Paediatric and Young Adult Manifestations and Outcomes of Multiple Endocrine Neoplasia Type 1

Madhuni Herath; Venkat Parameswaran; Michael Thompson; Michelle Williams; John Burgess

Disclosures

Clin Endocrinol. 2019;91(5):633-638. 

In This Article

Methods

A retrospective study of patients with a confirmed MEN1 pathogenic genotype (Tasman 1 splice-site mutation; NM_130799.2:c.446–3 C > G heterozygous) undergoing surveillance at the Royal Hobart Hospital was conducted.[8,16] The research was approved by the Royal Hobart Hospital Institutional Human Research Ethics Committee.

The Tasman 1 genealogy spans six generations and includes over 2500 individuals.[8,16] Review of clinical records identified 180 eligible patients for whom clinical records, imaging and pathology results were available at age <22 years. Prospective phenotype screening of the Tasman 1 kindred commenced in the 1980s when the Tasman 1 kindred was initially identified.[16–18] Children identified as MEN1 positive through cascade screening typically commence regular screening at age 10 years, although frequency of radiological screening is limited compared with their adult counterparts, and clinical, biochemical and radiographic screening methods have varied with available technology over the past four decades.[18]

Serum calcium, prolactin, gastrin, abdominal ultrasound imaging was routinely employed from the early 1980s, with CT pituitary initially, and then, MRI pituitary was introduced in the late 1980s. The current annual screening investigations include measurement of serum calcium (corrected and ionized), PTH, IGF-1, prolactin, gastrin, pancreatic polypeptide, vasoactive intestinal peptide, glucose, insulin and alpha subunit.[8,16,18] Imaging by second yearly abdominal ultrasound and fourth yearly MRI pituitary is conducted to identify asymptomatic pathology. Imaging is conducted more frequently if indicated based on emergent abnormalities or symptoms. Fourth yearly FDG-PET/CT imaging is conducted after 18 years of age. Symptomatology and the results of biochemical testing and imaging guide additional investigations and treatment.

The age cut-off of <22 years was arbitrarily chosen to reflect the age-related use of screening and investigation modalities in the Tasman 1 cohort. We have typically reserved the use of investigations involving ionizing radiation until patients are aged between 18 and 21 years. Up to age 22 years was therefore chosen as the cut-point for young adult inclusion in this study to optimize the availability of phenotype information while avoiding unnecessary overlap with our previous publications describing the adult phenotype in Tasman 1.

Data from medical and archival records were utilized to assemble a retrospective subgroup of 96 MEN 1–positive patients born prior to 1965, and a prospective subgroup of 84 MEN 1–positive patients born from 1965 onwards. The prospective subgroup experienced some or all of their childhood and adolescence within the period from the early 1980s when prospective MEN 1 case screening was available to members of the Tasman 1 genealogy. In keeping with previously published criteria, MEN 1 diagnosis required either the molecular diagnosis of the Tasman 1 MEN 1 mutation or obligate inheritance based on genealogical criteria.[2]

Statistical Methods

Numerical data are presented as mean ± standard deviation or median and interquartile range (IQR). Normally distributed variables were analysed using t test and categorical data by Fisher's exact test, respectively. A two-tailed P value ≤ .05 was used to define statistical significance with statistical analysis performed using GraphPad Prism (GraphPad Software Inc.) and Stata V15.1 for Windows (StataCorp LP).

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