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J Endocrinol Metab. 2014;4(5-6):153-154 Ectopic Cushing Syndrome Due to Colon Cancer With Dual Bryndis Baldvinsdottira, Jon G. Jonassonb, c, Uggi P. Agnarssonc, d, Helga A. Sigurjonsdottirc, e, f ology ward at Landspitali University Hospital in Reykjavik, Iceland (LSH) with NSTEMI, hypertension and heart failure We report a case of colon cancer, and the most interesting presenta- following a 7-day stay at a primary hospital (HSU). She had tion was Cushing's syndrome (CS). A 72-year-old woman was diag- been admitted to HSU with increased fatigue, ankle edema nosed with CS when admitted to hospital because of NSTEMI and and resistant hypertension. There she was found to be hyper- heart failure. The patient succumbed to her illness only 4 weeks after glycemic, hypokalemic and hypertensive. Medical treatment presentation. The colon cancer was a combined adenocarcinoma and was without success. At arrival to LSH she had hypertension small cell carcinoma, solely the latter component responsible for pro- (169/66 mm Hg), hyperglycemia (serum glucose level 23.6 ducing adrenocorticotropin hormone (ACTH).
mmol/L) and profound hypokalemia (serum potassium levels 2.0 mmol/L), despite ongoing potassium-sparing anti-hyper- Keywords: Colon cancer; Cushing's syndrome; Ectopic Cushing's
tensive treatment (enalapril 10 mg daily, losartan 50 mg daily syndrome; ACTH; Small cell cancer; Adenocarcinoma; Hyperten- and spironalactone 50 mg daily).
sion; Hypokalemia She had cushingoid appearance with central obesity, moon-face and thinning of the skin, but not stria or hirsutism. The patient had been treated for hypertension for several years with no history of hypokalemia. Serum levels of potassium 2 months earlier were normal. She complained of muscle weak- Ectopic secretion of adrenocorticotropin hormone (ACTH) is ness. Serum cortisol level, measured at 16:30 pm was 2,613 a rare cause of Cushing's syndrome (CS), and when diagnosed nmol/L (reference: 170 - 700 nmol/L).
the primary tumor is most often lung cancer. Colon cancer as a Morning serum cortisol levels and plasma ACTH were cause is extremely rare in spite of being among the most com- 3,113 nmol/L (reference: 170 - 700 nmol/L) and 769 ng/L (ref- mon malignancies in the general population.
erence: 0 - 46 ng/L), respectively. After low-dose overnight, To our knowledge, there are only 10 [1-3] reported cases dexamethason suppression test (DST), with 1 mg dexametha- of ACTH-secreting colon cancer cases in the literature.
sone given orally at 23:00 pm, serum cortisol level at 8:00 am was not suppressed, 3,416 nmol/L. A 2-day low dose DST (0.5 Case Report
mg every 6 h for 48 h) was performed without suppression of morning serum levels of cortisol that were 4,675 nmol/L at the start of the test, 4,679 nmol/L after 24 h DST and 4,919 nmol/L A 72-year-old Caucasian woman was admitted to the cardi- after 48 h suppression. Plasma ACTH level was 4,658 ng/L (reference: 0 - 46 ng/L) 24 h after the 2-day DST.
Computed tomography (CT) of the abdomen showed a Manuscript accepted for publication December 15, 2014 solid tumor of uncertain etiology at the recto-sigmoid junction and widespread metastases in the liver and lymph nodes.
aDepartment of Medicine, Landspitali University Hospital, Reykjavik, Iceland A CT of the thorax showed metastases in the lungs, and Department of Pathology, Landspitali University Hospital, Reykjavik, Ice- magnetic resonance imaging (MRI) of the pituitary gland was cFaculty of Medicine, University of Iceland, Reykjavik, Iceland dDepartment of Cardiology, Landspitali University Hospital, Reykjavik, Ice- The 24 h urine sample for 5-HIAA, adrenalin, noradrena- lin, dopamin, VMA, metanephrin and normetanephrin, was eDepartment of Endocrinology, Landspitali University Hospital, Reykjavik, During the hospital stay, the patient needed high doses of Corresponding Author: Helga A. Sigurjonsdottir, Department of Endocrinol- potassium supplementation as well as anti-hypertensive and ogy and Metabolism, Landspitali University Hospital 108, Reykjavik, Iceland. Email: firstname.lastname@example.org insulin treatment. Over the course of several days the patient's state worsened. She passed away only 26 days after her first admittance to LSH and 33 days after she was first admitted Articles The authors Journal compilation J Endocrinol Metab and Elmer Press Inc™ www.jofem.org This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited Ectopic Cushing Syndrome J Endocrinol Metab. 2014;4(5-6):153-154 ing the hospital period she needed large doses of potassium supplements by infusion. The autopsy results support the clini- cal and radiologic findings. The colon cancer was of a very unusual morphologic type showing both conventional colonic adenocarcinoma, as well as but predominantly a small cell car- cinoma histology. The explosive elevation of ACTH secretion from 769 to 4,658 ng/L in 17 days, and the resistant hyperten- sion, hyperglycemia and hypokalemia give the impression that the tumor was growing at an extremely fast rate. Unfortunately the first plasma ACTH levels did not arrive until 1 week after they were taken. Retrospectively, there were some alarming clinical signs during the hospital admission, i.e., the extreme hypertension and hypokalemia. In spite of that, the extreme progress of the disease and the profound metastatic growth of the tumor indicate that earlier diagnoses during the hospital stay would not have changed the outcome. The symptoms of hypercortisolism were the clinical signs of this malignant co- Figure 1. Biopsy from primary tumor in colon. On the left is a classic
lon cancer, and possibly the myocardial infarct and heart fail- adenocarcinoma of colon (A) and on the right a small cell carcinoma ure were secondary to that. Apart from a similar case  in 2010 there has been no report on this kind of tumor in the Eng- to the primary hospital. Autopsy revealed a primary tumor in lish literature in recent years. A thorough literature search for the sigmoid colon. The tumor proved to be a combined ad- similar cases was performed and revealed only 10 previously enocarcinoma and small cell carcinoma. The adenocarcinoma reported cases of CS caused by ectopic ACTH producing colon component was a conventional colonic type adenocarcinoma. cancer. Another astonishing factor about this case is that the The small cell (neuroendocrine carcinoma) component had the primary colon cancer had dual morphology, both adenocarci- same appearance as the well known small cell anaplastic car- noma and small cell carcinoma. Neuroendocrine tumors of the cinoma of the lung. Immunohistochemical stain of the primary colon are extremely rare, estimated less than 1% of colorectal tumor showed the adenocarcinoma to be positive for CK20. cancers with bad overall outcome. They behave aggressively The small cell carcinoma was positive for neuron specific eno- as most patients have metastases at the time of diagnosis [4, 5].
lase (NSE), chromogranin, synaptophysin and ACTH (in less than 5% of the SCC tumor cells) (Fig. 1). Widespread metasta- ses were present in the body, but solely from the small cell car- cinoma component of the tumor. Lymph node metastases were 1. Sehgal R, Mchayleh W, Reider J, et al. Adenocarcinoma detected in the pericolonic, peripancreatic, para-aortical and of Colon Presenting As Cushing's syndrome. Journal of mediastinal lymph nodes. Massive metastases were also pre- Clinical Oncology. 2010;28:126-127.
sent in the liver and lungs. No abnormal growth was detected 2. Miura K, Demura H, Sato E, Sasano N, Shimizu N. A in the bone marrow and the megakaryocytes were normal. An case of ACTH-secreting cancer of the colon. J Clin Endo- immunohistochemical stain for ACTH was performed on one crinol Metab. 1970;31(5):591-595.
of the metastases, and this illustrated positive tumor cells as 3. Anthoney DA, Dunlop DJ, Connell JM, Kaye SB. Colon- well as in the primary tumor.
ic adenocarcinoma associated ectopic ACTH secretion: a case history. Eur J Cancer. 1995;31A(12):2109-2112.
4. Bernick PE, Klimstra DS, Shia J, Minsky B, Saltz L, Shi W, Thaler H, et al. Neuroendocrine carcinomas of the co- lon and rectum. Dis Colon Rectum. 2004;47(2):163-169.
We present a very unusual type of colon cancer presenting with 5. Jung SH, Kim HC, Yu CS, Chang HM, Ryu MH, Lee JL, CS. The explosive progression of the disease is alarming. The Kim JS, et al. [Clinicopathologic characteristics of colo- patient passed away only 33 days following admission to a rectal neuroendocrine tumor]. Korean J Gastroenterol. hospital. Two months earlier she was normokalemic, but dur- Articles The authors Journal compilation J Endocrinol Metab and Elmer Press Inc™ www.jofem.org
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