Thirty-one consecutive patients (age <18 y) with GH (growth hormone) deficiency were evaluated. Only one child had a family history of GH deficiency. Growth hormone deficiency (GHD) was diagnosed on the basis of short stature (height below 3rd percentile)(6); height velocity less than 4 cm/year beyond 3 years of age; bone age <2 SD of chronological age(7) and peak growth hormone (GH) response <7ng/mL to two pharmacological stimuli (clonidine and insulin induced hypoglycemia) on different days. A value of <3 ng/mL was defined as severe GHD. Patients were assessed for other associated pituitary hormone deficiencies. Respective hormones deficiencies were adequately replaced before subjecting them to GH dynamics. In adolescent subjects, priming with conjugated equine estrogen was done. Two millimeter contiguous sagital and coronal T1 and T2 weighted MR images were obtained using 1.5 Tesla superconducting unit (Magnetom; V₆₃ or SP₆₃, Siemens, Germany). The images were evaluated for any central nervous system malformations with specific attention to the location and size of the anterior pituitary, its stalk and posterior pituitary bright spot by neuroradiologist. Radiological diagnosis of empty sella was a subjective one, with presence of invagination of CSF space into the sella. Hypoplastic pituitary gland was defined as crescentic glandular tissue seen at the floor of the sella, with maximum measurable height of <2 mm. The stalk was reported normal, absent or redundant(8).

The mean (±SD) age of these children was 10.5 ± 4.2 y (range 1-17 y). Of 31 patients, 8 had isolated growth hormone deficiency (IGHD) (6 boys) and 7 of them had a peak GH response of <3 ng/mL. Of the remaining 23 patients with multiple pituitary hormone deficiency (MPHD) (17 boys), all had GH deficiency and 16 had peak GH response <3 ng/mL. TSH deficiency was observed in 15 subjects and ACTH deficiency in 10 subjects. Seventeen out of 19 adolescent patients had gonadotropin deficiency, 4 had low prolactin and 3 had ADH deficiency. In MPHD group (n=23), 14 had vertex and 7 had breech presentation and 2 required lower segment caesarian section, whereas in IGHD group 6 had vertex and 2 had breech presentation. The presenting manifestations included linear growth failure (100%), micropenis (25%), neonatal hypoglycemia (6%) and prolonged severe jaundice (6%). Midline defects were present in one patient.

TABLE I



MRI Abnormalities in Growth Hormone Deficiency

MR imaging abnormalities are shown in Table I. Number of imaging abnormalities per patient were comparable in children with IGHD and MPHD groups (2.37 vs 2.69, P=0.06). Table II shows the correlation between MRI findings and the severity of GH deficiency. Number of abnormalities per patient was higher in group with GH levels <3 ng/mL (2.9 vs 1.8, P= 0.06) irrespective of number of hormone deficiencies. Absent/ectopic posterior pituitary bright spot (EPPBS), the hallmark of transection syndrome, strongly correlated with presence of hypoplastic pituitary (<2mm, r=0.54). Sixteen patients had complete MR tetrad, which was more prevalent in IGHD than in MPHD group (75% and 44%, P = 0.01), and it correlated with presence of severe GHD (r= 0.57, P=0.01). All children with breech presentation had structural abnormalities of the pituitary gland compared to those who had vertex (100% vs 60%, P=0.03) and it correlated with presence of severe GHD (r=0.54, P=0.04). Hypoplastic anterior pituitary and EPPBS were common in the breech group as compared to vertex (P= 0.01 and 0.03, respectively).

TABLE II



Correlation of Structural Abnormalities on MRI and GH Levels 

Structural pituitary abnormalities occur in approximately 50-70% of patients with congenital form of GHD(9-14). These abnormalities are more prevalent in patients with MPHD (90%) than in IGHD (20-50%)(14). Contrary to other studies, we observed almost similar prevalence of imaging abnormalities in IGHD and MPHD groups and this is possibly explained by more number of patients with severe GHD (<3 ng/mL) in IGHD group. It has been reported in the literature that patients with severe GHD invariably have structural abnormalities of the pituitary gland and if imaging is normal in them, a hormonal re-evaluation is recommended(15). Four patients in MPHD group with severe GHD had normal imaging and this observation was surprising. This can be explained by Pit-1 and Prop-1 transcription factor mutation in some of these patients, which may be associated with normal imaging(16).

Contributors: PD compiled data and drafted the paper. AB conceived the study and edited the manuscript. PS: review of imaging and editing. RR: compilation of data and editing. SB: patient management, manuscript editing. AB will serve as guarantor.

Funding: None.

Competing interests: None stated.