Short stature is a common concern that necessitates pediatric endocrinology evaluation. Growth hormone (GH) deficiency is often included as an etiology. Brain and pituitary Magnetic Resonance Imaging (MRI) with gadolinium-based contrast agents (GBCAs) is the imaging modality of choice in assessing patients with GH deficiency. Given the significant strides made in MRI technology that allow improved spatial and contrast resolution, the necessity of using contrast material when obtaining brain and pituitary MRI in cases of short stature and isolated GH deficiency should be reassessed. We preformed a retrospective review of otherwise healthy patients with short stature and/or GH deficiency who underwent brain and pituitary MRI without and with contrast, to assess the benefit of contrast administration.
Introduction: Short stature is a common concern that necessitates pediatric endocrinology evaluation. The etiologies of short stature are diverse. GH deficiency is often included as an etiology although it accounts for only 1-2% of short stature cases. The prevalence of GH deficiency is reported to be ~ 1:3500. The vast majority of GH deficiency cases are idiopathic in nature with only 20% due to organic causes. The organic causes of GH deficiency include congenital central nervous system (CNS) anomalies, tumors and other pathologic conditions that involve the pituitary-hypothalamic region. As a result, the radiological assessment of the hypothalamic-pituitary region is considered standard of care for evaluating patients with GH deficiency. Although brain and pituitary MRI is the imaging modality of choice in assessing patients with GH deficiency, its yield in cases of isolated GH deficiency is very low. In a study of 40 otherwise normal patients with isolated GH deficiency, 35 (87.5%) had normal brain MRIs. The abnormal findings of brain MRI in the minority of isolated GH deficiency cases included pituitary hypoplasia, pituitary stalk agenesis, lack of the normal T1-weighted pituitary hyperintensity in the posterior part of the sella turcica, and the presence of a high-intensity signal at the infundibular level representing ectopic neurohypophysis. Traditionally, these brain and pituitary MRI images are obtained with the use of contrast material (gadolinium). The main purpose of using contrast material is for the evaluation of pituitary microadenomas. Given the fact that significant strides made in MRI technology and pituitary microadenomas are not appeared to be associated with GH deficiency, the necessity of using contrast material when obtaining brain and pituitary MRI in cases of short stature and isolated GH deficiency should be reassessed. GBCAs have been shown to deposit in different tissues including the kidneys and the brain. The risk increases with repeated doses. The clinical significance of this deposition is unclear at this time but warrants caution especially in pediatric population who have a longer expected lifespan to manifest any delayed effects. Allergic reactions and gastrointestinal symptoms in pediatric patients can occur with GBCA administration, although the incidence is low. Using contrast material also increases the total cost of the MRI study and prolongs the time needed to complete it. Moreover, in order to use contrast material, intravenous venous (IV) access is required which causes discomfort and additional stress to children and their families.
Therefore, we performed a retrospective review of otherwise healthy patients with short stature and/or growth hormone deficiency who underwent brain and pituitary MRI without and with contrast, to assess whether contrast administration led to diagnoses that would have otherwise been missed and/or impacted the patient’s clinical course.Objectives: - To compare the diagnostic yield of non-contrast MRI with pre and post-contrast MRI of the brain and pituitary in evaluation of pediatric patients with short stature and/or growth hormone deficiency.- A secondary objective is to measure the size of the pituitary gland and correlates it with peak growth hormone levels (using insulin/argenine).
Methodology: We included patients who underwent brain/pituitary MRI with/without contrast performed at our institution between Jan 2013-Dec 2018 who have short stature/GH deficiency. We excluded patients with known diagnosis of other pituitary hormone deficiencies prior to obtaining MRI studies, genetic and neurological disorders, known tumors/malignancies of any type, or renal failure. Two pediatric neuroradiologists independently reviewed the brain and pituitary MRI of these patients (each read 50% of the cohort) blinded to the clinical data and diagnoses. Each radiologist initially reviewed only the non-contrast portions of the studies, and subsequently, the same radiologist reviewed the entire study, including pre- and post-contrast portions in a separate session. The two sessions were 6 weeks apart to avoid recall bias. Several imaging findings including size and morphology of pituitary gland, presence of congenital anomalies or focal lesions and any associated intracranial findings systematically recorded, and subsequently analyzed.
Hypotheses: 1.The incidence of finding congenital pituitary cysts is the same when obtaining brain/pituitary MRI imaging using gadolinium contrast versus when not using contrast in patients with short stature and or isolate GH deficiency.
2.The incidence of discovering abnormal infundibulum is the same when obtaining brain/pituitary MRI imaging using gadolinium contrast versus when not using contrast in patients with short stature and or isolate GH deficiency. 3.Small pituitary size correlate with GH deficiency.
Results: -We identified 327 patients with short stature/GH deficiency from Jan 2013-Dec 2018-224 (68.5%) are males and 103 (31.5%) are females. -The mean age at the time of imaging is 10 years and the median is 11 years. -161 (49.24%) have height z-score < -2.25 and 166 (50.76%) have height z-score > -2.25.-82 (25.07%) have IGF1 z-score for age < -2, 102 (31.19%) have z-score ≥-2 to ≤ -1, 141 (43.12%) have z-score > -1 and 2 (0.62%) have no level done.-63 (19.27%) have GH peak <5, 87 (26.61%) have GH peak 5-7.99, 53 (16.21%) have GH peak 8-9.99, 30 (9.17%) have GH peak > 10 and 94 (28.75%) did not undergo GH provocative testing. -The kappa coefficient for pars intermedia cyst on pre vs. post contrast imaging is 0.74 and 0.55 for the infundibulum on pre vs. post contrast imaging. -The mean pituitary height for patients with IGF z-score < -2 is 3.9 mm, 4 mm for z-score ≥- 2 to ≤ -1 and 4.3 mm for z-score > -1-The mean pituitary height for patients with peak GH < 5 is 3.8 mm, 4.2 mm for peak 5-7.99, 4.3 mm for peak 8-9.99 and 4.4 mm for peak > 10.
Conclusion: This question has not been answered or even raised in the literature. Our findings suggest that the there is no added benefit to use gadolinium when obtaining brain/pituitary MRI for the evaluation of GH deficiency/short stature. Furthermore, it seems that there is an association between the pituitary height and the GH status of the cohort which is in line with previous published studies.