Endocrinology and Metabolism

Review Article

Hypothalamus and pituitary gland
Update on Current Evidence for the Diagnosis and Management of Nonfunctioning Pituitary Neuroendocrine Tumors: Elizabeth Whyte, Masahiro Nezu, Constance Chik, Toru Tateno; Endocrinol Metab. 2023;38(6):631-654. Published online November 15, 2023; DOI: https://doi.org/10.3803/EnM.2023.1838

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Pituitary neuroendocrine tumors (PitNETs) are the third most frequently diagnosed intracranial tumors, with nonfunctioning PitNETs (nfPitNETs) accounting for 30% of all pituitary tumors and representing the most common type of macroPitNETs. NfPitNETs are usually benign tumors with no evidence of hormone oversecretion except for hyperprolactinemia secondary to pituitary stalk compression. Due to this, they do not typically present with clinical syndromes like acromegaly, Cushing’s disease or hyperthyroidism and instead are identified incidentally on imaging or from symptoms of mass effects (headache, vision changes, apoplexy). With the lack of effective medical interventions, first-line treatment is transsphenoidal surgical resection, however, nfPitNETs often have supra- or parasellar extension, and total resection of the tumor is often not possible, resulting in residual tumor regrowth or reoccurrence. While functional PitNETs can be easily followed for recurrence using hormonal biomarkers, there is no similar parameter to predict recurrence in nfPitNETs, hence delaying early recognition and timely management. Therefore, there is a need to identify prognostic biomarkers that can be used for patient surveillance and as therapeutic targets. This review focuses on summarizing the current evidence on nfPitNETs, with a special focus on potential new biomarkers and therapeutics.

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Phenotype Transformation of PitNETs
Zhenwei Li, Yinzi Wu, Guannan He, Renzhi Wang, Xinjie Bao
Cancers.2024; 16(9): 1731. CrossRef

Case Reports

Thyroid
A Calcitonin-Negative Neuroendocrine Tumor Derived from Follicular Lesions of the Thyroid: Ga Young Kim, Chul Yun Park, Chang Ho Cho, June Sik Park, Eui Dal Jung, Eon Ju Jeon; Endocrinol Metab. 2015;30(2):221-225. Published online December 9, 2014; DOI: https://doi.org/10.3803/EnM.2015.30.2.221

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Neuroendocrine lesions of the thyroid are rare. The most common types are medullary thyroid carcinomas (MTCs) and C-cell hyperplasia. MTCs originate from thyroid parafollicular cells that secrete calcitonin which serves as a serum marker of MTCs. Here, the rare case of a calcitonin-negative neuroendocrine tumor (NET) derived from follicular lesions of the thyroid is described. A 34-year-old man presented at our hospital for the surgical management of an incidental thyroid nodule that was observed on an ultrasound sonography (USG) of the neck. Initially, USG-guided aspiration cytology was performed, and a MTC was suspected. The expressions of thyroglobulin and thyroid transcription factor-1, which are thyroid follicular cell markers, and synaptophysin and chromogranin A, which are neuroendocrine markers, was confirmed following surgical pathology. However, the staining of calcitonin, a marker of MTCs, was not observed. A nonmedullary NET of the thyroid is uncommon, and the distinction between calcitonin-negative NETs and MTCs of the thyroid may be important due to differences in their clinical courses and management.

Citations

Citations to this article as recorded by

Calcitonin-Negative Neuroendocrine Carcinoma of the Thyroid Gland: Case Report and Literature Review
Ricardo Fernández-Ferreira, Ildefonso Roberto De la Peña-López, Karla Walkiria Zamudio-Coronado, Luis Antonio Delgado-Soler, María Eugenia Torres-Pérez, Christianne Bourlón-de los Ríos, Rubén Cortés-González
Case Reports in Oncology.2021; 14(1): 112. CrossRef
Calcitonin-negative neuroendocrine tumor of the thyroid with metastasis to liver-rare presentation of an unusual tumor: A case report and review of literature
Huai-Jie Cai, Han Wang, Nan Cao, Bin Huang, Fan-Lei Kong, Li-Ren Lu, Ya-Yuan Huang, Wei Wang
World Journal of Clinical Cases.2020; 8(1): 179. CrossRef
Medullary thyroid carcinoma with double negative calcitonin and CEA: a case report and update of literature review
Claudio Gambardella, Chiara Offi, Guglielmo Clarizia, Roberto Maria Romano, Immacolata Cozzolino, Marco Montella, Rosa Maria Di Crescenzo, Massimo Mascolo, Angelo Cangiano, Sergio Di Martino, Giancarlo Candela, Giovanni Docimo
BMC Endocrine Disorders.2019;[Epub] CrossRef
Calcitonin negative Medullary Thyroid Carcinoma: a challenging diagnosis or a medical dilemma?
Claudio Gambardella, Chiara Offi, Renato Patrone, Guglielmo Clarizia, Claudio Mauriello, Ernesto Tartaglia, Francesco Di Capua, Sergio Di Martino, Roberto Maria Romano, Lorenzo Fiore, Alessandra Conzo, Giovanni Conzo, Giovanni Docimo
BMC Endocrine Disorders.2019;[Epub] CrossRef
Calcitonin-Negative Neuroendocrine Tumor of the Thyroid
Megan Parmer, Stacey Milan, Alireza Torabi
International Journal of Surgical Pathology.2017; 25(2): 191. CrossRef
Clinical and pathological analysis of 19 cases of medullary thyroid carcinoma without an increase in calcitonin
Qiufeng Zhou, Shuanglei Yue, Ye Cheng, Ju Jin, Haimiao Xu
Experimental and Toxicologic Pathology.2017; 69(8): 575. CrossRef
Primary Calcitonin-negative Neuroendocrine Tumor
Sabri Özden, Aysel Colak, Baris Saylam, Ömer Cengiz
World Journal of Endocrine Surgery.2017; 9(3): 104. CrossRef
LONG-TERM RESULTS OF SURGICAL TREATMENT OF PATIENTS WITH FOLLICULAR TUMORS OF THE THYROID
I. N. Zubarovskiy, M. V. Mikhailova, S. K. Osipenko
Grekov's Bulletin of Surgery.2015; 174(5): 32. CrossRef

A Case of Ectopic ACTH Syndrome Associated with Metastatic Prostate Cancer.: Eun Ky Kim, Soo Heon Kwak, Hwa Young Ahn, Ah Reum Khang, Hyo Jin Park, So Yeon Park, Sang Eun Lee, Hak Chul Jang, Seong Yeon Kim, Young Joo Park; Endocrinol Metab. 2012;27(3):237-243. Published online September 19, 2012; DOI: https://doi.org/10.3803/EnM.2012.27.3.237

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Abstract PDF: Ectopic adrenocorticotropic hormone (ACTH) syndrome is mostly associated with neuroendocrine tumors and small cell carcinoma of the lung. This syndrome of prostate cancer is rare and has been reported in only a few cases. We report a patient with ectopic ACTH production associated with metastatic prostate cancer. A 70-year-old patient with metastatic prostate cancer was admitted to our hospital with septic shock. He had a history of hormonal therapy and transurethral prostatectomy. Adrenocortical function was checked due to consistent fever and poor general condition, which revealed markedly increased levels of basal plasma ACTH and serum cortisol. The patient did not present typical signs of the Cushing's syndrome, however, hypokalemia and a history of hypertension were found. He died in days as a result of multi-organ failure. On pathology, the prostatectomy specimen showed a tumor composed of mixed populations of adenocarcinoma and small cell carcinoma. The tumor cells in the small cell component were positive for chromogranin and ACTH. Although neuroendocrine differentiation in prostate cancer is rare, etopic ACTH production should be considered in patients with prostate cancer as well as in clinical features of ACTH hypersecretion.

A Case of von Hippel-Lindau Disease Presenting with Pancreatic Neuroendocrine Tumor.: Jung Hun Ohn, Junghee Kim, Hyun Jung Lee, Won Woo Seo, Yul Hwang-Bo, Eun Shil Hong, Jin Joo Park, Seong Yeon Kim; Endocrinol Metab. 2011;26(1):89-91. Published online March 1, 2011; DOI: https://doi.org/10.3803/EnM.2011.26.1.89

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Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder that results from a germline mutation of the VHL gene. The affected individuals might develop several benign or malignant tumors such as central nervous system or retinal haemangioblastomas, endolymphatic sac tumors, renal cell carcinomas, pheochromocytomas or pancreatic cysts and neuroendocrine tumors. We report here on a case of a 21 year old female with von Hippel-Lindau disease and she presented with only pancreatic neuroendocrine tumor and no evidence of haemangioblastomas or other visceral complications. Further, direct sequencing of the VHL gene reveals a novel germline frameshift mutation of codon 198 from the deletion of nucleotide 592 (cytosine), leading to truncation of the VHL protein.

Citations

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Germline mutation of Glu70Lys is highly frequent in Korean patients with von Hippel–Lindau (VHL) disease
Sena Hwang, Cheol Ryong Ku, Ji In Lee, Kyu Yeon Hur, Myung-Shik Lee, Chul-Ho Lee, Kyo Yeon Koo, Jin-Sung Lee, Yumie Rhee
Journal of Human Genetics.2014; 59(9): 488. CrossRef

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