57. Pathophysiology of growth

From greek.doctor

Physiology of growth

For optimal growth must several factors be fulfilled:

  • Sufficient protein intake – ca 1 g protein per kg body weight per day, where 50% of these are complete proteins
  • Sufficient Ca, Mg and P intake
  • Sufficient vitamin and trace element intake
  • Sufficient calorie intake
  • Normal function of the relevant hormones
    • Growth hormone
    • Thyroid hormones
    • Sexual hormones
    • Insulin
    • Vitamin D

The mean growth rate after 3 years old is around 6 cm per year. Peak growth rate is reached during puberty, around 12-13.

Growth hormone (GH) is, like the name implies, the most important hormone here. It is produced in the anterior pituitary in response to GHRH (growth hormone releasing hormone). Its level is highest during the night. The secretion of GH increases in response to:

  • Hypoglycaemia
  • Physical exercise
  • Protein-rich food
  • Stress
  • Sleep

The physiological effects of growth hormone include:

  • Decreasing glucose uptake of cells
  • Increasing gluconeogenesis
  • Increasing lipolysis
  • Increasing protein synthesis
  • Increasing production of insulin-like growth factor 1 (IGF-1) in the liver
    • Thickening of the chondral part of the epiphyseal plate
    • General anabolic effects

The main anabolic effect of GH comes from the increased levels of IGF-1. IGF-1 actually binds to insulin-receptors, which is what gave it its name, but the action of IGF-1 on insulin receptors is weaker than that of insulin, so it actually decreases insulin’s effects by antagonism.

Short stature

Short stature or dwarfism is defined as a child whose height is at least two standard deviation below the mean for children of the same age and sex. It may occur as a result of genetic, endocrine and metabolic disorders. Short stature isn’t necessarily pathological, as genetic factors account for 80% of height development and some families are just inherently smaller. It is pathological if there is growth failure.

Growth failure (or growth retardation) refers to a child whose growth rate is lower than normal. This is always pathological and leads to short stature. There can be many reasons for growth failure, both endocrine and not endocrine:

  • Decreased nutrient availability
    • Malabsorption
    • Protein deficiency
    • Starvation
  • Glucocorticoid excess
    • Glucocorticoid treatment
    • Cushing disease
  • Chronic hypoxia
  • Diabetes mellitus
  • Hypothyroidism
  • Genetic defects
    • Turner syndrome
    • Down syndrome
  • Vitamin D deficiency (Rickets)
  • Liver failure
  • Kidney failure
  • Childhood neglect/deprivation and abuse
  • GH deficiency (Pituitary dwarfism)

Pituitary dwarfism develops due to GH deficiency, often as part of a hypopituitarism. If only GH is affected dwarfism is the only symptom. If there is panhypopituitarism there will be more severe symptoms as well.

Pituitary dwarfism isn’t apparent until the age of 3-5, as other factors influence growth when in utero. Adults pituitary dwarfs are smaller than 140 but their growth is proportional, meaning that the body is proportional to the low height. Their mental development is normal, but sexual development is often impaired.

The causes of pituitary dwarfism are:

  • Hypothalamic disease
  • Hypopituitarism
  • Laron syndrome – where the GH receptor is mutated and insensitive to GH
  • Pigmy people – an ethnic group whose average height is less than 150 cm. GH and IGF-1 levels are normal.

Adult growth hormone deficiency obviously can’t influence growth like childhood growth hormone deficiency does, but it still causes symptoms. It’s most frequently caused by acquired hypothalamic or pituitary damage. Patients present with decreased energy, increased body fat-to-muscle ratio, hyperinsulinism (with tendency for hypoglycaemia) and reduced cardiac function.

Tall stature and abnormally rapid growth

Tall stature is defined as a child whose height is at least two standard deviation above the mean for children of the same age and sex. In most cases it’s normal and not pathological, but it can be due to an underlying pathology as well.

Gigantism is the condition where there is growth hormone overproduction already in childhood, leading to tall stature. This only occurs if the GH excess occurs before the epiphyseal plates close. Gigantism is most frequently caused by a GH-secreting adenoma in the anterior pituitary.

Acromegaly is the where the growth hormone overproduction starts in adulthood, after the epiphyseal plates close. The body’s height cannot increase, but the acral (extremities) parts still can. Like gigantism it’s most frequently caused by a GH-secreting adenoma in the anterior pituitary. The characteristics are:

  • Enlarged and widened nose, ear, jaw, hands and feet
  • Enlarged larynx -> deeper voice
  • Hair becomes more rough
  • Cardiovascular disease
    • Hypertension
    • Hypertrophic cardiomyopathy
  • Enlarged pharynx -> obstructive sleep apnoea
  • Visceromegaly – especially the lungs, heart, kidney and stomach
  • Nerve compression
    • Carpal tunnel syndrome
    • Thoracic outlet syndrome
  • Type III (“other”) diabetes mellitus – due to the anti-insulin effect
  • Bilateral hemianopsia – if caused by a pituitary tumor that compresses the optic chiasm