Central diabetes insipidus is a common indication for MR imaging of the pituitary hypothalamic axis in children. The clinical presentation often includes polyuria, polydipsia, and nocturia related to impaired secretion of antidiuretic hormone. Imaging will generally demonstrate absence of a normal posterior bright spot, and there may be an associated abnormality involving the pituitary infundibulum and/or hypothalamus. The underlying etiology can be idiopathic, post-traumatic, postsurgical, congenital, neoplastic, autoimmune, infectious, or inflammatory. Understanding the normal pituitary anatomy and MRI appearance as well as the characteristic imaging findings of many common causes of central diabetes insipidus is paramount.
The pituitary gland has two distinct origins. The anterior gland (adenohypophysis) arises from Rathke’s pouch on the roof of the foregut. The posterior pituitary (neurohypophysis) and median eminence of the hypothalamus arise from neuroectoderm in the floor of the forebrain.1 The infundibulum arises from the ventromedial hypothalamus and is a variably hollow tube containing cerebrospinal fluid (CSF) referred to as the infundibular recess of the third ventricle. The pars intermedia is between the adenohypophysis and neurohypophysis. The pars tuberalis extends from the hypothalamus along the infundibulum before entering the adenohypophysis (Figure 1).
The anterior pituitary gland is larger than the posterior lobe and makes up two-thirds of the total pituitary volume. The anterior pituitary gland consists of 5 separate cell types each of which secrete different hormones. The anterior pituitary hormones include adrenocorticotropic hormone (ACTH), growth hormone (GH), follicle-stimulating hormone (FSH) and luteinizing hormone (LH), prolactin (PRL), and thyrotropin-stimulating hormone (TSH). Discussion of these individual hormones is beyond the scope of this article.
The posterior lobe of the pituitary gland consists of pituicytes, tanycytes, and the terminal portion of axons whose cell bodies are within the hypothalamus. Paraventricular and supraoptic nuclei within the hypothalamus produce vasopressin and oxytocin. These posterior pituitary hormones are then transported from the hypothalamus through the infundibulum into the posterior lobe of the pituitary gland. These neurosecretory granules (neurophysins) are thought to contain proteins that produce the hyperintense intrinsic T1 signal within the posterior lobe of the pituitary gland.2,3 Vasopressin, also known as antidiuretic hormone (ADH), is a nonapeptide that is important in maintaining osmoregulation, cardiovascular control, and homeostasis. The most important stimuli that evoke vasopressin release are increased plasma osmolality, decreased arterial pressure, and reduced cardiac filling. Oxytocin stimulates milk ejection from the breast in response to suckling and stimulates uterine contraction during labor to deliver the fetus and placenta.4
In the fetus and neonate, the anterior lobe of the pituitary gland has a convex superior margin and hyperintense T1 signal in relation to the cortex or gray matter (Figure 2). The size of the anterior lobe and hyperintense T1 signal within the anterior lobe will slowly diminish until two months after birth. At two months, the anterior pituitary will assume the appearance expected in a child. That is, the anterior lobe will have a flat or slightly concave superior margin and T1 signal intensity similar to gray matter (Figure 3).
The posterior pituitary gland has hyperintense T1 signal in relation to the brain at birth and this will continue into adulthood. The normal posterior pituitary bright spot should measure 1.2 to 8.5 mm in the long axis and 0.4 to 4.4 mm in the short axis. All neonates and children should have a posterior pituitary bright spot; absence is always abnormal. Up to 48% of normal adults will have absence of the posterior pituitary bright spot.5,6 Why the posterior bright spot is not visualized in all normal adults remains unknown. One theory is that the amount of ADH stored in the posterior pituitary decreases with age, leading to a gradual decrease in size and then disappearance of the bright spot in some normal adult patients.5,6
The normal pituitary infundibulum should smoothly taper from superior to inferior. The AP and transverse diameters of the normal pituitary infundibulum are 2.32 +/- 0.39 mm and 2.16 +/- 0.37 mm at the insertion into the pituitary gland, respectively, and are 3.25 +/- 0.43 mm and 3.35 +/- 0.44 mm at the level of the optic chiasm. The length of the infundibulum measures 5.91 +/- 1.24 mm, and the depth of the infundibular recess is 4.69 +/- 0.87 mm.7 The signal intensity of the normal pituitary infundibulum on T1-weighted imaging should be slightly less than the optic chiasm and always less that the posterior pituitary gland. The pituitary infundibulum lacks a blood-brain barrier and, therefore, enhances intensely.
Idiopathic central diabetes insipidus causes 12% to 50% of cases of central diabetes insipidus in children.8,9 The majority of these patients will present with absence of the posterior pituitary bright spot on MR imaging. Patients may also have anterior pituitary hormone deficiencies. The pituitary infundibulum may be normal or thickened at presentation. On follow-up imaging, the infundibulum may change in thickness over time.8,9 No focal-enhancing mass will be detected on imaging. As the name implies, the etiology of this condition remains unknown and this remains a diagnosis of exclusion.
An ectopic posterior pituitary bright spot will have a characteristic appearance on MR imaging, as the bright spot will be within the infundibulum or hypothalamus instead of within the dorsal aspect of the sella (Figure 4). Early descriptions of an ectopic posterior pituitary gland proposed an underlying traumatic etiology. However, more recent studies have favored an underlying genetic basis for the disorder.10,11 An ectopic posterior pituitary bright spot can be seen in patients with congenital pituitary hypoplasia and associated growth hormone deficiency. There may be associated hypoplasia or absence of the adenohypophysis and pituitary infundibulum. When the posterior pituitary bright spot is ectopic, there is a higher incidence of associated brain and skull-base anomalies as well as callosal anomalies. There are also associations with Chiari I malformation, septo-optic dysplasia, periventricular gray matter heterotopia, microcephaly, persistent cranio-pharyngeal canal, basilar impression, medial deviation of the carotid arteries, cerebellar atrophy, single central incisor tooth, vermian dysplasia, and Kallmann syndrome.12
Germ cell tumors include germinomas, nongerminomatous germ cell tumors, and teratomas. These most commonly present along the midline involving the pineal region (45%) and/or suprasellar region (30%).1 Additional sites include the basal ganglia, cerebellopontine angle, cerebellum, and the spinal cord. These tumors may be mature or immature and can present with malignant degeneration. Suprasellar germ cell tumors originate within the infundibular recess of the hypothalamus. Infiltration of the infundibulum by the tumor will result in disruption of the axons that carry ADH from the paraventricular and supraoptic nuclei of the hypothalamus to the posterior pituitary gland.1 This will result in diabetes insipidus characterized by excessive thirst, electrolyte imbalance, and frequent urination. The normal pituitary bright spot will be absent on MRI. An important note is that when children present with diabetes insipidus related to a germinoma, the only finding that may be present on the initial brain MRI is absence of the normal posterior pituitary bright spot. This is related to the germinoma being exceedingly small and essentially undetectable by MRI. It is imperative to follow these children with serial MRIs, as the germinoma will grow over time and become detectable with imaging. Current thinking is to follow these children with serial MRIs for at least 3 years. If no abnormality develops on MRI after 3 years, the frequency of follow-up MRIs can be decreased.9
All histologic subtypes of germinomas are relatively hypercellular. Therefore, these tumors demonstrate high attenuation on CT and are isointense to gray matter on T1- and T2-weighted sequences. These tumors do not have a blood-brain barrier and will demonstrate avid postcontrast enhancement (Figure 5). Following treatment of the germinoma, the absence of the posterior pituitary bright spot will last forever and clinical symptoms of diabetes insipidus will persist.1
Langerhans cell histiocytosis (LCH) is the most common histiocytic disorder of the central nervous system (CNS). LCH is a clonal proliferative disorder of cells of the mononuclear phagocytic and dendritic cell system of unknown pathophysiology and is considered a mix between immune dysregulation, inflammation, and malignancy. Classic pathologic findings include histocytes with cleaved nuclei (coffee bean) that have CD1a and CD207 cell surface antigens in a background of plasma cells, multinucleated giant cells, lymphocytes, and eosinophils.13 Clinical presentations of LCH are variable and range from single-organ involvement to extensive multisystem involvement. Most frequently involved sites include bone, skin, spleen, liver, lymph nodes, and thymus. Calvarial and bone lesions will show preferential involvement of the outer table compared to the inner table, creating the characteristic “bone in bone” appearance. Near complete height loss of a vertebral body “vertebral plana” is often seen in the spine. When LCH involves the CNS, which occurs in 4% to 25% of patients, the most common location involved is the pituitary infundibulum.13,14 Granulomas will develop within the pituitary infundibulum, hypothalamus, and adjacent subarachnoid space. These granulomas will demonstrate avid postcontrast enhancement and result in expansion of the infundibulum and hypothalamus (Figure 6). Once approximately 80% of the axons carrying ADH within the infundibulum are disrupted, the clinical symptoms of diabetes insipidus will begin and the posterior pituitary bright spot will disappear.1,15 In patients who present with multisystem involvement, the diagnosis may potentially be made from biopsy of enlarged lymph nodes or spine lesions rather than the pituitary infundibulum. Following treatment of LCH, the normal posterior pituitary bright spot will reappear and symptoms of diabetes insipidus should resolve.
Lymphocytic hypophysitis is a neuroendocrine disorder characterized by autoimmune infiltration of the pituitary gland by lymphocytes and plasma cells. The disorder can be divided into two subtypes: adenohyphysitis (LAH), which involves the anterior pituitary gland, and infundibuloneurohyphophysitis (LINH), which involves the posterior pituitary gland, infundibulum, and hypothalamus. LINH can occur in both adults and children and often will present clinically with acute onset of diabetes insipidus and headache. MR imaging will show enlargement of the infundibulum, hypothalamus, and potentially the pituitary gland. Infiltration of the infundibulum will often result in absence of the normal posterior bright spot. The enlarged structures will demonstrate avid postcontrast enhancement (Figure 7). Imaging characteristics are often identical to suprasellar germinomas and LCH.1,16
Craniopharyngiomas account for 50% of suprasellar tumors in children.1 The adamantinomatous type is the most common in children. These tumors most commonly arise from the tuber cinereum of the hypothalamus but can also arise from the pituitary gland, infundibulum, or infrasellar sphenoid bone. If the tumor disrupts the axons between the hypothalamus and posterior pituitary gland, there will be associated absence of the posterior pituitary bright spot. These tumors often contain cystic and solid components. The cystic components have variable T1 signal and hyperintense T2 signal. The solid tissue within the tumor will enhance and the cysts will demonstrate peripheral enhancement (Figure 8). Approximately 90% of craniopharyingiomas will contain a component of calcification. The calcification may be thin and along the margin of a cyst “eggshell” pattern or course within the solid portion of the mass. A mixed cystic and solid, partially calcified, enhancing mass in the suprasellar region in a child is almost always a craniopharyngioma.1,17
Sarcoidosis is an idiopathic systemic granulomatous disorder that results in the development of noncaseating granulomas in various organs. The etiology of sarcoidosis remains unknown. Studies have shown that both genetic and environmental factors may play a role in the development of the disease. Symptomatic CNS sarcoidosis is present in 5% to 15% of patients with sarcoidosis and most of these patients have extra neural manifestations of sarcoidosis. Isolated involvement of the CNS is rare, involving only 1% of all patients with sarcoidosis.18,19 Sarcoidosis can involve the leptomeninges, dura, and brain parenchyma (Figure 9). Sarcoid granulomas can form anywhere within the brain parenchyma and are often found within the hypothalamus and pituitary infundibulum, which may result in diabetes insipidus. The parenchymal lesions will demonstrate hypointense T1 signal, hypointense T2 signal, and avid postcontrast enhancement. The definitive diagnosis of neurosarcoidosis requires biopsy; however, in many instances this may not be feasible. The probable diagnosis can be made with the confirmation of systemic sarcoidosis, CSF studies, and MRI features of neurosarcoidosis.
Meningitis is one of the most common extrapulmonary manifestations of infection by Mycobacterium tuberculosis. Tuberculomas, meningovasculitis, and miliary involvement of the CNS can all also occur in children with tuberculosis. Infiltration of the pituitary infundibulum by the thick exudate related to TB meningitis or development of a tuberculoma within the infundibulum can result in diabetes insipidus. Brain tuberculomas show different imaging features at each stage of evolution. These are divided into noncaseating tuberculomas, solid caseating tuberculomas, and tuberculomas with central liquefaction. Noncaseating tuberculomas are solid lesions without necrosis and demonstrate hypointense T1 signal, hyperintense T2 signal, and homogenous enhancement. Solid caseating tuberculomas have a central caseating zone of necrosis and demonstrate isointense to hypointense T1 signal, slightly T2 hypointense signal, and ring enhancement. The last stage of brain TB are tuberculomas with central liquefaction and have a similar appearance to other infectious intracranial abscesses. These abscesses will demonstrate central T1 hypointensity, central T2 hyperintensity, central diffusion restriction, and ring enhancement (Figure 10). Unlike bacterial abscesses, TB abscesses elicit little surrounding vasogenic edema. The diagnosis of CNS TB can often be made with CSF studies and MRI findings.20,21
Wolfram syndrome is a rare autosomal recessive disorder (1 in 770,000) featuring diabetes insipidus, diabetes mellitus, optic atrophy, and deafness. The gene for Wolfram syndrome has been mapped to chromosome 4p, which is responsible for endoplasmic reticulum stress-mediated cell death. Typical MR brain findings include absence of the normal posterior pituitary bright spot, bilateral intraorbital and intracranial optic nerve atrophy, T2 hyperintense signal in the pons, and progressive brainstem and cerebellar atrophy. No current treatments are available for this disease and life expectancy is approximately 30 years.22,23
Central diabetes insipidus commonly will manifest on imaging with absence of the normal posterior pituitary bright spot; this absence in children is always abnormal. Idiopathic central diabetes insipidus is a diagnosis of exclusion. A normal brain MRI (except for absence of the posterior pituitary bright spot) in a child with central diabetes insipidus does not exclude a germinoma or LCH. The lesion may be undetectable at initial MRI, and follow-up imaging is critical. Lymphocytic hypophysitis can have identical imaging characteristics to germinoma and LCH but is more common in young adults than children. Craniopharyngiomas commonly have a combination of cysts, solid enhancing components, and calcifications, making them easier to diagnose with imaging alone. Isolated neurosarcoidosis is rare so the diagnosis can often be made with identification of lesions involving different parts of the body. Signs of systemic infection may be present in patients with CNS involvement with tuberculous, and CSF studies can be helpful.
Cornwell, BO. Absence of the Normal Posterior Pituitary Bright Spot in Children. J Am Osteopath Coll Radiol. 2021;10(2):15-21.