In preparing this case report, we noted brief mentions in the endocrine literature, but not in the sports medicine literature, of sport-related concussion in children leading to hypopituitarism.
Traumatic brain injury is receiving considerable attention as a cause of hypopituitarism in adults because of the growing body of evidence that some symptoms of TBI, including mild TBI, may have a neuroendocrine basis. Mild TBI is characterized by cognitive impairment and memory loss. Secondary symptoms that persist after trauma (ie, postconcussion syndrome
) include additional cognitive problems, headaches, anxiety, fatigue, and psychosocial problems. Ten years ago, symptoms persisting past 3 months were thought to be primarily psychological in origin, but we now recognize that demonstrable neurologic conditions may contribute to these symptoms.
Sophisticated techniques able to pinpoint subtle changes in the brain strongly indicate that neuroendocrine disorders may be causing some symptoms persisting for many months after injury.
Prevalence studies indicate that hypopituitarism and the associated decline of growth hormone, adrenal hormones, and gonadal hormones accompany 15% to nearly 60% of all TBIs.
The severity of hormonal disturbances generally corresponds with TBI severity, but even minor head trauma can contribute to pituitary dysfunction.
For instance, Bondanelli et al
reported signs of pituitary dysfunction in 37.5% of their subjects with mild TBI versus 59.3% of subjects with severe TBI. Pituitary disturbances can be overlooked because many of the symptoms are masked by identical postconcussion symptoms or overshadowed by more noticeable symptoms.
Hypopituitarism symptoms may not show up for several years after TBI, which is long after most patients with mild injuries are monitored for complications. This fact has prompted some authors
to suggest that hypopituitarism may be undiagnosed in many patients with mild TBI.
Several direct and indirect factors have been strongly implicated when traumatic insult leads to pituitary insufficiency. Penetrating force can, in severe cases, damage the pituitary directly. Alternately, and more commonly, transection of the infundibulum, intracranial shear forces at the dural reflection that provides a partial covering for the sella, impaired perfusion, and inflammation are suspected.
The pituitary's location deep within the skull offers some protection from mechanical trauma, but magnetic resonance imaging and computed tomography scans have revealed that this location actually makes it vulnerable to portal vascular injury and edema, which can further lead to ischemia or necrosis (
). Even trauma that does not cause fracture may result in subdural hemorrhage and high intracranial pressure, which can predispose an individual to pituitary damage. Unfortunately, current brain imaging techniques can neither confirm nor entirely rule out abnormal function of a structurally intact pituitary gland.
It is not surprising then that the imaging of our patient showed no evidence of pituitary damage. The diagnosis of hypopituitarism is thus made by weighing the body of test results, reinforced by consistency with the mechanism of injury: in our case, head trauma.
Pituitary gland anatomy. The hypophyseal portal vascular system in the stalk is particularly vulnerable to injury. Encasement of the lobes by the bones of the pituitary fossa may result in high pressures following edema.
Hypopituitarism, pituitary insufficiency, and multiple pituitary hormone deficiency all describe underperformance of the anterior pituitary gland, with or without concomitant posterior pituitary insufficiency (eg, diabetes insipidus). Because the hypothalamus releases hormones into the hypophyseal portal vasculature, regulating secretion of downstream hormones by the pituitary gland, injury to the hypothalamus may result in hypopituitarism. Pituitary problems often follow a predictable path from the most vulnerable to the least vulnerable functions: growth hormone, gonadotropins, TSH, and then ACTH. Deficiencies in these hormones create further irregularities in hormone secretion in downstream glands. Because some of the injury mechanisms may be transient, may develop slowly, or may resolve without complications, hormonal imbalances seen just after injury may not correlate with hormonal levels 1 year later.
Growth hormone deficiency leads to a lack of growth in children, but less commonly recognized is that growth hormone remains necessary in adults, albeit at lower concentrations, to maintain proper body composition. Additional symptoms of growth hormone deficiency include lowered initiative, energy level, and exercise performance and, sometimes, poorer mental functions. Growth hormone replacement therapy by injection is currently the only successful treatment option.
Gonadotropin deficiency (LH, FSH) in males leads to failure of testicular growth (teens) or shrinkage of testicular size (adults). Testosterone production declines and, thus, reduced libido, poor erectile and ejaculatory function, loss of mustache and body hair, weakness, and anemia may eventually be noted. In premenopausal women, secondary amenorrhea is usually noticed promptly when gonadotropin secretion plummets. Disinhibition of prolactin may lead to galactorrhea and, in severe cases, interferes with any residual gonadotropin function.
Deficient TSH leads to underproduction of thyroid hormone, resulting in decreased energy, increased need to sleep, intolerance to cold, constipation, dry skin, aching muscles, mental slowing, and secondary growth hormone deficiency.
Adrenocorticotropin hormone deficiency directly results in decreased secretion of cortisol by the adrenal glands, which is generally regarded as the most life-threatening of the hormone deficiencies. Symptoms of gradual decline in cortisol production (fatigue, weakness, nausea, and apathy) can be subtle and nonspecific and, therefore, are often overlooked. These symptoms can easily be mistaken for postconcussion depression. As the deficiency progresses, or in cases of rapid onset, symptoms can include psychosis, abnormal electrolytes, and vascular collapse, which can be fatal. Damage to the posterior pituitary may cause antidiuretic hormone deficiency and lead to symptoms consistent with diabetes insipidus.