P3D382: Leuprolide Remediable Hypothalamic Instability? Coincidence or Cause?

Introduction: Advances in neonatal care have led to remarkable survival outcomes, particularly in the extremely premature. Those who survive extreme prematurity are often impacted by varying degrees of neurodevelopmental disability. Clinical course is highly variable with extreme heterogeneity of outcomes, often leaving clinicians in a position to think outside the box for treatment of medical issues. We describe the case of a 4-year-old male with recurrent hypothalamic instability in whom the identification and treatment of precious puberty uncovered a potential link between these two entities that has not be previously described.

Case Description: 4-year-old male with complex history; extreme prematurity complicated by intraventricular hemorrhage with post-obstructive hydrocephalus and significant porencephaly was evaluated by pediatric endocrinology. In 6 months, patient had 5 PICU admissions, each admission for respiratory illness and hypothermia resulting from dysautonomia. The most recent ICU admission, exam notable for several long, coarse pubic hairs on leading to this referral for evaluation of puberty. Physical exam notable for testes 4mL bilaterally (>3mL consistent with puberty), several SMR 2 pubic hairs surrounding the scrotum and SMR 3 phallus. Central puberty was confirmed by laboratory testing as follows: LH 4.65 mIU/mL (>0.2 puberty), Testosterone 176.6 ng/dL (>20 puberty), Androstenedione 25 ng/dL and DHEA 13.1 mcg/dL. Additional evaluation of the hypothalamic-pituitary axis included; TSH, FT4, IGF-1, IGBP3, ACTH, Cortisol, and PRL which were all unrevealing. Patient started treatment for precocious puberty with leuprolide 1-month depot. After successful confirmation of puberty suppression, transitioned to 3-month 30mg leuprolide depot. Two months following the second 3-month dose, patient developed new pubic hairs, axillary body and new hypothalamic changes. Repeat labs at that time demonstrated breakthrough from puberty suppression. Increasing the dosing interval suppressed pubertal progression and extinguished hypothermia episodes.

Discussion: Initiation of pubertal suppression with leuprolide resulted in resolution of recurrent hypothermia, revealing a potential but yet to be described link between hypothalamic activity and precocious puberty. Children with neurodevelopmental disabilities due structural changes to brain anatomy are at increased likelihood to develop endocrine dysfunction. The link between structural brain differences and centrally mediated premature puberty has been well described. Hypothalamic instability, improving with leuprolide treatment and reoccurring when treatment effect is waning, has not been previously described.

Conclusion: We describe a previously unknown yet fortuitous effect of leuprolide treatment, uncovering a potential link at the neurotransmitter level. Comprehensive medical coverage for children with neurodevelopmental disabilities is a major factor in retention of active-duty service members. Health care providers in Exceptional Family Member Program (EFMP) heavy military treatment facilities care for a disproportionately high number children with complex health care needs. Broad understanding of the array of medical comorbidities is essential to provide optimal care and avoid potential hospitalizations.