03c-GrowthHormone-2

Growth Hormone Regulation

  • Growth hormone (GH) release is regulated by two factors:

    • Positive factor: GHRH (Growth Hormone-Releasing Hormone)

    • Negative factor: SST (Somatostatin)

  • Hypothalamic Nuclei Involved:

    • Arcuate nucleus

    • Periventricular nucleus

  • Insulin-like Growth Factors (IGF):

    • IGF-1

    • IGF-2

Pathophysiology of Growth Hormone

  • Excess Growth Hormone:

    • Gigantism: Occurs due to overproduction of GH before puberty.

    • Acromegaly: Results from GH overproduction after puberty.

Diagnosing Growth Hormone Deficiency

  • Investigations for GH Deficiency:

    • Measure GH levels through multiple blood draws across one day to assess the frequency and amplitude of hormone peaks.

    • GH levels are normally low; assess IGF levels as well.

  • Clinical Manifestations of GH Deficiency:

    • Short stature

    • Decreased muscle mass

    • Increased adipose tissue

  • Diagnosis:

    • Evaluate GH and IGF levels

    • Determine if deficiency is untreated dwarfism or related to another cause.

  • Treatment Options:

    • Administration of synthetic GH or IGF

    • Possible GHRH administration.

Types of Dwarfism

  • Laron Dwarfism:

    • Inherited in an autosomal recessive pattern.

    • Characteristics include shorter stature, underdeveloped mandible, depressed nose bridge, and truncal obesity.

    • Mechanism of Deficiency:

      • Patients may have low IGF levels; may not respond to GH due to missing or defective GH receptors despite normal or elevated levels of GH.

    • Diagnosis:

    • Examine IGF levels to identify binding issues.

Variation in Dwarfism Cases

  • African Pygmies:

    • Display normal GH levels but lower IGF-1 levels, yet they are present.

    • Hypopituitary Cases:

      • Present with low GH and IGF levels.

    • Under-nutrition:

      • May contribute to conditions, potentially resulting from missing binding proteins for GH.

    • Treatment:

      • Hormonal therapy, such as GH and thyroid hormone for pituitary dwarfism.

Permissive Role of Hormones

  • Role of Hormones in Sensitivity:

    • Hormone A (e.g., Thyroid Hormone) must be present for hormone B (e.g., epinephrine) to exert its full effects.

  • Mechanisms of Interaction:

    1. Changes in the number of receptors (e.g., TH increases adrenergic receptors).

    2. Alteration of receptor affinity for the ligand.

    3. Actions at the level of G proteins, including regulation.

    4. Regulation of effector units involved in hormone signaling.

Thyroid Hormone Effects on Growth

  • General Effects:

    • Facilitates overall growth including bones and hair; increases the number of GH and IGF receptors.

  • Experimental Evidence from Rodents:

    • Growth hormone can be detected postnatal day 18-19; removal of the thyroid gland leads to decreased levels of GH in the pituitary and reduced numbers of somatotrophs.

  • Impact of Thyroid Hormone during Development:

    • The greatest influence occurs during childhood, correlating with intense somatic and linear growth.