Saturday, April 27, 2013

My Very Own "CSI: Cyclical Cushing's"



HAS AN ENDOCRINOLOGIST EVER TOLD YOU THAT CYCLICAL CUSHING'S WAS NEW OR RARE?

For the past six years or 2,190 days, my battle with Cushing's has been a lopsided fight. As a new patient, I went in totally unarmed, with only my patient history, medical knowledge, lab protocals, medical literature, etc. We all know, facts, stories, labs, and witnesses weren't enough to corroborate this bizarre tale of strange physical deformities and an emotional roller coaster ride.  We were completely unarmed against the MDs who stood before us.  

I have spent my time in the chat room trenches with our Cushie platoon, breaking down all the information, developing hypotheses, discussing theories, and offering help. It's very difficult to move beyond that when we, the patients, have critical information about our peers yet it goes unpublished by our doctor friends in the endocrinology.

For example, many endocrinologists I know tell me that cyclical Cushing's is very rare, fairly new, and poorly defined. Cyclical Cushing's is not well understood in the medical literature. Although I respond with a "Well, we have a lot of friends on the message boards with Cyclical Cushing's, so that doesn't do much good for me," it is undoubtedly a conversation killer. My having no come back to that questionable remark about the RARITY of Cyclical Cushing's has always bothered me to the core.

Well, I've complained about that before, but TODAY what is chapping my hide is this article I found after a simple Google search for the keywords Cyclical Cushing's.

First, you will read in the abstract that more than five cases were cyclical. By the end, there are more.


Second, I was really beside myself in a FIT when I reviewed the dates for these articles in the Selected References.  I will highlight some below. You will see some medical journal articles cited from 1956 and later.  Cyclical Cushing's has been studied and written on 50 years before I sought diagnosis and treatment in 2007. Why did these endocrinologist bozos act like they didn't know anything about cyclical Cushing's? What are these teachers teaching these endocrinologists in medical school? Why did they all treat me like there was just NO POSSIBLE WAY I had cyclical Cushing's and thereby must just be depressed, fat, extra body-haired, bruised, forgetful but rageful person. I am so furious that I always pressed for more information about cyclical Cushing's, and few had a comprehensivie answer explaining what we DO know about the matter.

Please take the time to read this article below, as my flabbergasted mind and I sit here wondering how these countless endiots could not remember even ONE of the 13 articles referenced in the article alone that studies fluctuating or cyclical cortisol when I questioned them about cyclical cushing's.


Another choice bit: the referenced articles below were published in 1956, 1958, 1961, 1973, 1975, 1976 (2), 1979 (3), 1980, 1982, and 1985. Any one of these show researchers had already discovered the distinct subset of cyclical Cushing's patients and tried to determine the best way to diagnose and treat patients.  From what I have seen 30 to 55 years later to the present, it seems that garden-variety endocrinologists and even well renowned pituitary centers have been riding on the diabetes bus (obesity! heart attacks! exercise! insulin!) all the while totally neglecting data that others clearly have shown us so long before. 


Does anyone coming out of medical school know how to research and prepare a proper literature review? Do they just ignore the clankiness of old articles and focus on single-hospital data studies?  I am mean, come on, people!  Do I have to do everything?  


When I cool down, I'll begin to read the articles post below (with links). I am truly interested to figure out who knew what and when.  This is my own CSI: Cyclical Cushing's.   

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PMCID: PMC1418075


Five cases of cyclical Cushing's syndrome.

A B Atkinson, A L Kennedy, D J Carson, D R Hadden, J A Weaver, and B Sheridan


British Medical Journal (Clinical Research Ed) . 1985 November 23; 291(6507): 1453–1457.

Abstract

Reported cases of cyclical Cushing's syndrome are rare. Of 14 successive patients with Cushing's syndrome nine collected sequential urine samples for the estimation of cortisol:creatinine ratio. Five had cyclical Cushing's syndrome while two had considerable variation in urinary cortisol excretion without a cyclical pattern being established. Two of the five patients with a cyclical syndrome had paradoxical responses to dexamethasone. In only one patient with a cyclical pattern did the cortisol:creatinine ratio fall after treatment with bromocriptine or cyproheptadine, or both. The high incidence of the cyclical form of Cushing's syndrome has important clinical implications. A high index of suspicion of the syndrome is required in patients with symptoms or signs of Cushing's syndrome but with normal cortisol values, in patients with fluctuating cortisol values, and in patients with anomalous responses to dexamethasone. Because of possible variations in steroidogenesis the results of drug studies in Cushing's syndrome must be interpreted cautiously.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article(989K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References
These references are in PubMed. This may not be the complete list of references from this article.
  • Bailey RE. Periodic hormonogenesis--a new phenomenon. Periodicity in function of a hormone-producing tumor in man. J Clin Endocrinol Metab. 1971 Mar;32(3):317–327.[PubMed]
  • Brown RD, Van Loon GR, Orth DN, Liddle GW. Cushing's disease with periodic hormonogenesis: one explanation for paradoxical response to dexamethasone. J Clin Endocrinol Metab. 1973 Mar;36(3):445–451. [PubMed]
  • BIRKE G, DICZFALUSY E. Fluctuation in the excretion of adrenocortical steroids in a case of Cushing's syndromeJ Clin Endocrinol Metab. 1956 Feb;16(2):286–290. [PubMed]
  • Chajek T, Romanoff H. Cushing syndrome with cyclical edema and periodic secretion of corticosteroids. Arch Intern Med. 1976 Apr;136(4):441–443. [PubMed]
  • Liberman B, Wajchenberg BL, Tambascia MA, Mesquita CH. Periodic remission in Cushing's disease with paradoxical dexamethasone response: an expression of periodic hormonogenesis.J Clin Endocrinol Metab. 1976 Oct;43(4):913–918. [PubMed]
  • Oates TW, McCourt JP, Friedman WA, Agee OF, Rhoton AL, Thomas WC., Jr Cushing's disease with cyclic hormonogenesis and diabetes insipidus. Neurosurgery. 1979 Nov;5(5):598–603. [PubMed]
  • Cook DM, Kendall JW, Jordan R. Cushing syndrome: current concepts of diagnosis and therapy. West J Med. 1980 Feb;132(2):111–122. [PMC free article] [PubMed]
  • Schteingart DE, McKenzie AK. Twelve-hour cycles of adrenocorticotropin and cortisol secretion in Cushing's diseaseJ Clin Endocrinol Metab. 1980 Nov;51(5):1195–1198.[PubMed]
  • Jordan RM, Ramos-Gabatin A, Kendall JW, Gaudette D, Walls RC. Dynamics of adrenocorticotropin (ACTH) secretion in cyclic Cushing's syndrome: evidence for more than one abnormal ACTH biorhythm. J Clin Endocrinol Metab. 1982 Sep;55(3):531–537. [PubMed]
  • Crapo L. Cushing's syndrome: a review of diagnostic tests. Metabolism. 1979 Sep;28(9):955–977. [PubMed]
  • Riad-Fahmy D, Read GF, Gaskell SJ, Dyas J, Hindawi R. A simple, direct radioimmunoassay for plasma cortisol, featuring a 125I radioligand and a solid-phase separation technique. Clin Chem. 1979 May;25(5):665–668. [PubMed]
  • Cook JG. Factors influencing the assay of creatinine. Ann Clin Biochem. 1975 Nov;12(6):219–232. [PubMed]
  • Atkinson AB, Chestnutt A, Crothers E, Woods R, Weaver JA, Kennedy L, Sheridan B. Cyclical Cushing's disease: two distinct rhythms in a patient with a basophil adenoma. J Clin Endocrinol Metab. 1985 Feb;60(2):328–332. [PubMed]
  • Scott RS, Espiner EA, Donald RA. Intermittent Cushing's disease with spontaneous remission.Clin Endocrinol (Oxf) 1979 Nov;11(5):561–566. [PubMed]
  • PASQUALINI RQ, GUREVICH N. Spontaneous remission in a case of Cushing's syndrome. J Clin Endocrinol Metab. 1956 Mar;16(3):406–411. [PubMed]
  • BASSOE HH, EMBERLAND R, STOA KF. Fluctuating steroid excretion in Cushing's syndromeActa Endocrinol (Copenh) 1958 Jun;28(2):163–168. [PubMed]
  • Aber CP, Cheetham HD. Cyclical Cushing's SyndromeBr Med J. 1961 Feb 4;1(5222):336–338.[PMC free article] [PubMed]
  • Blau N, Miller WE, Miller ER, Jr, Cervi-Skinner SJ. Spontaneous remission of Cushing's syndrome in a patient with an adrenal adenoma. J Clin Endocrinol Metab. 1975 Apr;40(4):659–663. [PubMed]
  • Green JR, van't Hoff W. Cushing's syndrome with fluctuation due to adrenal adenoma. J Clin Endocrinol Metab. 1975 Aug;41(2):235–240. [PubMed]
  • Bochner F, Burke CJ, Lloyd HM, Nurnberg BI. Intermittent Cushing's diseaseAm J Med.1979 Sep;67(3):507–510. [PubMed]
  • Halberg F, Engeli M, Hamburger C. The 17-ketosteroid excretion of a healthy man on weekdays and weekends. Exp Med Surg. 1965;23(1):61–69. [PubMed]
  • Costello RT. Subclinical Adenoma of the Pituitary Gland. Am J Pathol. 1936 Mar;12(2):205–216.1. [PMC free article] [PubMed]
  • Burrow GN, Wortzman G, Rewcastle NB, Holgate RC, Kovacs K. Microadenomas of the pituitary and abnormal sellar tomograms in an unselected autopsy series. N Engl J Med. 1981 Jan 15;304(3):156–158. [PubMed]
  • Spark RF, Dickstein G. Bromocriptine and endocrine disorders. Ann Intern Med. 1979 Jun;90(6):949–956. [PubMed]
  • Lamberts SW, Klijn JG, de Quijada M, Timmermans HA, Uitterlinden P, de Jong FH, Birkenhäger JC. The mechanism of the suppressive action of bromocriptine on adrenocorticotropin secretion in patients with Cushing's disease and Nelson's syndrome. J Clin Endocrinol Metab. 1980 Aug;51(2):307–311. [PubMed]
  • Kennedy AL, Sheridan B, Montgomery DA. ACTH and cortisol response to bromocriptine, and results of long-term therapy, in Cushing's disease. Acta Endocrinol (Copenh) 1978 Nov;89(3):461–468. [PubMed]
  • Krieger DT, Amorosa L, Linick F. Cyproheptadine-induced remission of Cushing's disease. N Engl J Med. 1975 Oct 30;293(18):893–896. [PubMed]
  • Grant DB, Atherden SM. Cushing's disease presenting with growth failure: clinical remission during cyproheptadine therapy. Arch Dis Child. 1979 Jun;54(6):466–468. [PMC free article][PubMed]
  • Hsu TH, Gann DS, Tsan KW, Russell RP. Cyproheptadine in the control of Cushing's disease.Johns Hopkins Med J. 1981 Aug;149(2):77–83. [PubMed]