Medullary Thyroid Carcinoma Manifesting as an Ovarian Mass: Case Report and Review of Literature

ObjectiveTo report the uncommon case of a woman with abdominal pain and a complex adnexal mass, who was subsequently found to have medullary thyroid carcinoma (MTC) metastatic to the ovary.MethodsWe present the clinical history, physical findings, laboratory and imaging studies, and pathologic findings in a woman with metastatic MTC and locally aggressive disease. The genetic associations, variable clinical course, and histopathologic findings in MTC are reviewed.ResultsA 38-year-old woman with abdominal and pelvic pain underwent a computed tomographic scan of the abdomen, which showed a complex left adnexal mass. After laparoscopic left oophorectomy, histopathologic analysis of the resected ovary suggested the presence of a metastatic neuroendocrine tumor. The patient recovered but was referred to the surgery clinic 3 months later because of hoarseness, a left neck mass, and left-sided vocal cord paralysis. Further work-up was suggestive of MTC, which prompted RET testing for multiple endocrine neoplasia. The patient underwent left thyroid lobectomy and selective lymph node dissection but later required tracheostomy because of tumoral invasion of the trachea, laser debulking of the tumor, and external beam radiation therapy. One year postoperatively, development of a metastatic lesion in her right ovary necessitated a second oophorectomy.ConclusionMTC usually manifests as a solitary thyroid nodule but should be considered in patients with metastatic lesions characterized by neuroendocrine features. This unusual case highlights the biologic and clinical variability of this often aggressive thyroid cancer, which necessitates an attentive work-up, a rigorous operative strategy, and a periodic postoperative surveillance program. (Endocr Pract. 2008;14:351-357)     

A Novel Double Mutation Val648ile and Val804leu of Ret Proto-Oncogene in Multiple Endocrine Neoplasia Type 2

Objective: We report the case of a female patient with multiple endocrine neoplasia type 2A (MEN2A) who was found to have a double mutation in the RET (rearranged during transfection) proto-oncogene.Methods:RET mutational analysis was performed by Sanger DNA sequencing.Results: The proband was a compound heterozygote for the RET germline mutations Val648Ile and Val804Leu on exons 11 and 14, respectively. Genetic analysis of family members showed the presence of the Val648Ile mutation in all except 1 daughter who carried the Val804Leu mutation. However, none of them showed any clinical, biochemical, or histologic signs of neoplastic disease either in the thyroid or adrenal gland. Furthermore, a daughter and the proband's sister who underwent a prophylactic thyroidectomy did not show pathologic evidence of C-cell disease.Conclusions: We hypothesize that the combined effect of the 2 mutations may have induced the development of pheochromocytoma (PHEO) in our patient. Thus, in the presence of single RET-induced mild medullary thyroid cancer (MTC) phenotype, the search for additional genetic anomalies may lead to the discovery of rare but potentially more aggressive double mutation genotypes.Abbreviations: ACTH = adrenocorticotropic hormone ATA = American Thyroid Association CT = calcitonin FMTC = familial medullary thyroid cancer HSCR = Hirschsprung disease MEN2A/B = multiple endocrine neoplasia type 2A/2B MTC = medullary thyroid cancer PHEO = pheochromocytoma RET = rearranged during transfection SDHB/D = succinate dehydrogenase subunits B/D VHL = Von Hippel-Lindau     

Incidental Finding of Metastatic Papillary Thyroid Carcinoma in a Patient with Primary Hyperparathyroidism

ObjectiveTo report on the management of a patient with the rare concurrence of primary hyperparathyroidism and incidentally found metastatic papillary thyroid carcinoma in an adjacent lymph node.MethodsWe present a case report, including scintigraphic and histologic documentation, and a summary of the related literature.ResultsPrimary hyperparathyroidism with concomitant occurrence of nonmedullary thyroid carcinoma is rare, occurring in less than 4% of patients. We report a case of a 53-year-old woman with no prior history of endocrine disease with primary hyperparathyroidism and an incidental finding of a concurrent thyroid carcinoma. In this patient, technetium 99m scintigraphy revealed a parathyroid adenoma beneath the inferior pole of the left thyroid bed. Parathyroidectomy was performed successfully with no complications. The final pathology examination showed a large parathyroid adenoma with an incidental finding of a small adjacent lymph node containing metastatic papillary thyroid carcinoma. The patient subsequently underwent total thyroidectomy, and the pathology evaluation revealed papillary thyroid carcinoma, follicular variant.ConclusionTo our knowledge, this case of concomitant primary hyperparathyroidism and papillary thyroid cancer is unique in the way in which the diagnosis of metastatic papillary thyroid cancer was made. The presence of parathyroid adenoma should not exclude the diagnosis of thyroid carcinoma; therefore, careful thyroid evaluation should be considered for all patients with primary hyperparathyroidism. (Endocr Pract. 2007;13:380-383)     

Metastatic Renal Cell Carcinoma to the Thyroid Gland

ObjectiveTo examine the presentation, diagnosis, and appropriate management of renal clear cell carcinoma metastasis to the thyroid gland.MethodsWe describe a clinical case of solitary thyroid metastasis from renal clear cell carcinoma and present a comprehensive review of the related English-language literature. Common patterns of presentation and generalized overall management recommendations are evaluated and summarized.ResultsEight years after nephrectomy for renal carcinoma at age 61 years, a man presented with a thyroid mass. Cytology and histopathologic surgical findings were consistent with a solitary metastasis most compatible with metastatic clear cell carcinoma from his previous renal carcinoma. After left thyroid lobectomy and isthmusectomy, the patient remains disease-free 5 years later. Although uncommon, nearly 150 cases of clinically recognized metastatic renal cell carcinoma to the thyroid have been reported in the English-language literature. Metastatic disease from the kidney to the thyroid gland can occur more than 20 years after nephrectomy with the average time interval being 7.5 years. Obtaining a full clinical history in any patient who presents with a thyroid nodule is essential to allow consideration of possible metastatic disease from previous primary tumor. Metastatic disease to the thyroid gland can be correctly diagnosed preoperatively. If metastatic renal cancer is limited to the thyroid gland only, prompt, appropriate surgical intervention can be curative.ConclusionMetastatic renal carcinoma to the thyroid should be considered in any patient presenting with a thyroid mass and a medical history of renal cell carcinoma. (Endocr Pract. 2008;14:1040-1046)     

Unusual Initial Manifestation of Metastatic Follicular Carcinoma of the Thyroid with Thyrotoxicosis Diagnosed by Technetium Tc 99m Pertechnetate Scan: Case Report and Review of Literature

ObjectiveTo report a case of metastatic thyroid cancer diagnosed on a technetium Tc 99m pertechnetate (TcO₄^–) thyroid scan.MethodsWe present the clinical findings, laboratory results, imaging studies, and surgical pathology report in a man with thyrotoxicosis in whom metastatic well-differentiated thyroid cancer was diagnosed incidentally on a routine TcO₄ ^– thyroid scan in the setting of a presumed diagnosis of benign toxic thyroid disease. In addition, we review the literature regarding coexistence of metastatic thyroid cancer and thyrotoxicosis.ResultsA 68-year-old man with thyrotoxicosis was referred for radioiodine therapy. A routine TcO₄^- thyroid scan revealed high-grade extrathyroidal uptake in the right upper hemithorax as well as in the left side of the thorax. In view of this finding, radioiodine treatment was deferred; further imaging with computed tomography revealed a 6.5-cm mass in a rib on the right side. A biopsy of the rib confirmed the presence of metastatic follicular carcinoma of the thyroid. Scintigraphy revealed sites of metastatic involvement predominantly in the bones along with a cold nodule in the left thyroid lobe, consistent with the primary tumor.ConclusionThis case emphasizes the impact of scintigraphic findings on determining the correct management of a patient who would have otherwise undergone inappropriate treatment. Through an extensive literature review, the incidence of malignant involvement in hyperfunctioning thyroid glands and the possible role of sodium iodide symporter expression by thyroid cancer metastatic lesions in preoperative detection of metastatic sites are addressed. (Endocr Pract. 2009;15:458-462)     

Demografía,características clínicas y genéticas de pacientes con carcinoma medular de tiroides en los últimos 16 años en Castilla-La Mancha

ObjectiveMedullary thyroid cancer is a rare tumor that is more aggressive and has a worse prognosis than differentiated thyroid cancer. The purpose of this study was to report the demographic, clinical, and genetic characteristics of patients seen in the health care system of the community of Castilla-La Mancha over a 16-year period.Patients and methodsData were collected through a review of patients’ medical records.ResultsThe medical records of 58 patients (mean age at diagnosis, 51 years; range, 6-82 years; 63.8% women) were reviewed. Prevalence rate was 2.84 cases per 100,000 inhabitants, with a high variability between areas (range, 0-5.4 cases per 100,000 inhabitants). Familial cases accounted for 34.5% of all medullary thyroid cancers, and the most common mutation was C634Y. The condition was most commonly diagnosed following palpation of a cervical lump (70.6%). At diagnosis, 56 of 58 patients underwent ultrasound and 8 of 58 patients were tested for serum calcitonin. Tumor multicentricity was reported in 59 and 50% of patients with multiple endocrine neoplasia syndrome type 2A and 2B, respectively, and in no sporadic cases. Fifty-two percent of patients had an advanced stage (iii or iv) at diagnosis. Median follow-up was 36 months (interquartile range, 14-210); 11 patients were lost to follow-up.ConclusionsIn Castilla-La Mancha, medullary thyroid cancer is diagnosed by cervical ultrasound, rather than calcitonin assay. There is a high prevalence of both familial and sporadic medullary thyroid cancer, and a significant variability in the type of proto-oncogen rearranged during transfection mutation as compared to the rest of the Spanish population.     

Papillary Carcinoma of the Thyroid with Fibromatosislike Stroma: Case Report and Review of Literature

ObjectiveTo describe a case of papillary carcinoma of the thyroid with fibromatosislike stroma, emphasize the need for a diligent search for papillary thyroid cancer in the presence of a fibroproliferative lesion, highlight the peculiar hormonal response of the stromal component, and review the pertinent literature.MethodsWe present the clinical, laboratory, radiologic, and pathologic findings in a patient with papillary carcinoma of the thyroid with fibromatosislike stroma and review the related published material.ResultsA 29-year-old woman presented to our surgical department because of a large mediastinal mass. She underwent surgical removal of the mass by means of a median sternotomy and neck extension. Pathology examination revealed macroscopically tan scarlike tissue, which by histologic study consisted of a dominant fibroproliferative lesion overshadowing a minor component of papillary carcinoma of the thyroid. Further neck exploration with total thyroidectomy revealed multifocal papillary carcinoma of the thyroid. Postoperatively, the patient received radioiodine treatment. A local and aggressive recurrent tumor was observed during a subsequent pregnancy; the lesion was not amenable to complete resection but fascinatingly responded to antiestrogen therapy (orally administered tamoxifen).ConclusionThe presence of a fibroproliferative lesion could be misleading. A diligent search should be made for a papillary thyroid carcinoma component within fibromatosislike stroma. The mode of manifestation of the tumor and its response to hormonal manipulation are distinctive features of this case. (Endocr Pract. 2010;16:650-655)     

Medullary Thyroid Carcinoma

ObjectiveThis review outlines advances in the diagnosis, genetic testing, and progress in medullary thyroid cancer (MTC) treatment in light of the most recent evidence.MethodsEnglish-language articles pertaining to MTC published up to 2012 were reviewed. The pertinent articles and their references were obtained and those considered relevant were reviewed for inclusion.ResultsMTC is an uncommon neuroendocrine malignancy that accounts for 5% of thyroid cancers. MTC presents in sporadic and familial forms (multiple endocrine neoplasia [MEN] 2A, MEN 2B, or familial MTC syndromes). The familial forms are secondary to germline mutations in the REarranged during Transfection (RET) proto-oncogene. Early diagnosis and treatment is paramount. Genetic testing has made possible early detection in asymptomatic carriers and high-risk patients, with early or prophylactic surgery being curative in many. All carriers of an RET mutation should be evaluated and treated surgically for MTC. The primary treatment in all patients diagnosed with MTC is total thyroidectomy with central lymph node dissection. Calcitonin and carcinoembryonic antigen levels can be used as prognostic factors and as tumor markers. If elevated, further investigation, including use of imaging modalities, may be necessary for evaluation of metastatic disease. Surgery remains the main treatment for local and locally advanced disease.ConclusionMTC is rare, but morbidity and mortality remain high if untreated. Genetic testing should be offered to all patients. Treatment of choice remains total thyroid-ectomy and central lymph node dissection. Palliative treatment for advanced disease includes surgery, radiation, standard chemotherapy, chemoembolization and more recently, targeted therapies (tyrosine kinase inhibitors). (Endocr Pract. 2013;19:703-711)     

Precocious Puberty and Large Multicystic Ovaries in Young Girls with Primary Hypothyroidism

ObjectiveTo describe 2 cases of primary hypothy-roidism, precocious puberty, large multicystic ovaries, possible diagnostic dilemma, unilateral oophorectomies, and subsequent response to levothyroxine replacement therapy.MethodsWe present the clinical, biochemical, radiologic, and histopathologic findings in 2 patients with rare cases of Van Wyk-Grumbach syndrome and megaovaries, who underwent unilateral oophorectomy.ResultsTwo patients, an 8-year-old girl and a 3-year-old girl (cases 1 and 2, respectively), were referred to our center. Both patients presented with precocious puberty and vaginal bleeding and had undergone unilateral oophorectomy before referral. In the first patient (case 1), the surgical intervention was a consequence of torsion of the left megaovary, necessitating emergency oophorecto-my. Oophorectomy in the second patient (case 2) was a result of initial diagnostic confusion, inasmuch as a sex-cord stromal tumor was suspected. A detailed history, physical examination, and laboratory results pointed toward primary hypothyroidism due to Hashimoto’s thy-roiditis and thyroid dysgenesis, respectively. Serial ultra-sound studies of the abdomen and pelvis revealed large multicystic ovaries, with progressive enlargement (includ-ing regrowth from an apparent ovarian “postsurgical remnant”). Both patients responded dramatically after initiation of levothyroxine replacement therapy, with no further vaginal bleeding and reversal of megaovary to normal size (in case 1).ConclusionIn a highly selected minority of children with untreated primary hypothyroidism, there is development of precocious puberty and progressively enlarging multicystic ovaries. The precise endocrine, neuroanatomic, and neurophysiologic bases for this phenomenon are unclear. Nevertheless, the entire clinicopathologic picture,including giant ovaries, dramatically reverts to normal status with the restoration of a euthyroid state by means of simple levothyroxine replacement therapy. (Endocr Pract. 2007;13:652-655)     

Targeted Therapy for Endocrine Cancer: The Medullary Thyroid Carcinoma Paradigm

ObjectiveTo provide an overview of a new approach for treatment of medullary thyroid carcinoma (MTC) and other endocrine tumors.MethodsThis review compiles recent information from the medical literature and scientific meetings focused on the use of tyrosine kinase inhibitors (TKIs) for the treatment of MTC and other endocrine tumors.ResultsThe elucidation during the past 2 decades of multiple genetic abnormalities in endocrine tumors has provided specific targets for therapy. The identification of activating mutations of the RET tyrosine kinase receptor in both hereditary and sporadic MTC makes this malignant disease an excellent model for examination of the effect of a group of small organic molecule TKIs for treatment of metastatic MTC. Clinical trials with several TKIs targeting RET and other tyrosine kinase receptors have shown positive results with generally tolerable toxicity. Approximately one-third to one-half of patients with MTC have a reduction in tumor size of 0% to 50%, with the longest treatment duration of approximately 4 years. The most common treatment-related toxic effects are cutaneous effects, nausea, and diarrhea. Cardiovascular toxicity, such as hypertension, prolongation of the corrected QT interval, or heart failure, is uncommon but may be serious.ConclusionDespite promising initial results, these studies are in their early stages, and none of these therapies is currently approved by the US Food and Drug Administration for treatment in the United States. These studies highlight the potential for targeting endocrine cancer signaling pathways and provide a paradigm for treatment of endocrine cancer. (Endocr Pract. 2009;15:597-604)     

Delayed treatment of papillary thyroid carcinoma arising from struma ovarii in a patient with history of bilateral salpingo-oophorectomy: a case report

ObjectiveWe present a case of papillary thyroid carcinoma arising from struma ovarii treated erroneously as ovarian adenocarcinoma for more than 3 years.MethodsWe report clinical, surgical, laboratory, and imaging findings of the study patient and review the relevant literature.ResultsA 64-year-old woman was treated for ovarian adenocarcinoma for more than 3 years before it was determined that she likely had papillary thyroid carcinoma arising from struma ovarii. This is the first reported case of thyroid carcinoma arising from struma ovarii in a patient with a history of bilateral salpingo-oophorectomy. Possible etiologies include residual ovarian tissue after oophorectomy, ectopic thyroid, or metastatic thyroid cancer.ConclusionsIt is important to include struma ovarii and thyroid carcinoma arising from struma ovarii in the differential diagnosis, even with a history of bilateral salpingo-oophorectomy. This case emphasizes the importance of effective communication among the pathologist, oncologist, and surgeon to ensure timely initiation of appropriate therapy and reduced patient morbidity. (Endocr Pract. 2012;18:e1-e4)     

Multidisciplinary Approach including Receptor Radionuclide Therapy with 90Y-DOTATOC ([90Y-DOTA0,Tyr3]-OCTREOTIDE) and 177Lu-DOTATATE ([177Lu-DOTA0,Tyr3]-OCTREOTATE) in Ectopic Cushing Syndrome from Ametastatic Gastrinoma: A Promising Proposal

ObjectiveTo present a case of a young woman with Cushing syndrome caused by ectopic production of adrenocorticotropic hormone from a metastatic pancreatic gastrin-secreting endocrine carcinoma, who had a good response to combination peptide receptor radionuclide therapy.MethodsWe review the history, physical examination, laboratory investigations, and radiographic findings in this unusual patient. Moreover, the multimodal interventions are described and discussed.ResultsIn a 38-year-old woman with typical signs of cortisol excess, laboratory studies revealed diabetes mellitus, hypokalemia, and high levels of adrenocorticotropic hormone, plasma cortisol, and urinary cortisol. Abdominal computed tomography showed a 4-cm pancreatic mass and multiple metastatic lesions in the liver, and ectopic Cushing syndrome was diagnosed. Treatment consisted of surgical debulking of the tumor, ketoconazole, somatostatin analogues, chemoembolization of the liver metastatic lesions, and peptide receptor radionuclide therapy with the radiolabeled somatostatin analogues ⁹⁰Y-DOTATOC ([⁹⁰Y-DOTA⁰,Tyr³]-octreotide) and ¹⁷⁷Lu-DOTATATE ([¹⁷⁷Lu-DOTA⁰,Tyr³]-octreotate). The 5¹/2-year follow-up showed positive results, which included complete regression of all clinical and hormonal evidence of the tumor and substantial decrease in the size and number of hepatic metastatic lesions. The patient achieved and still maintains an optimal quality of life.ConclusionTo the best of our knowledge, this is the first report of a multidisciplinary approach including peptide receptor radionuclide therapy with ⁹⁰Y-DOTATOC and ¹⁷⁷Lu-DOTATATE, which proved to be effective in improving clinical outcome in a case of metastatic endocrine carcinoma of the pancreas in conjunction with ectopic Cushing syndrome. In this unusual case, the patient has one of the longest durations of survival in this setting described in the literature. (Endocr Pract. 2008; 14:213-218)     

Metastatic Struma Ovarii Treated With Total Thyroidectomy and Radioiodine Ablation

ObjectiveTo present a rare case of metastatic struma ovarii, review the related literature, and discuss the management.MethodsA case report of a patient with metastatic struma ovarii is presented. The treatment plan, postoperative care, and follow-up are discussed. We conducted a MEDLINE search of the English-language literature seeking additional cases of metastatic struma ovarii. In addition to the current case, the previous 40 cases of metastatic struma ovarii were reviewed and analyzed.ResultsThe mean age of the patients at presentation was 43 years. All patients underwent resection of the primary tumor. The most common sites of involvement for struma ovarii metastatic disease have been the peritoneum, mesentery, and omentum. After primary tumor resection, a wide range of additional treatments have been used, including chemotherapy, resection of metastatic disease, external beam radiation therapy, and radioiodine ablation.ConclusionIn cases of metastatic struma ovarii, we recommend total thyroidectomy in conjunction with radioiodine scanning and radioiodine ablation. Thyroglobulin levels should be followed as a tumor marker, and diagnostic radioiodine scans should be performed to screen for residual or recurrent disease. Although this treatment strategy is well established for thyroid cancer, long-term outcomes of this treatment for struma ovarii are still unknown. (Endocr Pract. 2009;15:167-173)     

Incidental Radiologic Finding of an Anterior Superior Mediastinal Mass Masquerading as Metastatic Thyroid Cancer in Patients with Treated Thyroid Cancer

ObjectiveTo demonstrate that an anterior superior mediastinal mass on radiologic imaging may represent an incidental finding and not metastases in patients with a history of treated well-differentiated thyroid cancer.MethodsWe report the clinical presentation and outcomes of 4 patients with a history of thyroid cancer who were incidentally found to have anterior superior mediastinal masses on imaging. We also review the relevant literature.ResultsFour young adults with a history of stage I papillary thyroid cancer treated with total thyroidectomy and radioiodine were incidentally found to have thymic enlargement on imaging studies within a 3-year posttreatment window. In each case, this enlargement was believed to be secondary to thymic hyperplasia and not metastatic disease, and each patient has exhibited a benign clinical course. Review of the literature revealed few reports of an association between thymic hyperplasia and thyroid cancer.ConclusionsThymic hyperplasia may be discovered on posttreatment imaging studies in patients with a history of well-differentiated thyroid cancer, particularly in young adults who have received radioiodine therapy. Recognition of the possible coexistence of this incidental finding in patients with thyroid cancer may help to avoid unnecessary invasive procedures and treatments. (Endocr Pract. 2011;17:65-69)     

Unusual Case of Multiple Endocrine Neoplasia Type 2A Syndrome Without Medullary Thyroid Carcinoma

ObjectiveTo present an unusual case of multiple endocrine neoplasia type 2A (MEN 2A) syndrome and to describe how this case differs from the typical clinical features and usual genetic variations seen in classic MEN 2A syndrome.MethodsWe describe the work-up, diagnosis, and treatment course of a patient who presented with multifocal pheochromocytomas, parathyroid adenoma, thyroid abnormalities, and a RET mutation.ResultsA 65-year-old man with previously treated pheochromocytoma presented with a parathyroid adenoma, multiple thyroid nodules, and a RET polymorphism. C-cell hyperplasia (CCH) or medullary thyroid carcinoma (MTC) occurs with nearly 100% penetrance in patients with MEN 2A syndrome. Our patient did not have CCH or frank MTC, but he expressed the other manifestations of the MEN 2A syndrome.ConclusionMEN 2A syndrome is characterized by the occurrence of MTC, pheochromocytomas, and parathyroid hyperplasia or adenomas. It is inherited in an autosomal dominant fashion, and more than 80% of patients with MEN 2A have a specific substitution on codon 634 of the RET proto-oncogene. Despite the nearly 100% penetrance of MTC or CCH in patients with MEN 2A, our patient did not have this. Additionally, he exhibited a RET mutation that is uncommonly seen in classic MEN 2A syndrome. Our patient may have a MEN 2A variant or a pseudo-MEN 2A syndrome. (Endocr Pract. 2011;17:e4-e7)     

Transformation of a Pituitary Macroadenoma into to a Corticotropin-Secreting Carcinoma Over 16 Years

ObjectiveTo describe a case of a pituitary macroadenoma that differentiated into a corticotropin (ACTH)-secreting carcinoma with metastasis to the thigh.MethodsWe present a case report with a 16-year follow-up that includes anatomic and endocrine documentation of the history of an ACTH-secreting carcinoma.ResultsA 32-year-old woman presented for evaluation in 1989 because of visual feld defects. Magnetic resonance imaging revealed a locally invasive 3-cm macroadenoma. She had no clinical signs of cortisol excess. The patient underwent surgical debulking followed by a course of radiation directed to the pituitary. Results from retrospective immunohistochemical staining with antibodies against ACTH, prolactin, and MIB-1 were negative. Postoperatively, she could not be weaned from exogenous steroids without developing symptoms of adrenal insuffciency. In 1995, she developed left facial palsy and diplopia caused by tumor growth. In 1997, the patient developed progressive symptoms of cortisol excess, which continued after exogenous steroid replacement was discontinued. The patient’s clinical status continued to deteriorate because of local mass effect from tumor growth and uncontrolled hypercortisolism. She underwent bilateral adrenalectomy in 2003. The patient remained debilitated in a long-term care facility for 2 years when she was found to have a mass on her left hip. Biopsy results of the obturator muscle revealed metastatic tumor of neuroendocrine origin with strong reactivity to ACTH antibodies and MIB-1 labeling in 8% of tumor cell nuclei.ConclusionA pituitary tumor can transform into an ACTH-secreting carcinoma in an indolent manner. Patients with invasive pituitary adenomas require long-term surveillance to monitor for differentiation into pituitary carcinoma. (Endocr Pract. 2007;13:463-471)     

Neuroendocrine Thymic Carcinoma Metastatic to the Parathyroid Gland that was Reimplanted into the Forearm in Patient with Multiple Endocrine Neoplasia Type 1 Syndrome: A Challenging Management Dilemma

ObjectiveTo describe a unique case of a metastatic thymic carcinoma to the hyperplastic parathyroid gland and to present a challenging management dilemma.MethodsOur patient is 60-year-old, intellectually disabled man with history of the multiple endocrine neoplasia type 1 (MEN1) syndrome, a surgery in 1985 for hypercalcemia with removal of one parathyroid gland, surgery in 2007 with findings of extensively necrotic well differentiated neuroendocrine carcinoma (carcinoid tumor) of the thymus. In 2012, he presented with persistent hypercalcemia (calcium level 11.7 mg/dL [range, 8.6-10.2]), and a parathyroid hormone (PTH) level of 225 pg/mL (range, 15-65 pg/mL). He underwent a repeat neck exploration with removal of 2 small inferior and a large left superior 4.5 × 2.5 × 1.5cm parathyroid glands, all of which showed hyperplasia on intraoperative frozen section. A small portion of the superior gland was reimplanted into the patient’s forearm. Final pathology showed the presence of a focus of neuroendocrine tumor within the left superior parathyroid gland with immunostain identical to the thymic carcinoma. His postoperative PTH level was 14 pg/mL and calcium 8.5 mg/dL. A positron emission tomography – computed tomography (PET-CT) and octreotide scans revealed an extensive metastatic disease within the lung, mediastinum, and bones.ResultsWe decided to leave a portion of the reimplanted parathyroid gland with possible metastatic thymic carcinoid in his forearm because of the presence a widespread metastatic disease and his intellectual disability that would result in noncompliance with calcium replacement in case of permanent hypocalcemia.ConclusionMetastatic thymic carcinoma to the parathyroid gland has never been reported in the literature. We have described the first case and presented a challenging management dilemma. (Endocr Pract. 2013;19:e163-e167)     

Ectopic Acromegaly due to A Pancreatic Neuroendocrine Tumor Producing Growth Hormone-Releasing Hormone

ObjectiveTo present a case of acromegaly due to ectopic growth hormone-releasing hormone (GHRH) secretion from a pancreatic neuroendocrine tumor in the context of multiple endocrine neoplasia type 1 (MEN 1).MethodsWe describe the clinical, imaging, and pathologic findings of the study patient.ResultsA 46 year old woman presented with clinical and biochemical findings diagnostic of acromegaly. Magnetic resonance imaging showed a 1.2-cm sellar mass. Following resection of the macroadenoma, serum insulinlike growth factor 1 (IGF-1) and growth hormone (GH) levels remained unchanged. Pathologic examination revealed adenomatous changes, including a nonsecretory focus and a prolactin immunopositive area (GH stain negative in both). Octreotide long-acting release was ineffective. Search for an ectopic tumor included normal octreoscan and abdominal computed tomography. GHRH was greater than 1000 pg/mL. Repeated abdominal computed tomography documented a 6.2-cm mass in the tail and body of the pancreas. Distal pancreatectomy revealed a pancreatic neuroendocrine tumor that stained positive for GHRH. Postoperatively, serum GHRH and IGF-1 normalized. Re-evaluation of the initial pituitary pathologic specimen revealed additional somatotroph hyperplasia of the adjacent, normal pituitary gland. Primary hyperparathyroidism was diagnosed, and multigland parathyroid hyperplasia was noted at surgery. Genetic testing was positive for a mutation in the MEN1 gene.ConclusionThis patient’s acromegaly was resistant to somatostatin analogue therapy, reflecting the negative octreoscan imaging. In addition, this case is novel because the patient presented with pituitary adenomatous changes, which were presumably associated with MEN 1 and/or possibly the elevated GHRH levels. (Endocr Pract. 2011; 17:79-84)     

Cushing Syndrome Secondary to A Thymic Carcinoid Tumor Due to Multiple Endocrine Neoplasia Type 1

ObjectiveTo present an Iranian patient with a nonclassic form of multiple endocrine neoplasia type 1 (MEN 1) who presented with ectopic Cushing syndrome (CS) secondary to a corticotropin (ACTH)-producing thymic neuroendocrine tumor (NET), recurrent renal stones, and a giant cell granuloma of the jaw due to primary hyperparathyroidism (PHPT) without involvement of the pituitary or pancreas.MethodsRelevant imaging and hormonal evaluations were performed. The patient was operated on 2 occasions for a thymic NET and on 3 occasions for PHPT. DNA from a peripheral blood sample was extracted for sequencing of the MEN1 gene.ResultHistopathologic evaluation of the thymic tumor removed during the first surgery showed an atypical carcinoid tumor with a Ki-67 labeling index of 5%. Evaluation after the second surgery revealed an invasive carcinoid tumor with a Ki-67 labeling index of 30%.Parathyroid pathology was suggestive of glandular hyperplasia. Menin gene sequencing revealed a novel frameshift mutation c.1642_1648dup in exon 10.ConclusionThis case of MEN 1 is unusual because most thymic NETs in MEN 1 are nonfunctional, and secretion of ACTH or other ectopic hormones rarely occurs. In patients presenting with thymic NETs, the possibility of MEN 1 should be considered, especially in the presence of hyperparathyroidism. This case also demonstrates that the behavior of thymic NETs can change over time from slow-growing tumors to highly invasive neoplasia, and that ectopic ACTH can be produced by these tumors in the context of MEN 1. (Endocr Pract. 2011;17:e92-e96)     

Rhabdomyolysis after Withdrawal of Thyroid Hormone in a Patient with Papillary Thyroid Cancer

ObjectiveTo report a case of rhabdomyolysis presenting with severe hyperkalemia after withdrawal of thyroid hormone in a patient with differentiated thyroid cancer.MethodsWe describe the clinical and laboratory findings of the study patient and review the relevant literature.ResultsA 54-year-old man with progressive generalized weakness and myalgias presented with acute renal failure and hyperkalemia. He had undergone total thyroidectomy for papillary thyroid cancer 6 weeks earlier and had discontinued thyroid hormone 2 weeks before his current presentation in preparation for thyroid remnant ablation. He had a history of multiple colon and small-bowel resections for familial adenomatous polyposis and desmoid tumor. He was severely dehydrated on examination. Laboratory tests results included the following values: creatine phosphokinase, 5265 U/L (reference range, 52-336 U/L); creatinine, 2.1 mg/dL; potassium, > 8.0 mEq/L; and thyrotropin, 92.2 mIU/L. His condition was diagnosed as rhabdomyolysis, and his fluid deficit and hyperkalemia were treated aggressively. Cardiac status remained stable, and both acute renal failure and hyperkalemia improved. He then received remnant ablation, and thyroid hormone was restarted. His muscle complaints resolved over the following 3 months.ConclusionsHypothyroidism-induced rhabdomyolysis can occur during thyroid hormone withdrawal and can present with life-threatening hyperkalemia. Patients undergoing thyroid hormone withdrawal should be assessed for risk of rhabdomyolysis, and preventive strategies should be implemented, including prevention of dehydration.The use of recombinant thyrotropin, rather than thyroid hormone withdrawal, should be considered in those who are at high risk for such complications. (Endocr Pract. 2008;14:1023-1026)