Keywords

1 Epidemiology and Clinical Presentation

  • Hypoplasia of the pituitary gland, infundibulum, septum pellucidum, corpus callosum, and optic nerve(s) may be seen in an isolated fashion or in combination with one another. These related midline developmental anomalies are thought to represent a spectrum of congenital and developmental conditions with varying degrees of penetrance, including holoprosencephaly and/or septo-optic dysplasia (SOD) [1].

  • Pituitary hypoplasia may occur as an isolated entity (IPH) or in association with various (often overlapping) syndromes [2]:

    • Septo-optic dysplasia (SOD, de Morsier’s syndrome)

    • Kallmann syndrome

    • Holoprosencephaly

    • Coffin-Siris syndrome [3]

    • Worster-Drought syndrome (congenital bilateral perisylvian syndrome) [4]

    • Hall-Pallister syndrome [5]

  • Although usually sporadic conditions, pituitary hypoplasia and related midline anomaly spectrum disorders have been associated with mutations in a number of genes:

    • Pit-1 [6, 7]

    • Sonic Hedgehog (SHH)

    • Growth hormone-releasing hormone (GHRH) receptor [8, 9]

    • HESX1 [10]

    • SOX2 and SOX3

    • Additional genes on the long arm of chromosome 14 [11]

  • Isolated pituitary hypoplasia most commonly affects the growth hormone (GH), thyroid, and prolactin axes. Most patients with pituitary hypoplasia present with short stature. Clinically, these syndromes are known as isolated GH deficiency or combined pituitary hormone deficiency [12–14].

  • Pituitary hypoplasia may be accompanied by adrenal cortical hypoplasia [15].

  • Optic nerve hypoplasia is a leading cause of congenital blindness and is typically diagnosed on funduscopic examination. Additional midline anomalies are often identified with neuroimaging studies [16].

  • Septo-optic dysplasia (SOD) and septo-optic-pituitary dysplasia are developmental disorders that involve hypoplasia of one or more midline structures. These conditions have been associated with maternal drug and alcohol use and in rare cases can be congenital.

    • The incidence of SOD is 1 in 10,000 newborns.

    • Affected expression of hypothalamic Sonic Hedgehog (SHH) has been shown to cause classic SOD [17].

    • The most common finding is optic nerve hypoplasia. Pituitary hypoplasia, agenesis of the septum pellucidum, and cortical developmental malformations can all be seen in combination or as isolated entities. Concurrent pituitary hypoplasia is seen in 64 % of patients with optic nerve hypoplasia, and agenesis of the septum pellucidum is seen in 50 % [12, 18].

    • Patients with SOD often present with developmental delay, communication difficulties, visual loss, nystagmus, and hypopituitarism.

    • The presence and degree of endocrinopathy correlate with the absence of multiple midline structures. Patients with absence of the septum pellucidum and hypothalamic-pituitary axis on MRI have the highest degree of endocrinopathy [19].

  • Rarely, isolated pituitary stalk hypoplasia, also known as the pituitary stalk interruption syndrome (PSIS), can be seen [20]. This discrete entity has been associated with genes involved in holoprosencephaly (SHH, TGIF, SIX3).

2 Imaging Features

  • Hypoplasia of the pituitary gland, infundibulum, septum pellucidum, corpus callosum, and/or optic nerve(s) can be seen on MRI (Fig. 68.1) [18, 20].

    Fig. 68.1
    figure 1

    Pituitary hypoplasia. (a) Sagittal T1-weighted precontrast MR image. (b) Coronal T1-weighted precontrast image. The anterior pituitary gland is hypoplastic and the posterior pituitary T1 shortening is visible in the center of the sella. The stalk is present

    Full size image

  • The height of a hypoplastic pituitary gland, when present, is typically less than 3 mm; the normal height is more than 5 mm [8].

  • An ectopic pituitary gland may be visualized [21].

  • In patients with congenital GH deficiency, the triad of an ectopic posterior pituitary (EPP), pituitary aplasia/hypoplasia, and stalk defects is correlated with the presence of other endocrine abnormalities (Fig. 68.2) [22].

    Fig. 68.2
    figure 2

    Pituitary hypoplasia. Sagittal T1-weighted precontrast MR image. There is a T1-hyperintense spot in the infundibular recess, indicating ectopic neurohypophysis, and the pituitary stalk is not seen. The anterior pituitary gland is present in the sella

    Full size image

  • The presence of diabetes insipidus has been shown to correlate with loss of the posterior pituitary bright spot [23, 24].

  • Pituitary hypoplasia or ectopia can be associated with agenesis of an internal carotid artery [25, 26].

  • On MRI, the cross-sectional area of the optic nerve can be used to support the diagnosis of optic nerve hypoplasia [27].

3 Clinical Management

  • Clinical management is centered on prompt diagnosis and hormone replacement.

  • Favorable responses to GH replacement have been shown in many patients [28].

  • Multidisciplinary management is recommended for patients with any midline developmental disorders. Among the clinicians required may be endocrinologists, ophthalmologists, psychiatrists, neurologists, neurosurgeons, genetic counselors, and visual and occupational therapists.