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# Medullary thyroid carcinoma

A rare thyroid cancer of the calcitonin-making C cells. About a quarter of cases are inherited (RET gene, MEN 2), so relatives are tested.

Updated 2026-11-01

## Structures involved

Tap one to see what it is and open it in 3D.

- [Thyroid gland](https://durgical.com/en/anatomy/thyroid-gland/)
- [Neck lymph nodes](https://durgical.com/en/anatomy/lymph-nodes-of-neck/)
- [Recurrent laryngeal nerves](https://durgical.com/en/anatomy/recurrent-laryngeal-nerve/)
- [Parathyroid glands](https://durgical.com/en/anatomy/parathyroid-glands/)
- [Trachea](https://durgical.com/en/anatomy/trachea/)

## Why it happens

- [Oncogenes: RAS, MYC, HER2, BCR-ABL and the table to know](https://durgical.com/en/general-pathology/oncogenes-ras-myc-her2-bcr-abl-and-the-table-to-know/)
- [Hereditary cancer syndromes: the table to know](https://durgical.com/en/general-pathology/hereditary-cancer-syndromes-the-table-to-know/)
- [Tumour markers: serum and tissue, and what each one is for](https://durgical.com/en/general-pathology/tumour-markers-serum-and-tissue-and-what-each-one-is-for/)
- [Calcium regulation: PTH, vitamin D and calcitonin](https://durgical.com/en/physiology/calcium-regulation-pth-vitamin-d-and-calcitonin/)
- [Receptor tyrosine kinases](https://durgical.com/en/biochemistry/topics/receptor-tyrosine-kinases/)
- [Carcinoembryonic antigen (CEA)](https://durgical.com/en/biochemistry/topics/carcinoembryonic-antigen/)

## Show 1 more

- [Thyroid follicles, C cells and parathyroid](https://durgical.com/en/histology/thyroid-follicles-c-cells-and-parathyroid/)

## What it is

A neuroendocrine malignancy arising from the parafollicular (C) cells of the thyroid, which derive from the neural crest and secrete calcitonin. It does not take up iodine or depend on TSH, so it behaves differently from the follicular-cell thyroid cancers. It occurs sporadically or as part of multiple endocrine neoplasia type 2 (MEN 2A, MEN 2B) and familial MTC.

## Who gets it

Accounts for roughly 1 to 2% of thyroid cancers. About three quarters of cases are sporadic, usually presenting in the fourth to sixth decade; the hereditary forms appear earlier, in MEN 2B even in early childhood. Latin American series, including Colombian and Brazilian families, report the same RET hotspot mutations seen elsewhere, and cascade testing of relatives is recommended.

## Causes

- Sporadic: somatic RET mutations in most tumours, sometimes RAS mutations
- Hereditary: germline gain-of-function RET proto-oncogene mutations, autosomal dominant
- MEN 2A: MTC with pheochromocytoma and primary hyperparathyroidism
- MEN 2B: MTC with pheochromocytoma, mucosal neuromas and a marfanoid habitus, typically the most aggressive form

## Risk factors

- Family history of MTC, pheochromocytoma or MEN 2
- Known germline RET mutation
- Personal history of pheochromocytoma or mucosal neuromas

## Pathophysiology

Activating RET mutations drive C-cell hyperplasia, which progresses to multifocal, often bilateral carcinoma in the hereditary forms; sporadic tumours are usually single and unilateral. The tumour secretes calcitonin and carcinoembryonic antigen (CEA), which serve as tumour markers; high calcitonin and other peptides can cause secretory diarrhoea and flushing. Histology shows nests of cells in an amyloid stroma derived from calcitonin. Spread is early to central and lateral [neck lymph nodes](https://durgical.com/en/anatomy/lymph-nodes-of-neck/), then to liver, lung and bone.

## Classification

- Sporadic MTC (about 75%)
- Hereditary MTC: MEN 2A, MEN 2B and familial MTC
- Hereditary risk categories by RET codon (highest, high, moderate) guide the timing of prophylactic thyroidectomy

## Symptoms and signs

- Painless, firm thyroid nodule, often in the upper part of the lobes
- Enlarged neck lymph nodes
- Hoarseness, difficulty swallowing or breathing with local invasion
- Watery diarrhoea and facial flushing in advanced disease with high calcitonin
- Features of associated tumours: episodic hypertension, headache and sweating (pheochromocytoma); mucosal neuromas of lips and [tongue](https://durgical.com/en/anatomy/tongue/) (MEN 2B)

## Red flags

- Paroxysmal hypertension, palpitations and headache in a patient awaiting thyroid surgery (unrecognised pheochromocytoma)
- Stridor or rapidly progressive hoarseness
- Rapidly rising calcitonin or CEA after surgery (short doubling time)
- Child with mucosal neuromas or a family history of MEN 2

## Diagnosis

**Clinical**
Neck examination of the nodule and lymph nodes, family history of thyroid cancer, pheochromocytoma or hyperparathyroidism, and examination for mucosal neuromas and marfanoid habitus.

**Tests**
Fine-needle aspiration cytology, with calcitonin immunostaining or calcitonin measured in the washout fluid. Serum calcitonin and CEA (diagnostic and baseline markers). Germline RET testing in every patient with MTC. Before any neck surgery, plasma or urine metanephrines to exclude pheochromocytoma, and serum calcium and PTH.

**Imaging**
Neck ultrasound of the thyroid and all lymph-node compartments is first-line. With high calcitonin, CT of the neck and [chest](https://durgical.com/en/anatomy/region/chest/), [liver](https://durgical.com/en/anatomy/liver/) MRI or multiphase CT and bone imaging stage distant disease; functional PET imaging is used in selected cases.

## Differential diagnosis

- Papillary and follicular thyroid carcinoma
- Benign thyroid nodule or multinodular goitre
- Anaplastic thyroid carcinoma and thyroid lymphoma
- Metastasis to the thyroid
- Other causes of raised calcitonin (chronic [kidney](https://durgical.com/en/anatomy/kidney/) disease, proton pump inhibitor use, other neuroendocrine tumours)

## Goal of treatment

Remove all disease in the neck at the first operation, exclude or treat pheochromocytoma first, protect the parathyroids and laryngeal nerves, and identify at-risk relatives early enough to prevent cancer.

## Treatment

**Surgical**
Total thyroidectomy with central neck dissection, plus lateral neck dissection when nodes are involved. A pheochromocytoma, if present, is removed first after alpha-blockade.

**Surgical**
Prophylactic total thyroidectomy in RET mutation carriers, timed by mutation risk class (in the first year of life for the highest-risk MEN 2B mutations).

**Medical**
Levothyroxine replacement after thyroidectomy, aimed at normal thyroid function rather than TSH suppression. Radioactive iodine is not effective. Selective RET inhibitors and multikinase inhibitors are used for progressive metastatic disease.

**Procedure**
External beam radiotherapy or local therapies for selected unresectable or symptomatic disease, such as bone metastases.

**Follow-up**
Lifelong calcitonin and CEA with doubling times, neck ultrasound, and serum calcium after surgery; annual screening for pheochromocytoma and hyperparathyroidism in hereditary cases.

## Complications

- Hypoparathyroidism and hypocalcaemia after surgery
- [Recurrent laryngeal nerve](https://durgical.com/en/anatomy/recurrent-laryngeal-nerve/) injury with hoarseness
- Local recurrence and neck node metastases
- Distant metastases to liver, lung and bone
- Hypertensive crisis from an unrecognised pheochromocytoma during surgery

## Prognosis

Outcome depends mainly on stage at diagnosis: disease confined to the thyroid is often cured, while nodal and distant spread lower survival. Postoperative calcitonin and CEA levels and their doubling times predict recurrence. Children who have prophylactic surgery before the cancer develops have an excellent outlook.

## Prevention

- Genetic counselling and RET testing of first-degree relatives of anyone with hereditary MTC
- Early prophylactic thyroidectomy in RET mutation carriers

## Test yourself

Think of the answer, then tap the question to see it.

## Which cells give rise to medullary thyroid carcinoma and which tumour markers are followed?

Parafollicular C cells (neural crest origin); calcitonin and CEA.

## What must be excluded before thyroid surgery in a patient with MTC, and why?

Pheochromocytoma, by measuring metanephrines, because an unrecognised one can cause a hypertensive crisis under anaesthesia; it is removed first.

## Which gene is tested in every patient with MTC?

The RET proto-oncogene (germline testing), because a positive result defines MEN 2 and leads to testing of relatives.

## Why is radioactive iodine not used to treat MTC?

C cells do not concentrate iodine, so the tumour does not take it up.

## What are the components of MEN 2A and MEN 2B?

MEN 2A: MTC, pheochromocytoma and hyperparathyroidism. MEN 2B: MTC, pheochromocytoma, mucosal neuromas and marfanoid habitus.

[Add to my cards (5)](https://durgical.app/estudiar/?add=/en/conditions/medullary-thyroid-carcinoma/)

## Related conditions

- [Thyroid cancer (papillary)](https://durgical.com/en/conditions/thyroid-cancer/)
- [Thyroid nodule](https://durgical.com/en/conditions/thyroid-nodule/)
- [Multiple endocrine neoplasia (MEN 1, 2A, 2B)](https://durgical.com/en/conditions/multiple-endocrine-neoplasia/)
- [Phaeochromocytoma](https://durgical.com/en/conditions/phaeochromocytoma/)
- [Primary hyperparathyroidism](https://durgical.com/en/conditions/primary-hyperparathyroidism/)
- [Hypoparathyroidism (incl. post-thyroidectomy hypocalcaemia)](https://durgical.com/en/conditions/hypoparathyroidism/)
- [Marfan syndrome](https://durgical.com/en/conditions/marfan-syndrome/)
- [Carcinoid syndrome](https://durgical.com/en/conditions/carcinoid-syndrome/)
- [Hypothyroidism](https://durgical.com/en/conditions/hypothyroidism/)

Educational information, not medical advice. For any symptom, see a health professional.

Sources: [Thyroid cancer - medullary carcinoma: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/000374.htm) (MedlinePlus Medical Encyclopedia (U.S. National Library of Medicine), 2025); [Medullary Thyroid Cancer | American Thyroid Association](https://www.thyroid.org/medullary-thyroid-cancer/) (American Thyroid Association, 2025).

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Source: https://durgical.com/en/conditions/medullary-thyroid-carcinoma/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/conditions/medullary-thyroid-carcinoma/