Empty sella syndrome in a male child with failure to thrive.

Empty sella syndrome (ESS) is commonly seen in adult and is considered as an infrequent finding in childhood. It may be diagnosed incidentally on imaging in asymptomatic children. However, most of the children with ESS present with features of hypothalamic-pituitary dysfunction. We report a case of ESS in a child with features of failure to thrive as well as hypopituitarism and review the literature briefly on the subject.

Introduction

Empty sella syndrome (ESS) is defined as the herniation of the subarachnoid space into the sella turcica through the sellar diaphragm, which is commonly associated with nonvisualization or some degree of flattening of the pituitary gland.[1] ESS is seen commonly in the adult patient and was first described by Busch[2] in 1951. Few case reports of ESS in children are described in the literature. ESS in children commonly present with hypothalamo-pituitary dysfunction,[3] diabetes insipidus, diabetes mellitus, optic atrophy, and nerve deafness (known as DIDMOAD syndrome),[4] in Bardet–Biedl syndrome[5] and growth hormone deficiency with 18P monosomy,[6] visual symptoms and cerebrospinal fluid (CSF) rhinorrhea.[7] In children, radiological incidence of primary ES was reported as 1–48% with a male: female ratio of 1.4:1.0.[8] Failure to thrive is a condition where a child's growth fails to meet the expected value for the child at that age. We report a child who presented to pediatric outpatient department (OPD) with features of failure to thrive and was found to have ESS and hypopituitarism on imaging and investigation.

Case Report

A 4-year-old male child born by nonconsanguineous marriage presented to pediatric OPD with complaint of abdominal distension, poor weight gain, and short stature. No history of polyuria or polydipsia was present. He had no previous history of trauma or operation. He was born by normal vaginal delivery at term and was vaccinated as per national immunization programme of India. He had no past history of tuberculosis or chronic illness. He was examined and found to have 8 kg weight (below 5th percentile), 82 cm height (below 5th percentile) and diagnosed as failure to thrive. He was admitted in our hospital for further evaluation. Central nervous system, cardio-respiratory system and per abdominal examination were normal. His visual acuity was 6/6 in both eyes with normal funduscopy study of eyes. His vitals were within normal limit for age. Complete hemogram and urine examination were normal. Urine specific gravity and urine osmolality (670 mOsm/kg) were normal. Mantoux and HIV ELISA test were negative. Ultrasonography study of abdomen and chest radiograph study was normal. Magnetic resonance imaging (MRI) of brain and pituitary was advised to rule out hypothalamo-pituitary dysfunction. Contrast enhanced MRI revealed normal size sella turcica, thinned out enhancing pituitary gland (2 mm height) in the bottom of sella, midline infundibulum, and nonvisualization of T1-weighted bright spot of posterior pituitary gland. Rest of sella turcica was filled with CSF signal. No intra sellar herniation of optic chiasma or no hydrocephalus was seen. Visualized brain parenchyma was normal [Figures 1 and 2]. Radiological diagnosis of ESS was given. Serum hormonal assay revealed low level of FT3 (66.86 pg/mL, FT4 (2.77 ng/mL), thyroid - stimulating hormone (2.67 mIU/mL), and low level of serum cortisol (3.4 ugm/dL). Growth hormone level was low (2.8 ng/L) on insulin tolerance test. Posterior pituitary hormone such antidiuretic hormone assay (1.3 pg/ml) and serum osmolality (260 mOsm/kg) were normal. He developed one episode of generalized tonic-clonic seizure with hyponatremia on 2nd day of hospitalization for which he was shifted to intensive care unit and treated conservatively with antiepileptic and hormone supplements. Serum glucose, calcium, phosphorus, albumin and alkaline phosphate were within normal limit. The patient was asymptomatic and discharged on 10th day of hospitalization. On follow-up examination, the patient gradually gained weight and revealed normal hormonal levels with hormonal supplements.

Figure 1

Magnetic resonance imaging of sella turcica shows predominantly cerebrospinal fluid bright signal inside sella in T2-weighted sagittal image (a) and very thin enhancing compressed pituitary gland along the floor of sella with central positioned pituitary stalk in postcontrast enhanced images (b-d)

Figure 2

Magnified magnetic resonance imaging of sella turcica (sl) shows empty sella in sagittal T2-weighted image (a), thinned out enhancing pituitary parenchyma with centrally placed stalk (st) in coronal postcontrast image of brain (b)

Discussion

Sheehan and Summers introduced the term “empty sella” (ES) in 1949 while describing pituitary necrosis in postpartum women.[9] An ES turcica results when CSF enters the sella turcica and compresses the pituitary gland until it lines the sellar floor or wall. The primary empty sella turcica develops when CSF enters the sella turcica through the opening of diaphragm sellae and may or may not be associated with increased intracranial pressure. Secondary ES occurs due to injury to the pituitary gland itself or as a result of surgical or radiation treatment.[10] Primary ESS is commonly associated with hydrocephalus, herniation of optic chiasma, optic nerve and suprasellar arachnoid cistern. In secondary ES, the adhesion in sella following surgery, radiation, and infection prevent intrasellar herniation of suprasellar structure.[11] In our case, the patient had no history of previous operation or prolonged infection and was diagnosed to have primary ESS. The incidence of ESS is about 8–35% in the general population,[12] and varies from 1.2% (children without symptoms) to 68% (children with known endocrinopathy) in children. ESS in children is associated commonly with growth hormone deficiency, hypogonadism or multiple pituitary hormone deficiency. ESS may be detected incidentally in asymptomatic children on imaging.[10] Involvement of the posterior pituitary gland is very rare in the case of ESS.[13] Our patient had hypothyroidism, hypercortisolism, low growth hormone. Posterior pituitary hormone assay was normal. He had no features of posterior pituitary dysfunction.

Failure to thrive is a descriptive term rather than a diagnosis and is defined as a condition where the growth of a child fails to attain the normal expected growth parameter for a child at that age. It results from a variety of causes, which are traditionally classified into organic and nonorganic type of failure to thrive. The nonorganic failure is seen in the child below 5 years of age due to emotional deprivation, neglect, child abuse and due to accident. Failures to thrive due to the organic cause are more prevalent in our country in comparison to developed country and results most commonly due to tuberculosis, urinary tract infection and other causes under 5 years age.[1415] In our case, the child had no evidence of infection and history of nonorganic cause of failure to thrive. On investigation, he was found to have primary ESS.

Computed tomography is sensitive but not specific to diagnose ES. ES, cystic intrasellar tumor, and third ventricular recess cannot be distinguished confidently in axial CT image. CT study of ES demonstrates infundibulum surrounded by hypodense CSF, inside widened sella turcica known as infundibulum sign[16] High-resolution MRI using thin section coronal and sagittal T1-weighted images through the pituitary-hypothalamic axis before and after intravenous administration of gadolinium is the investigation of choice for pituitary lesion. Dynamic contrast study is proven to be the best imaging tools for detection of microadenoma of pituitary gland. Computed tomography may be needed to see calcification or hemorrhage in pituitary fossa.[17] In ESS, the pituitary gland is variably flattened; frequently or only a thin rim of tissue along the sella floor. The only differential diagnosis is that of an arachnoid cyst occupying the superior portion of the sella turcica, which can be distinguished from ES by the position of the pituitary stalk. In ES, the stalk is normal in position, whereas space-occupying cysts cause it to be obliterated or displaced.[18] Absent posterior pituitary T1-weighted bright spot is commonly seen in hypoplastic pituitary gland or ESS and is associated with multiple pituitary hormone deficiency, isolated growth hormone deficiency, and diabetes insipidus.[19] In our case, the posterior pituitary bright spot was not seen in MRI of pituitary gland.

There is no definite treatment policy for ESS in children. The primary ESS with endocrine dysfunction is managed with hormonal supplementation depending on the type of hormone deficiency. In the case of secondary ES, the patient management depends on the etiopathogenesis of ESS.[11] Surgical indication for correction of symptomatic ESS is controversial and rare. Visual disturbance and cerebrospinal rhinorrhea are the main indications for surgery. Packing of sella by use of fat, muscles, dural substitute, cartilage, bone, ceramic substance or titanium plate through intradural or extradural approach have been described in adult. The extradural approach is preferred over intradural approach due to decreased risk of over packing, involving less trauma, no manipulation of sellar and suprasellar structure.[20]

Conclusion

Empty sella syndrome is rare in children and commonly detected on imaging due to endocrine dysfunction. MRI of pituitary gland is the modality of choice for ESS. Primary ESS with hypopituitarism is managed with hormonal supplements and secondary ESS is treated depending on the etiopathogenesis.