Question 1

What is the Meaning of Hepatic GH Resistance?

Accepted Answer

Hepatic GH Resistance describes a state where the liver shows reduced responsiveness to Growth Hormone, despite normal or elevated circulating levels. This impaired sensitivity primarily results in diminished production of Insulin-like Growth Factor-1 (IGF-1), a crucial mediator of GH actions, reflecting a functional disconnect in the somatotropic axis.

Question 2

What is the Context of Hepatic GH Resistance?

Accepted Answer

This resistance occurs within the somatotropic axis, a critical endocrine pathway regulating growth and metabolism. The liver is the primary target organ for Growth Hormone, translating its signals into systemic IGF-1 production. When hepatic GH resistance develops, this central communication pathway is disrupted, affecting the balance of anabolic and catabolic processes.

Question 3

What is the Significance of Hepatic GH Resistance?

Accepted Answer

Clinically, hepatic GH resistance contributes to various health concerns. In children, it impedes linear growth, as seen in Laron syndrome. For adults, this resistance often underlies metabolic dysregulation, including insulin resistance and dyslipidemia, common in chronic liver disease, obesity, and type 2 diabetes. This impacts diagnostic and therapeutic approaches.

Question 4

What is the Mechanism of Hepatic GH Resistance?

Accepted Answer

Hepatic GH resistance involves impaired signaling at or downstream of the Growth Hormone receptor (GHR) on hepatocytes. This can stem from reduced GHR expression or compromised post-receptor pathways, particularly the JAK2-STAT5b pathway. Inadequate STAT5b activation prevents proper IGF-1 gene transcription, leading to diminished IGF-1 synthesis.

Question 5

What is the Application of Hepatic GH Resistance?

Accepted Answer

Hepatic GH resistance commonly manifests in chronic illness states, notably severe liver dysfunction, malnutrition, and inflammatory conditions. Individuals often present with elevated Growth Hormone alongside low IGF-1, a pattern distinct from primary GH deficiency. This understanding guides clinicians in interpreting endocrine profiles and selecting appropriate interventions.

Question 6

What is the Metric of Hepatic GH Resistance?

Accepted Answer

Assessing hepatic GH resistance typically involves measuring serum Growth Hormone and Insulin-like Growth Factor-1 levels. A characteristic finding is elevated or normal GH coupled with low IGF-1, indicating a lack of hepatic response. Further evaluation may include assessing specific GH-binding protein levels or, in research settings, analyzing GH receptor expression.

Question 7

What is the Risk of Hepatic GH Resistance?

Accepted Answer

Failure to recognize and manage hepatic GH resistance can lead to persistent metabolic disturbances, including impaired glucose tolerance and adverse lipid profiles. In children, prolonged resistance compromises normal growth. Administering exogenous Growth Hormone without addressing resistance may yield minimal therapeutic benefit and could potentially exacerbate metabolic imbalances, underscoring accurate diagnosis.

Hepatic GH Resistance

Meaning

Context

Significance

Mechanism

Application

Metric

Risk

How Does Insulin Resistance Directly Affect Growth Hormone Pulsatility?