Central Hypogonadism and Acquired Growth Hormone Deficiency Secondary to Sellar Mass From Traumatic Brain Injury: Missed Diagnosis in Childhood

Hypopituitarism secondary to brain injury remains significantly under diagnosed. We report a case of childhood growth hormone (GH) deficiency with hypogonadism diagnosed 15 years later.

Case Description:

A 27 year old Hispanic male presented to the clinic with symptoms of delayed puberty. Most notably, absence of morning erections, significant weight gain of 40 pounds and no change in height after age 10 years. Growth velocity charts were unavailable. Clinical history was negative intellectual disabilities, hypotonia, hyperphagia, facial dimorphism or family history of genetic disorders. On physical exam, he was found to be at Tanner stage 2 with absence of facial hair, micro-phallus (penile size 4 cm), pre-pubertal testicular size (5 cc) and arm span to height of 3 cms. His maximum height was 70 inches. There were no cushingoid features. Incidentally, patient reported history of traumatic head injury at 4 years of age. No work up was done at that time. Initial work up revealed total testosterone 17 ng/mL (264-916), FSH 1.3 mIU/mL (1.5-12.4), LH 3.4 mIU/mL (1.7-8.6), AM cortisol 18 ug/dL, ACTH 33 pg/mL, IGF-1 56 ng/mL (100-306) with Z score -3.3 (-2 to +2), prolactin 66 ng/mL (4-15), TSH 1.8uIU/mL (0.45-5.5), free T4 0.85 ng/dL (0.8-1.7) normal electrolytes and kidney function. Given significantly low testosterone and GH with mildly elevated cortisol, further work up showed normal dexamethasone suppression test (AM cortisol < 1 ug/mL) and serum iron studies. Patient failed Glucagon stimulation test indicating true GH deficiency. Baseline GH and IGF-1 were both low at 0.4 ng/mL and 86 ng/mL respectively. GH trend every 30 minutes for 4 hours post Glucagon injection (1 mg injection) showed peak level 0.7 ng/mL (normal: > 1 ng/ml in obese patients). Following this, pituitary MRI with contrast showed a left sided 1.2 cm sellar mass displacing the pituitary gland to the right with signal pattern suggesting old hemorrhagic/proteinaceous products. Diagnosis of HPA axis suppression with somatotropic and gonadotrophic deficiencies secondary to TBI was made. Hand films showed complete skeletal maturation. Patient was started on Testosterone injections that resulted in improvement in his sexual symptoms. Testicular size increased to 8 cc bilaterally and penile length to 5 cm. Given complete skeletal maturation, it was debated whether GH supplementation would be beneficial. We decided to consider GH injections in the future for cardiovascular/bone health benefits.

Discussion:

Hypopituitarism from traumatic brain injury should be investigated in a timely manner to minimize neuroendocrine dysfunction and improve quality of life outcomes. GHD is the most frequent pituitary deficiency in such cases followed by central hypogonadism.