Endocrinology and Metabolism

Case Report

Thyroid
Medullary Thyroid Carcinoma with Ectopic Adrenocorticotropic Hormone Syndrome: Hong Seok Choi, Min Joo Kim, Chae Ho Moon, Jong Ho Yoon, Ha Ra Ku, Geon Wook Kang, Im Il Na, Seung-Sook Lee, Byung-Chul Lee, Young Joo Park, Hong Il Kim, Yun Hyi Ku; Endocrinol Metab. 2014;29(1):96-100. Published online March 14, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.1.96

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Ectopic adrenocorticotropic hormone (ACTH) syndrome is caused most frequently by a bronchial carcinoid tumor or by small cell lung cancer. Medullary thyroid carcinoma (MTC) is a rare etiology of ectopic ACTH syndrome. We describe a case of Cushing syndrome due to ectopic ACTH production from MTC in a 48-year-old male. He was diagnosed with MTC 14 years ago and underwent total thyroidectomy, cervical lymph node dissection and a series of metastasectomies. MTC was confirmed by the pathological examination of the thyroid and metastatic mediastinal lymph node tissues. Two years after his last surgery, he developed Cushingoid features, such as moon face and central obesity, accompanied by uncontrolled hypertension and new-onset diabetes. The laboratory results were compatible with ectopic ACTH syndrome. A bilateral adrenalectomy improved the clinical and laboratory findings that were associated with Cushing syndrome. This is the first confirmed case of ectopic ACTH syndrome caused by MTC in Korea.

Citations

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Rapid response of hypercortisolism to vandetanib treatment in a patient with advanced medullary thyroid cancer and ectopic Cushing syndrome
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Namgok Lecture 2013

Obesity and Metabolism
Ectopic Fat Assessment Focusing on Cardiometabolic and Renal Risk: Soo Lim; Endocrinol Metab. 2014;29(1):1-4. Published online March 14, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.1.1

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It is well known that people with high levels of body fat are at higher risk for developing diabetes mellitus, kidney disease, and cardiovascular disorders. Since individuals who are slightly overweight, or even individuals of normal weight, can vary in body fat distribution, their metabolic profiles and the degree of association of these profiles with cardiometabolic risk factors may differ. Fat distribution might be more of a predictive factor for cardiorenometabolic risk than obesity itself, which has led researchers to investigate whether ectopic fat accumulation may partially account for the development of cardiorenometabolic disorders. In addition to visceral obesity, fat can accumulate in the liver and muscle, and these intrahepatic and intramuscular lipid stores are associated with insulin resistance and adverse metabolic phenotypes. More recently, pericardial fat, perivascular fat, and perirenal fat were found to be associated with coronary atherosclerosis, cardiovascular diseases, and kidney damage, respectively. Thus, regional fat distribution may play a key role in understanding the development of cardiorenometabolic diseases in nonobese people.

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Case Reports

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 Ectopic Neurohypophysis Presenting with Hypogonadism.: In Woon Baek, Ji Hyun Kim, Guk Jin Lee, Kyoung Eun Lee, Hae Lim Lee, Hye Won Lee, Nam Yong Kim, Yon Kwon Ihn, Seung Hyun Ko, Seung Hwan Lee, Je Ho Han; Endocrinol Metab. 2011;26(1):67-71. Published online March 1, 2011; DOI: https://doi.org/10.3803/EnM.2011.26.1.67

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Abstract PDF

Pituitary stalk interruption and ectopic neurohypophysis seen on magnetic resonance Imaging (MRI) are often associated with either isolated growth hormone (GH) deficiency or combined anterior pituitary hormone deficiency, but their pathogenesis is not clear and the clinical data regarding these anatomical defect is limited. We experienced a 23-year-old male with the absence of secondary sexual characteristics and this was accompanied with pituitary stalk dysgenesis and ectopic neurohypophysis. He received growth hormone for a year when he was 12 years old due to his short stature. Sella MRI showed no visible pituitary stalk with minimal high signal change, suggesting ectopic neurohypophysis. The combined pituitary stimulation test revealed blunted responses of growth hormone, follicle stimulating hormone and luteinizing hormone. For the hypogonadotropic hypogonadism, the patient was given testosterone intramuscularly and he gradually developed secondary sexual characteristics. We concluded that the hypogonadism and growth hormone deficiency in this patient was caused by hypopituitarism due to pituitary stalk dysgenesis and ecopic nuerohypophysis.

Citations

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MRI of ectopic posterior pituitary gland with dysgenesis of pituitary stalk in a patient with hypogonadotropic hypogonadism
Ashim Kumar Lahiri, Ramanivas Sundareyan, David Jenkins, Anjumara Nilak
Radiology Case Reports.2018; 13(4): 764. CrossRef
Hypothalamic Hypopituitarism Caused by Pituitary Stalk Dysgenesis
Seong-Ju Lee, Hye-Jin Yoon, A-Reum Cho, Yoo-Jin Um, Keun-Young Park, Dong-Mee Lim, Byung-Joon Kim
Korean Journal of Medicine.2013; 85(4): 420. CrossRef

Ectopic ACTH Syndrome with Bilateral Pheochromocytoma in Multiple Endocrine Neoplasia Type 2A.: Ji Mi Moon, Yoon Jung Kim, Young Jin Seo, Hye Yoon Choi, Joo Hyong Kim, Ju Ri Park, Yun Jeong Lee, Hee Young Kim, Sin Gon Kim, Dong Seop Choi; J Korean Endocr Soc. 2009;24(4):265-271. Published online December 1, 2009; DOI: https://doi.org/10.3803/jkes.2009.24.4.265

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Abstract PDF

Multiple endocrine neoplasia type 2A (MEN 2A) is an autosomal dominant syndrome characterized by the presence of medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism. MEN 2A arises due to a germline missense mutation of the RET proto-oncogene. Specific RET mutation analysis has revolutionized the diagnosis and therapy of this disorder, and early thyroidectomy may have lowered the morbidity and mortality associated with these diseases. Ectopic adrenocorticotropic hormone (ACTH) syndrome is characterized by hypercortisolism due to the hypersecretion of ACTH outside of the pituitary gland; the most common causes are malignancies, but rarely adrenal pheochromocytoma may be the cause.

Citations

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Pheochromocytoma With High Adrenocorticotropic Hormone Production Capacity Without Pigmentation and Cushingoid Symptoms: A Case Report With a Literature Review
Gen Mizutani, Masashi Isshiki, Eisuke Shimizu, Daigo Saito, Akira Shimada
Cureus.2024;[Epub] CrossRef
Ectopic ACTH- and/or CRH-Producing Pheochromocytomas
Patrick F Elliott, Thomas Berhane, Oskar Ragnarsson, Henrik Falhammar
The Journal of Clinical Endocrinology & Metabolism.2021; 106(2): 598. CrossRef
Severe Cushing Syndrome Due to an ACTH-Producing Pheochromocytoma: A Case Presentation and Review of the Literature
Jenan N Gabi, Maali M Milhem, Yara E Tovar, Emhemmid S Karem, Alaa Y Gabi, Rodhan A Khthir
Journal of the Endocrine Society.2018; 2(7): 621. CrossRef
Adrenocorticotropic hormone (ACTH)-producing pheochromocytoma presented as Cushing syndrome and complicated by invasive aspergillosis
Jae Ho Cho, Da Eun Jeong, Jae Young Lee, Jong Geol Jang, Jun Sung Moon, Mi Jin Kim, Ji Sung Yoon, Kyu Chang Won, Hyoung Woo Lee
Yeungnam University Journal of Medicine.2015; 32(2): 132. CrossRef

A Case of Pneumocystis Carinii Pneumonia and Cutaneous Nocardiosis Associated with Ectopic ACTH Syndrome.: Hee Sun Jung, Seung Hwan Lee, Hee Yeon Kim, Eun Ho Chu, Kang Woo Lee, Mi Ja Kang, Ji Hyun Kim, Hyuk Sang Kwon, Kun Ho Yoon, Bong Yun Cha, Ho Young Son; J Korean Endocr Soc. 2008;23(1):44-50. Published online February 1, 2008; DOI: https://doi.org/10.3803/jkes.2008.23.1.44

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Abstract PDF: Cushing's syndrome is characterized by hypercortisolism and impairment of cell-mediated immune function, increasing the risk of opportunistic infection, as occurs in other immunocompromised groups such as organ transplant recipients, patients with lymphoreticular malignancy, or acquired immunodeficiency syndrome. We report a case of a 68-year-old woman who was affected with pneumocystis carinii pneumonia (PCP) 8 years ago and cutaneous nocardiosis this year. The patient was diagnosed with ectopic ACTH syndrome 8 years ago, but no ectopic ACTH secreting focus was found in radiologic imaging studies. She recovered from PCP and cutaneous nocardiosis after antibiotic (trimethoprim-sulfamethoxazole) administration. After the infection resolved, she underwent laparoscopic bilateral adrenalectomy and was not longer hypercortisolemic.

A Case of Ectopic ACTH Syndrome Associated with Small Cell Lung Cancer Presented with Hypokalemia.: Hong Jun Yang, Hea Jung Sung, Ji Eun Kim, Hyo Jin Lee, Jin Min Park, Chan Kwon Park, Eun Suk Roh, Jae Hyung Cho, Seung Hyun Ko, Ki Ho Song, Yu Bai Ahn; J Korean Endocr Soc. 2007;22(5):359-364. Published online October 1, 2007; DOI: https://doi.org/10.3803/jkes.2007.22.5.359

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Abstract PDF

We report a case of a 73-year-old female patient who was diagnosed with ectopic ACTH syndrome caused by small cell lung cancer. We initially presumed that the patient was in a state of mineralocorticoid excess, because she had hypertension and hypokalemic alkalosis. This was however excluded because her plasma renin activity was not suppressed and her plasma aldosterone/plasma renin activity ratio was below 25. Moreover, her 24 hour urine free cortisol level was elevated and her serum cortisol levels after a low dose dexamethasone suppression test, were not suppressed. Furthermore, her basal plasma ACTH and serum cortisol levels increased and her serum cortisol level after a high dose dexamethasone suppression test was not suppressed. We performed studies to identify the source of ectopic ACTH syndrome and found a 3 cm-sized mass in the patient's right lower lobe of her lung, which was eventually diagnosed as small cell lung cancer following a bronchoscopic biopsy. In conclusion, Cushing's syndrome, and in particular ectopic ACTH syndrome, must be considered in the differential diagnosis of mineralocorticoid-induced hypertension. The excessive cortisol saturates the 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) activity, which in turn, inactivates the conversion of cortisol to cortisone in the renal tubules. Moreover, excessive cortisol causes binding to the mineralocorticoid receptors, causing mineralocorticoid hypertension, characterized by severe hypercortisolism.

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Emergencia hipertensiva como debut de síndrome de Cushing paraneoplásico
E. Rubio González, M. de Valdenebro Recio, M.I. Galán Fernández
Hipertensión y Riesgo Vascular.2024; 41(2): 135. CrossRef
Management of small cell lung cancer complicated with paraneoplastic Cushing’s syndrome: a systematic literature review
Yanlong Li, Caiyu Li, Xiangjun Qi, Ling Yu, Lizhu Lin
Frontiers in Endocrinology.2023;[Epub] CrossRef
Ectopic Cushing Syndrome in Adenocarcinoma of the Lung: Case Report and Literature Review
Rana Al-Zakhari, Safa Aljammali, Basma Ataallah, Svetoslav Bardarov, Philip Otterbeck
Cureus.2021;[Epub] CrossRef
A Case of Ectopic Adrenocorticotropic Hormone Syndrome in Small Cell Lung Cancer
Chaiho Jeong, Jinhee Lee, Seongyul Ryu, Hwa Young Lee, Ah Young Shin, Ju Sang Kim, Joong Hyun Ahn, Hye Seon Kang
Tuberculosis and Respiratory Diseases.2015; 78(4): 436. CrossRef

Upper Airway Obstruction Caused by Intratracheal Ectopic Thyroid Tissue during Pregnancy.: Eun Young Lee, Byung Wan Lee, Jhingook Kim, Sung Jin Bae, Tae Sik Jung, Hye Seung Jung, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim, Jae Hoon Chung; J Korean Endocr Soc. 2005;20(4):413-420. Published online August 1, 2005; DOI: https://doi.org/10.3803/jkes.2005.20.4.413

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Abstract PDF

Herein is report an extremely rare case of an intratracheal ectopic thyroid gland related with pregnancy. A 34-year-old woman, in gestational week 11, presented with stridor, progressive dyspnea and a choking sensation during her second pregnancy. Computed tomography of the neck and chest revealed a round intratracheal mass obstructing the airway. A bronchoscopic biopsy with LASER cauterization was performed, and the histological finding revealed normal thyroid tissue. The external thyroid of the patient was evaluated, but only found benign nodules in the thyroid gland. She underwent a segmental resection of the trachea, including the mass and the 1st tracheal cartilage. The histological findings revealed the intratracheal mass to be composed of benign thyroid tissue with nodular hyperplasia. After surgery, no pulmonary symptoms were evident. This case suggested the effect of pregnancy on thyroid tissue stimulatied due to a combination of an increasing human chorionic gonadotropin(hCG) level and relative iodine deficiency during pregnancy. This is the first report on the detection of intratracheal ectopic thyroid tissue during pregnancy in Korea.

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A case of mediastinal ectopic thyroid presenting with a paratracheal mass
Eun Roh, Eun Shil Hong, Hwa Young Ahn, So-Yeon Park, Ho Il Yoon, Kyong Soo Park, Young Joo Park
The Korean Journal of Internal Medicine.2013; 28(3): 361. CrossRef

A Case of Ectopic ACTH Syndrome Associated with Bronchial Carcinoid.: Young Jin Choi, Sang hyen Joo, Sun Hye Shin, Ok Nyu Kong, Jun Hyeop An, Young Dae Kim, Seok Man Son, In Joo Kim, Yong Ki Kim; J Korean Endocr Soc. 2004;19(1):76-81. Published online February 1, 2004

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Abstract PDF: Fifteen percent of patients with Cushing's syndrome could be accompanied with nonpituitary tumors that secrets ACTH-the ectopic ACTH syndrome. Among them, bronchial carcinoid is one of the rare causes of the ectopic ACTH syndrome. We experienced a 60-year-old woman who showed conditions of weight gain, generalized edema, hypokalemia, diabetes mellitus, and right middle lung mass. Histologically, the tumor was diagnosed with bronchial carcinoid and was confirmed as an ectopic ACTH syndrome through immunohistochemical staining of ACTH. After resection of the lung mass, blood sugar, electrolytes, generalized weakness, and blood pressure improved.

2 Cases of Ectopic ACTH Syndrome due to Thymic Neuroendocrine Carcinoma Associated with Different Clinical Manifestations.: Yu Jeong Park, Moon Kyu Lee, Jong Ryeal Hahm, Jung Ho Do, Sang Taek Heo, Ju Sung Kim, Yong Ki Min, Myung Shik Lee, Kwang Won Kim, Joung Ho Han; J Korean Endocr Soc. 2001;16(1):115-122. Published online February 1, 2001

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Abstract PDF: Primary neuroendocrine carcinoma of the thymus (formerly known as thymic carcinoids) are unusual tumors that account for 5% of all anterior mediastinal neoplasms. Thymic neuroendocrine carcinomas exhibit a much more aggressive behavior than those originating from other foregut locations and are associated with the ectopic ACTH syndrome in 38% of cases. Patients having a thymic neuroendocrine carcinoma usually present with symptoms such as chest tightness, dyspnea, a palpable neck mass and sometimes a weight gain. We report on 2 patients with thymic neuroendocrine carcinoma who showed different clinical manifestations each other. One presented with a typical. Cushingoid appearance and the other had symptoms of fatigue and weight loss which is a common symptom of malignant tumors.

A Case of Ectopic ACTH Syndrome Caused by Thymic Carcinoid Tumor and Localized by PET.: Jong Chul Won, Sung Kwan Hong, Hyun Ju Lee, Sang Ook Kim, Yun Hee Jeong, Dae Hyuk Moon, Dong Kwan Kim, Kyung Yub Kong, Jae Sung Lee, Ki Soo Kim; J Korean Endocr Soc. 1999;14(4):771-778. Published online January 1, 2001

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Abstract PDF: Ectopic ACTH syndrome is frequently caused by lung cancer and uncommonly by other tumors such as thymic carcinoid. For its treatment, early diagnosis and complete resection is irresponsible, but some cases are remained unlocalized in spite of all diagnostic modalities. Here we report a case of ectopic ACTH syndrome which was localized by PET but could not be localized by conventional technique. A tumor at thymic area was ACTH secreting thymic carcinoid which was operated but couldnt resect completly. Glucocorticoid hypersecretion was persisted with chemotherapy, radiotherapy, and ketoconazole treatment. Patient died of sepsis after 12 months of diagnosis.

A Case of Delayed Puberty due to Hypoplasia of Anterior Pituitary Gland with Pituitary Stalk Agenesis and Ectopic Neurohypophysis.: Seung Yong Shin, Jin Young Kim, Seung Jae Yoon, Sung Ki Kim, Seong Bin Hong, Yeo Joo Kim, Moon Suk Nam, Mi Rim Kim, Yong Seong Kim; J Korean Endocr Soc. 1999;14(3):578-586. Published online January 1, 2001

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Abstract PDF: Hypopituitarism is not a common cause of delayed puberty, however it should always be considered, especially if there are such signs as severe dwarfism, dollish face, truncal obesity, small hands and feet, and microgenitalia. Either congenital or acquired, hypopituitarism can be resulted from hypothalamic and hypophyseal lesions. The clinical feature can be diverse depending on age of the patients, rate of progression, degree of hormone deficiency and characteristics of the lesion. The recent high interest in delayed puberty and the improved detection of hypothalamic hypophyseal lesions using combined pituitary fuction stimulation test, brain CT and MRJ, has made the differential diagnosis of hypopituitarism possible as the cause of delayed puberty. MRI has shown hypophyeal hypoplasia accompanied by anterior pituitary hypoplasia and ectopic neurohypophysis in some of the patients with hypopituitasm, and although the anatomical abnormality around the hypophysis in these patients is considered the reason for hypopituitarism, the pathogensis of which has not yet to be known. We, here, report a case of delayed puberty by hypopituitarism due to hypoplasia of anterior pituitary gland, pituitary stalk agenesis and ectopic neurohypophysis with brief review of the litereature.

Original Article

Clinical Features of Ectopic Thyroid Gland.: Jin Chul Park, Jung Hyun Oh, Sang Yub Nam, Ji Sung Yoon, Kyu Jang Won, In Ho Cho, Hyung Woo Lee, Choong Ki Lee, Jae Tae Lee; J Korean Endocr Soc. 1998;13(4):563-571. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Ectopic thyroid gland is relatively rare condition and a developmental anomaly characterized by an aggregated of thyroid tissue in the midline anywhere from the base of the tongue to the mediastinum. The role of ectopic thyroid in the pathogenesis of non-goitrous sporadic cretinism and primary hypothyroidism has been emphasized. 19 cases of ectopic thyroid for 12 years was presented with Tc-pertechnetate or radioactive iodine, which were diagnosed by scintigraphy. METHODS: We wish to report these 19 cases and 12 cases of brief review of literatures on the incidence, etiology and development, symptomatology, diagnosis and treatment of ectopic thyroid gland was done. RESULTS: The most frequent incidental age was between the age 1 year and 29 years. And the frequency of ectopic thyroid was about 7 times more common in female(27 cases) than in male(4 cases). The location of ectopic thyroid were found to be lingual in 18 cases, sublingual in 9 cases, prelaryngeal in 1 case, and combine with lingual and sublingual in 3 cases. In chief complaints, palpable mass was most common and there were foreign body sensation on throat, dysphagia, dysphonia, and hoarseness. In 15 cases of hypothyroidism, l2 cases were taken thyroid hormone replacement therapy, 1 case was removed ectopic thyroid gland. In 2 of 10 cases of euthyroidism, replacement of thyroid hormone were done and 2 cases were removed ectopic thyroid gland, in 6 cases of unknown thyroid function, 1 case was removed ectopic thyroid gland and 131I therapy was done in 1 case, and others were observed with following up thyroid function test. CONCLUSION: These results suggest that the long terms thyroid function test, thyroglossal duct eyst and malignant change in ectopic thyroid tissue when finding the ectopic thyroid in thyroid scintigraphy were recommended highly.

Case Reports

A Case of Thymic Carcinoid Tumor Associated with Ectopic ACTH Syndrome.: Kwan Woo Lee, Young Goo Shin, Sung Keun Lee, Sung Kyu Lee, Yun Suk Chung, Hyun Man Kim, Yo Han Cho, Kwang Hyun Ko, Jung Sun Kim, Chul Shim; J Korean Endocr Soc. 1997;12(4):647-654. Published online January 1, 2001

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Abstract PDF: The syndrome of ectopic production of ACTH by non-pituitary neoplasm occurs with various types of tumors. ACTH-producing thymic carcinoid tumor is rare and has not been reported in Korea. We have experienced a 36-year-old male patient with ACTH-producing thymic carcinoid tumor, presenting symptoms of generalized weakness and weight gain. Clinical presentation, radiologic and hormonal evaluation, and pathologic examination were compatible with ACTH-producing thymic carcinoid tumor. The immunohistochemical staining of the thymic carcinoid tumor showed positivity for ACTH. Primary and metastatic tumor and both adrenal glands were resected. Radiation therapy and chemotherapy were performed. The prognosis of this patient is thought to be poor.

A Case of Pheochromocytoma associated with Ectopic ACTH Syndrome.: Young Sun Hong, Hee Jin Kim, Yeon Ah Sung, Nan Ho Kyung, Ho Jung Kim, Sung Sook Kim; J Korean Endocr Soc. 1997;12(1):99-104. Published online January 1, 2001

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Abstract PDF: The syndrome of ectopic production of ACTH by non-pituitary neoplasm occur with various types of tu#rnors. Pheochromocytoma is a rare, but one of the important causes of this syndrome. Recently we experienced a 36-year-old male patient with ACTH-producing pheochromocytoma. After left adrenalectomy, serum ACTH level retumed to the normal range. The patient became normotensive without antihypertensive agents and hyperglycemia resolved and insulin therapy was discontinued. Secretion of ACTH was confirmed by immunohistochemical stain.

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