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 Table of Contents  
CASE REPORT
Year : 2016  |  Volume : 5  |  Issue : 1  |  Page : 61-63

Hypothalamic pituitary axis dysfunction in a neonate with severe Hypoxic-ischemic encephalopathy


1 Department of Paediatric Endocrinology, Alder Hey Children's Hospital NHS Trust, Liverpool, Merseyside L12 2AP, United Kingdom
2 Department of Neonatology, Women's and Children's Hospital, Wirral University Teaching Hospital NHS Foundation Trust, Wirral, Merseyside CH49 5PE, United Kingdom

Date of Web Publication6-Jan-2016

Correspondence Address:
Sanjeev Rath
Neonatal Unit, Women's and children hospital, Wirral University Teaching Hospital NHS Foundation Trust, Upton Road, Wirral, Merseyside, CH49 5PE
United Kingdom
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2249-4847.165691

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  Abstract 

Severe hypoxic-ischemic encephalopathy (HIE) in the newborn period is known to cause multi-organ dysfunction. Our index case describes a 40 weeks newborn infant who was born in a depressed state with poor cord gases and Apgar scores and needed cardiopulmonary resuscitation. During the 2nd week of life, the newborn infant became polyuric with persistent hypernatremia along with problems in maintaining body temperature. Investigations revealed the newborn infant to suffer from neurogenic diabetes insipidus, secondary adrenal, and thyroid insufficiency. Magnetic resonance imaging of the brain showed abnormal heterogeneous signals within the thalami and basal ganglia consistent with severe HIE. Commencement of regular desmopressin, hydrocortisone, and levothyroxine resulted in the improvement of hypernatremia, polyuria, thyroid functions, and serum cortisol levels but unstable thermoregulation continued to persist. Such multiple endocrinopathies involving both the anterior and posterior pituitary gland and hypothalamus as sequelae to severe HIE in newborn infants have not been widely reported in the literature.

Keywords: Adrenal insufficiency, diabetes insipidus, hypopituitarism, neonatal encephalopathy, thermoregulation


How to cite this article:
Giri D, Rath S, Babarao S. Hypothalamic pituitary axis dysfunction in a neonate with severe Hypoxic-ischemic encephalopathy. J Clin Neonatol 2016;5:61-3

How to cite this URL:
Giri D, Rath S, Babarao S. Hypothalamic pituitary axis dysfunction in a neonate with severe Hypoxic-ischemic encephalopathy. J Clin Neonatol [serial online] 2016 [cited 2019 Dec 15];5:61-3. Available from: http://www.jcnonweb.com/text.asp?2016/5/1/61/165691


  Introduction Top


Multi-organ dysfunction involving myocardium, liver, kidneys, bowels, and coagulopathies are well-described in the literature after severe hypoxic-ischemic encephalopathy (HIE) in newborn infants.[1] The occurrence of neurogenic diabetes insipidus (DI) is described in patients following HIE and it usually develops immediately or days after the insult.[2] Neurogenic DI caused by hypoxia/ischemia can be an ominous sign of severe brain damage in children with HIE.[2] Hypopituitarism as a sequel to HIE although rare can develop several weeks after the onset of DI.[3] The development of pituitary dysfunction is usually secondary to interruption of blood supply thereby causing resultant hypoxia to the pituitary.[4] The duration and the extent of interruption of blood supply may have a role in the degree of the damage. We report a case of severe HIE with a rare complication of hypothalamic-pituitary dysfunction.


  Case Report Top


A female newborn infant was born at 40 weeks gestation by normal vaginal delivery. She was born in a depressed state with low Apgar scores and poor cord gas (pH: 6.76, BE: 18.3) and needed cardiopulmonary resuscitation in the delivery suite.

During the first week, the newborn infant was hemodynamically unstable and received total body therapeutic hypothermia and multiple supportive therapies involving ventilation, nitric oxide, inotropes, Vitamin K, fresh frozen plasma for coagulopathy, antibiotics, fluid management for acute kidney injury, and anticonvulsants for seizures. Cerebral function monitoring (CFM) showed severely abnormal trace along with multiple seizure episodes [Figure 1] consistent with the clinical picture of severe HIE. Magnetic resonance imaging of brain performed on day 7 showed heterogeneous signal abnormality in the regions of thalami and basal ganglia consistent with significant HIE [Figure 2]. The newborn infant finally became stable and got extubated by the end of the 1st week.
Figure 1: Cerebral function monitoring showing burst suppression pattern along with multiple seizure episodes

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Figure 2: Magnetic resonance imaging brain showing heterogeneous signal abnormality in the regions of thalami and basal ganglia

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In the 2nd week of life, during routine investigations a persistent hypernatremia (plasma sodium: 150–157 mmol/L) was noted in multiple blood samples. A review of the fluid intake and output revealed that the newborn infant was polyuric (urine output of 5–6 ml/kg/h). The plasma osmolality was recorded as 312 mosm/kg with a urine osmolality of 256 mosm/kg [Table 1]. A diagnosis of DI was strongly suspected, and during the same period, the newborn infant was noted to have persistently low body temperatures (35–35.7°C) and had to be nursed in a heated cot. The diagnosis of DI compounded with unstable thermoregulation raised the possibilities of hypothalamic/pituitary injury. This led to further testing of endocrine functions. Baseline anterior pituitary hormone testing showed a low adrenocorticotrophic hormone (ACTH) of 1.5 pmol/L (2–11 pmol/L), with a low cortisol <30 nmol/L. Synacthen test showed a baseline cortisol response of 30 nmol/L and a peak of 483 nmol/L at 60 min consistent with a suboptimal response, confirming the diagnosis of secondary adrenal insufficiency [Table 1]. Thyroid hormone profile showed a normal thyroid stimulating hormone of 7.3 mU/L (0.96–13.68 mU/L) along with a low thyroxine (T4) of 9.6 pmol/(11.5–22.7 pmol/L) [Table 1]. These laboratory results in association with low ACTH and suboptimal Synacthen test strongly pointed toward secondary hypothyroidism.
Table 1: Blood investigations showing pituitary functions

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Following consultation with a pediatric endocrinologist, the newborn infant was supplemented with desmopressin, hydrocortisone, and levothyroxine. Starting desmopressin resulted in the improvement of plasma osmolality (288 mmol/kg) with normalization of the plasma sodium levels (135–141 mmol/L) and of polyuria. Hydrocortisone and thyroxine supplementation resulted in the improvement of the plasma cortisol and thyroid function but unstable thermoregulation continued to remain as an issue and baby had to be nursed in the heated cot until discharge. The newborn infant developed intractable seizures, progressively worsening neurology, and during one of the follow-ups with the multidisciplinary team developed lower respiratory tract infection and died at home at an age of 6 months.


  Discussion Top


Birth asphyxia causes 23% of all neonatal deaths worldwide.[5],[6],[7] HIE is mainly a clinical diagnosis, supported by CFM. The estimation in cord blood/blood of elevated serum concentrations of protein S-100, brain-specific creatine kinase, and neuron-specific enolase may help indicate moderate and severe HIE as early as 2 h after birth.[8] Brain hypoxia and ischemia due to systemic hypoxemia, reduced cerebral blood flow, or both are the primary physiological processes that lead to hypoxic-ischemic encephalopathy.[5],[6],[7] Neurogenic DI has been reported in children with severe HIE [2] as is the association of subarachnoid hemorrhage and diabetic ketoacidosis.[9],[10],[11] The neurohypophyseal system has many neurosecretory cells with an intricate bilateral blood supply making the supraoptic and paraventricular nuclei much resistant to the disruption in cerebral circulation and the resultant hypoxemia.[3] In some experimental studies, it has been demonstrated that development of DI in animal models is associated with a loss of 90% of the neurosecretory cells indicating that the appearance of DI following brain injuries denotes widespread neurologic damage.[3] Studies have shown that the interval of onset of DI from the time of the hypoxic injury could be variable. The mean interval between the hypoxic insult and the onset of DI was 4.07 days and ranged from 2 h to 13 days. The majority (86%) of patients developed DI within 6 days after the hypoxic insult.[2],[4] Our index case was identified to develop problems in the 2nd week of the illness. We postulate, the problem of unstable thermoregulation could be explained by the damage to the hypothalamic thermoregulatory center, DI could be explained by the damage sustained either to the supraoptic nuclei in the anterior hypothalamus blocking the release of vasopressin or insult to posterior pituitary itself. Secondary adrenal and thyroid insufficiency may be due to the affection of the anterior pituitary or defective secretion of the releasing hormones from the hypothalamus. Development of hypopituitarism as a sequel of HIE in adult patients is well-described but its occurrence as a sequel to HIE in a neonate is not widely reported.[3] The endocrinopathies encountered in our index case clearly demonstrate the involvement of anterior, posterior pituitary, and the hypothalamic pituitary (HP) axis.


  Conclusion Top


Neurogenic DI and anterior pituitary dysfunction, although rare complications can develop following severe HIE in the neonatal period. Vigilance in monitoring fluid balance, serum electrolytes, and baseline pituitary function can help earlier identification of the endocrinopathies arising secondary to the involvement of pituitary and the HP axis. This could help the medical team in initiating appropriate treatment.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Shah P, Riphagen S, Beyene J, Perlman M. Multiorgan dysfunction in infants with post-asphyxial hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed 2004;89:F152-5.  Back to cited text no. 1
    
2.
Lufkin EG, Reagan TJ, Doan DH, Yanagihara. Acute cerebral dysfunction in diabetic ketoacidosis: Survivial followed by panhypopituitarism. Metabolism 1977;26:363-9.  Back to cited text no. 2
    
3.
Lee YJ, Huang FY, Shen EY, Kao HA, Ho MY, Shyur SD, et al. Neurogenic diabetes insipidus in children with hypoxic encephalopathy: Six new cases and a review of the literature. Eur J Pediatr 1996;155:245-8.  Back to cited text no. 3
    
4.
Su DH, Liao KM, Chen HW, Huang TS. Hypopituitarism: A sequela of severe hypoxic encephalopathy. J Formos Med Assoc 2006;105:536-41.  Back to cited text no. 4
    
5.
Perlman JM. Brain injury in the term infant. Semin Perinatol 2004;28:415-24.  Back to cited text no. 5
    
6.
Grow J, Barks JD. Pathogenesis of hypoxic-ischemic cerebral injury in the term infant: Current concepts. Clin Perinatol 2002;29:585-602, v.  Back to cited text no. 6
    
7.
Janet M. Rennie. Rennie and Roberton's Textbook of Neonatology. 5th ed. Metabolic and Endocrine disorders. Churchill Livingstone. 2012. p. 869-70.  Back to cited text no. 7
    
8.
Nagdyman N, Kömen W, Ko HK, Müller C, Obladen M. Early biochemical indicators of hypoxic-ischemic encephalopathy after birth asphyxia. Pediatr Res 2001;49:502-6.  Back to cited text no. 8
    
9.
McMahon AJ. Diabetes insipidus secondary to hydrocephalus. Postgrad Med J 1988;64:724.  Back to cited text no. 9
    
10.
Glauser FL. Diabetes insipidus in hypoxemic encephalopathy. JAMA 1976;235:932-3.  Back to cited text no. 10
    
11.
Lee YJ, Lee SG, Kwon TW, Park KM, Kim SC, Min PC. Neurologic complications after orthotopic liver transplantation including central pontine myelinolysis. Transplant Proc 1996;28:1674-5.  Back to cited text no. 11
    


    Figures

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