DISORDERS OF GROWTH AND DEVELOPMENT

Growth is dependent on GH, IGF, sex steroids, thy­roid hormones, paracrine growth factors and cytokines. Growth also requires caloric energy, amino acids, vi­tamins and trace metals. Short stature results due to intrinsic and extrinsic factors which impair growth.

Growth  GHD Causes may be :

• Most common cause of GHD in children is idiopathic.
• Most common cause of GHD in adults is a pituitary adenoma or treatment of the adenoma with surgery or radiotherapy:
• · Hormonal disorders
• · Systemic disorders
• · Genetic disorders
• · Hereditary disorders

• GH deficiency causes short stature, increased fat, high pitched voice, hypoglycemia, micropenis.

 Growth Classic Stage Theories

Growth  GHD CLINICAL PRESENTATION —

• GHD can be divided into congenital and acquired forms.
• A variety of congenital genetic causes of GHD:
• GH secretagogue receptor gene defects
• GH gene defects
• Transcription factor defects (PIT-1, PROP-1, LHX3/4, HESX-1, and PITX-2)
• GHRH receptor gene defects
• GH receptor/postreceptor defects
• Prader-Willi syndrome
• The single most important clinical manifestation of GHD of all causes is growth failure, and careful documentation of growth rate is critical to making the correct diagnosis.

Physical Exam Growth  GHD 

• •Children with GHD:

  • Most common presentation is short stature
  • Assess pubertal status using Tanner staging system.
  • Severe GHD children have maxillary hypoplasia and forehead prominence; kewpie doll appearance.
  • Accurately measure height and weight.
  • Newborns may present with hypoglycemia, jaundice, or micropenis.

• •Adults:

  • Decreased lean body mass
  • Poor bone density

Associated Conditions

• Macroadenoma
• Sarcoidosis
• Sheehan syndrome

Treatment

• is replacement with GH 0.05 mg/kg/day subcutaneously for growth of 10 cm/year.

Growth  GHD Adult GH deficiency

• is caused by hypothalamic or pituitary damage of area secreting GH. Later there may be FSH / ~H, TSH and ACTH deficiency also.
• There is lean body with fat abdomen, and increased waist size, hyperlipidemia, hypertension,’ left ventricu­lar dysfunction.

Growth  GHD Treatment ,

• Replacement of GH 1.25 mg/day. Women require higher levels then men.
• Liquid solutions for SC injection: These are available in multidose pen devices.
• Encapsulated GH in glycolide microspheres for deep SC administration.
• Either 1.5 mg/kg body weight once a month or 0.75 mg/kg twice a month.
• Daily therapy is more effective than 3-times-a-week therapy. The recommended dose is 0.04 mg/kg/d for children

Acromegaly

• This is due to increased secretion of growth hormone due to pituitary adenoma, extrapituitary tumors, hy­pothalamic tumors, pancreatic islet cell tumor, adre­nal and thyroid tumors, pheochromocytoma.
• It is diagnosed at the age of 10 years or more. There is frontal bossing (prominent forehead), in­creased hand and foot size, wide thick jaw, space be­tween incisor teeth, thick heal pads, coarse facial fea­tures, large nose, muscle weakness, oily skin, cardi­omegaly, thick tongue etc. Patient looks abnormally huge.
• There is premature coronary heart disease, cardiomy­opathy, arrhythmias and death. These patients have obstructive sleep apnea, diabetes mellitus, colonic malignancy.

Differential Diagnosis

• Down syndrome
• Idiopathic short stature
• Noonan syndrome
• Prader-Willi syndrome
• Renal failure
• Russell- Silver syndrome
• Small size for gestational age in newborns
• Turner syndrome

Lab diagnosis:

• IGF-I (insulin-like growth factor) level is elevated.
• There is failure of GH suppression in response to glu­cose load (75 g glucose).
• Thyroid-stimulating hormone (TSH) (hypothyroidism should be excluded as a cause)
• Serum electrolytes (low bicarbonate levels may indicate renal tubular acidosis)
• IGF-1, IGFBP-3
• Multiple GH levels

Treatment

• Surgical resection (transsphenoidal) Somatostatin analogues-Octreotide acetate
• Bromocriptine, a dopamine agonist may suppress GH
• Irradiation
• Stereotactic ablation by gamma knife.