Ann W. Gramza
Endocrine tumors arise from hormone-secreting glands. They may be sporadic or part of a familial cancer syndrome (Table 33.1), the most common being the multiple endocrine neoplasia syndromes. With the exception of thyroid cancer, endocrine tumors are often difficult to diagnose and treat effectively. They may cause morbidity and mortality through local and distant metastasis or through systemic effects caused by hormones produced by tumor cells. While relatively uncommon as a group, thyroid cancer has increased in incidence over the last decade more than any other malignancy. The most common endocrine tumors include
■Thyroid carcinoma
■Parathyroid carcinoma
■Adrenocortical carcinoma (ACC)
■Pheochromocytoma
■Carcinoid tumors
■Pancreatic neuroendocrine tumors (NETs).
THYROID CARCINOMA
General
Epidemiology
■Thyroid cancer is the most common endocrine malignancy, and now the fifth most common cancer in women.
■The incidence has been increasing for the past three decades, with a current estimate of more than 56,000 men and women to be diagnosed with thyroid cancer in 2012. The increase in incidence extends to both men and women.
■Mortality has also been rising for the past two decades. The precise reasons for the increase in incidence and mortality are unknown.
■The ratio of female to male patients is approximately 3:1.
Risk Factors
■The best-established risk factor for thyroid cancer is exposure to ionizing radiation during childhood.
■A family history of thyroid cancer and history of a benign thyroid condition such as goiter or nodule also confer an increased risk of thyroid cancer.
Prognosis
■Prognosis varies by thyroid cancer subtype, but the overall 5-year relative survival is nearly 98%. This is because more than 80% of cases are papillary thyroid cancer (PTC), the subtype with the best survival.
Differentiated Thyroid Cancer: Papillary, Follicular, Hurthle Cell
■More than 90% of all thyroid cancers are a subtype of differentiated thyroid cancer (DTC).
■PTC is the most common subtype (80% to 85%).
■PTC is generally unilateral, but may be multifocal within a lobe. Variants include tall cell, columnar, and diffuse sclerosing.
■PTC metastasizes primarily via lymphatic invasion; vascular invasion is uncommon.
■Genetic alterations involved in the MAPK signaling pathway are found in at least 75% of PTC cases. BRAFV600E mutation is found in approximately 45% of PTCs, while RET rearrangements are found in approximately 25% Activating point mutations in the RAS oncogenes occur in approximately 10% of cases.
■Follicular thyroid cancer (FTC) is the second most common type of thyroid carcinoma, comprising 10% to 15% of thyroid cancers.
■FTC typically disseminates hematogenously, with metastases to bone and lung being most common in advanced disease.
■RAS point mutations and the PAX8/PPARγ translocation are the most common genetic alterations in FTC.
■Hurthle cell cancer (HCC) is also referred to as oxyphilic or oncocytic thyroid cancer, and represents approximately 5% of all DTCs. It is often considered a variant of FTC with less sensitivity to radioiodine and a more aggressive clinical course.
Clinical Presentation
■Most patients present with an asymptomatic thyroid nodule. Clinical symptoms may include the following:
•Hoarseness caused by invasion of the recurrent laryngeal nerve or by direct compression of the larynx
•Cervical lymphadenopathy
•Dysphagia
•Horner syndrome (miosis, partial ptosis, hemifacial anhidrosis)
Diagnosis
■Evaluation of any suspected thyroid nodule >1 cm should include a serum TSH and thyroid ultrasound. If a nodule is seen on ultrasound:
•If TSH is normal or high, a fine-needle aspirate (FNA) should be done.
•If the TSH is low, the nodule should be evaluated by radionuclide scan to see if it is hyperfunctioning. Hyperfunctioning nodules are benign and patients with them should be treated for hyperthyroidism.
■Up to 30% of FNAs are indeterminate; therefore, a definitive diagnosis is often not made until the nodule is resected. A new gene expression classification assay was able to predict benign pathology when FNA cytology was indeterminate, and may allow a more conservative approach for those who would otherwise undergo a diagnostic surgical procedure.
■Carcinoma is suggested by the following clinical findings: a history of head and neck radiation, family history of thyroid cancer, exposure to ionizing radiation, rapid growth of the nodule, hoarseness, vocal cord paralysis, and lymphadenopathy. There may also be specific features on ultrasound that are suggestive of possible malignancy.
■Staging for DTC incorporates age. For patients ≤45 years old, the most advanced they can be is stage II given their excellent prognosis.
Treatment
Surgery
■Total thyroidectomy is recommended for a DTC lesion >1 cm, a lesion that extends beyond thyroid, or for patients with history of prior exposure to ionizing radiation to head/neck.
■Unilateral lobectomy with en bloc resection of tumor may be considered for a DTC lesion <1 cm or for follicular lesion with no evidence of multicentric disease.
■Modified radical neck dissection should be done for regional lymph node metastases.
■Thyroidectomy should be performed in patients with distant metastases to permit treatment with radioiodine, which can still be curative.
Adjuvant Therapy
■Treatment with radioiodine (I-131, RAI) is used to ablate normal residual thyroid tissue, treat micrometastases, and decrease cancer-related death, tumor recurrence, and development of distant metastases. Table 33.2 outlines indications for iodine-131 treatment after surgery.
■Adjuvant external beam radiotherapy is sometimes recommended for those patients with gross or microscopic residual disease or those with high-risk histology and visible extrathyroidal extension. Locally recurrent disease not amenable to surgery or radioiodine therapy can also be treated with external beam radiotherapy.
Targeted Therapy/Chemotherapy
■Patients with advanced disease that is refractory to I-131 and unresectable should participate in a clinical trial when possible. These patients are often treated with a small molecule VEGFR inhibitor (off label) based on phase II studies that have shown responses and clinical benefit. Traditional systemic chemotherapy has largely been ineffective. Isolated metastases can be treated with external beam radiotherapy.
Medullary Thyroid Cancer
■Medullary thyroid cancer (MTC) is a calcitonin-secreting tumor of the parafollicular (C) cells occurring either sporadically (75% of cases) or as a part of hereditary syndrome (25% of cases). The hereditary syndromes are the multiple endocrine neoplasia type 2 syndromes (MEN 2A or 2B) and familial medullary thyroid cancer (FMTC) (see Table 33.3).
■MEN 2 and FMTC are autosomal dominant syndromes caused by germline RET oncogene mutations. Somatic RET mutations also occur in approximately 50% of sporadic MTC.
■MTC represents 3% to 5% of all thyroid cancer cases.
■Sporadic tumors tend to be solitary, whereas familial tumors tend to be bilateral and multifocal.
Clinical Presentation
■Patients typically present with an asymptomatic thyroid mass. Some may also have local symptoms such as dysphagia, dyspnea, or hoarseness.
■Approximately 10% will present with systemic symptoms usually consisting of bone pain, flushing, and/or diarrhea.
■Approximately 50% of patients present with regional lymphadenopathy.
■Distant metastases typically occur in late-stage disease and usually involve lung, liver, bones, and adrenal glands.
Diagnosis
■Guidelines for evaluation of thyroid nodules should be followed as described for DTC.
■If the FNA is suggestive of MTC, further evaluation should consist of calcitonin and CEA measurement and genetic testing for germline RET mutations.
Treatment
■Total thyroidectomy with central lymph node dissection is the appropriate surgery.
■Surgery and/or external beam radiotherapy can be used for residual or recurrent disease treatment; however, the survival benefit for either modality is unclear.
■Patients with advanced, progressing, or symptomatic residual or recurrent disease not appropriate for surgery or radiation therapy should be considered for systemic therapy.
■Both vandetanib and cabozantinib have recently been approved by the US FDA for the treatment of advanced MTC based on improvement in progression-free survival in phase III trials. No improvement in overall survival has been demonstrated; therefore, patients with indolent disease should consider observation until their disease becomes necessary to treat. See Table 33.4 for vandetanib and cabozantinib dosing.
■Traditional systemic chemotherapy has largely been ineffective.
Anaplastic Thyroid Cancer
■Anaplastic thyroid cancer (ATC) is a rare, high-grade, aggressive malignancy that accounts for 2% to 5% of all thyroid carcinomas. Up to 50% of patients have antecedent or concurrent history of DTC. Disease-specific mortality is nearly 100%.
■Patients typically present with a rapidly enlarging neck mass.
■Approximately 90% will have locoregional or distant metastases at the time of diagnosis.
■Treatment is primarily palliative and often aimed at preventing asphyxiation, the most common cause of death in these patients. It can consist of surgery, radiation, chemotherapy, or a combination of these modalities.
Other Thyroid Cancers
■Primary thyroid lymphoma
■Metastasis to the thyroid
PARATHYROID CARCINOMA
Clinically, it is important to distinguish this disease from other benign disorders that cause hyperparathyroidism. Parathyroid carcinoma accounts for less than 1% of cases of hyperparathyroidism.
Epidemiology and Natural History
■Parathyroid carcinoma occurs in <1 per million individuals per year, predominantly diagnosed in the fifth or sixth decade of life.
■Germline or somatic mutations of the HRPT2 tumor suppressor gene are detected in the majority of cases.
■Ten-year survival rate is approximately 70%; however, 40% to 60% will recur after initial surgery.
■Morbidity and mortality are usually related to hypercalcemia rather than complications of metastases.
Clinical Presentation
Patients typically present with the following:
■Symptoms of hypercalcemia, with calcium levels usually >14 mg/dL
■Elevated parathyroid hormone levels
■Palpable neck mass in up to 70%
■Metastases to cervical lymph nodes, lungs bone, or liver in approximately 10%
Diagnosis
■Parathyroid carcinoma is difficult to diagnose preoperatively; differential includes parathyroid adenoma and hyperplasia.
■Most parathyroid carcinomas are diagnosed at surgery; however, some are not diagnosed until local recurrence or metastases. This is because there are no definitive histopathologic features to differentiate carcinoma from adenoma.
■FNA is inappropriate for diagnosis.
Treatment
Surgery
■Treatment consists of parathyroidectomy with en bloc resection of tumor and involved structures. This may include the ipsilateral lobe of thyroid. Radical lymph node dissection is not recommended.
■Recurrent tumor and oligometastases should also be resected.
Radiation
■Parathyroid tumors are generally not radiosensitive.
■Small retrospective studies suggest there may be improved local control with postoperative radiotherapy for high-risk patients.
■Radiation may have palliative benefit.
Medical Therapy
■Chemotherapy efficacy is limited to case reports, and there is no standard regimen.
■Management of hypercalcemia is essential while treating parathyroid carcinoma.
ADRENOCORTICAL CARCINOMA
Epidemiology
■ACC is a rare malignancy arising from the adrenal cortex, with 1 to 2 cases per million population per year.
■It has a bimodal age distribution, with a first peak in children younger than 5 years and a second peak in adults in their fourth to fifth decade.
■Most cases are sporadic, but it can be a component of a hereditary syndrome (Li-Fraumeni, Beckwith-Wiedemann) (see Table 33.1).
Clinical Presentation
Symptoms may arise from the effects of local mass or distant metastases. Approximately 50% of patients present with evidence of hormonal excess consisting of
■Hypercortisolism (Cushing syndrome)
■Virilization/feminization
■Mineralocorticoid excess
Diagnosis
■Imaging studies can usually distinguish benign adenomas from ACC.
■Biochemical evaluation (urinary steroids and suppression tests) should be conducted if clinically warranted.
■FNA cannot differentiate an adrenal adenoma from ACC, and should only be done if the adrenal mass is suspected to be a metastasis from another malignancy.
■Diagnosis is often confirmed upon surgical resection; however, histologic differentiation of adrenocortical adenomas and carcinomas is challenging.
■Carcinomas tend to display mitotic activity, aneuploidy, and venous invasion. Carcinomas may also secrete abnormal amounts of androgens and 11-deoxysteroids.
Treatment
Surgery
■A tumor with local invasion and nodal involvement, tumor invading adjacent organs, or any tumor with distant metastases constitutes stage IV disease.
■En bloc resection is initially appropriate for stages I to III.
■Debulking of unresectable or stage IV disease should be considered, particularly for symptom relief from hormone-secreting tumors; local recurrence and metastatic disease require further resection when feasible.
■In general, adrenal tumors >6 cm (or <6 cm but suspected of being malignant) should be resected via open adrenalectomy and not laparoscopically.
Adjuvant Therapy
■Adjuvant mitotane may improve survival for patients with stage I to III disease who have undergone a complete resection. An international prospective randomized trial comparing mitotane to placebo in this patient population is currently ongoing.
Advanced Disease
■For advanced disease, mitotane monotherapy induces hormonal response rates in up to 75% of patients with functional tumors, with no change in overall survival.
■Combination chemotherapy with mitotane plus etoposide, doxorubicin, and cisplatin demonstrated better rates of response and disease-free survival than mitotane plus streptozotocin in patients with advanced disease.
■Radiofrequency ablation may also be implemented for local control or metastases in patients with unresectable disease.
■See Table 33.4 for detailed chemotherapy regimens.
Prognosis
■5-year survival rate: 38% to 60%.
■Prognosis is better in children.
■Common sites of distant metastasis are liver, lung, lymph nodes, and bone.
PHEOCHROMOCYTOMA
Epidemiology
■Catecholamine-secreting tumor of the adrenal medulla chromaffin cells with an incidence of <1 per 100,000 person-years.
■Up to 25% of cases are associated with a familial genetic syndrome such as MEN 2 or von Hippel-Lindau disease (see Table 33.1).
■Found in <0.2% of patients with hypertension.
Clinical Presentation
■The classic triad of symptoms includes headache, sweating, and tachycardia. Clinical features of pheochromocytomas are summarized in Table 33.5.
■Pheochromocytomas are generally indolent, with morbidity and mortality related to the tumors’ secretory products.
■Approximately 10% of pheochromocytomas are bilateral, with occurrence more frequent in familial syndromes.
■Approximately 10% of pheochromocytomas are extra-adrenal; these tumors are more likely to be malignant.
■Less than 10% are malignant; metastasis is most common in lung, brain, and bone.
Diagnosis
■Measurement of 24-hour urinary-fractionated metanephrines is the most specific tool for diagnosis of pheochromocytoma.
■Plasma-fractionated metanephrines measurement is the most sensitive test, but has a high rate of false positives.
■Clonidine suppression test is recommended for indeterminate plasma catecholamine or metanephrine levels, both of which will not be suppressed in patients with pheochromocytoma.
■CT and MRI are equally sensitive diagnostic tools for pheochromocytoma.
■Labeled metaiodobenzylguanidine (131I-MIBG), which is structurally similar to norepinephrine, is taken up and concentrated in adrenergic tissue. It is highly sensitive and specific for malignant tumors and familial syndromes, but is inferior to bone scan for detecting bone metastases.
■Vascular invasion and extension into the cortex may be seen with both benign and malignant tumors.
■The only absolute criterion for malignancy is the presence of secondary tumors in sites where chromaffin cells do not usually exist.
Treatment
Surgery
■Surgery is the mainstay of treatment and should be considered for primary, recurrent, and metastatic disease.
■Appropriate preoperative evaluation and α ± β-blockade are required to minimize risk of hypertensive crisis.
■Laparoscopy is acceptable if imaging reveals no obvious tumor invasion or metastases.
Radiation
■Radiation has a limited role in the treatment of pheochromocytoma, but may be used for bone and soft-tissue metastases.
■Therapeutic doses of 131I-MIBG in patients showing evidence of radiotracer uptake on MIBG scans have provided both radiographic and symptomatic responses.
Chemotherapy/Targeted Therapy
■In a small study (14 patients) with metastatic, malignant pheochromocytoma, the combination of cyclophosphamide, vincristine, and dacarbazine had a biochemical response of 79%, with a 57% reduction in measurable disease and median duration of response >20 months.
■Responses have also been reported with the targeted agent sunitinib.
■See Table 33.4 for detailed chemotherapy regimens.
NEUROENDOCRINE TUMORS
NETs are cancers of the interface between the endocrine system and the nervous system. These rare tumors are distinguished from most other solid tumors by their ability to secrete biologically active molecules that can produce systemic syndromes. The 2010 WHO classification separates NETs into well-differentiated and poorly differentiated based on tumor grade, mitotic count, and Ki-67 proliferation index. The most common types of NETs are carcinoid tumors and pancreatic NETs, both of which are typically well differentiated.
Carcinoid Tumors
■Incidence in the United States is approximately 2 per 100,000 individuals.
■Carcinoids are slow-growing malignant tumors that arise from enterochromaffin cells of the aerodigestive tract.
■They are traditionally categorized by their embryonic origin and are most commonly found in the foregut (bronchial) and small intestine.
■The typical carcinoid syndrome consists of flushing and diarrhea and is seen most often with small intestine carcinoid tumors.
■Carcinoid syndrome is observed in 10% of patients, especially those with liver metastases, retroperitoneal disease, or disease outside of the GI tract where excessive hormones can bypass metabolism in liver.
■Features of foregut, midgut, and hindgut carcinoids are outlined in Table 33.6.
Treatment
■Abdominal and rectal carcinoids tend to be small (2 cm). Surgery involves segmental resection with mesenteric lymphadenectomy.
■Appendiceal carcinoid is often discovered incidentally. If it is >2 cm or there is invasion or positive margins, right hemicolectomy is recommended. Right hemicolectomy is more controversial for tumors that are <2 cm and confined to the appendix.
■Liver metastases can be treated locally with surgical debulking, hepatic arterial embolization, chemoembolization, cryotherapy, or radiofrequency ablation.
■Patients with carcinoid syndrome should be treated with a somatostatin analog such as octreotide. Octreotide has also demonstrated antitumor activity, potentially improving time to progression.
■Carcinoids are resistant to most chemotherapeutic agents. Active agents include 5-fluorouracil, capecitabine, streptozocin, doxorubicin, and interferon. Chemotherapy is typically reserved for patients who are progressing with no other treatment options. See Table 33.4 for detailed systemic therapy regimens.
■Radiation therapy is for palliation only.
Pancreatic Neuroendocrine Tumors
Pancreatic NETs, also known as islet cell tumors, arise from the hormone-secreting cells of the pancreas. Up to 75% are nonfunctioning and not associated with clinical syndromes. The functioning pancreatic NETs and are categorized by the hormone and clinical syndrome they produce. Pancreatic NETs comprise approximately 3% of all pancreatic tumors, are generally well differentiated, and malignant. They are associated with familial syndromes in up to 25% of cases (see Table 33.1).
Gastrinoma (Zollinger-Ellison Syndrome)
Gastrinoma is a tumor that secretes gastrin. Primary tumors predominate in the pancreatic head but may also develop in the small intestine or stomach.
Epidemiology
■Gastrinoma occurs in 0.1% to 1% of patients with peptic ulcer disease.
■They are usually diagnosed between the third and sixth decades but can occur at any age.
■Approximately 20% of gastrinomas are associated with the familial syndrome MEN 1, and 80% are sporadic. Sporadic tumors often have somatic mutations in the MEN1 gene.
■Approximately one-third of patients with gastrinoma have metastatic disease at diagnosis.
Diagnosis and Clinical Presentation
■Patients typically present with severe, often refractory peptic ulcer disease accompanied by abdominal pain and diarrhea.
■Diagnosis is made by a fasting gastrin level: >1,000 pg/mL with a gastric acid pH <5.0 or gastrin level that increases by ≥200 pg/mL within 15 minutes of intravenous infusion of secretin.
■Other common diagnostic procedures include ultrasonography, CT scan, MRI, endoscopic ultrasonography, angiography, and octreotide scan.
Treatment
■Medical therapy is standard for gastrinoma associated with MEN 1, given that tumors are often multifocal and incurable. Some surgeons will offer resection with the intent of reducing future morbidity from metastatic disease.
■Surgical resection with exploratory laparotomy is curative in up to 50% of patients with sporadic gastrinoma without metastatic disease.
■The goal of medical therapy is to control gastrin secretion and acid production. Therapies include proton pump inhibitors, somatostatin analogs (e.g., octreotide), and tumor embolization.
■Both sunitinib and everolimus were approved for the treatment of progressive, well-differentiated pancreatic NETs. Approval was based on improved progression-free survival.
■Cytotoxic chemotherapy can also be used for metastatic disease. Active chemotherapeutic agents include streptozotocin, doxorubicin, temozolomide, 5-fluoruracil, and dacarbazine.
■See Table 33.4 for detailed chemotherapy regimens.
■For those patients with liver metastases, liver-directed therapies such as embolization, radiofrequency ablation, and cryosurgery are options.
Insulinoma
Epidemiology
■Insulinoma is the most common type of functioning pancreatic NET.
■It occurs most commonly in the fifth decade of life, with a slight female predominance.
■Most insulinomas are solitary and approximately 10% are malignant, as defined by the presence of metastases.
Diagnosis and Clinical Presentation
■Three criteria, known as Whipple triad, suggest insulinoma:
•Symptoms known or likely to be caused by hypoglycemia (confusion, personality change, palpitations, diaphoresis, tremulousness)
•Hypoglycemia during symptoms
•Relief of hypoglycemia symptoms when glucose is raised to normal
■An inappropriately high level of insulin during an episode of hypoglycemia establishes the presence of insulinoma.
■Asymptomatic patients may be diagnosed after prolonged fasting by testing levels of serum glucose, insulin, and C-peptide every 6 to 12 hours.
Treatment
■Surgery is the treatment of choice for insulinoma and is most often curative.
■Patients with recurrent disease that includes liver metastases can be treated with surgical resection (when possible) or liver-directed therapy such as chemoembolization or radiofrequency ablation.
■Refractory hypoglycemia can be treated with oral diazoxide, which inhibits pancreatic secretion of insulin and stimulates release of catecholamine and glucose from the liver.
■Both sunitinib and everolimus have been approved for the treatment of progressive, well-differentiated pancreatic NETs. Approval was based on improved progression-free survival.
■Cytotoxic chemotherapy can also be used for metastatic disease. Active chemotherapeutic agents include streptozotocin, doxorubicin, temozolomide, 5-fluoruracil, and dacarbazine.
■See Table 33.4 for detailed chemotherapy regimens.
VIPoma (Verner-Morrison Syndrome)
■VIPoma is a rare NET that usually originates in the pancreas and produces vasoactive intestinal peptide (VIP).
■Elevated serum VIP establishes the presence of VIPoma.
■Patients present with watery diarrhea, hypokalemia, and hypo- or achlorhydria.
■Diarrhea may be treated effectively with somatostatin analogs, which decrease VIP secretion. Interferon-α can also be used.
■Patients with recurrent disease that includes liver metastases can be treated with surgical resection (when possible) or liver-directed therapy such as chemoembolization or radiofrequency ablation.
■Both sunitinib and everolimus have been approved for the treatment of progressive, well-differentiated pancreatic NETs. Approval was based on improved progression-free survival. See Table 33.4 for detailed chemotherapy regimens.
Glucagonoma
■Glucagonoma is a rare tumor of the pancreas that results in overproduction of the hormone glucagon.
■Serum levels of glucagon >500 pg/mL are diagnostic of glucagonoma.
■Glucagonoma leads to diabetes, weight loss, anemia, and increased risk of thromboembolism.
■Patients commonly present with necrolytic migratory erythema, which may be treated with zinc supplements and amino acid infusion.
■Surgery, somatostatin analogs, anticoagulants, and targeted therapy/chemotherapy (as described for the other pancreatic NETs) are therapeutic options for glucagonomas.
Somatostatinoma
■Somatostatinoma is a tumor of the endocrine pancreas that secretes excess somatostatin. The tumor inhibits secretion of insulin, other pancreatic hormones, pancreatic enzymes, and gastric acid production.
■Surgery is the treatment of choice, but targeted therapy/chemotherapy (as described for the other pancreatic NETs) is indicated for unresectable disease.
REVIEW QUESTIONS
1.A 36-year-old woman is found to have a 3 cm thyroid mass, enlarged neck lymph nodes, and multiple subcentimeter bilateral pulmonary nodules. Subsequent biopsies of both a lung nodule and the thyroid mass revealed PTC. What is the appropriate next step in this patient’s management?
A.Diagnostic radioactive iodine whole-body scan to evaluate sites of disease
B.Total thyroidectomy and lymphadenectomy
C.Radioactive iodine treatment
D.Doxorubicin-based combination chemotherapy
E.Clinical trial with a kinase inhibitor
2.A 23-year-old male with a history of MEN2A and MTC presents for follow-up. He was originally diagnosed 5 years ago when a thyroid mass was noted incidentally following a car accident. He subsequently underwent a total thyroidectomy with central and right neck dissections. Today, his review of systems is negative. On physical examination, his neck is notable for well-healed surgical scars and no palpable nodules or lymph nodes. The rest of the examination is unremarkable. Laboratory studies reveal normal serum chemistries, CBC, and TSH. His calcitonin from today is 93 and has been stable since his thyroidectomy. Which of the following is the most appropriate next step in his management?
A.Radioactive iodine whole-body scan and treatment with radioactive iodine if the scan is positive for disease.
B.Contrast-enhanced CT or MRI of the neck, chest, and abdomen with liver protocol for initial staging followed by treatment with vandetanib 300 mg daily. Repeat calcitonin in 2 to 3 months.
C.Contrast-enhanced CT or MRI of the neck, chest, and abdomen with liver protocol for staging. If imaging is negative, repeat serum calcitonin in 6 months.
D.Treat his neck with external beam radiotherapy.
E.Increase his levothyroxine dose to suppress TSH to <0.1. Repeat his calcitonin and TSH levels in 6 weeks.
3.A 50-year-old female with a history of ACC presents for consultation regarding further management. She underwent resection 1 year ago, and now presents with left flank pain, weight gain, weakness, and uncontrolled hypertension. She is found to have a 7.5 cm mass in the left renal fossa and multiple lesions consistent with metastatic disease. A CT-guided biopsy confirms ACC recurrence. She is judged unresectable. Of the treatment options listed, which should be started immediately?
A.Streptozocin
B.Combination chemotherapy with cisplatin, doxorubicin, and etoposide
C.Sunitinib
D.Mitotane
E.Hydrocortisone
4.A 55-year-old male presents with severe abdominal pain and diarrhea. Evaluation by EGD reveals a 1 cm duodenal ulcer, and biopsies are negative for Helicobacter pylori. A serum gastrin level is elevated at 1,300 pg/mL. What is the next appropriate step in his evaluation?
A.Octreotide scan
B.Secretin stimulation test
C.EUS
D.CT scan of the abdomen
E.131I-MIBG scan
Suggested Readings
1.Abeloff M, Armitage J, Niederhuber J, Kastan M, McKenna W, eds. Abeloff: Clinical Oncology. 4th ed. Philadelphia, PA: Elsevier; 2008.
2.Cooper DS, Doherty GM, Haugen BR, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009;19(11):1167-1214.
3.Falconi M, Bartsch DK, Eriksson B, et al. ENETS Consensus Guidelines for the management of patients with digestive neuroendocrine neoplasms of the digestive system: well-differentiated pancreatic non-functioning tumors. Neuroendocrinology. 2012;95(2):120-134.
4.Fassnacht M, Terzolo M, Allolio B, et al. Combination chemotherapy in advanced adrenocortical carcinoma. N Engl J Med. 2012;366:2189-2197.
5.Goldstein RE, O’Neill JA Jr., Holcomb GW 3rd, et al. Clinical experience over 48 years with pheochromocytoma. Ann Surg. 1999;229(6):755.
6.Hemminki K, Li X. Incidence trends and risk factors of carcinoid tumors: a nationwide epidemiologic study from Sweden. Cancer. 2001;92(8):2204.
7.Hundahl SA, Fleming ID, Fremgen AM, Menck HR. A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985–1995. Cancer. 1998;83:2638-2648.
8.Kloos RT, Eng C, Evans DB, et al. Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid. 2009;19:565-612.
9.Kurzrock R, Sherman SI, Ball DW, et al. Activity of XL184 (Cabozantinib), an oral tyrosine kinase inhibitor, in patients with medullary thyroid cancer. J Clin Oncol. 2011;29:2660-2666.
10.Lodish MB, Stratakis CA. Rare and unusual endocrine cancer syndromes with mutated genes. Semin Oncol. 2010;37(6):680-690.
11.Luton JP, Cerdas S, Billaud L, et al. Clinical features of adrenocortical carcinoma, prognostic factors, and the effect of mitotane therapy. N Engl J Med. 1990;322:1195-1201.
12.Moertel CG, Lefkopoulo M, Lipsitz S, et al. Streptozocin-doxorubicin, streptozocin-fluorouracil or chlorozotocin in the treatment of advanced islet-cell carcinoma. N Engl J Med. 1992;326(8):519-523.
13.Nikiforov YE, Nikiforova MN. Molecular genetics and diagnosis of thyroid cancer. Nat Rev Endocrinol. 2011;7(10):569-580.
14.Raymond E, Dahan L, Raoul JL, et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med. 2011;364(6):501-513.
15.Schlumberger MJ. Papillary and follicular thyroid carcinoma. N Engl J Med. 1998;338:297-308.
16.Sherman SI. Thyroid carcinoma. Lancet. 2003;231:501-511.
17.Strosberg JR. Update on the management of unusual neuroendocrine tumors: pheochromocytoma and paraganglioma, medullary thyroid cancer and adrenocortical carcinoma. Semin Oncol. 2013;40(1):120-133.
18.Strosberg JR, Fine RL, Choi J, et al. First-line chemotherapy with capecitabine and temozolomide in patients with metastatic pancreatic endocrine carcinomas. Cancer. 2011;117(2):268-275.
19.Veytsman I, Nieman L, Fojo T. Management of endocrine manifestations and the use of mitotane as a chemotherapeutic agent for adrenocortical carcinoma. J Clin Oncol. 2009;27(27):4619-4629.
20.Wells SA, Robinson BG, Gagel RF, et al. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol. 2012;30:134-141.
21.Yao JC, Hassan M, Phan A, et al. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008;26(18):3063.
22.Yao JC, Shah MH, Ito T, et al. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med. 2011;364(6):514-523.