Clinical and radiological correlation in congenital hypopituitarism - a retrospective study
Date
2024-02
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Stellenbosch : Stellenbosch University
Abstract
ENGLISH ABSTRACT: Background: Congenital hypopituitarism can present with either an isolated pituitary hormone deficiency or multiple pituitary hormone deficiencies. This can either be caused by abnormal development of the pituitary gland (for example anterior pituitary hypoplasia, absent or interrupted pituitary stalk, ectopic posterior pituitary gland) or an abnormality or disease process involving the hypothalamus (for example holoprosencephaly, corpus callosum agenesis).1,2 Structural abnormalities of the hypothalamic-pituitary axis are observed in these patients, with magnetic resonance imaging (MRI) being the modality of choice.3 Multiple studies have shown a stronger association between multiple pituitary hormone deficiencies (MPHD) and structural abnormalities observed on MRI when compared to isolated growth hormone (GH deficiency). There has also been a correlation seen between severe GH deficiency and the number of radiological abnormalities detected.8-10,23,25 An ideal paediatric MRI pituitary protocol should include T1-weighted sagittal plane, before and after contrast, T1-weighted coronal plane, before and after contrast, a T2-weighted coronal plane, as well as a T2-weighted axial plane.3 These image slices should ideally be 1,5mm slices thick.3,5 At Tygerberg Hospital (TBH) an adult pituitary protocol is being followed, which includes all the same planes as the ideal paediatric protocol. The only difference is that the TBH protocol does not specify the slice thickness. Primary objectives: • To identify all the paediatric and adolescent patients, known with congenital hypopituitarism, at the Paediatric Endocrine unit of TBH in South Africa, over a 12-year period (01/08/2007 - 21/12/2019); • to describe the type and number of hormone deficiencies in each patient; • to identify their clinical presentation; • to document the structural brain abnormalities related to the hypothalamic-pituitary axis on the MRI reports. Secondary objective: • To review whether a recommended MRI protocol was followed at the Radiology Department of TBH when imaging was conducted for patients with congenital hypopituitarism; https://scholar.sun.ac.za 5 • to describe the level of expertise of the radiologist reporting the scan. Methods: A retrospective, descriptive study was done at TBH. The inclusion criteria were all paediatric and adolescent patients with congenital hypopituitarism diagnosed by the Paediatric Endocrine Unit, over a 12-year period (01/08/2007 -31/12/2019) who had an MRI of the pituitary region done. Data was collected from Enterprise Content Management (ECM) and Electronic Continuity of Care (ECCR) notes, as well as from endocrine duplicate folders. IgF-1, IgFBP-3, and growth hormone (GH) stimulation tests with clonidine and glucagon were done to determine the presence of GH deficiency. The cut off used was GH peak < 3µg/L peak value with stimulation testing), https://scholar.sun.ac.za 7 had pituitary stalk abnormalities, compared to none in those with non-severe GH deficiency (p = 0,052). A high percentage of patients with severe GH deficiency (62,5%) had an abnormal MRI, compared to those with non-severe GH deficiency (16,7%), with a p value of 0,127. Twenty-three (67,6%) of the MRIs done followed an ideal MRI protocol. Thirty-one (91,0%) MRIs were done with gadolinium and twenty-six (76,5%) had the correct image slice thickness. Seven (20,6%) MRIs were done in infancy, 16 (47,1%) in pre-school age and 11 (32,4%) in school-going children. Twenty-six (76,5%) MRIs were requested by the paediatric endocrine unit, two by ophthalmology, two by neonatology and two by general paediatrics. Genetics and neurology both requested one of the MRIs. One MRI was reported by a neuroradiologist, and 33 by general radiologists, of which 5/33 were reported by consultants with a special interest in neurology. Conclusion: Based on the study only non-pituitary structural abnormalities appear to be predictive of MPHD. Due to the small sample size, neither MPHD nor the severity of GH deficiency seem to be associated with midline structural abnormalities. Irrespective of the above limitations, the results do suggest that EPP, pituitary stalk abnormalities and a triad could be predictive of MPHD; this would need to be confirmed with a larger study. Similarly, pituitary stalk abnormalities may be associated with severe GH deficiency. Confirmed GH deficiency was present in about three quarters of all the patients of the study, with ACTH deficiency and GH deficiency being the most common deficiencies seen in those with MPHD, followed by TSH deficiency and then ADH deficiency. Patients with severe GH deficiency had a high frequency of structural abnormalities compared to those with non-severe GH deficiency. MPHD were more common than IPHD in patients with congenital hypopituitarism. The risk of developing ADH deficiency and TSH deficiency in the absence of a posterior pituitary bright spot were significant, compared to those without an absent posterior pituitary bright spot. In patients with pituitary stalk abnormalities a higher risk of TSH deficiency was seen compared to those without stalk abnormalities. The risk of TSH deficiency was also high in patients with EPP and a triad, with the risk of developing central diabetes insipidus also being high in patients with EPP. Only two thirds of the patients had a correct MRI pituitary protocol, with many different general radiologists, in most cases, reporting MRIs. A prospective study with a bigger sample size, as well as thorough documentation of birth history, clinical presentation and laboratory tests is recommended. Testing for mutations and single nucleotide https://scholar.sun.ac.za 8 polymorphisms (SNPs) of genes such as HESX1, SOX2, LHX4, and ROBO1 may be helpful to confirm possible associations. The current MRI pituitary protocol should include correct slice thickness, as well as measurements of the anterior pituitary gland. It is also recommended to have one or two dedicated consultants, preferably a paediatric radiologist or neuro-radiologist, reporting all paediatric MRIs of the hypothalamic-pituitary axis to ensure consistency.
AFRIKAANSE OPSOMMING: Geen opsomming beskikbaar.
AFRIKAANSE OPSOMMING: Geen opsomming beskikbaar.
Description
Thesis (MMed)--Stellenbosch University, 2024.