Familial MEN2A Syndrome with Hereditary Medullary Thyroid Cancer

Abstract

Keywords: MEN2A syndrome; Familial medullary thyroid carcinoma; RET gene.

INTRODUCTION

Multiple endocrine neoplasia (MEN) syndromes are infrequent inherited disorders in which more than one endocrine gland develops benign or malignant tumors or grow excessively without forming tumors. There are 3 well-known forms of MEN syndromes - MEN1, MEN2A, and MEN2B and a newly documented one - MEN4. All these types have autosomal dominant predispositions. The MEN1 gene is responsible for MEN1 disease, RET proto-oncogene for MEN2 and CDNK1B for MEN4. This case describes a familial medullary cell carcinoma of the thyroid gland (FMTC) with inheritance in 3 generations with 5 family members affected.

CASE REPORT

73-year-old men was admitted to emergency department in serious condition – diarrhea, wight loss, skin flushing and lower extremity weakness. Objectively – dehydration, massive neck lymphadenopathy, large nodular goiter.  Radiologically - metastatic process in the lungs, liver, bones, neck and mediastinal lymph nodes. Thyroid CORE biopsy and laboratory evaluation showed ACTH-secreting MTC. The patient died one month after the diagnosis established. Because of severe MTC, the relatives of the patient underwent preventive testing for MEN2A syndrome. All patients underwent fine needle aspiration and were tested for carcinoembryonic antigen (CEA), serum fasting calcitonin and RET gene mutation.

Patients’ son is 49 years old and asymptomatic. USG showed - colloidal nodose thyroid gland and nodule in the right lobe (TIRADS 4a). His daughter is 26-year-old and asymptomatic. USG showed – thyroid gland nodule (TIRADS 4a). Patients another son is 44 years old and asymptomatic. USG showed - nodules in both lobes (TIRADS 4a). His daughter is 16-year-old and asymptomatic. USG showed - a small nodule with microcalcifications in the right lobe (TIRADS 5). All patients were diagnosed with - medullary thyroid carcinoma with heterozygous variant in the RET gene. All patients underwent total thyroidectomy with central/lateral lymph node dissection.

SUMMARY

This case reports MEN2A syndrome with familial medullary cell carcinoma of the thyroid gland with inheritance in 3 generations. Four of the five tested family members were asymptomatic but with suspicious changes in thyroid ultrasound. Therefore, this case represents the importance of testing family members before they develop any symptoms.

CONCLUSIONS

The most common MTC presentation is a solitary thyroid nodule without any symptoms.  It is important to detect the risk factors for familial MEN syndrome. After the diagnosis of MTC is made, other family members must be evaluated for fasting calcitonin, CEA, thyroid ultrasound, and RET gene mutation.

REFERENCES

1. Yasir M, Mulji NJ, Kasi A. Multiple Endocrine Neoplasias Type 2. In: Treasure Island (FL): StatPearls Publishing; August 14, 2023.
2. Wijewardene AA, Glastras SJ, Learoyd DL, Robinson BG, Tsang VHM. ACTH-secreting medullary thyroid cancer: a case series.Endocrinol Diabetes Metab Case Rep. 2017; 2017:16-0110. Published 2017 May 17. doi:10.1530/EDM-16-0110