Cargando…

Leukocytosis and PTHrP-Mediated Hypercalcemia: Ominous Signs in an Indolent Thyroid Nodule

Introduction/Background: Anaplastic thyroid cancer is a rare thyroid malignancy with a bad prognosis. There are few systemic markers, as thyroglobulin is not usually synthesized in these poorly differentiated malignancies. Clinical Case - Diagnostic Evaluation, Treatment, and Follow Up: A 70-year ol...

Descripción completa

Detalles Bibliográficos
Autores principales: Gerwer, Johanna Elizabeth, Thomas, Robert L, Orosco, Ryan K, Choe, Charles, McCowen, Karen C
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8090070/
http://dx.doi.org/10.1210/jendso/bvab048.1822
_version_ 1783687192997003264
author Gerwer, Johanna Elizabeth
Thomas, Robert L
Orosco, Ryan K
Choe, Charles
McCowen, Karen C
author_facet Gerwer, Johanna Elizabeth
Thomas, Robert L
Orosco, Ryan K
Choe, Charles
McCowen, Karen C
author_sort Gerwer, Johanna Elizabeth
collection PubMed
description Introduction/Background: Anaplastic thyroid cancer is a rare thyroid malignancy with a bad prognosis. There are few systemic markers, as thyroglobulin is not usually synthesized in these poorly differentiated malignancies. Clinical Case - Diagnostic Evaluation, Treatment, and Follow Up: A 70-year old man presented in 2016 with a right thyroid nodule, slowly growing since 2012. The nodule was 10cm on neck CT and ultrasound showed a hyperechoic mass with central hypoechoic area, and coarse calcifications. Fine needle biopsy showed a follicular neoplasm. By 2019, neck CT showed enlargement of the nodule to 13 cm. Repeat thyroid biopsy was benign. Lobectomy was recommended due to size but not performed. In 2020, he developed neck discomfort and painful thigh swelling. WBC was significantly elevated at 27,000 (4000-10000) /mm3. Ultrasound showed no evidence of necrosis or abscess in the nodule. WBC rose progressively to 96,000/mm3 (ANC 94,200). CT chest showed further enlargement of the thyroid mass, a soft tissue shoulder mass and lung nodules suspicious for metastases. Laryngoscopy revealed a distorted larynx from external compression, and possible vocal-fold involvement (motion impairment) without airway compromise. Biopsy of the shoulder mass, lung nodule, and thigh masses all showed metastatic anaplastic thyroid cancer. Full infectious disease evaluation and molecular testing for BCR-ABL and JAK2 mutations were negative. Thus, leukocytosis was determined to be reactive in the setting of malignancy. Serum calcium of 14.7 mg/dL (8.5 - 10.6mg/dL) prompted hospital admission. Bone metastases were not visible on imaging. Hypercalcemia was treated effectively (to 8.3mg/dL) with IV fluids, calcitonin and IV bisphosphonates. Workup revealed suppression of PTH to 4 pg/mL (15-65 pg/mL) and low 25 Vitamin D of 21 ng/mL (30-80ng/L). Subsequently PTHrP was elevated at 53.4 pmol/L (<2.3pmol/L) and 1,25 Vitamin D inappropriately normal at 48.9 pg/mL (20- 79.3pg/mL), suggested humoral hypercalcemia of malignancy. The patient declined further treatment beyond hospice care. Clinical Lesson/Conclusion: Significant, sudden leukocytosis and hypercalcemia prompted further evaluation of his long-standing apparently benign thyroid nodule leading to a diagnosis of anaplastic thyroid cancer. Presumably this mass had been a follicular thyroid cancer, misdiagnosed on cytology, that subsequently de-differentiated. There are uncommon reports of leukocytosis complicating anaplastic thyroid cancer, where elevated GCSF and IL-6 were noted. We suspect this same etiology here. Hypercalcemia is extremely rare other than one report of PTHrP-secreting anaplastic thyroid cancer. Thus, high, rising calcium and PTHrP levels may reflect level of disease activity in anaplastic thyroid cancer.
format Online
Article
Text
id pubmed-8090070
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-80900702021-05-06 Leukocytosis and PTHrP-Mediated Hypercalcemia: Ominous Signs in an Indolent Thyroid Nodule Gerwer, Johanna Elizabeth Thomas, Robert L Orosco, Ryan K Choe, Charles McCowen, Karen C J Endocr Soc Thyroid Introduction/Background: Anaplastic thyroid cancer is a rare thyroid malignancy with a bad prognosis. There are few systemic markers, as thyroglobulin is not usually synthesized in these poorly differentiated malignancies. Clinical Case - Diagnostic Evaluation, Treatment, and Follow Up: A 70-year old man presented in 2016 with a right thyroid nodule, slowly growing since 2012. The nodule was 10cm on neck CT and ultrasound showed a hyperechoic mass with central hypoechoic area, and coarse calcifications. Fine needle biopsy showed a follicular neoplasm. By 2019, neck CT showed enlargement of the nodule to 13 cm. Repeat thyroid biopsy was benign. Lobectomy was recommended due to size but not performed. In 2020, he developed neck discomfort and painful thigh swelling. WBC was significantly elevated at 27,000 (4000-10000) /mm3. Ultrasound showed no evidence of necrosis or abscess in the nodule. WBC rose progressively to 96,000/mm3 (ANC 94,200). CT chest showed further enlargement of the thyroid mass, a soft tissue shoulder mass and lung nodules suspicious for metastases. Laryngoscopy revealed a distorted larynx from external compression, and possible vocal-fold involvement (motion impairment) without airway compromise. Biopsy of the shoulder mass, lung nodule, and thigh masses all showed metastatic anaplastic thyroid cancer. Full infectious disease evaluation and molecular testing for BCR-ABL and JAK2 mutations were negative. Thus, leukocytosis was determined to be reactive in the setting of malignancy. Serum calcium of 14.7 mg/dL (8.5 - 10.6mg/dL) prompted hospital admission. Bone metastases were not visible on imaging. Hypercalcemia was treated effectively (to 8.3mg/dL) with IV fluids, calcitonin and IV bisphosphonates. Workup revealed suppression of PTH to 4 pg/mL (15-65 pg/mL) and low 25 Vitamin D of 21 ng/mL (30-80ng/L). Subsequently PTHrP was elevated at 53.4 pmol/L (<2.3pmol/L) and 1,25 Vitamin D inappropriately normal at 48.9 pg/mL (20- 79.3pg/mL), suggested humoral hypercalcemia of malignancy. The patient declined further treatment beyond hospice care. Clinical Lesson/Conclusion: Significant, sudden leukocytosis and hypercalcemia prompted further evaluation of his long-standing apparently benign thyroid nodule leading to a diagnosis of anaplastic thyroid cancer. Presumably this mass had been a follicular thyroid cancer, misdiagnosed on cytology, that subsequently de-differentiated. There are uncommon reports of leukocytosis complicating anaplastic thyroid cancer, where elevated GCSF and IL-6 were noted. We suspect this same etiology here. Hypercalcemia is extremely rare other than one report of PTHrP-secreting anaplastic thyroid cancer. Thus, high, rising calcium and PTHrP levels may reflect level of disease activity in anaplastic thyroid cancer. Oxford University Press 2021-05-03 /pmc/articles/PMC8090070/ http://dx.doi.org/10.1210/jendso/bvab048.1822 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Thyroid
Gerwer, Johanna Elizabeth
Thomas, Robert L
Orosco, Ryan K
Choe, Charles
McCowen, Karen C
Leukocytosis and PTHrP-Mediated Hypercalcemia: Ominous Signs in an Indolent Thyroid Nodule
title Leukocytosis and PTHrP-Mediated Hypercalcemia: Ominous Signs in an Indolent Thyroid Nodule
title_full Leukocytosis and PTHrP-Mediated Hypercalcemia: Ominous Signs in an Indolent Thyroid Nodule
title_fullStr Leukocytosis and PTHrP-Mediated Hypercalcemia: Ominous Signs in an Indolent Thyroid Nodule
title_full_unstemmed Leukocytosis and PTHrP-Mediated Hypercalcemia: Ominous Signs in an Indolent Thyroid Nodule
title_short Leukocytosis and PTHrP-Mediated Hypercalcemia: Ominous Signs in an Indolent Thyroid Nodule
title_sort leukocytosis and pthrp-mediated hypercalcemia: ominous signs in an indolent thyroid nodule
topic Thyroid
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8090070/
http://dx.doi.org/10.1210/jendso/bvab048.1822
work_keys_str_mv AT gerwerjohannaelizabeth leukocytosisandpthrpmediatedhypercalcemiaominoussignsinanindolentthyroidnodule
AT thomasrobertl leukocytosisandpthrpmediatedhypercalcemiaominoussignsinanindolentthyroidnodule
AT oroscoryank leukocytosisandpthrpmediatedhypercalcemiaominoussignsinanindolentthyroidnodule
AT choecharles leukocytosisandpthrpmediatedhypercalcemiaominoussignsinanindolentthyroidnodule
AT mccowenkarenc leukocytosisandpthrpmediatedhypercalcemiaominoussignsinanindolentthyroidnodule