From eyelid bumps to thyroid lumps: report of a MEN type IIb family and review of the literature.
OBJECTIVE
We present a two-generation family with multiple endocrine neoplasia (MEN) type IIb diagnosed by their ophthalmologists based on characteristic ophthalmic findings.


METHODS
A family consisting of a 33-year-old female proband and her 8- and 7-year-old children had prominent corneal nerves; eyelid, lip, and tongue nodules; and a characteristic facies. A polymerase chain reaction-based genetic assay was obtained to detect the genetic mutation most commonly associated with MEN type IIb. Serum calcitonin and urine catecholamine studies were obtained.


RESULTS
Molecular genetic studies detected in all 3 patients a mutation at codon 918 of the RET proto-oncogene known to be present in 95% of the cases of MEN type IIb. Serum calcitonin was elevated in the proband and her son. Urine catecholamine levels were elevated in the proband. Surgical treatment and histologic analysis confirmed pheochromocytoma and medullary thyroid carcinoma (MTC) in the proband. Surgical exploration revealed the MTC to be metastatic to the liver.


CONCLUSIONS
This family demonstrates the characteristic findings of MEN type IIb: prominent corneal nerves in a clear stroma and multiple submucosal neuromas of the conjunctiva, eyelids, lips, and tongue. Ophthalmologists have a critical role to play in recognizing these signs, because the early diagnosis of medullary thyroid carcinoma and pheochromocytoma may be life saving.
Jacobs
J M
JM
Department of Ophthalmology, University of Colorado Health Sciences Center, Denver, USA.
Hawes
M J
MJ
D000310:Adrenal Gland Neoplasms / Q000175:diagnosis*; D000328:Adult; D002116:Calcitonin / Q000097:blood; D018276:Carcinoma, Medullary / Q000175:diagnosis*; D002395:Catecholamines / Q000652:urine; D002648:Child; D003315:Cornea / Q000294:innervation; D004252:DNA Mutational Analysis; D029721:Drosophila Proteins; D005142:Eyelid Neoplasms / Q000175:diagnosis*; D005260:Female; D006801:Humans; D008048:Lip Neoplasms / Q000175:diagnosis; D008113:Liver Neoplasms / Q000556:secondary; D008297:Male; D018814:Multiple Endocrine Neoplasia Type 2b / Q000175:diagnosis* / Q000235:genetics; D009463:Neuroma / Q000175:diagnosis*; D010673:Pheochromocytoma / Q000175:diagnosis*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D013964:Thyroid Neoplasms / Q000175:diagnosis*; D014062:Tongue Neoplasms / Q000175:diagnosis; D014276:Trigeminal Nerve / Q000473:pathology
D002395:Catecholamines; D029721:Drosophila Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D002116:Calcitonin; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila