Results of early thyroidectomy for medullary thyroid carcinoma in children with multiple endocrine neoplasia type 2

doi:10.1016/0022-3468(86)90037-0

Journal of Pediatric Surgery

Volume 21, Issue 12, December 1986, Pages 1190-1194

https://doi.org/10.1016/0022-3468(86)90037-0 Get rights and content

Abstract

Children with multiple endocrine neoplasia type 2 (MEN2) often develop medullary carcinoma of the thyroid (MCT) or its precursor, C-cell hyperplasia. Survival results are improved if malignancy is diagnosed early from the results of plasma immunoreactive calcitonin (iCT) measurement. The effect of early detection and thyroidectomy in children with MEN2 syndrome was determined by reviewing the experience between 1975 and 1985. Seventeen children with MEN2 who were 12 years old or younger underwent a total thyroidectomy for MCT or C-cell hyperplasia. iCT was measured in all patients preoperatively and postoperatively. Of the 17 children, 14 (82%) had MEN2a and 3 (18%) had MEN2b. There were 14 (82%) female and three (18%) male patients; their mean age was 6.97 years (range 1.5 to 12 years). In all patients, the diagnosis of MCT was made from initial elevated levels of iCT after stimulation with pentagastrin. Three patients had clinical evidence of disease preoperatively. All patients underwent a total thyroidectomy and lymph nodes were removed from the central zone; a neck dissection was performed in the three with clinically obvious disease. MCT with C-cell hyperplasia was found in 11 children and C-cell hyperplasia alone in six. Of the 11 with carcinoma, eight had bilateral disease and three unilateral. Six children had bilateral C-cell hyperplasia. All 17 children were alive and feeling well at the time of this report; however, three had evidence of metastatic disease according to iCT measurements. None of the children had recurrent nerve injuries; one had evidence of hypoparathyroidism. All 14 children with occult disease diagnosed by iCT determinations survived and remained free of disease at follow-up. The three children with clinical disease when first examined, although alive, are presumed to have persistent metastatic disease. The youngest child with C-cell hyperplasia at operation was 20 months old, and the youngest with MCT was 3 years old. Therefore, we recommend initiating screening at age 1 year and total thyroidectomy when the diagnosis is made.

References (14)

GW Sizemore et al.
Multiple endocrine neoplasia type 2
Clin Endocrinol Metab
(1980)
GW Sizemore et al.
Epidemiology of medullary carcinoma of the thyroid gland: A 5-year experience (1971–1976)
Surg Clin North Am
(1977)
RC Bartlett et al.
A neuropolyendocrine syndrome: Mucosal neuromas, pheochromocytoma and medullary thyroid carcinoma
Oral Surg Oral Med Oral Pathol
(1971)
SA Wells et al.
Early diagnosis and treatment of medullary thyroid carcinoma
Arch Intern Med
(1985)
GC Chong et al.
Medullary carcinoma of the thyroid gland
Cancer
(1975)
GW Sizemore et al.
Stimulation tests for diagnosis of medullary thyroid carcinoma
CF Russell et al.
The surgical management of medullary thyroid carcinoma
Ann Surg
(1983)

There are more references available in the full text version of this article.

Cited by (55)

Prophylactic thyroidectomy in multiple endocrine neoplasia 2 (MEN2) patients with the C634Y mutation: A long-term follow-up in a large single-center cohort
2019, European Journal of Surgical Oncology
Citation Excerpt :
The discovery in 1993 of the RET oncogene changed the way in which this disease was treated, as it became possible to carry out thyroidectomy in patients with this mutation before MTC could develop [1,2,7–9]. In this context we should pay particular attention to the controversy in recent years regarding prophylactic thyroidectomy in terms of levels of calcitonin (Ct) and the patient's age [10–15]. Currently, the American Thyroid Association (ATA) recommends carrying out thyroidectomy in MEN2 patients aged ≤5 years with the most common mutation (codon 634); the ATA also recommends central neck dissection (CND) when basal calcitonin (bCt) levels go above 40 pg/mL [1,16].
Medullary thyroid carcinoma (MTC) is the main cause of death in multiple endocrine neoplasia 2A (MEN2A) patients. It is therefore important to treat this disease at an early stage. The mutation in codon 634 is considered to be associated with an aggressive clinical course, whereas the C634Y mutation may result in a more indolent course. Prophylactic thyroidectomy is performed before thyroid disease occurs. However, controversy surrounds this disease regarding levels of calcitonin (Ct) and age. In this context, few studies have investigated this mutation over a long period.
To analyze a large cohort of patients with the C634Y mutation who received prophylactic thyroidectomy.
In a group of 110 MEN2 patients, we analyzed those with the C634Y mutation who had received prophylactic thyroidectomy (absence of clinical and radiological thyroid disease) treated in a tertiary referral hospital between 1983 and 2016. MTC is related to age and Ct. Statistical analysis was performed using the χ² test, partial correlations, and logistic regression.
Fifty patients with a mean age of 12 ± 9 years were analyzed; 56% of these had MTC (100% stage I). There was no case of hypoparathyroidism or permanent recurrent damage. MTC was associated mainly with age (OR 1.38). One 5-year-old patient presented with MTC. Mean follow-up time was 16 ± 6 years, and no cases of recurrence were observed.
Performing prophylactic thyroidectomy in patients with the C634Y mutation allows us to cure the disease without causing long-term complications. Our results support the notion that age <5 years should be a criterion for carrying out prophylactic thyroidectomy in these patients.
Endocrine Disorders and Tumors
2010, Ashcraft's Pediatric Surgery
Cancer of the Thyroid
2010, Leibel and Phillips Textbook of Radiation Oncology, Third Edition
ENDOCRINE DISORDERS AND TUMORS
2009, Ashcraft's Pediatric Surgery, Fifth Edition
Medullary Thyroid Carcinoma
2007, Hematology/Oncology Clinics of North America
Citation Excerpt :
The goal of this test is to identify presymptomatic gene carriers at risk for developing MTC. Several studies have shown that prophylactic thyroidectomy is associated with significant improvement in morbidity and mortality [50,51]. The optimal timing for genetic analysis and prophylactic surgical intervention has been a focus of intense debate.
Medullary thyroid carcinoma is a neuroendocrine tumor derived from the C cells of the thyroid gland and accounts for approximately 5% of all thyroid carcinomas. Approximately 30% of the cases are associated with an autosomal dominant syndrome called multiple endocrine neoplasia type 2, and the identification of these individuals is important because affected family members may benefit from an early diagnosis. The treatment of this disease is predominantly surgical, and the impact of radiotherapy and chemotherapy is limited. The identification of the associated molecular events has lead to the development of specific molecular targeted agents that may change the way this disease is treated in the near future.
Chapter 8 Medullary thyroid carcinoma
2006, Advances in Molecular and Cellular Endocrinology
Citation Excerpt :
In a report from the Mayo Clinic, two-thirds of hereditary MTC patients with positive nodes died, and no patient with positive nodes had normal calcitonin levels after a median follow-up of 15.7 years [51]. Numerous studies of patients with MEN 2A treated for MTC have demonstrated a direct correlation between early diagnosis and the cure of the disease [52–57]. Clearly, early diagnosis and treatment are of significant importance.
This chapter provides an overview of medullary thyroid carcinoma (MTC), which is a type of thyroid cancer that arises from the neuroendocrine C cells. These parafollicular cells are neural crest derivatives and are part of the amine precursor uptake and decarboxylation (APUD) group of neuroendocrine cells. The C cells comprise only 1% of the total thyroid mass and are dispersed throughout the gland, with the highest concentration in the upper poles. The C cells are named so because of their unique ability to secrete the hormone calcitonin. C cells are capable of secreting other hormones, including carcinoembryonic antigen (CEA), histaminase, neuron-specific enolase, adrenocortical-stimulating hormone (ACTH), gastrin-related peptide, serotonin, and chromogranin. MTC tumors are usually well demarcated, firm, gray-white, and gritty. Microscopically, there are uniform polygonal cells with finely granular eosinophilic cytoplasm with central nuclei. Varying numbers of spindle cells are present in nearly all tumors.

View all citing articles on Scopus

^☆: Presented before the 17th Annual Meeting of the American Pediatric Surgical Association, Toronto, Ontario, May 14–17, 1986.

View full text

Results of early thyroidectomy for medullary thyroid carcinoma in children with multiple endocrine neoplasia type 2☆

Abstract

Clin Endocrinol Metab

Surg Clin North Am

Oral Surg Oral Med Oral Pathol

Early diagnosis and treatment of medullary thyroid carcinoma

Arch Intern Med

Medullary carcinoma of the thyroid gland

Cancer

Stimulation tests for diagnosis of medullary thyroid carcinoma

The surgical management of medullary thyroid carcinoma

Ann Surg