A Boy with Small Stature – A Case Study

 

 

D. Aleksijević1,  V. Smolka1, E. Klásková1, P. Venháčová1 , D. Krahulík2,  K. Michálková3, V. Mihál1, J. Zapletalová1

 

1. Pediatric Clinic, Faculty of Medicine, University of Palacky and University Hospital Olomouc,

2. Neurosurgical Clinic Faculty of Medicine, University of Palacky and University Hospital Olomouc,

3. Radiological Clinic Faculty of Medicine, University of Palacky and University Hospital Olomouc

 

Introduction

 

Brain injuries in children and adolescents are a major cause of serious morbidity and mortality, and thus they become a serious medical and social problem (1,2).

In the European Union countries the incidence of brain injuries is reported to be 185-250 cases per 100,000 children below 15 years old. About 6% of children die due to the injuries. The consequences in survivors may be different - from varying degrees of disability to long-term cognitive, psychological or social problems (3).

Also significant is the so-called post-traumatic hypopituitarism. Hormonal dysfunction may develop as early as the acute post-traumatic phase. In 70% of injuries it occurs during the first year after the injury (reference?) .  It is not uncommon for hormonal disorders to manifest several years after the injury (1,2,4).

Failure of hormonal production (particularly glucocorticoids) can be acutely life threatening to the patient. Unrecognized and untreated chronic deficit is accompanied by apathy, tiredness, muscle weakness and mental inefficiency and may worsen neurological symptoms, complicate rehabilitation and may be the cause of mental disorders (5).

Description of the case

A four-year old boy was admitted to a children's department after falling on his head. He had severe impairment of consciousness with tonic-clonic seizures (Glasgow Coma Scale 5/15).

 

CT_Scan.jpg

Figure 1: CT scan findings: Frontal bone fracture, subarachnoid haemorrhage, contusion of the frontal lobes.

The CT scan of the brain demonstrated frontal bone fracture, subarachnoid haemorrhage and contusion of the frontal lobes (Figure 1). Due to the severity of the findings, the boy was transferred to a specialized centre, where he underwent neurosurgery – for elevation and repair of cranial bone fragments. The boy spent a total of 12 days at the intensive care and resuscitation unit,  during which a total of 5 days of mechanical lung ventilation were required. He suffered from transient diabetes insipidus, which was corrected with adiuretin.  The chest radiograph identified secondary findings of old serial fractures of the ribs and humerus.

Given this finding, physical abuse was suspected, which was later confirmed. The child was placed in a foster home. Due to the placement in the foster home the boy seriously suffered and was in the care of a psychologist. He was tired, bradypsychic, and reacted badly to even mild physical stress. Six months after the injury the boy developed secondary epilepsy, for which he was treated with valproate and neuroleptics.

At 10 years of age the boy was sent to endocrinology because of serious delay in growth, which, according to the reconstructed growth curve followed the craniotrauma. Bone age was delayed by 6 years of age against the calendar age. He was examined for a basic hormonal and biochemical profile. Low levels of IGF 1 (insulin-like growth factor 1) fell in the band of -3.4 SDS, therefore he was indicated for a stimulated secretion of a growth hormone test.

After administration of Mestinon and Katapressan the maximum value of the growth hormone was 2.9 mIU/L, after clonidine it was 6.8 mIU/L (normal is above 20 mIU/L). A test for insulin-induced hypoglycaemia from the secondary epilepsy was negative. Other hormonal tests (TSH, fT4, fT3, cortisol, ACTH, prolactin) were normal. However, the hormonal status of the boy was monitored at regular intervals. 

He had a very positive response to treatment with growth hormones (see Figure 2). At the age of 15 years, he still suffers from three year delay of bone maturation. The levels of gonadotropic hormones and degree of sexual maturation correspond to the biological age of the boy (FSH 3.2 IU/L, LH 2 IU/L). We cannot exclude even partial hypogonadotropic hypogonadism.

 growth_curve.jpg

Figure 2:  Growth curve of the boy. The first arrow shows the time of the head injury, the second arrow shows the start of treatment with a growth hormone.

Discussion

 

The boy was diagnosed with partial hypopituitarism as a likely consequence of a brain injury, which occurred due to abuse by his mother.

The association of late consequences after brain injury with subsequent hormonal disorder is often neglected, even though the results of numerous retrospective and rare prospective longitudinal studies in adults exhibit the prevalence of this disorder affecting at least one hormonal axis in 28%-69% cases (6). Clinical diagnosis of post-traumatic hypopituitarism in adults is more difficult than in children because the symptoms are usually vague (fatigue, impaired concentration, weight gain, abnormal sexual appetite, etc.) and can be masked by ? neurological symptoms or associated with psychological trauma.

The Bevengov’s meta-analysis (4,6) from the year 2000 shows that the manifestation of hormonal deficiency occurs most often during the 6 to 12 months after the injury, however an interval of several weeks to several years cannot be excluded. Mostly, somatotropic and gonadotrophic axis are affected. It was shown that the severity of injury is in direct correlation with the emergence of endocrine disorders. Assessed groups were quite different with respect to the age of the patient and the interval from injury.

For the paediatric (child and adolescent) population the manifestations of endocrine dysfunction are prominent – they usually affect growth and sexual development, but as in adults, partial hormonal endocrine deficits can manifest very quietly. The occurrence of post-traumatic hypopituitarism and its impact on morbidity and mortality in children is definitely even less well known than in adults, as well as the possibilities and effects of treatment. From the results of published retrospective studies it is clear that the frequency of post-traumatic hypopituitarism is significantly lower in children than in adults.  It is about 15-20% (7) lower. The reason for this may be that the child's brain is more resistant to external insults, but this assumption is not supported by the findings of post-mortems, where structural changes are the same in children as in adults or in studies, that on the contrary, show that a child's brain has less reparatory and regenerative capacity (6.8).

The most probable hypothesis seems to be the fact that most of the children after a brain injury are not systematically monitored in this respect, and as with adults, possible hormonal insufficiency is masked by the general post-traumatic symptoms or neurological symptoms, which are the focus of all the attention in aftercare. The situation in children is all the more striking because in an individual with incomplete physical development, an unrecognized and therefore untreated hormonal disorder may significantly and permanently affect body growth, sexual maturation and neurocognitive function.

Conclusion

Although hypopituitarism occurs frequently after brain injury, it is generally not diagnosed and treated. Successful diagnosis for children and adolescents, requires not only the cooperation between ICU physicians, neurologists, endocrinologists, but also the assessment of GPs, who know the child and his/her family well and can longitudinally assess the physical development of the child and his/her behaviour. They may, in cooperation with the parents, be the first ones to notice specific abnormalities - growth failure, changes in weight, fatigue, weakness, low intellect, insomnia, impaired concentration, impaired school performance, etc.

It is necessary to pay special attention to the risks from a brain injury, not only in terms of subsequent neurological, rehabilitation, neurosurgical, psychological-psychiatric care, but also in terms of endocrinologic care.

Basic hormonal screening should be performed in every patient after a traumatic brain injury, not only in the acute phase after hospitalization, but also in an interval of 6-12 months after the injury, regardless of the patient’s current clinical status. Early and proper diagnosis of hormonal disorders allows for adequate hormonal substitution, which can significantly alleviate the traumatic consequences, positively affect physical and mental development, and thus improve the overall quality of life.

Reference

  1. Cyran E. Hypophysisenschadigung durch Schadelbasis fracture. Dtsch Med Wochenschr, 1918, 44: 1261 – 1270.
  2. Escamilla RF, Lisser H. Simmonds disease. J Clin Endocrinol Metab, 1942; 2: 65-96.
  3.  Masson F, Salmi LR, Maurette P. Characteristics of head trauma in children: epidemiology and 5-years folow up. Arch Pediatr, 1996, 3: 651-660
  4. Benvenga S, Campenni A, Ruggeri RM, Trimarchi F. Hypopituitarism secondary to head trauma. J Clin Endocrinol Metab, 2000; 85: 1353-1360.
  5. Agha A, Rogers B, Myllote D et al. Neuroendocrine dysfunction in the acute phase of traumatic brain injury. Clin Endocrinol, 2004, 60(5): 584-591
  6. Zapletalová J., Aleksijević D., Smolka V., Krahulík D., Fryšák Z. Posttraumatický hypopituitarizmus u dětí a dospívajících. Čes. Slov. neurologie a neurochirurgie 2010, 73/106(4): 398-401
  7. Aleksijević D., Zapletalová J., Smolka V., Klásková E., Wiedermann J., Krahulík D., Vaverka J., Fryšek Z. Neuroendokrinní dysfunkce u dětí a dospívajících po úrazu mozku. Čes.Slov. neurologie a neurochirurgie 2010, 73/106(4):409-414
  8. Gaetz M. The neurophysiology of brain injury. Clin Neurophysiol, 2004, 115: 4-18.

 

Corresponding Author 

 

D. Aleksijević

Pediatric Clinic, Faculty of Medicine
University of Palacky and University Hospital Olomouc