Endocrine Abstracts

In cases of ret-oncogene positive Medullary Thyroid Carcinoma (MTC), national guidelines advocate screening of 1st degree relatives with the Pentagastrin Stimulation Test (PST) to identify those with C-cell hyperplasia, and therefore at risk of MTC. Prophylactic thyroidectomy is recommended in those with positive tests. We highlight the difficulties of quantifying risk in the relatives of a ret-negative patient.

A 30 year-old man presented with a tender neck swelling. Ultrasound demonstrated lymphadenopathy and a cystic (16×30 mm) thyroid mass. Fine needle aspirate confirmed metastatic medullary carcinoma. There was no family history or features of multiple endocrine neoplasia. Genetic analysis excluded known RET mutations involved in hereditary MTC (exons 8,10–16).

His parents and four siblings were screened using the PST. Parents’ tests were normal. Two siblings had repeatedly abnormal tests despite normal thyroid and parathyroid function and underwent thyroidectomy. Histology showed hyperplasia in one and was normal in the other.

The case raises several questions:

Should screening have occurred? The patient’s young age (<35 years) together with the aggressiveness of the malignancy made us concerned about the possibility of an unidentified germline mutation, and so screening was offered.

Does PST aid management in this case? The parents negative testing, together with the negative genetics in the index case, make it more than 90% probable that this is sporadic MTC. However, the 2 siblings with positive screening, together with one with histological C-cell hyperplasia complicates the picture, particularly when C- cell hyperplasia occurs in 30% of the background population.

Should the children of the sibling with positive PST be screened? C-cell hyperplasia in a sibling raises the possibility of an un-identified mutation (with incomplete penetrance), and so could support continued screening.

Our case highlights the need for clearer guidance as to the management of ret-negative MTC.