1. Overview
Ghrelin is a 28–amino acid peptide hormone predominantly produced by specialized cells in the stomach. It is a multifaceted gut hormone that exerts its biological effects by activating the growth hormone secretagogue receptor (GHS-R). It is widely known as the “hunger hormone” because it stimulates appetite, increases food intake, promotes fat deposition, and triggers the release of growth hormone from the pituitary gland.
As an orexigenic peptide, it plays a central role in energy balance by signaling nutritional status to the hypothalamus. It functions in physiological opposition to leptin, a hormone that suppresses appetite, thereby maintaining equilibrium between energy intake and expenditure.
2. Symptoms
Ghrelin itself does not cause symptoms; however, abnormal levels are associated with clinical conditions related to appetite regulation, metabolism, and growth hormone secretion.
Elevated ghrelin levels are observed in conditions characterized by increased appetite or compensatory hunger signaling, such as anorexia nervosa, cancer cachexia, and Prader–Willi syndrome. These states may present with excessive hunger, weight dysregulation, or muscle wasting.
Reduced ghrelin levels are often seen in obesity and metabolic syndrome and may be associated with impaired appetite signaling, insulin resistance, and altered energy homeostasis.
3. Causes
Alterations in ghrelin levels arise from metabolic, endocrine, and gastrointestinal factors. Its secretion increases during fasting and decreases after food intake, reflecting its role in short-term appetite regulation.
Chronic conditions such as obesity, type 2 diabetes mellitus, and metabolic syndrome are associated with lower circulating ghrelin levels. Conversely, ghrelin levels are elevated in states of negative energy balance, including cachexia, anorexia nervosa, chronic obstructive pulmonary disease (COPD), and after eradication of Helicobacter pylori.
It also influences glucose and insulin metabolism and contributes to cognitive function, mood regulation, and muscle performance, suggesting a broader physiological impact beyond appetite control.
4. Risk Factors
Risk factors associated with abnormal ghrelin regulation include obesity, metabolic syndrome, diabetes mellitus, chronic inflammatory conditions, eating disorders, gastrointestinal motility disorders such as gastroparesis, and chronic alcohol use.
Patients with growth hormone disorders may also exhibit altered levels, as ghrelin directly stimulates growth hormone secretion. In Prader–Willi syndrome, markedly elevated levels correlate with hyperphagia and severe obesity.
Lifestyle factors, nutritional status, and underlying endocrine or metabolic diseases significantly influence ghrelin secretion and action.
5. Prevention and Clinical Management
This testing is primarily used as an adjunctive diagnostic and research tool rather than a routine clinical test. Indications include evaluation of obesity, metabolic syndrome, cancer cachexia, anorexia nervosa, gastroparesis, alcohol addiction, and assessment of growth hormone disorders. It is also widely used in research focused on appetite regulation, energy homeostasis, and bariatric surgery outcomes.
Sample collection for ghrelin measurement requires strict handling protocols due to the hormone’s instability. Ghrelin is rapidly degraded by hydrolysis to des-acyl ghrelin; therefore, blood samples must be collected in EDTA tubes containing aprotinin under cooled conditions. Plasma should be acidified to a pH of 3–4 and stored at 4°C to maintain stability. Fasting samples are recommended for accurate interpretation.
Laboratory estimation methods include enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA), and advanced mass spectrometry techniques used mainly in research settings. The reported normal plasma ghrelin-like immunoreactivity concentration is approximately 166.0 ± 10.1 fmol/mL, as measured by RIA.
Clinically, ghrelin measurement aids in differentiating growth hormone deficiency from constitutional growth delay, evaluating metabolic risk in obesity, assessing compensatory appetite signaling in cachexia or anorexia nervosa, and understanding hyperphagia in Prader–Willi syndrome. In type 2 diabetes, reduced levels may reflect insulin resistance.
Despite its physiological importance, these tests have limitations. The hormone has a short half-life, exists in multiple molecular forms, and shows significant fluctuation with nutritional status. These factors complicate consistent measurement and limit its routine clinical use. Consequently, this testing is more commonly applied in research than in standard diagnostics, and results must be interpreted cautiously alongside clinical findings.
