ESPE Abstracts

Introduction: We report two siblings presenting with pre-pubertal gynaecomastia and macro-orchidism, who were later diagnosed with Peutz-Jeghers Syndrome (PJS) secondary to a STK11 gene variant. Importantly neither child fulfilled the clinical criteria for diagnosis at presentation, with no muco-cutaneous pigmentation nor gastrointestinal symptoms.

Case report: Sibling 1 was referred to Paediatric Endocrinology aged 4 years with unilateral gynaecomastia. Examination revealed right-sided gynaecomastia and pre-pubertal macro-orchidism (4mls) without evidence of virilisation (P1, G1) or testicular lumps. Investigations indicated a normal prolactin level, an undetectable oestradiol level, normal tumour markers and low or undetectable androgen levels. An LHRH test demonstrated a pre-pubertal response. A urine steroid profile was normal and a bone age was not advanced. MRI of the pituitary and abdomen/pelvis did not identify any abnormalities. Six-monthly clinical follow-up did not identify acceleration in height velocity, virilisation or progression of gynaecomastia. Testicular volumes slowly increased to 6mls by the age of 9 years without virilisation. During this time, Sibling 2 was referred to Paediatric Endocrinology aged 3 years. Examination revealed bilateral gynaecomastia and pre-pubertal macro-orchidism (4mls) also without evidence of virilisation (P1, G1) or testicular lumps. Baseline investigations were similarly normal. A testicular ultrasound identified bilateral testicular microlithiasis. Neither child had muco-cutaneous pigmentation nor gastrointestinal symptoms. Genetics revealed a heterozygous variant c.910C>T p.(Arg304Trp) in exon 7 of the STK11 gene in both siblings and their father. Their father subsequently underwent a capsule endoscopy, which identified multiple intestinal polyps throughout his small bowel and confirmed the pathogenicity of this variant and a diagnosis of PJS.

Discussion: Making an early diagnosis of PJS is important so that necessary cancer surveillance can be instituted. Pertinent endocrinology learning points from this case are as follows. Firstly, PJS is a recognised cause of pre-pubertal gynaecomastia due to overexpression of aromatase. We are the first to report a diagnosis of PJS following presentation with pre-pubertal unilateral gynaecomastia and without muco-cutaneous pigmentation or gastrointestinal symptoms. Ongoing surveillance for signs of oestrogen excess (increasing height velocity, advancing bone age and progressing gynaecomastia) is essential, as aromatase inhibitors may be a future consideration. Secondly, PJS is associated with Large Cell Calcifying Sertoli Cell Tumours (LCCSCT). Annual screening via testicular examination and ultrasound is important. In the case of sibling 2, bilateral testicular microlithiasis was not thought to be indicative of widespread tumour. Thirdly, genetic testing and investigation of parents may help confirm a diagnosis in children.