Quantification of appetite-regulating hormones in children with hypothalamic and common obesity
Hoong-Wei Gan, Clare Leeson, Helen Aitkenhead, Helen Alexandra Spoudeas, Mehul Tulsidas DattaniAbstract
Context
The pathophysiology of hypothalamic obesity (HyOb) remains incompletely understood with no effective treatments.
Objective
We examined differences in appetite-regulating hormone concentrations between patients with HyOb, common obesity and lean controls.
Design
Multiway cross-sectional case-control study of patients aged 2-19 years.
Setting
Two tertiary paediatric endocrinology centres.
Patients
Cases were obese (BMI >+2 SDS, “HyOb”) and lean (“HyLean”) patients with congenital (septo-optic dysplasia) or acquired (suprasellar brain tumour) hypothalamic disorders. Controls had common obesity (“Ob”) or non-hypothalamic disorders and normal BMI (“Lean”).
Main outcome measures
Relationships between the Dykens’ Hyperphagia Questionnaire Score (DHQS), plasma or serum concentrations of leptin, insulin, α-melanocyte stimulating hormone (αMSH), brain-derived neurotrophic factor (BDNF), oxytocin, acylated ghrelin, agouti-related peptide (AgRP) and copeptin, and BMI SDS.
Results
DHQS did not differ between HyOb and Ob patients (24 (17-34) vs 24 (18-31)) but correlated with BMI SDS in patients with hypothalamic disorders (p = 0.02). HyOb and Ob patients exhibited similarly increased anorexigens (insulin, leptin) and decreased orexigens (ghrelin, AgRP) compared to HyLean and Lean patients. The rate of BMI increase was independently associated with lower αMSH (β=-0.23 (-0.36 to -0.11), p = 0.0007) and ghrelin (β=-0.004 (-0.01 to 0.00), p = 0.001) concentrations, suggesting that αMSH replacement may be a therapeutic target for HyOb. HyLean patients demonstrated intermediate insulin responses to glucose compared to other subcohorts.
Conclusions
In our cohort, patients with HyOb appeared indistinguishable from Ob in terms of their appetite and appetite-regulating neuroendocrine circuitry. Higher αMSH concentrations are associated with reduced weight gain and may be a target for therapeutic intervention.