Endocrine Abstracts

Introduction: Germline mutations in tumour suppressor gene PTEN cause heterogeneous phenotypes, that comprise the spectrum of PTEN-hamartoma tumour syndrome (PHTS). Manifestations include macrocephaly, developmental delay, cutaneous lesions, intestinal polyposis and increased risk of neoplasms. Thyroid nodules are identified in about 75% of patients and follicular cell-derived cancer affects 35% of cases, some of which diagnosed as early as 7 years old.

Case 1: 6 year old boy, with macrocephaly and autism; genetic test revealed a heterozygous mutation in PTEN (c.359C > A – p.Ala120Glu). Thyroid ultrasound (US) at 6.5 years was normal. At 7 years, US showed 3 nodules: in right lobe (RL), 3.3 mm hyperechoic nodule and 5.8 mm hypoechoic nodule; in left lobe (LL), 3.9 mm hypoechoic nodule. TSH and thyroid antibodies were normal. At 9 years, US showed: in RL, 4.7 mm hyperechoic nodule, with irregular margins; in RL-isthmus transition, 9.3 mm hypoechoic nodule; in LL, 5.6 mm hypoechoic nodule. At 10 years and 9 months, fine-needle aspiration cytology (FNAC) of RL-isthmus transition nodule showed FLUS. Thyroidectomy was performed at 11 years; pathology revealed nodular hyperplasia.

Case 2: 8 year old boy, with macrocephaly, learning difficulties, mucocutaneous lesions and lipomas; PTEN sequencing revealed a heterozygous frameshift mutation (c.412dup – p.Tyr138LeufsTer42). Thyroid US showed several hypoechoic, regular-margin nodules, the larger in LL with 9 mm; several suspicious lymph nodes. He had normal TSH, but calcitonin 15.2 pg/ml (N < 8.4). He was submitted to thyroidectomy at 9.5 years; pathology revealed nodular hyperplasia with two follicular adenomas and reactive adenitis.

Case 3: 6 year old boy with macrocephaly, developmental delay, intestinal polyposis and iron-deficiency anemia. Genome sequencing revealed a deletion on chromosome 10 (10q23.1q23.31), involving PTEN and BMPR1A genes. At 6 years and 11 months, US showed enlarged thyroid, with no nodules. At 12 years, US showed a RL nodule with 9 mm and two LL nodules, the larger with 9 mm. He had normal TSH and positive anti-thyroglobulin antibodies. FNAC of RL nodule revealed a benign lesion. At 15 years, US showed in RL a heterogeneous nodule with 21 mm; in LL, a hypoechoic nodule with 16 mm, an area of confluent nodules with 36 mm and other multiple smaller nodules; multiple enlarged lymph nodes. He is waiting for thyroidectomy.

Conclusions: PHTS patients must be evaluated annually with thyroid US, starting after diagnosis. The high risk of carcinoma in young age and the diagnostic difficulties due to multiple thyroid nodules often leads to thyroidectomy in suspicious cases.