User:Karishma.Patel.8/Pituitary Stalk Interruption Syndrome

Pituitary stalk interruption syndrome (PSIS) is a congenital defect seen in around 1 in 200,000 live births, and has been shown to affect males disproportionately. PSIS is often detected during the neonatal period or in early childhood, and manifests with varying degrees of severity. Ultimately, PSIS disrupts the pituitary stalk, which facilitates communication between the hypothalamus and the pituitary gland in the brain.

First observed in 1987 with the help of MRI,  PSIS is typically characterized by any combination of three classic phenotypes: an absent or thin pituitary stalk, an absent or ectopic posterior pituitary, and an aplastic or hypoplastic anterior pituitary. In addition to this triad, patients present with a variety of manifestations. Those most commonly seen include seizures, intellectual disability, developmental delay, septo-optic dysplasia, genital hypoplasia, cryptorchidism, hypoglycemia, short stature, primary amenorrhea, diabetes insipidus, adrenal hypoplasia, hypothyroidism, delayed puberty, and failure to thrive.

The exact causes of PSIS are still unknown, but two broad classes of suspected causes include genetic and traumatic causes. A multitude of genes, including PROP1, PIT1, HESX1, SOX2 and SOX3, OTX1 and OTX2, PAX6, ARNT2, PROKR2, TGIF, LHX3 and LHX4, SHH, GPR161, and CDON produce transcription factors and protein products essential for proper Pituitary Stalk development and function. Mutations in any of these genes may therefore be implicated in PSIS. These mutations may be X-linked or have polygenic inheritance, while others may be spontaneous. On the other hand, perinatal events like breech delivery itself or ischemia during a breech delivery, head trauma during delivery , hypoxia of the hypothalamus during birth , and dystocia are also linked to PSIS. However, it is still unclear whether these physical events during delivery cause PSIS, or the hormonal deficiencies related to PSIS lead to these physical events during birth.

PSIS is suspected in cases where patients show a collection of the aforementioned presentations, or if there is a family history of pituitary hormone deficiency. Diagnosis is then preferentially confirmed by MRI, or by CT if MRI is unavailable to the patient.

Treatment usually consists of taking replacement hormones, and is tailored to remediate the varying presentations of each patient. Early diagnosis and intervention are critical to optimal patient outcomes.

Presentation
Affected individuals may present with hypoglycemia during the neonatal period, or with growth retardation during childhood (those diagnosed in the neonatal period appear to be affected by a particularly severe form of the disorder). PSIS is a common cause of congenital hypopituitarism, and causes a permanent growth hormone deficit. Some PSIS-affected individuals may also present with adrenal hypoplasia (5-29%), diabetes insipidus (5-29%), primary amenorrhea (5-29%), hypothyroidism (30-79%), failure to thrive (80-99%), septo-optic dysplasia (5-29%), and Fanconi anaemia. PSIS may be isolated, or, commonly, present with extra-pituitary malformations.

PSIS features in neonates (may) include:


 * hypoglycaemia (30-79%)
 * (prolonged) jaundice
 * micropenis (30-79%)
 * cryptorchidism (5-29%)
 * delayed intellectual development
 * death in infancy (5-29%)
 * congenital abnormalities

PSIS features in later childhood (may) include:


 * short stature (80-99%)
 * seizures (5-29%)
 * hypotension
 * delayed intellectual development
 * delayed puberty (30-79%)

PSIS is associated with a higher frequency of breech presentation, Caesarean section, and/or low Apgar score, though these are likely consequences rather than causes.

Cause
The cause of the condition is as of yet unknown. Rare genetic mutations may cause familial cases, however, these account for less than 5% of cases.

Diagnosis
The diagnosis is confirmed through MRI.

Management
Treatment should commence as soon as a diagnosis is established to avoid complications, and consists of hormone replacement, particularly with growth hormone.

Prognosis
Prognosis is generally good in cases of prompt diagnosis and management. Delays may lead to seizures (due to hypoglycemia), hypotension (due to cortisol deficiency), and/or intellectual disability (due to thyroid endocrine deficits). Due to the before-mentioned factors, mortality and morbidity is higher than that of the general population, particularly during the first 2 years of life.