Cushing's Disease / Syndrome - A Knol by Robin S

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Robin S wrote this as a knol. It's a great resource explaining Cushing's Disease and Syndrome.
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  2/26/12Cushing's Disease/Syndrome ‑ a knol by Robin S1/‑s‑disease‑syndrome# Cushing's Disease/Syndrome and related endocrine disorders Cushing's Disease/Syndrome is caused by an overproduction of the hormonecortisol. There are several reasons why that happens. Other endocrine disordersmay be caused by or related to the cause for Cushing's.Contents What is Cushing's Disease/Syndrome?What is cyclic/episodic/intermittent Cushing's?How does diurnal variation/circadian rhythm vary in Cushing's?Testing 101: IntroductionTesting 101: ImagingTesting 101: Biochemical AnalysisTesting 101: IPSS (aka BIPSS)Testing 101: Growth Hormone DeficiencyWhat types of tumors are associated with Cushing's?more What is Cushing's Disease/Syndrome? There are two terms used with Cushing's: Disease and Syndrome. They signify thesource of the illness, although the presentation is pretty much the same with both.Cushing's Disease is hypercortisolism due to a pituitary source of stimulation. Cushing'sSyndrome is hypercortisolism due to an ectopic or adrenal source. There really is a thirdtype of Cushing's called iatrogenic Cushing's which results from the overuse of corticosteriod medications. And actually another type called pseudo-Cushing's.Cushing's Disease/Syndrome (CD/CS) is an endocrine disorder caused by chronicexposure of the body's tissues to excess levels of cortisol - a hormone naturally producedby the adrenal gland. Pituitary adenomas, usually benign, secrete increased amounts of ACTH (adrenocorticotropic hormone), a substance that controls the release of cortisol inthat feedback loop I mentioned the other day. It typically causes an overproduction of cortisol. Tumors of the adrenal gland and ectopic ACTH producing tumors can cause similar problems withcortisol overproduction.What are the symptoms? The most common symptoms are:StriaeBuffalo humpHigh blood pressure (often hard to control even with medication)  2/26/12Cushing's Disease/Syndrome ‑ a knol by Robin S2/‑s‑disease‑syndrome# High blood sugars and/or insulin resistanceInsomniaFatigueAltered diurnal rhythm (See following post)Secondary hypothyroidismLow hormones such as FH, LSH, testosterone, growth hormoneLow Vitamin DLow ferritinUnexplained muscle, bone, and joint painEasy bruisingDifficulty when drawing bloodUpper body obesityMuscle weaknessIncreased facial hair/body hair (hirsutism)Loss of hair on headLoss of menstrual cycle and/or ovulationLoss of libidogalactorrheaNot everyone has all the symptoms. And the weight gain can vary by individual. Some folks don't gain alot. Others do. Without prompt treatment for Cushing's syndrome, other complications may occur, such as:Bone loss (osteoporosis), due to the damaging effects of excess cortisolHigh blood pressure (hypertension)Kidney stones  2/26/12Cushing's Disease/Syndrome ‑ a knol by Robin S3/‑s‑disease‑syndrome# DiabetesUnusual infectionsHypothyroidismWhen the cause of Cushing's syndrome is a pituitary tumor (Cushing's disease), it can sometimes lead toother problems, such as interfering with the production of other hormones that the pituitary controls. It canalso affect the optic nerves and carotid arteries if large. The majority of pituitary tumors that cause Cushing'sdisease are small (less than one cm in size).Long-Term Remission Rates After Pituitary Surgery for Cushing's Disease: the Need for Long-TermSurveillancesays:  Morbidity and mortality are higher in patients with Cushing's disease, with vascular disease a frequent cause of death.[2,32,33] Cardiovascular complications, including coronary heart disease, congestive heart disease and cerebrovascular events, contribute to the morbidity and mortality of patients with undiagnosed or untreated Cushing's disease.[34,35] Early diagnosis and successful treatment of Cushing's disease istherefore most important. What is cyclic/episodic/intermittent Cushing's? Episodic/intermittent/cylic Cushing's has more aliases than a CIA operative. And I'm sure there are someI've left out. Episodic Cushing’s syndrome (CS) is a rare disorder, characterized by repeated episodes of cortisol excess interspersed by periods of normal cortisol secretion. The so-called cycles of hypercortisolismcan occur regularly or irregularly with the phases ranging from days to years.In comparison, florid or classical Cushing's shows evidence of continual or almost continualhypercortisolism. There is a school of thought which says these are really very rapidly cycling forms of Cushing's. However, there does not seem to be a consensus on that in the literature and in the research.Frankly, I don't know if anyone has done enough testing daily to figure it out.According to someresearch done in the Netherlands, As with classic hypercortisolism, cyclic CS is foundmore commonly among women than men, with a female to male ratio of 3:1 (Table 2). The disorder usuallybecomes manifest in the fifth decade, but may present from early infancy until older age (highest reportedage at presentation being 72 years). Other clinical studies say, The features of endogenous hypercortisolism (especially, when mild) are proteanand coincide with many common clinical conditions like the dysmetabolic syndrome (1, 2). Screeningstudies in high-risk populations have discovered unsuspected CS in as many as 2–5% of patients withdiabetes mellitus (3–7) and suggest that mild CS is more common than previously appreciated. InCyclical Cushing's syndrome: an updatethe full text article says, Cyclical Cushing's syndrome is apattern of hypercortisolism in which the biochemistry of cortisol production fluctuates rhythmically. Thissyndrome is often associated with fluctuating symptoms and signs. This type of case was initially thought tobe rare. It has, however, recently been recognized as occurring much more frequently. The phenomenon isimportant because it can, if not recognized, lead to errors in diagnosis and differential diagnosis of thesyndrome and in assessment of therapeutic outcomes. All of these can have very serious clinicalconsequences.   2/26/12Cushing's Disease/Syndrome ‑ a knol by Robin S4/‑s‑disease‑syndrome# How does diurnal variation/circadian rhythm vary inCushing's? We hear a lot about cortisol and how lowering it by lowering stress can affect our weight. I'm sureyou've seen the ads for the cortisol-slimming drugs/herbs, too. And we are talking about thesame hormone. What is cortisol, anyway?Cortisol is a corticosteroid hormone produced by the adrenal cortex, the outer layer of theadrenal glands which are essentially lying on top of the kidneys. Without it we die. It is thehormone that responds to stress , both good and bad. It affects levels of multiple other hormones and electrolytes, which is another topic for another day. However, the short of it is, it isvery important in thehomeostasisof the body.When the body is functioning normally, cortisol is regulated by the pituitary in a negativefeedback loop with ACTH (adrenocorticotropic hormone). Basically, the pituitary produces ACTH when the body's cortisol level is low, which stimulates the adrenals to produce cortisol. ACTH is pulsatile, which means it is produced in spurts instead of evenly or consistently.In a normal person, cortisol is the highest around 8 a.m. and decreases to about half that valuearound 4 p.m. By midnight (give or take an hour each way), cortisol should be about zero or close to it with blood and salivary levels. This is a normal diurnal variation. It is also called thecircadian rhythm.When one has Cushing's, this circadian rhythm is lost, and the normal diurnal variation changes.Cushing's patients have flat diurnal levels of cortisol, or even higher levels at night instead of inthe morning.Endotext.comexplains it really well. Their diagram shows thedifference between normal serum cortisol levels and the levels for those who have Cushing's. (Click on the link to see the picturebetter.)Where does that take us? Well, to testing. Because of this changefrom normal to warped diurnal rhythm (or lack of), testing cortisollevels can be very useful when diagnosing Cushing'sSyndrome/Disease.The article, Cushing's Syndrome by John Newell-Price, Xavier Bertagna, Ashley B Grossman,Lynnette K Nieman, Lancet 2006; 367: 1605–17,Division of Clinical Sciences, University of Sheffi eld, Northern General Hospital, Sheffi eld, UK (J Newell-Price FRCP); says: Midnight plasma cortisol or late-night salivary cortisol: Normal circadian rhythm of cortisol secretion is lost in patients with Cushing’s syndrome. A single sleeping midnight plasma cortisol concentration of less than 50 nmol/L effectively excludes Cushing’s syndrome at the time of thetest and this might be especially helpful in patients in whom there has been incompletesuppression on dexamethasone testing. Concentrations of more than 50 nmol/L are noted inindividuals with Cushing’s syndrome, even those who suppress serum cortisol on low-dosedexamethasone testing,96 but this cutoff lacks specificity because patients with acute illnessalso have values above this concentration. An awake midnight concentration of cortisol in
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