Hypopituitarism after multiple concussions: a retrospective case study in an adolescent male.

OBJECTIVE: To describe the development of hypopituitarism in an adolescent athlete after multiple concussions and to raise awareness among sports medicine clinicians concerning the growing concern of hypopituitarism in concussion injury surveillance and management. BACKGROUND: A 14-year-old, previously healthy male athlete suffered 4 head traumas over a 4-month period. The first 3 traumas were considered by the athlete to be minor and were not reported to medical personnel. The fourth trauma was a medically diagnosed concussion suffered during soccer play. Over the next year, the patient noted a decline in strength and conditioning and a failure to grow. DIFFERENTIAL DIAGNOSIS: After physical examination and a full battery of endocrine tests, the patient, then 16.5 years old, was diagnosed with hypopituitarism. Follow-up interviews provided evidence that at least 2 of the 3 head injuries suffered before the last concussion could also be considered concussions, which may have contributed to the severity of the last head injury. TREATMENT: The patient is currently being treated with physiologic replacement hormones (growth hormone, cortisol, and thyroxine), with resumption of linear growth and strength. He is progressing well. UNIQUENESS: In the past few years in the medical literature, increased attention has been drawn to the occult occurrence of hypopituitarism after traumatic brain injury in adults. Initial reports indicate that children are also at risk. To our knowledge, this is the first reported case of hypopituitarism after mild traumatic brain injury in the sports medicine literature. CONCLUSIONS: Symptoms of hypopituitarism are often masked by trauma and postconcussion symptoms and may not appear until months or years after the trauma incident, which can lead to significant delay in proper diagnosis and treatment. We urge greater vigilance by, and training of, sports medicine clinicians toward the goal of recognizing the possibility of pituitary disorders after sports concussion.

Identification of hemopexin as a GH-regulated gene.

A cDNA library from the liver of a growth hormone (GH)-treated hypophysectomized rat was constructed and screened for GH-inducible genes (GIGs). Three cDNAs specific for putative GIG mRNAs (GIG-3, -7 and -12) were isolated and, when sequenced, were found to be homologous to portions of rat hemopexin, a Class 2 acute-phase gene. Hemopexin is an essential heme scavenger produced primarily in the liver, which upon binding to free heme, transports it to the liver where the heme iron is re-utilized. Hemopexin has not been previously described as being GH-responsive. GIG-3 and GIG-12 encode overlapping portions of the entire coding sequence starting within a few hundred base pairs from the 5' end of the hemopexin mRNA, and GIG-7 encodes the 3'-most end of the hemopexin mRNA. Northern analysis and ribonuclease protection assays of RNA from livers of control rats using the cDNA probes demonstrated a major transcript of approximately 2.0 kb. The hemopexin mRNA was low or undetectable in livers of hypophysectomized rats. Daily treatment with bovine growth hormone (bGH) for 10 days restored hemopexin mRNA to levels comparable or greater than that of intact rats. GH-dependence in cultured rat H4IIE hepatoma cells was then examined. Using hemopexin cDNA probes (GIG-3, -7, and -12) we identified a mRNA on Northern blots, which increased in concentration following bGH, compared with untreated cells. When measured by ribonuclease protection assay, a maximal increase in hemopexin mRNA concentration was obtained following 4-6 h of bGH administration. We conclude that hemopexin is a GH-inducible gene in rat liver in vivo and in cultured rat hepatoma cells.

Regulation of hemopexin transcription by calcium ionophores and phorbol ester in hepatoma cells.

Hemopexin (Hx) is an acute-phase hepatic protein, whose transcription is upregulated by IL-6. The transcription rate of Hx was found to be increased 11-fold by the calcium ionophore A23187, 25-fold by the calcium ionophore ionomycin, and 4-5-fold by phorbol 12-myristate 13-acetate (PMA) in serum-starved H4IIE rat hepatoma cells. Insulin did not affect the transcription rate of Hx. These findings are consistent with involvement of intracellular calcium concentrations and activation of protein kinase C (PKC) action in the regulation of Hx.