurgance of interest in urinary GH measurements now that more sensitive GH assays are available. A 24 h or an overnight urine collection without preservatives is required. It is preferable to keep the urine stored at 4°C until the collection is completed. An ultrasensitive GH assay is required to detect the low levels associated with GH deficiency. The reliability of using urinary GH assays to screen short children for GH deficiency is currently being evaluated.

Insulin-like growth factor I (IGF-I) is GH-dependent and, as expected, the serum levels of this peptide are low in GH deficiency. Random measurements are too nonspecific for diagnostic use as levels are low in young children and are also affected by liver disease and hypothyroidism. Elevated GH and decreased IGF-I levels are characteristic of Laron’s dwarfism.

Exercise

This test should be performed using a bicycle ergometer to generate a standard amount of work which will vary according to the age and size of the child.

One should aim for a physical exertion between 150 and 300 kilopond. m/min equivalent to about 50 per cent maximal working capacity.

• Child fasted

• Blood sample at t = − 30 and 0 min

• Exercise and bicycle for 10 min (t = 10 min)

• Collect blood samples at t = 10 and 20 min.

If a bicycle ergometer is not available, the following exercise test is sometimes useful to perform:

• Child fasted

• Blood sample at t = 0 min

• Run up and down stairs for 20 min

• Child should be tired, but not exhausted; heart rate should not exceed 180/min

• Blood sample at end of exercise (t = 20 min)

• Rest for 20 min; repeat blood sample (t = 40 min).

Interpretation: A GH level > 15 mU/l excludes GH deficiency. Lower values do not necessarily indicate GH deficiency. If necessary proceed to pharmacological tests. About 20 per cent of exercise-induced tests give false positive results for GH deficiency. Some protocols suggest priming the child with propanolol orally 0·5 mg/kg (maximum dose 40 mg) 1 hour before the test to enhance the GH response. This carries a risk of hypoglycaemia

Sleep

Ideally this test should be performed with EEG monitoring if available.

• Insert i.v. line before bedtime

• Collect 2 blood samples 20 min apart while child awake

• Collect 2 blood samples 20 min apart between stages III and IV

• If no EEG recording, collect 2 samples 20 min apart between 30 and 90 min after onset of sleep.

    Interpretation: GH levels during waking hours usually low; the rise in nocturnal levels occurs during stage III and IV sleep equivalent to slow wave sleep. Values > 15 mU/l exclude GH deficiency.

    The pulsatile release of GH during a 12–24 h period is studied mainly as part of research protocols. The frequency of blood sampling is usually every 15–20 min and the GH profile is analysed in relation to pulse frequency and amplitude, the integrated concentration of GH during the study period and the area under the curve of the GH profile. Computer programs are available for these detailed analyses.

Pharmacological

Children with short stature and delayed puberty should be primed with sex hormones just prior to the GH stimulation test The criterion is based on bone age. In delayed puberty and a bone age 10 years or less (determined by Tanner–Whitehouse method) boys are given one dose of Sustanon* 100 mg i.m. 3–5 days before the test; girls are given ethinyl oestradiol 100 μg orally each day for 3 days prior to the test.

Insulin-induced Hypoglycaemia (Insulin Tolerance Test, ITT)

Stress resulting from hypoglycaemia is the stimulus for GH release, believed to be mediated via an α-adrenergic pathway. The dangers are obvious. Contra-indications to performing this test include a history of convulsions, previous hypoglycaemic episodes, and diabetes mellitus.

During an ITT, the following are measured—blood glucose, GH, cortisol and PRL.

• Child must be fasted

• Arrange with laboratory for immediate analysis of blood glucose levels; also monitor capillary blood glucose values using suitable glucose oxidase reagent strips and a glucose meter

• Establish reliable i.v. line

• Draw up 20 ml of 50 per cent dextrose solution in a syringe ready for use

• Prepare bolus dose of short-acting insulin (Actrapid); usual dose is 0·1–0·15 U/kg body weight. Reduce to 0·05 U/kg if pituitary insufficiency (particularly ACTH deficiency) is strongly suspected

• Collect baseline samples at t = − 30 and 0 min for blood glucose, GH, cortisol, PRL

• At t = 0 min, inject insulin bolus i.v.

• Collect samples at t = 15, 30, 45, 60, 90, 120 min for blood glucose and GH

• Collect samples at t = 30, 60, 120 for cortisol and PRL.

Symptoms of hypoglycaemia usually occur 15–30 min after the insulin injection. If severe, collect an immediate blood sample for hormone analysis, then give i.v. dextrose. At the end of the test, give the child a glucose-containing drink and a meal. DO NOT allow home until observations are satisfactory.

Interpretation: The blood glucose should decrease by 50 per cent or more of the basal value (t = 0 min) and/or there should be symptoms and signs of hypoglycaemia—drowsiness, sweating, headache (occasionally nausea and vomiting). With adequate hypoglycaemia, peak GH levels < 7 mU/l indicate GH deficiency. This is excluded with peak GH levels > 15 mU/l. Levels between 7–15 mU/l may indicate partial GH deficiency, but this requires confirmation with a second, different test of GH secretion.

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Erscheint lt. Verlag 22.10.2013
Sprache englisch
Themenwelt Sachbuch/Ratgeber Gesundheit / Leben / Psychologie Krankheiten / Heilverfahren
Medizinische Fachgebiete Innere Medizin Endokrinologie
Medizin / Pharmazie Medizinische Fachgebiete Pädiatrie
ISBN-10 1-4831-8352-1 / 1483183521
ISBN-13 978-1-4831-8352-7 / 9781483183527
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