GHD Presenting During Childhood

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GHD/insufficiency and hypopituitarism can present in infancy and childhood in the following clinical settings: hypoglycemia; growth failure (<7 cm/yr prior to age 3 yr, <4.5-5.0 cm/yr from age 3 yr to puberty, <5.5-6.0 cm/yr during pubertal yr); diabetes insipidus; disorders of pubertal development including micropenis and pubertal delay; children with visual, neurological abnormalities and developmental defects; characteristic truncal obesity.

GHD/insufficiency should be considered in children with abnormal linear growth for age, subnormal height (>2 SD below mean for age), delayed bone age, absence of organic disease that could cause growth failure, and normal body proportions. The diagnostic protocols used to detect (GHD) can be classified as either pharmacologic (use of provocative agents) or physiologic (measurement of spontaneous endogenous GH secretion). Standard provocative stimuli include insulin-induced hypoglycemia, arginine, clonidine, levodopa, propranolol, levodopa plus propranolol, and glucagon. Physiologic stimuli include exercise, sleep, diurnal GH secretory profile, IGF1 (previously known as Somatomedin-C), and IGFBP3. The diagnosis of GH deficiency/insufficiency is based on two provocative stimuli with peak GH <10 ^g/L or 7 ^g/L (using polyclonal GH radioimmunoassay) in the appropriate clinical setting. Our preferred diagnostic test provides comprehensive information at one sitting about the hypothalamic-pituitary endocrine axis as well as assesses GH secretion after two separate stimuli (Table 2). Insulin-induced hypoglycemic challenge should not be used in children with seizure

Table 1

Causes of GH Deficiency or Defective GH Action

Acquired GH Deficiency

Congenital GH Deficiency


Neurosecretory dysfunction CNS tumors:

Craniopharyngioma Dysgerminoma Optic glioma Hamartoma


Perinatal insult: breech deliveries, hypoxemia asphyxia, difficult forceps delivery, intracranial hemorrhage, precipitous or prolonged delivery, twin pregnancy Child abuse Accidental trauma Inflammatory diseases: Viral encephalitis Bacteria, group B streptococcal meningitis, etc. Fungal

Granulomatous: tuberculosis, syphilis, sarcoidosis, unknown etiology Autoimmunity:

lymphocytic hypophysitis Irradiation:

CNS radiation for brain tumors, leukemia Vascular lesions:

Aneurysms, pituitary vessels Infarction Hematologic disorders: Hemochromatosis Sickle cell disease Thalassemia Histiocytosis

Transient defects in GH secretion or action: Peripuberty (secretion) Primary hypothyroidism (secretion, action)

Psychosocial stress (secretion, action) Malnutrition (action) Glucocorticoid excess (?) Drug use

Decreased GH secretion: Idiopathic Hereditary:

autosomal recessive, or dominant Embryologic defects:

Aplasia, hypoplasia, ectopia Anencephaly, arrhinencephaly Septo-optic dysplasia Midline facial dysplasia Empty sella syndrome Miscellaneous syndromes Biologically inactive GH Neurosecretory dysfunction GH resistance:

Laron type dwarfism (GH receptor deficiency) Pygmy type dwarfism IGF-1 Resistance

(IGF deficiency)

Time (min)

Table 2

Comprehensive Hypothalamic—Pituitary Testing Performed Over Limited Time Interval (4.5 h)a

Combined Insulin Tolerance-TRH-GnRH Arginine Stimulation Studyb



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