From eyelid bumps to thyroid lumps: report of a MEN type IIb family and review of the literature

Ophthalmic Plast Reconstr Surg. 2001 May;17(3):195-201. doi: 10.1097/00002341-200105000-00009.

Abstract

Purpose: 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.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adrenal Gland Neoplasms / diagnosis*
  • Adult
  • Calcitonin / blood
  • Carcinoma, Medullary / diagnosis*
  • Catecholamines / urine
  • Child
  • Cornea / innervation
  • DNA Mutational Analysis
  • Drosophila Proteins*
  • Eyelid Neoplasms / diagnosis*
  • Female
  • Humans
  • Lip Neoplasms / diagnosis
  • Liver Neoplasms / secondary
  • Male
  • Multiple Endocrine Neoplasia Type 2b / diagnosis*
  • Multiple Endocrine Neoplasia Type 2b / genetics
  • Neuroma / diagnosis*
  • Pheochromocytoma / diagnosis*
  • Point Mutation
  • Polymerase Chain Reaction
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases / genetics
  • Thyroid Neoplasms / diagnosis*
  • Tongue Neoplasms / diagnosis
  • Trigeminal Nerve / pathology

Substances

  • Catecholamines
  • Drosophila Proteins
  • MAS1 protein, human
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins
  • Calcitonin
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases
  • Ret protein, Drosophila