Bentham Science Logo

New Emirates Medical Journal

Volume 3, 2 Issues, 2022
ISSN: 0250-6882 (Online)
This journal supports open access

Open Access Article

Pituitary Stalk Interruption Syndrome in a Newborn with Encephalopathy: A Case Report



Mary J. Jose1, *, Lara M. Leijser1, 3, Anvita Pauranik2, Harish Amin1
1 Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, Canada
2 Department of Diagnostic Imaging, Cumming School of Medicine, University of Calgary, Calgary, Canada
3 Alberta Children’s Hospital Research Institute, Calgary, Canada

Abstract

Background:

Pituitary Stalk Interruption Syndrome is a rare midline brain anomaly involving the pituitary gland that leads to a variable degree of pituitary hypofunction with a classic neuroimaging finding of the ectopic posterior pituitary, thin or absent pituitary stalk, and anterior pituitary hypoplasia.

Case Presentation:

We present the case of a term newborn who developed encephalopathy and respiratory distress during the neonatal period and was later diagnosed with Pituitary Stalk Interruption Syndrome.

Conclusion:

Genetic defects have been identified in 5% of cases, and at times there are associated extra pituitary malformations. In spite of being a well-described syndrome, a detailed description of its neonatal presentation and course is lacking in the literature.

Keywords: Neonatal encephalopathy, Pituitary stalk interruption syndrome, Ectopic posterior pituitary gland, Combined pituitary hormone deficiency, Central hypothyroidism, Growth hormone deficiency.


Article Information


Identifiers and Pagination:

Year: 2022
Volume: 3
Issue: 2
E-location ID: e030322201667
Publisher Id: e030322201667
DOI: 10.2174/03666220303155523

Article History:

Received Date: 30/5/2021
Revision Received Date: 8/9/2021
Acceptance Date: 20/12/2021
Electronic publication date: 15/03/2022
Collection year: 2022

© 2022 Jose et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


* Address correspondence to this author at the Department of Pediatrics, Section of Neonatology, Cumming School of Medicine, University of Calgary, HMRB room 274; 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada;
Tel: (403) 944-4638; E-mail: mailtomarysuma@yahoo.com





1. INTRODUCTION

Neonatal Encephalopathy, defined as a state of disturbed neurological function in the newborn, is typically a manifestation of hypoxic-ischemic injury. Nonetheless, it can also be due to other underlying conditions, including congenital infections, meningitis, intracranial bleeds, genetic syndromes, metabolic disorders, central nervous system anomalies, neuromuscular and cardiac disorders, epilepsy syndromes, and non-accidental brain injury. We have described a full-term newborn who developed encephalopathy during the neonatal period and was subsequently diagnosed with Pituitary Stalk Interruption Syndrome, a rare midline brain anomaly. In spite of being a well-described syndrome, a detailed description of its neonatal presentation and course is lacking in the literature.

2. CASE PRESENTATION

A term baby boy was born to a primiparous mother whose pregnancy was complicated by appropriately treated non-primary genital herpes, bicornate uterus, and persistent breech presentation from 28 weeks gestation. All antenatal ultrasound scans were normal, including the mid-gestation anomaly scan, and there was no substance abuse, smoking, or alcohol consumption throughout pregnancy. An elective Caesarean section under spinal anesthesia was done at term for breech presentation.

During induction of anesthesia, a brief drop in fetal heart rate to 80 beats/minute was noted with quick recovery to baseline. The baby was born with no respiratory effort and bradycardia (40 beats/minute) requiring active resuscitation, including intubation at 4 minutes. The Apgar scores were 1 and 9, respectively, 1 and 5 minutes of life. By 10 minutes, he had spontaneous breaths, limb movements, and an appropriate tone. His umbilical cord arterial pH was 7.07, with a base deficit of 8. He was admitted to the NICU on assisted ventilation for post-resuscitation care and unexplained perinatal depression with respiratory distress.

In the first four hours, his issues were respiratory distress requiring assisted ventilation and surfactant with X-ray suggestive of Respiratory Distress Syndrome (RDS), hypotension responsive to a saline bolus, and hypoglycemia with the lowest level being 1.4 mmol/L, requiring 3 dextrose boluses and a glucose infusion rate as high as 11.3 mg/kg/min. His neurological assessment was normal, and no seizures were seen. A complete blood count and blood culture were drawn, and empirical antibiotics were started. A decision to extubate was made around 4 hours of life, as he required minimal assisted ventilation and was hemodynamically stable with no signs of encephalopathy. Following extubation, he had profound apnea with bradycardia necessitating emergent reintubation (without pre-medication). He drifted into hypotension refractory to two inotropes and metabolic acidosis. There was concurrent deterioration in his neurological status in terms of emerging lethargy, reduced spontaneous movements, poor respiratory effort, and hypotonia. No seizures or other abnormal movements were observed. In this context, hydrocortisone was given, after which his blood pressure normalized, acidosis resolved and facilitated quick weaning and discontinuation of inotropes by 20 hours of age.

With regard to anthropometry, his weight was 3.2 kg, length 52 cm, and head circumference 35 cm corresponding to 38th centile, 87th centile, and 66th centile, respectively, on World Health Organization growth charts. Physical examination revealed subtle dysmorphisms, including bilateral low set ears, bilateral preauricular pits, a small café-au-lait spot over the right temple, and a high arched palate. His head circumference was normal, and he had normal genitalia with normal penile length and no cryptorchidism. Serial neurologic assessments in the first hours of life were normal. Abnormal neurological findings were noticed from 4 hours of age and were profound for the first 2 days of life. At the peak of his encephalopathy (6 hours to 2 days), he showed minimal response to stimulation, hypotonia (axial more than appendicular), poor respiratory effort, brisk deep tendon reflexes, and depressed primitive reflexes. He never received sedation. Apart from the hypotension, his cardiovascular examination was normal, and there was no organomegaly. The findings in the initial respiratory system examination were suggestive of RDS.

The common etiologies for NE, like HIE, sepsis, and Herpes Encephalitis seemed less likely here because of the comprehensive prenatal surveillance, non-primary herpes infection appropriately treated with valacyclovir, no evident perinatal risk factors or signs for sepsis or HIE, delivery by C-section, reassuring cord blood gas and normal neurologic examination in the early hours of life. The transient fetal bradycardia during the induction of anesthesia seemed an unusual event. Given the unexpected and atypical clinical presentation of NE with mild dysmorphic features, we considered CNS malformations, metabolic disorders, and genetic disorders as potential underlying causes, and investigations were directed accordingly.

Blood and CSF infection panel testing was negative for bacteria and viruses. Basic urine and serum metabolic screen profile were normal. The blood-spot screen and hearing screen were normal. Karyotyping showed 46XY and Chromosomal Microarray was normal. An echocardiogram showed normal anatomy and function. Furthermore, the cranial ultrasound was normal.

His tone, activity, and responsiveness improved by day 3, but it took about 3 weeks to establish well-coordinated oral feeding. When things seemed to be better on day 3, there was an increasing ventilation requirement with the X-ray again showing features of RDS, and the second dose of surfactant was given with good clinical response. He was extubated on day 5 to nasal flow and subsequently to room air by 14 days of life. Hydrocortisone was weaned and discontinued on day 5. Parenteral dextrose was gradually weaned over 5 days to full enteral feeding, and he maintained euglycemia. Given the unusual presentation, antibiotics were given for 7 days and acyclovir for 5 days despite negative results.

On brain Magnetic Resonance (MR) imaging done on day 7, findings were consistent with pituitary stalk interruption syndrome (PSIS) related to ectopic posterior pituitary location and lack of normal pituitary infundibulum. The posterior pituitary bright spot was ectopic, located at the level of the median eminence of the hypothalamus instead of the usual location within the Sella turcica. The pituitary infundibulum was not clearly defined and was considered either absent or severely hypoplastic. The anterior pituitary gland was very small in size, lacking the usual normal T1 hyperintensity which is seen in newborns related to maternal hormones. An additional finding was the presence of bridging across the floor of the third ventricle due to hypothalamic adhesion. No cortical malformation or evidence of acute insult to the brain due to hypoglycemia or hypoxia were noted (Fig. 1).

Following the neuroimaging, the Endocrinology opinion was sought, and further workup was done (Table 1). Anterior pituitary hormone profile at two weeks of age showed definite central hypothyroidism (Thyroid Stimulating Hormone (TSH) – 0.02 milli international unit per liter (IU/L) and Thyroxine -30.2 picomoles/ liter). The Growth hormone (GH) value was 2.5microgram per liter, Luteinizing Hormone (LH) < 1 IU/L, Follicle Stimulating Hormone (FSH) <1 IU/L and Testosterone <0.2millimoles/liter. They were low, suggesting a deficiency, but not low enough to necessitate the start of replacement therapy. The cortisol response to Adrenocorticotrophic Hormone (ACTH) stimulation test was age-appropriate. Given these findings, he was initiated on thyroid replacement therapy alone with a plan to closely monitor his pituitary function on an outpatient basis. Ophthalmology assessment ruled out optic nerve dysplasia.

3. DIAGNOSIS

Consolidating the evident findings of low Apgar scores, hypoglycemia, NE, steroid-responsive hypotension, evident central hypothyroidism, low normal levels of GH, LSH, FSH as well as testosterone, dysmorphic facial features and MRI showing ectopic posterior pituitary location, abnormal pituitary infundibulum, and hypothalamic adhesions, the diagnosis of PSIS with a preoptic variant of holoprosencephaly was made.

Table 1
Pituitary hormone profile of the baby from the neonatal period to 6 months of age.

Fig. (1)
Sagittal T1, coronal T1, and coronal T2-weighted images of the neonate (1a-c) as compared to normal control of similar age (1d-f). Panel 1a shows the ectopic location of the posterior pituitary bright spot at the level of the median eminence of the hypothalamus, instead of the usual location within the sella turcica (panel 1d). Absent/severely hypoplastic pituitary stalk/infundibulum and a very small anterior pituitary are also seen. Note hypothalamic adhesion across the floor of the III ventricle.

At 6 months of age, apart from an intercurrent respiratory illness requiring hospitalization, he remains healthy. His growth and development are commensurate with his age. His blood glucose, electrolytes, blood gases have been normal at 6 months of age. His endocrine profile remains abnormal with very low Thyroid Stimulating Hormone (TSH) and borderline low normal values of GH, cortisol, testosterone, FSH, and LH (Table 1). He is regularly followed by pediatrics, developmental pediatrics, endocrinology, and neurology services.

4. DISCUSSION

PSIS is a congenital pituitary defect that falls in the spectrum of congenital midline abnormalities, with an estimated prevalence of about 0.5/100,000 [1]. PSIS causes Combined Pituitary Hormone Deficiency (CPHD), mostly anterior pituitary deficiency, with GH deficiency being the most common phenotype, and is unique due to the complex nature of its phenotype [2]. It invariably progresses to manifest complete CPHD with clinical signs emerging over time. The occurrence of PSIS is most often sporadic, and in less than 5% of cases, mutations in genes like HESX1, LHX4, OTX2, SOX3, and PROKR2 have been identified [3]. The onset of signs of hormone deficiency in the neonatal period indicates more severely affected pituitary development and CPHD, and only 15% of PSIS is diagnosed in the neonatal period, often due to under-recognition of symptomatology [4]. CPHD, if undiagnosed, poses a risk of morbidity and mortality associated with hypoglycemia, adrenal insufficiency causing circulatory failure and electrolyte imbalances, liver dysfunction, failure to thrive, and hypothyroidism affecting growth, neurodevelopment, and infertility [4]. This underscores the importance of having a higher index of suspicion of pituitary deficiency in the nursery when an infant presents with low Apgar scores, hypoglycemia, hypotension, or persistent jaundice that common causes like sepsis or HIE cannot explain.

The antenatal factors described in higher frequency in PSIS are breech presentation, male sex, as noted in our case, and low birth weight. Neonatal manifestations described are low Apgar scores, hypoglycemia, either persistent or transient, cryptorchidism/micropenis, prolonged hyperbilirubinemia and cholestasis, and a higher rate of NICU admissions [5, 6]. There are reports of ‘neonatal distress’ in PSIS, but there is no clear description of what this entails. The presence of RDS seen in our case has not been previously described in the context of PSIS. It could be secondary to adrenal dysfunction contributing to surfactant deficiency or dysmaturation [7, 8]. The hypoglycemia and hypotension, along with low cortisol level responsive to hydrocortisone, are possibly due to adrenal insufficiency that became apparent during a period of stress, birth being the most potent stressor for a newborn [7].

The two most commonly reported associated syndromes with PSIS are Septo-optic Dysplasia and holoprosencephaly. The morbidity associated with these conditions is exacerbated by PSIS [2].

CONCLUSION

In conclusion, PSIS is a rare but severe cause of CPHD which is associated with an increased risk of mortality and short and long-term morbidity. It can be diagnosed in the neonatal period if there is a high index of suspicion, especially in a newborn with unexpected and unexplained encephalopathy, hypoglycemia, circulatory instability, and cholestasis. Early diagnosis ensures timely initiation of hormone replacement therapy, prevention, and mitigation of complications of multiple hormone deficiencies. Close follow-up is vital to facilitate the growth and development of these infants to their maximum potential and address fertility issues as they transition to puberty [1, 9].

AUTHORS' CONTRIBUTIONS

Dr. Jim Jose and Dr. Leijser conceptualized and drafted the initial manuscript and reviewed and finalized the manuscript; Dr. Pauranik drafted the neuroradiology segment and figures for the manuscript; Dr. Amin critically reviewed the manuscript for important intellectual content.

LIST OF ABBREVIATIONS

PSIS  = Pituitary Stalk Interruption Syndrome
CPHD  = Combined Pituitary Hormone Deficiency
NE  = Neonatal Encephalopathy
RDS  = Respiratory Distress Syndrome
GH  = Growth Hormone
TSH  = Thyroid Stimulating Hormone
T4  = Thyroxine
LSH  = Luteinizing Hormone
FSH  = Follicle Stimulating Hormone
ACTH  = Adrenocorticotrophic Hormone
MRI  = Magnetic Resonance Imaging

ETHICS APPROVAL AND CONSENT TO PARTICIPATE

Not applicable.

HUMAN AND ANIMAL RIGHTS

Not applicable.

CONSENT FOR PUBLICATION

Written informed consent was obtained from the guardian.

STANDARDS OF REPORTING

CARE guidelines and methodologies were used in this study.

AVAILABILITY OF DATA AND MATERIALS

None.

FUNDING

None.

CONFLICT OF INTEREST

The authors declare no conflict of interest, financial or otherwise.

ACKNOWLEDGEMENTS

Declared none.

REFERENCES

[1] Wang CZ, Guo LL, Han BY, Su X, Guo QH, Mu YM. Pituitary stalk interruption syndrome: From clinical findings to pathogenesis. J Neuroendocrinol 2017; 29(1)
[http://dx.doi.org/10.1111/jne.12451] [PMID: 27917547]
[2] Vergier J, Castinetti F, Saveanu A, Girard N, Brue T, Reynaud R. Diagnosis of endocrine disease: Pituitary stalk interruption syndrome: Etiology and clinical manifestations. Eur J Endocrinol 2019; 181(5): R199-209.
[http://dx.doi.org/10.1530/EJE-19-0168]
[3] Bar C, Zadro C, Diene G, et al. Pituitary stalk interruption syndrome from infancy to adulthood: Clinical, hormonal, and radiological assessment according to the initial presentation. PLoS One 2015; 10(11): e0142354.
[http://dx.doi.org/10.1371/journal.pone.0142354] [PMID: 26562670]
[4] Pierce M, Madison L. Evaluation and initial management of hypopituitarism. Pediatr Rev 2016; 37: 370-6.
[http://dx.doi.org/10.1542/pir.2015-0081]
[5] Lichiardopol C, Albulescu DM. Pituitary stalk interruption syndrome: Report of two cases and literature review. Acta Endocrinol (Bucur) 2017; 13(1): 96-105.
[http://dx.doi.org/10.4183/aeb.2017.96] [PMID: 31149155]
[6] Murray PG, Hague C, Fafoula O, et al. Associations with multiple pituitary hormone deficiency in patients with an ectopic posterior pituitary gland. Clin Endocrinol (Oxf) 2008; 69: 597-602.
[http://dx.doi.org/10.1111/j.1365-2265.2008.03236.x]
[7] Dekowski SA, Snyder JM. The combined effects of insulin and cortisol on surfactant protein mRNA levels. Pediatr Res 1995; 38(4): 513-21.
[http://dx.doi.org/10.1203/00006450-199510000-00007] [PMID: 8559602]
[8] Marik PE. Mechanisms and clinical consequences of critical illness associated adrenal insufficiency. Curr Opin Crit Care 2007; 13(4): 363-9.
[http://dx.doi.org/10.1097/MCC.0b013e32818a6d74] [PMID: 17599004]
[9] Wang F, Han J, Wang Z, Shang X, Li G. Growth and adult height during human growth hormone treatment in chinese children with multiple pituitary hormone deficiency caused by pituitary stalk interruption syndrome: A single centre study. J Clinical Res Ped Endocrinol 2019; 12(1): 71.
[http://dx.doi.org/10.4274%2Fjcrpe.galenos.2019.2019.0086]

Editor-in-Chief

Abdullah Shehab
Emirates Cardiac Society
Emirates Medical Association
Dubai
(United Arab Emirates)
Biography
View Full Editorial Board

Annual Journal Metrics

Speed

Acceptance rate = 40%

Average review speed: 45 days average

18 days from acceptance to publication



Webmaster Contact: info@benthamscience.net