Atypical cause of short stature with growth hormone deficiency: Pituitary stalk interruption syndrome

Short stature, generalised weakness and easy fatigability.
Development milestones: normal.
X-ray of both hands with wrist for bone age: Bone age is less than chronological age of patient.
Hormonal values:
Growth Hormone: 0.127 ng/ml.
Free T4: 0.51 ng/dl.
S. TSH: 4.292 microIU/ml.
Insulin-like growth factor: <25 ng/ml.

On X-ray of both hands ossification of four carpal bones is seen. Lower end of ulna is not ossified, suggesting bone age of less than 8 years. (Fig. 1)

Ectopic posterior pituitary (as evidenced by hyperintense focus on T1W image) located at median eminence on mid-sagittal and coronal T1WI respectively (Fig. 2 and 3).

Hypoplastic anterior pituitary gland in pituitary fossa and non-visualisation of pituitary stalk on mid-sagittal and coronal T2WI respectively (Fig. 4 and 5).

Visualised brain was normal.

There are many causes of short stature in childhood. Pituitary stalk interruption syndrome (PSIS) is also a cause for growth retardation with growth hormone or multiple anterior pituitary hormone deficiency.
It is a rare congenital anomaly of the pituitary gland which causes deficiency of anterior pituitary hormones. PSIS has a classical triad which consists of absent or ectopic posterior pituitary gland, interrupted pituitary stalk and anterior pituitary hypoplasia or aplasia. [1]

Pituitary stalk interruption syndrome was firstly reported by Fujisawa et al. [2]
Estimated incidence rate of PSIS is 0.5/1, 000, 000 births. [3]

The pathogenesis of PSIS is unclear. It could be acquired due to injury to this region during birth or mutation during the embryonic period. Few mutations in the genes are found to be associated in patients with congenital hypo-pituitarism and PSIS. e.g. HESX1, SOX3, LHX4, OTX2, PIT1, PROP1, PROKR2 and TGIF genes. [3, 4, 5, 6] In our patient birth history was normal.

The clinical features of PSIS in the early neonatal period include cryptorchidism, micropenis, hypoglycaemia and jaundice. The most common presenting clinical feature of PSIS in childhood is short stature. In most patients, usually weight and height are less than the third percentile as compared to normal children. Delayed bone age is also seen in patients with PSIS. [3, 6] In our patient the presentation was short stature.

X-ray of the hand can be used for the bone age estimation in childhood. In our patient, bone age was between 6-8 years, which is significantly lower than the chronological age.

On MRI imaging, T1-weighted, T2-weighted and gadolinium-enhanced MRI brain images in sagittal and coronal plane show hypoplastic adenohypophysis with ectopic posterior pituitary and absent stalk. [1, 3, 7, 8] In our patient all of the three findings were present.

It is important that the patients receive long-term follow-up for the earliest diagnosis and management of hormone deficiency as soon as symptoms manifest. [8]

Although this is a rare disorder, a clinician and radiologist should always think of pituitary stalk interruption syndrome in case of short stature with growth hormone deficiency alone or multiple hormone deficiencies, because PSIS patients have an excellent prognosis to achieve normal height according to their age if they are diagnosed before the fusion of epiphyses. [1, 9]