LHRH deficiency (gonadotropin-releasing hormone deficiency)

Epidemiology

• 1 case per 10,000 men & 1 case per 50,000 women

Pathology

• loss of the normal pulsatile secretion of LHRH by the pituitary

Genetics

• defects in PROK2 & its receptor PROKR2 may inhibit migration of hypothalamic neurons secreting LHRH
• defects in GPR54, GnRHR, DAX1, leptin, TAC3, TACR3, NELF, SEMA3A, WDR11, KAL1, FGFR1, FGF8 suggested

Clinical manifestations

• generally presents when patient fails to begin puberty & does not develop secondary sexual characteristics
• boys may present with micropenis (30%)
• cryptorchidism 50% of boys
• newborn girls have no obvious abnormalities

Laboratory

• low serum testosterone in males
• low serum LH
• los serum FSH

Radiology

• magnetic resonance imaging of the inferior frontal region of the brain in the coronal plane is the most useful

Differential diagnosis

• anosmia suggests Kallmann syndrome

Management

• androgen replacement in males
  • start at age 14-15 years
  • oral, injectable, transdermal, & implantable (pellets) androgen formulations currently are available
• in adult males desiring fertility, a different approach to replacement therapy is employed
  • spermatogenesis can be restored with
    • a combination of hCG & human menopausal gonadotropin (FSH & LH]
    • a combintation of hCG & FSH alone
    • GnRH injections
      • 25-600 ng/kg every 2 hours delivered subcutaneously using a programmable portable infusion pump
• hormonal contraception in females
• in adult females desiring fertility, a different approach to replacement therapy is employed
  • exogenous stimulation of the ovaries is accomplished with various preparations of human menopausal gonadotropin composed of FSH with different concentrations of LH
  • intravenous pulsatile GnRH appears to have advantages over gonadotropins

More general terms

• hypopituitarism

Additional terms

• gonadotropin-releasing hormone/factor; gonadoliberin; LH/FSH-releasing hormone (GnRH, LHRH)
• Kallmann syndrome; hypogonadotropic hypogonadism & anosmia