Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Case report

Case report of severe Cushing’s syndrome in medullary thyroid cancer complicated by functional diabetes insipidus, aortic dissection, jejunal intussusception, and paraneoplastic dysautonomia: remission with sorafenib without reduction in cortisol concentration

Authors: Muhammad M. Hammami, Najla Duaiji, Ghazi Mutairi, Sabah Aklabi, Nasser Qattan, Mohei El-Din M. Abouzied, Mohamed W. Sous

Published in: BMC Cancer | Issue 1/2015

Login to get access

Abstract

Background

Normalization of cortisol concentration by multikinase inhibitors have been reported in three patients with medullary thyroid cancer-related Cushing’s syndrome. Aortic dissection has been reported in three patients with Cushing’s syndrome. Diabetes insipidus without intrasellar metastasis, intestinal intussusception, and paraneoplastic dysautonomia have not been reported in medullary thyroid cancer.

Case presentation

An adult male with metastatic medullary thyroid cancer presented with hyperglycemia, hypernatremia, hypokalemia, hypertension, acne-like rash, and diabetes insipidus (urine volume >8 L/d, osmolality 190 mOsm/kg). Serum cortisol, adrenocorticoitropic hormone, dehydroepiandrostenedione sulfate, and urinary free cortisol were elevated 8, 20, 4.4, and 340 folds, respectively. Pituitary imaging was normal. Computed tomography scan revealed jejunal intussusception and incidental abdominal aortic dissection. Sorafenib treatment was associated with Cushing’s syndrome remission, elevated progesterone (>10 fold), normalization of dehydroepiandrostenedione sulfate, but persistently elevated cortisol concentration. Newly-developed proximal lower limb weakness and decreased salivation were associated with elevated ganglionic neuronal acetylcholine receptor (alpha-3) and borderline P/Q type calcium channel antibodies.

Conclusion

Extreme cortisol concentration may have contributed to aortic dissection and suppressed antidiuretic hormone secretion; which combined with hypokalemia due cortisol activation of mineralocorticoid receptors, manifested as diabetes insipidus. This is the first report of paraneoplastic dysautonomia and jejunal intussusception in medullary thyroid cancer, they may be related to medullary thyroid cancer’s neuroendocrine origin and metastasis, respectively. Remission of Cushing’s syndrome without measurable reduction in cortisol concentration suggests a novel cortisol-independent mechanism of action or assay cross-reactivity. Normalization of dehydroepiandrostenedione sulfate and elevation of progesterone suggest inhibition of 17-hydroxylase and 21-hydroxylase activities by sorafenib.
Literature
1.
Boscaro M, Arnaldi G. Approach to the patient with possible Cushing’s syndrome. J Clin Endocrinol Metab. 2009;94:3121–31.CrossRefPubMed
2.
Isidori AM, Kaltsas GA, Pozza C, Frajese V, Newell-Price J, Reznek RH, et al. The ectopic adrenocorticotropin syndrome: clinical features, diagnosis, management, and long-term follow up. J Clin Endocrinol Metab. 2006;91(2):371–7.CrossRefPubMed
3.
Ilias I, Torpy DJ, Pacak K, Mullen N, Wesley RA, Nieman LK. Cushing’s syndrome due to ectopic corticotropin secretion: twenty years’ experience at the National Institutes of Health. J Clin Endocrinol Metab. 2005;90(8):4955–62.CrossRefPubMed
4.
Williams MD, Asa SL, Fuller GN. Medullary thyroid carcinoma metastatic to the pituitary gland: an unusual site of metastasis. Ann Diagn Pathol. 2008;12:199–203.CrossRefPubMed
5.
Santarpia L, Gagel RF, Sherman SI, Sarlis NJ, Evans DB, Hoff AO. Diabetes insipidus and panhypopituitarism due to intrasellar metastasis from medullary thyroid cancer. Head Neck. 2009;31:419–23.CrossRefPubMed
6.
Ba¨hr V, Franzen N, Oelkers W, Pfeiffer AFH, Diederich S. Effect of exogenous glucocorticoid on osmotically stimulated antidiuretic hormone secretion and on water reabsorption in man. Eur J Endocrinol. 2006;155:845–8.CrossRef
7.
Barbosa SL, Rodien P, Leboulleux S, Niccoli-Sire P, Kraimps JL, Caron P, et al. Ectopic adrenocorticotropic hormone –syndrome in medullary carcinoma of the thyroid: a retrospective analysis and review of the literature. Thyroid. 2005;15(6):618–23.CrossRefPubMed
8.
Baudry C, Paepegaey AC, Groussin L. Reversal of Cushing’s syndrome by vandetanib in medullary thyroid carcinoma. N Engl J Med. 2013;369:584–6.CrossRefPubMed
9.
Nella AA, Lodish MB, Fox E, Balis FM, Quezado MM, Whitcomb PO, et al. Vandetanib successfully controls medullary thyroid cancer-related Cushing syndrome in an adolescent patient. J Clin Endocrinol Metab. 2014;99:3055–9.CrossRefPubMedPubMedCentral
10.
Barroso-Sousa R, Lerario AM, Evangelista J, Papadia C, Lourenc Jr DM, Lin CS, et al. Complete resolution of hypercortisolism with sorafenibin a patient with advanced medullary thyroid carcinoma and ectopic ACTH (adrenocorticotropic hormone) syndrome. Thyroid. 2014;24(6):1062–6.CrossRefPubMed
11.
Petramala L, Cotesta D, Sapienza P, Zinnamosca L, Moroni E, di Marzio L, et al. A case of acute aortic dissection type B associated with Cushing’s syndrome. J Clin Med Res. 2009;1:50–2.PubMedPubMedCentral
12.
Marinis A, Yiallourou A, Samanides L, Dafnios N, Anastasopoulos G, Vassiliou I, et al. Intussusception of the bowel in adults: A review. World J Gastroenterol. 2009;15(4):407–11.CrossRefPubMedPubMedCentral
13.
Vernino S, Low PA, Fealey RD, Stewart JD, Farrugia G, Lennon VA. Autoantibodies to ganglionic acetylcholine receptors in autoimmune autonomic neuropathies. N Eng J Med. 2000;343:847–55.CrossRef
14.
Castro Cabezas M, Vrinten DH, Burgers JA, Croughs RJM. Central diabetes insipidus and Cushing’s syndrome due to ectopic ACTH production by disseminated small cell lung cancer: A case report. Neth J Med. 1998;53:32–6.CrossRefPubMed
15.
Agha A, Brennan S, Moore KB, Grogan L, Thompson CJ. Small-Cell lung cancer presenting as diabetes insipidus and Cushing’s syndrome. Pituitary. 2005;8(2):105–7.CrossRefPubMed
16.
Quinkler M, Meyer B, Bumke-Vogt C, Grossmann C, Gruber U, Oelkers W, et al. Agonistic and antagonistic properties of progesterone metabolites at the human mineralocorticoid receptor. Eur J Endocrinol. 2002;146:789–800.CrossRefPubMed
17.
Zhang S, Jonklaas J, Danielsen M. The glucocorticoid agonist activities of mifepristone (RU486) and progesterone are dependent on glucocorticoid receptor concentrations but not on EC50 values. Steroids. 2007;72(6–7):600–8.CrossRefPubMed
18.
Krasowski MD, Drees D, Morris CS, Maakestad J, Blau JL, Ekins S. Cross-reactivity of steroid hormone immunoassays: clinical significance and two-dimentional molecular similarity prediction. BMC Clin Pathol. 2014;14:33.CrossRefPubMedPubMedCentral
19.
Zengerling F, Streicher W, Schrader AJ, Schrader M, Nitzsche B, Cronauer MV, et al. Effects of sorafenib on C-terminally truncated androgen receptor variants in human prostate cancer cells. Int J Mol Sci. 2012;13:11530–42.CrossRefPubMedPubMedCentral
20.
Lee SW, Lee EK, Yun T, Won YW, Ko EJ, Choi M, et al. Recurrent hypoglycemia triggered by sorafenib therapy in a patient with hemangiopericytoma. Endocrinol Metab. 2014;29:202–5.CrossRef
21.
Lennon VA, Kryzer GE, et al. Calcium-channel antibodies in the Lambert-Eaton syndrome and other paraneoplastic syndromes. N Engl J Med. 1995;332:1467–74.CrossRefPubMed
22.
Titulaer MJ, Wirtz PW, Kuks JB, Schelhaas HJ, van der Kooi AJ, Faber CG, et al. The Lambert-Eaton myasthenic syndrome 1988–2008: A clinical picture in 97 patients. J Neuroimmunol. 2008;201–202:153–8.CrossRefPubMed
23.
Crone C, Christiansen I, Vissing J. Myopathic EMG findings and type II muscle fiber atrophy in patients with Lambert-Eaton myasthenic syndrome. Clin Neurophysiol. 2013;124:1889–92.CrossRefPubMed
24.
Jin M, Khan AI. Procalcitonin: Uses in the clinical laboratory for the diagnosis of sepsis. Labmed. 2020;41(3):173–7.
25.
Kaczka K, Mikosinski S, Fendker W, Celnik A, Pomorski L. Calcitonin and procalcitonin in patients with medullary thyroid cancer or bacterial infection. Adv Cli Exp Med. 2012;21(2):169–78.
26.
Schumm J, Pfeifer R, Ferrari M, Kuethe F, Figulla HR. An unusual case of progressive shock and highly elevated procalcitonin concentration. Am J Crit Care. 2010;1(19):96–3.CrossRef
27.
Moura MM, Cavaco BM, Pinto AE, Leite V. High prevalence of RAS mutations in RET-negative sporadic medullary thyroid carcinomas. J Clin Endocrinol Metab. 2011;96:E863–8.CrossRefPubMed
28.
Lam ET, Ringel MD, Kloos RT, Prior TW, Knopp MV, Liang J, et al. Phase II clinical trial of sorafenib in metastatic medullary thyroid cancer. J Clin Oncol. 2010;28:2323–30.CrossRefPubMedPubMedCentral
29.
Gorospe EC and Badamas J. Acute liver failure secondary to metastaic medullary thyroid cancer. Case Report in Hepatology. Volume 2011, Article ID 603757, 4 pages. Doi:10.1155/2011/603757.
30.
Van Hootegem A, Verslype C, Van Steenbergen W. Sorafenib-induced liver failure: A case report and review of the literature. Case Reports in Hepatology Volume 2011, Article ID 941395, 4 pages.
Metadata
Title
Case report of severe Cushing’s syndrome in medullary thyroid cancer complicated by functional diabetes insipidus, aortic dissection, jejunal intussusception, and paraneoplastic dysautonomia: remission with sorafenib without reduction in cortisol concentration
Authors
Muhammad M. Hammami
Najla Duaiji
Ghazi Mutairi
Sabah Aklabi
Nasser Qattan
Mohei El-Din M. Abouzied
Mohamed W. Sous
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1620-3

Other articles of this Issue 1/2015

BMC Cancer 1/2015 Go to the issue

Research article

A pooled shRNA screen for regulators of primary mammary stem and progenitor cells identifies roles for Asap1 and Prox1

Research article

Microarray profiling shows distinct differences between primary tumors and commonly used preclinical models in hepatocellular carcinoma

Research article

Impact of cancer and chemotherapy on autonomic nervous system function and cardiovascular reactivity in young adults with cancer: a case-controlled feasibility study

Research article

Relationship between body mass index and the expression of hormone receptors or human epidermal growth factor receptor 2 with respect to breast cancer survival

Research article

Enhanced efficacy of photodynamic therapy by inhibiting ABCG2 in colon cancers

Research article

Radiosensitization with combined use of olaparib and PI-103 in triple-negative breast cancer
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits