Medullary Thyroid Carcinoma

Endocrine

Clinicals - History

Fact Explanation
Lump at the base of the neck which moves with deglutition The thyroid gland is attached to the larynx by means of the suspensory ligament of Berry which is a condensation of pretracheal fascia. Therefore the thyroid gland will move with swallowing. Lump at the base of the neck which moves with deglutition
The thyroid gland is attached to the larynx by means of the suspensory ligament of Berry which is a condensation of pretracheal fascia. Therefore the thyroid gland will move with swallowing.
Hoarseness of voice Due to malignant infiltration of the ipsilateral recurrent laryngeal nerve. Hoarseness of voice
Due to malignant infiltration of the ipsilateral recurrent laryngeal nerve.
Dysphagia Due to malignant infiltration of esophagus. Dysphagia
Due to malignant infiltration of esophagus.
Respiratory difficulty Due to malignant infiltration of trachea. Respiratory difficulty
Due to malignant infiltration of trachea.
Diarrhea Due to increased intestinal electrolyte secretion secondary to high plasma Calcitonin levels. Diarrhea
Due to increased intestinal electrolyte secretion secondary to high plasma Calcitonin levels.
Weight loss Due to loss of appetite because of liver metastasis. Weight loss
Due to loss of appetite because of liver metastasis.
Bone pain Due to bone metastasis causing lytic lesions. Bone pain
Due to bone metastasis causing lytic lesions.
Palpitations, episodic sweating or any history of young hypertension To detect concomitant pheochromocytoma which is a part of Multiple Endocrine Neoplasia Type II. Palpitations, episodic sweating or any history of young hypertension
To detect concomitant pheochromocytoma which is a part of Multiple Endocrine Neoplasia Type II.
Constipation, polyuria, polydipsia, memory problems, depresssion These are symptoms of hypercalcaemia which is due to parathyroid hyperplasia which is a feature of MEN Type II. Constipation, polyuria, polydipsia, memory problems, depresssion
These are symptoms of hypercalcaemia which is due to parathyroid hyperplasia which is a feature of MEN Type II.
Family history of thyroid cancer, pheochromocytoma or sudden death. MEN 2A, MEN 2B and FMTC (Familial Medullary Thyroid Carcinoma) are inherited as an autosomal dominant disorder. Occult pheochromocytoma can cause sudden unexplained death. Family history of thyroid cancer, pheochromocytoma or sudden death.
MEN 2A, MEN 2B and FMTC (Familial Medullary Thyroid Carcinoma) are inherited as an autosomal dominant disorder. Occult pheochromocytoma can cause sudden unexplained death.

Clinicals - Examination

Fact Explanation
Dominant thyroid nodule at the base of the neck This could be present in up to 74.2% of patients. Dominant thyroid nodule at the base of the neck
This could be present in up to 74.2% of patients.
Palpable cervical lymph nodes Due to lymphadenopathy because of lymphatic spread. Palpable cervical lymph nodes
Due to lymphadenopathy because of lymphatic spread.
Jaundice Due to liver metastasis. Acute liver failure also can happen. Jaundice
Due to liver metastasis. Acute liver failure also can happen.
Bone tenderness Due to bone metastasis. Bone tenderness
Due to bone metastasis.
Elevated blood pressure This is significant in a young patient as an indicator of pheochromocytoma. Elevated blood pressure
This is significant in a young patient as an indicator of pheochromocytoma.
Tachycardia Can indicate the presence of pheochromocytoma. Tachycardia
Can indicate the presence of pheochromocytoma.
Marfanoid habitus (high-arched palate, pectus excavatum, bilateral pes cavus, scoliosis) To detect MEN Syndrome Type 2B. Marfanoid habitus (high-arched palate, pectus excavatum, bilateral pes cavus, scoliosis)
To detect MEN Syndrome Type 2B.
Neuromas on the eyelids, conjunctiva, nasal and laryngeal mucosa, tongue and lips. These are features of MEN Syndrome Type 2B. Neuromas on the eyelids, conjunctiva, nasal and laryngeal mucosa, tongue and lips.
These are features of MEN Syndrome Type 2B.
Prominent hypertrophied lips. Present in MEN Syndrome Type 2B. Prominent hypertrophied lips.
Present in MEN Syndrome Type 2B.
Multiple pruritic, hyperpigmented, lichenoid papules in tn the scapular area of the back. Present in MEN Type 2A. Multiple pruritic, hyperpigmented, lichenoid papules in tn the scapular area of the back.
Present in MEN Type 2A.

Investigations - Diagnosis

Fact Explanation
Fine Needle Aspiration Cytology Can detect typical cytological features thus establishing the diagnosis. Fine Needle Aspiration Cytology
Can detect typical cytological features thus establishing the diagnosis.
Serum Calcitonin levels This is a highly sensitive test for early diagnosis of Medullary Thyroid Cancer but confirmatory stimulation testing with pentagastrin is necessary in most cases to identify true positive increases. Serum Calcitonin levels
This is a highly sensitive test for early diagnosis of Medullary Thyroid Cancer but confirmatory stimulation testing with pentagastrin is necessary in most cases to identify true positive increases.

Investigations - Management

Fact Explanation
Serum Calcitonin To detect tumor recurrence. Serum Calcitonin
To detect tumor recurrence.
Serum carcinoembryonic antigen To detect tumor recurrence. Serum carcinoembryonic antigen
To detect tumor recurrence.
24- hour urine analysis for catecholamine metabolites like VMA (Vanillylmandelic acid) and metanephrine. In ruling out concomitant pheochromocytoma in patients with multiple endocrine neoplasia type 2A or 2B. Pheochromocytoma must be treated before Medullary Thyroid Carcinoma. 24- hour urine analysis for catecholamine metabolites like VMA (Vanillylmandelic acid) and metanephrine.
In ruling out concomitant pheochromocytoma in patients with multiple endocrine neoplasia type 2A or 2B. Pheochromocytoma must be treated before Medullary Thyroid Carcinoma.
Serum Calcium To exclude hyperparathyroidism. Serum Calcium
To exclude hyperparathyroidism.
Indirect layngoscopy To assess vocal cord function prior to surgery. Indirect layngoscopy
To assess vocal cord function prior to surgery.
Genetic testing to detect mutation of RET gene Screening - All people with a family history consistent with MEN 2 (Multiple Endocrine Neoplasia) or FMTC (Familial Medullary Thyroid Carcinoma) should be screened with RET testing. For MEN 2B this should be done shortly after birth. For MEN 2A and FMTC this should be done before 5 years of age. Genetic testing to detect mutation of RET gene
Screening - All people with a family history consistent with MEN 2 (Multiple Endocrine Neoplasia) or FMTC (Familial Medullary Thyroid Carcinoma) should be screened with RET testing. For MEN 2B this should be done shortly after birth. For MEN 2A and FMTC this should be done before 5 years of age.
Ultra Sound Scan of the neck to include the superior mediastinum, central and bilateral lateral neck compartments. Staging - To detect lymph node metastasis. Ultra Sound Scan of the neck to include the superior mediastinum, central and bilateral lateral neck compartments.
Staging - To detect lymph node metastasis.
CT scanning of chest and neck Staging - Only if there is regional lymph node involvement or calcitonin levels are more than 400pg/mL. To detect metastasis. CT scanning of chest and neck
Staging - Only if there is regional lymph node involvement or calcitonin levels are more than 400pg/mL. To detect metastasis.
Dual phase CT liver or MRI Staging - To detect liver metastasis. Dual phase CT liver or MRI
Staging - To detect liver metastasis.
Bone scintigraphy or MRI spine Staging - To detect bone metastasis. Bone scintigraphy or MRI spine
Staging - To detect bone metastasis.

Management - Supportive

Fact Explanation
Radiotherapy Palliative radiotherapy can play a valuable role in unresectable masses and painful bone metastases. Radiotherapy
Palliative radiotherapy can play a valuable role in unresectable masses and painful bone metastases.
Chemotherapy This is now rarely used. Doxorubicin produces symptomatic response in <30% of cases; most are partial and of short duration. Chemotherapy
This is now rarely used. Doxorubicin produces symptomatic response in <30% of cases; most are partial and of short duration.
Palliative care Gastrointestinal symptoms often respond well to symptomatic treatment (such as loperamide and/or codeine
phosphate).
Medical therapy should concentrate on symptom control.
Somatostatin analogues are a possible alternative, which may decrease tumor peptide release.
Symptomatic distant metastases may respond to surgery, EBRT, thermoablation and chemoembolization.
Patients with known bony metastases may benefit from biphosphonates or denosumab.
Palliative care
Gastrointestinal symptoms often respond well to symptomatic treatment (such as loperamide and/or codeine
phosphate).
Medical therapy should concentrate on symptom control.
Somatostatin analogues are a possible alternative, which may decrease tumor peptide release.
Symptomatic distant metastases may respond to surgery, EBRT, thermoablation and chemoembolization.
Patients with known bony metastases may benefit from biphosphonates or denosumab.

Management - Specific

Fact Explanation
Surgical management To achieve loco-regional control (the neck and superior mediastinum), and in some patients biochemical as well as clinical cure.
Patients with established MTC - total thyroidectomy and central compartment node dissection
Patients with incidental, sporadic (RET negative), unifocal micro MTC <5 mm - completion thyroidectomy is not essential.
Post-operative basal calcitonin should determine the need for further surgery.
Patients with clinical or radiologically involved lymph nodes in the lateral compartment - selective lateral
neck dissection of levels IIa–Vb.
Ipsilateral prophylactic lateral neck dissection is recommended in the presence of central compartment node metastases.
The need for lymph node dissection may not be apparent without histopathological confirmation of involved lymph nodes. Personalized decision Making is recommended based upon the probability of central compartment nodal metastases.
Surgical management
To achieve loco-regional control (the neck and superior mediastinum), and in some patients biochemical as well as clinical cure.
Patients with established MTC - total thyroidectomy and central compartment node dissection
Patients with incidental, sporadic (RET negative), unifocal micro MTC <5 mm - completion thyroidectomy is not essential.
Post-operative basal calcitonin should determine the need for further surgery.
Patients with clinical or radiologically involved lymph nodes in the lateral compartment - selective lateral
neck dissection of levels IIa–Vb.
Ipsilateral prophylactic lateral neck dissection is recommended in the presence of central compartment node metastases.
The need for lymph node dissection may not be apparent without histopathological confirmation of involved lymph nodes. Personalized decision Making is recommended based upon the probability of central compartment nodal metastases.
Adjuvant therapy External Beam Radio Therapy should be considered only once optimal surgery has
been performed and if there is significant risk of local recurrence.
Unlike differentiated thyroid cancer (DTC), radioiodine ablation or therapy are not options.
Adjuvant therapy
External Beam Radio Therapy should be considered only once optimal surgery has
been performed and if there is significant risk of local recurrence.
Unlike differentiated thyroid cancer (DTC), radioiodine ablation or therapy are not options.

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