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. [1,2,3]
Hoarseness of voice Due to malignant infiltration of the ipsilateral recurrent laryngeal nerve. [2]
Dysphagia Due to malignant infiltration of esophagus. [1]
Respiratory difficulty Due to malignant infiltration of trachea. [2]
Diarrhea Due to increased intestinal electrolyte secretion secondary to high plasma Calcitonin levels. [1]
Weight loss Due to loss of appetite because of liver metastasis. [2]
Bone pain Due to bone metastasis causing lytic lesions. [1]
Palpitations, episodic sweating or any history of young hypertension To detect concomitant pheochromocytoma which is a part of Multiple Endocrine Neoplasia Type II. [4]
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. [4]
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. [4]
References
  1. HUNDAHL SCOTT A., CADY BLAKE, CUNNINGHAM MYLES P., MAZZAFERRI ERNEST, MCKEE ROSEMARY F., ROSAI JUAN, SHAH JATIN P., FREMGEN AMY M., STEWART ANDREW K., H�LZER SIMON. Initial results from a prospective cohort study of 5583 cases of thyroid carcinoma treated in the United States during 1996. Cancer [online] 2000 July, 89(1):202-217 [viewed 12 August 2014] Available from: doi:10.1002/1097-0142(20000701)89:1<202::AID-CNCR27>3.0.CO;2-A
  2. KEBEBEW ELECTRON, ITUARTE PHILIP H. G., SIPERSTEIN ALLAN E., DUH QUAN-YANG, CLARK ORLO H.. Medullary thyroid carcinoma. Cancer [online] 2000 March, 88(5):1139-1148 [viewed 12 August 2014] Available from: doi:10.1002/(SICI)1097-0142(20000301)88:5<1139::AID-CNCR26>3.0.CO;2-Z
  3. KLOOS (CHAIR) RICHARD T., ENG CHARIS, EVANS DOUGLAS B., FRANCIS GARY L., GAGEL ROBERT F., GHARIB HOSSEIN, MOLEY JEFFREY F., PACINI FURIO, RINGEL MATTHEW D., SCHLUMBERGER MARTIN, WELLS SAMUEL A.. Medullary Thyroid Cancer: Management Guidelines of the American Thyroid Association. Thyroid [online] 2009 June, 19(6):565-612 [viewed 12 August 2014] Available from: doi:10.1089/thy.2008.0403
  4. MULLIGAN LOIS M., MARSH D. J., ROBINSON B. G., SCHUFFENECKER I., ZEDENIUS J., LIPS C. J. M., GAGEL R. F., TAKAI S.-I., NOLL W. W., FINK M., RAUE F., LACROIX A., THIBODEAU S. N., FRILLING A., PONDER B. A. J., ENG C.. Genotype-phenotype correlation in multiple endocrine neoplasia type 2: report of the International Mutation Consortium . [online] 1995 October, 238(4):343-346 [viewed 14 August 2014] Available from: doi:10.1111/j.1365-2796.1995.tb01208.x

Examination

Fact Explanation
Dominant thyroid nodule at the base of the neck This could be present in up to 74.2% of patients. [1,2,3]
Palpable cervical lymph nodes Due to lymphadenopathy because of lymphatic spread. [3]
Jaundice Due to liver metastasis. Acute liver failure also can happen. [1]
Bone tenderness Due to bone metastasis. [2]
Elevated blood pressure This is significant in a young patient as an indicator of pheochromocytoma.[4]
Tachycardia Can indicate the presence of pheochromocytoma. [4]
Marfanoid habitus (high-arched palate, pectus excavatum, bilateral pes cavus, scoliosis) To detect MEN Syndrome Type 2B. [4]
Neuromas on the eyelids, conjunctiva, nasal and laryngeal mucosa, tongue and lips. These are features of MEN Syndrome Type 2B. [4]
Prominent hypertrophied lips. Present in MEN Syndrome Type 2B. [4]
Multiple pruritic, hyperpigmented, lichenoid papules in tn the scapular area of the back. Present in MEN Type 2A. [4]
References
  1. GOROSPE EMMANUEL C., BADAMAS JEMILAT. Acute Liver Failure Secondary to Metastatic Medullary Thyroid Cancer. Case Reports in Hepatology [online] 2011 December, 2011:1-4 [viewed 12 August 2014] Available from: doi:10.1155/2011/603757
  2. HUNDAHL SCOTT A., CADY BLAKE, CUNNINGHAM MYLES P., MAZZAFERRI ERNEST, MCKEE ROSEMARY F., ROSAI JUAN, SHAH JATIN P., FREMGEN AMY M., STEWART ANDREW K., H�LZER SIMON. Initial results from a prospective cohort study of 5583 cases of thyroid carcinoma treated in the United States during 1996. Cancer [online] 2000 July, 89(1):202-217 [viewed 12 August 2014] Available from: doi:10.1002/1097-0142(20000701)89:1<202::AID-CNCR27>3.0.CO;2-A
  3. KLOOS (CHAIR) RICHARD T., ENG CHARIS, EVANS DOUGLAS B., FRANCIS GARY L., GAGEL ROBERT F., GHARIB HOSSEIN, MOLEY JEFFREY F., PACINI FURIO, RINGEL MATTHEW D., SCHLUMBERGER MARTIN, WELLS SAMUEL A.. Medullary Thyroid Cancer: Management Guidelines of the American Thyroid Association. Thyroid [online] 2009 June, 19(6):565-612 [viewed 12 August 2014] Available from: doi:10.1089/thy.2008.0403
  4. MULLIGAN LOIS M., MARSH D. J., ROBINSON B. G., SCHUFFENECKER I., ZEDENIUS J., LIPS C. J. M., GAGEL R. F., TAKAI S.-I., NOLL W. W., FINK M., RAUE F., LACROIX A., THIBODEAU S. N., FRILLING A., PONDER B. A. J., ENG C.. Genotype-phenotype correlation in multiple endocrine neoplasia type 2: report of the International Mutation Consortium . [online] 1995 October, 238(4):343-346 [viewed 14 August 2014] Available from: doi:10.1111/j.1365-2796.1995.tb01208.x

Differential Diagnoses

Fact Explanation
Metastases of gastroenteropancreatic (GEP) Neuro Endocrine Tumors (NET) Presents with a similar clinical picture. Normal circulating Calcitonin levels and negative immunohistochemistry with Calcitonin antibodies rule out the diagnosis of Medullary Thyroid Carcinoma. [1]
Thyroid lymphoma Presents with a thyroid nodule. Can be differentiated by Fine Needle aspiration Cytology. [2]
Follicular carcinoma of thyroid This also presents with a solitary nodule. However it can't be differentiated from a follicular adenoma without histological evaluation. [2]
Papillary carcinoma of thyroid Presents with a thyroid nodule. Can be differentiated by Fine Needle Aspiration Cytology (FNAC). [2]
Colloid nodules Can present as a solitary thyroid nodule. Fine Needle Aspiration Cytology (FNAC) helps in diagnosis. [2]
References
  1. LEBOULLEUX S, BAUDIN E, YOUNG J, CAILLOU B, LAZAR V, PELLEGRITI G, DUCREUX M, SCHAISON G, SCHLUMBERGER M. Gastroenteropancreatic neuroendocrine tumor metastases to the thyroid gland: differential diagnosis with medullary thyroid carcinoma. European Journal of Endocrinology [online] 1999 March, 140(3):187-191 [viewed 12 August 2014] Available from: doi:10.1530/eje.0.1400187
  2. MAZZAFERRI EL. Management of a solitary thyroid nodule. N Engl J Med [online] 1993 Feb 25, 328(8):553-9 [viewed 12 August 2014] Available from: doi:10.1056/NEJM199302253280807

Investigations - for Diagnosis

Fact Explanation
Fine Needle Aspiration Cytology Can detect typical cytological features thus establishing the diagnosis. [1]
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. [2,3]
References
  1. CHANG TC, WU SL, HSIAO YL. Medullary thyroid carcinoma: pitfalls in diagnosis by fine needle aspiration cytology and relationship of cytomorphology to RET proto-oncogene mutations. Acta Cytol [online] 2005 Sep-Oct, 49(5):477-82 [viewed 13 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/16334022
  2. COSTANTE GIUSEPPE, MERINGOLO DOMENICO, DURANTE COSIMO, BIANCHI DAVIDE, NOCERA MARIA, TUMINO SALVATORE, CROCETTI UMBERTO, ATTARD MARCO, MARANGHI MARIANNA, TORLONTANO MASSIMO, FILETTI SEBASTIANO. Predictive Value of Serum Calcitonin Levels for Preoperative Diagnosis of Medullary Thyroid Carcinoma in a Cohort of 5817 Consecutive Patients with Thyroid Nodules. The Journal of Clinical Endocrinology & Metabolism [online] 2007 February, 92(2):450-455 [viewed 13 August 2014] Available from: doi:10.1210/jc.2006-1590
  3. MACHENS A, LORENZ K, DRALLE H. Individualization of lymph node dissection in RET (rearranged during transfection) carriers at risk for medullary thyroid cancer: value of pretherapeutic calcitonin levels. Ann Surg [online] 2009 Aug, 250(2):305-10 [viewed 13 August 2014] Available from: doi:10.1097/SLA.0b013e3181ae333f

Investigations - Fitness for Management

Fact Explanation
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. [1,2]
Serum Calcium To exclude hyperparathyroidism. [2]
Indirect layngoscopy To assess vocal cord function prior to surgery. [3]
References
  1. KLOOS (CHAIR) RICHARD T., ENG CHARIS, EVANS DOUGLAS B., FRANCIS GARY L., GAGEL ROBERT F., GHARIB HOSSEIN, MOLEY JEFFREY F., PACINI FURIO, RINGEL MATTHEW D., SCHLUMBERGER MARTIN, WELLS SAMUEL A.. Medullary Thyroid Cancer: Management Guidelines of the American Thyroid Association. Thyroid [online] 2009 June, 19(6):565-612 [viewed 12 August 2014] Available from: doi:10.1089/thy.2008.0403
  2. PERROS PETROS, BOELAERT KRISTIEN, COLLEY STEVE, EVANS CAROL, EVANS RHODRI M, GERRARD BA GEORGINA, GILBERT JACKIE, HARRISON BARNEY, JOHNSON SARAH J, GILES THOMAS E, MOSS LAURA, LEWINGTON VAL, NEWBOLD KATE, TAYLOR JUDITH, THAKKER RAJESH V, WATKINSON JOHN, WILLIAMS GRAHAM R.. Guidelines for the management of thyroid cancer. Clin Endocrinol [online] December, 81:1-122 [viewed 13 August 2014] Available from: doi:10.1111/cen.12515
  3. CHANDRASEKHAR S. S., RANDOLPH G. W., SEIDMAN M. D., ROSENFELD R. M., ANGELOS P., BARKMEIER-KRAEMER J., BENNINGER M. S., BLUMIN J. H., DENNIS G., HANKS J., HAYMART M. R., KLOOS R. T., SEALS B., SCHREIBSTEIN J. M., THOMAS M. A., WADDINGTON C., WARREN B., ROBERTSON P. J.. Clinical Practice Guideline: Improving Voice Outcomes after Thyroid Surgery. Otolaryngology -- Head and Neck Surgery [online] December, 148(6 Suppl):S1-S37 [viewed 14 August 2014] Available from: doi:10.1177/0194599813487301

Investigations - Followup

Fact Explanation
Serum Calcitonin To detect tumor recurrence. [1,2]
Serum carcinoembryonic antigen To detect tumor recurrence. [1,2]
References
  1. KLOOS (CHAIR) RICHARD T., ENG CHARIS, EVANS DOUGLAS B., FRANCIS GARY L., GAGEL ROBERT F., GHARIB HOSSEIN, MOLEY JEFFREY F., PACINI FURIO, RINGEL MATTHEW D., SCHLUMBERGER MARTIN, WELLS SAMUEL A.. Medullary Thyroid Cancer: Management Guidelines of the American Thyroid Association. Thyroid [online] 2009 June, 19(6):565-612 [viewed 12 August 2014] Available from: doi:10.1089/thy.2008.0403
  2. LAURE GIRAUDET A., AL GHULZAN A., AUPERIN A., LEBOULLEUX S., CHEHBOUN A., TROALEN F., DROMAIN C., LUMBROSO J., BAUDIN E., SCHLUMBERGER M.. Progression of medullary thyroid carcinoma: assessment with calcitonin and carcinoembryonic antigen doubling times. European Journal of Endocrinology [online] 2008 February, 158(2):239-246 [viewed 14 August 2014] Available from: doi:10.1530/EJE-07-0667

Investigations - Screening/Staging

Fact Explanation
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. [1,2]
Ultra Sound Scan of the neck to include the superior mediastinum, central and bilateral lateral neck compartments. Staging - To detect lymph node metastasis. [2]
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. [2]
Dual phase CT liver or MRI Staging - To detect liver metastasis. [2,3]
Bone scintigraphy or MRI spine Staging - To detect bone metastasis. [2]
References
  1. KLOOS (CHAIR) RICHARD T., ENG CHARIS, EVANS DOUGLAS B., FRANCIS GARY L., GAGEL ROBERT F., GHARIB HOSSEIN, MOLEY JEFFREY F., PACINI FURIO, RINGEL MATTHEW D., SCHLUMBERGER MARTIN, WELLS SAMUEL A.. Medullary Thyroid Cancer: Management Guidelines of the American Thyroid Association. Thyroid [online] 2009 June, 19(6):565-612 [viewed 12 August 2014] Available from: doi:10.1089/thy.2008.0403
  2. PERROS PETROS, BOELAERT KRISTIEN, COLLEY STEVE, EVANS CAROL, EVANS RHODRI M, GERRARD BA GEORGINA, GILBERT JACKIE, HARRISON BARNEY, JOHNSON SARAH J, GILES THOMAS E, MOSS LAURA, LEWINGTON VAL, NEWBOLD KATE, TAYLOR JUDITH, THAKKER RAJESH V, WATKINSON JOHN, WILLIAMS GRAHAM R.. Guidelines for the management of thyroid cancer. Clin Endocrinol [online] December, 81:1-122 [viewed 14 August 2014] Available from: doi:10.1111/cen.12515
  3. DROMAIN C., DE BAERE T., LUMBROSO J., CAILLET H., LAPLANCHE A., BOIGE V., DUCREUX M., DUVILLARD P., ELIAS D., SCHLUMBERGER M., SIGAL R., BAUDIN E.. Detection of Liver Metastases From Endocrine Tumors: A Prospective Comparison of Somatostatin Receptor Scintigraphy, Computed Tomography, and Magnetic Resonance Imaging. Journal of Clinical Oncology [online] December, 23(1):70-78 [viewed 14 August 2014] Available from: doi:10.1200/JCO.2005.01.013

Management - General Measures

Fact Explanation
Radiotherapy Palliative radiotherapy can play a valuable role in unresectable masses and painful bone metastases. [1]
Chemotherapy This is now rarely used. Doxorubicin produces symptomatic response in <30% of cases; most are partial and of short duration. [1]
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. [1]
References
  1. PERROS PETROS, BOELAERT KRISTIEN, COLLEY STEVE, EVANS CAROL, EVANS RHODRI M, GERRARD BA GEORGINA, GILBERT JACKIE, HARRISON BARNEY, JOHNSON SARAH J, GILES THOMAS E, MOSS LAURA, LEWINGTON VAL, NEWBOLD KATE, TAYLOR JUDITH, THAKKER RAJESH V, WATKINSON JOHN, WILLIAMS GRAHAM R.. Guidelines for the management of thyroid cancer. Clin Endocrinol [online] December, 81:1-122 [viewed 14 August 2014] Available from: doi:10.1111/cen.12515

Management - Specific Treatments

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. [1,2,3]
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. [1,4]
References
  1. PERROS PETROS, BOELAERT KRISTIEN, COLLEY STEVE, EVANS CAROL, EVANS RHODRI M, GERRARD BA GEORGINA, GILBERT JACKIE, HARRISON BARNEY, JOHNSON SARAH J, GILES THOMAS E, MOSS LAURA, LEWINGTON VAL, NEWBOLD KATE, TAYLOR JUDITH, THAKKER RAJESH V, WATKINSON JOHN, WILLIAMS GRAHAM R.. Guidelines for the management of thyroid cancer. Clin Endocrinol [online] December, 81:1-122 [viewed 14 August 2014] Available from: doi:10.1111/cen.12515
  2. MACHENS ANDREAS, DRALLE HENNING. Biological Relevance of Medullary Thyroid Microcarcinoma. The Journal of Clinical Endocrinology & Metabolism [online] 2012 May, 97(5):1547-1553 [viewed 14 August 2014] Available from: doi:10.1210/jc.2011-2534
  3. MACHENS ANDREAS, DRALLE HENNING. Biomarker-Based Risk Stratification for Previously Untreated Medullary Thyroid Cancer. The Journal of Clinical Endocrinology & Metabolism [online] 2010 June, 95(6):2655-2663 [viewed 14 August 2014] Available from: doi:10.1210/jc.2009-2368
  4. COOPER DAVID S., DOHERTY GERARD M., HAUGEN BRYAN R., KLOOS RICHARD T., LEE STEPHANIE L., MANDEL SUSAN J., MAZZAFERRI ERNEST L., MCIVER BRYAN, SHERMAN STEVEN I., TUTTLE R. MICHAEL. Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Taskforce. Thyroid [online] 2006 February, 16(2):109-142 [viewed 14 August 2014] Available from: doi:10.1089/thy.2006.16.109