Cushing's Syndrome and aboout it(1).pptx

Cushing's syndrome definition, causes in males and females , normal level of hormone, clinical features , lab diagnosis, morphology

1. Cushing Syndrome

2. Cushing syndrome defination- Clinical features/abnormalities due to hypercortisolism (excessive production of glucocorticoid or cortisol) from any cause . Cushing disease- Pituitary dependent excessive ACTH secretion by pituitary corticotropin tumors.

3. Etiopathogenesis Causes: 1.Exogenous: Administration of corticosteroids(Iatrogenic). 2. Endogenous: ACTH dependent(80%): Primary hypersecretion of ACTH by pituitary diseases(Cushing disease)- ACTH secreting pituitary adenome or hyperplasia Secretion of ACTH by non pituitary neoplasms- small cell carcinoma lung, bronchial carcinoid. ACTH independent (20%) Primary adrenocortical neoplasms- adrenal adenoma and adrenal cortical carcinoma Primary cortical hyperplasia

4. ACTH secreting pituitary adenoma Male:female = 1:4 Age- young adults Causes: ACTH producing pituitary microadenoma- most common cause ACTH secreting macroadenoma Corticotroph cell hyperplasia without discrete adenoma Elevated ACTH -> nodular cortical hyperplasia -> hypercortisolism.

5. Secretion of ACTH by non pituitary tumors Males > females Age: 40 - 60 Causes: Small cell carcinoma of lung - most common cause Carcinoids Medullary carcinoma of thyroid PanNETs Neuroendocrine neoplasm - ectopic CRH -> ACTH secretion -> hypercortisolism

6. ACTH independent Cushing syndrome Increased cortiol serum levels - and low ACTH levels Causes- primary adrenal neoplasms Adrenocortical carcinoma- activating mutation of CTNNB1( beta catenin) Inactivating mutation of TP53, MEN1, PRKAR1A Bilateral marcronodular adrenal hyperplasia- ARMC5 ( tumor suppressor )

7. Clinical features of cushing syndrome

8. Lab diagnosis Urine and blood tests. These tests measure hormone levels and show if the body is making too much cortisol. For the urine test, you may be asked to collect your urine over a 24-hour period. Cortisol, ACTH and other hormones are be measured in urine and blood samples. Saliva test. Cortisol levels typically rise and fall during the day. In people without Cushing syndrome, cortisol drops in the evening. By looking at cortisol levels from a small sample of saliva collected at night, the health care team can see if cortisol levels are too high. Imaging tests. CT or MRI scans can take pictures of the pituitary and adrenal glands to see if anything shows up, such as tumors. Inferior petrosal sinus sampling. This test can help decide if Cushing syndrome is caused by an ACTH-producing pituitary adenoma, or ACTH-producing tumor in another organ. For the test, blood samples are taken from the veins that drain the pituitary gland, called the inferior petrosal sinuses.

9. CUSHING SYNDROME 11 Presentation - 12 January 2024 MORPHOLOGY The main lesions of Cushing syndrome are found in the pituitary and adrenal glands.The pituitary shows changes regardless of the cause.The most common alteration, resulting from high levels of endogenous or exogenous glucocorticoids, is termed Crooke hyaline change. In this condition, the normal granular, basophilic cytoplasm of the ACTH- producing cells in the anterior pituitary becomes homogeneous and paler.This alteration is the result of

10. 12 Presentation - 12 January 2024

11. The accumulation of intermediate keratin filaments in the cytoplasm, a finding that is also seen in “Crooke cell” corticotroph adenoma (discussed earlier). Depending on the cause of the hypercortisolism, the adrenals show one of the following abnormalities: (1) cortical atrophy, (2) diffuse hyperplasia, (3) macronodular or micronodular hyperplasia, and (4) an adenoma or carcinoma. In patients in whom the syndrome results from exogenous glucocorticoids, suppression of endogenous ACTH results in bilateral cortical atrophy, due to a lack of stimulation of the zonae fasciculata and reticularis by ACTH. The zona glomerulosa is of normal thickness in such cases, because this portion of the cortex functions independently of ACTH. In contrast, in cases of endogenous hypercortisolism, the adrenals either are hyperplastic or contain a cortical neoplasm. 13 Presentation - 12 January 2024

12. Diffuse hyperplasia is found in individuals with ACTH-dependent Cushing syndrome (Fig. 24.42). Both glands are enlarged, either subtly or markedly, weighing up to 30 g. The adrenal cortex is diffusely thickened and variably nodular, although the latter is not as pronounced as seen in cases of ACTH-independent nodular hyperplasia. Microscopically, the hyperplastic cortex demonstrates an expanded “lipid-poor” zona reticularis, comprising compact, eosinophilic cells, surrounded by an outer zone of vacuolated “lipid-rich” cells, resembling those seen in the zona fasciculata. Any nodules present are usually composed of vacuolated “lipid-rich” cells, which account for the yellow color of diffusely hyperplastic glands. In contrast, in macronodular hyperplasia the adrenals are almost entirely replaced by prominent nodules of varying sizes (10 to 30 mm), which contain an admixture of lipid-poor and lipid-rich cells. Unlike diffuse hyperplasia, the areas between the macroscopic nodules also demonstrate evidence of microscopic 14 Presentation - 12 January 2024

13. 15 Presentation - 12 January 2024

14. nodularity. Micronodular hyperplasia is composed of 1- to 3-mm (typically <10 mm) darkly pigmented (brown to black) micronodules with atrophic intervening areas (Fig. 24.43). The pigment is believed to be lipofuscin, a wear-and-tear pigment (Chapter 2). Primary adrenocortical neoplasms causing Cushing syndrome may be malignant or benign. Functional adenomas or carcinomas are not morphologically distinct from nonfunctioning adrenal neoplasms (described later). Both the benign and malignant lesions are more common in women in their 30s to 50s. Adre- nocortical adenomas are yellow tumors surrounded by thin or well-developed capsules, and most weigh less than 30 g. Microscopi- cally, they are composed of cells that are similar to those encountered in the normal zona fasciculata. The carcinomas associated with Cushing syndrome, by contrast, tend to be larger than the adenomas.These tumors (detailed later) are unencap- sulated masses frequently exceeding 200 to 300 g in weight that have all of the anaplastic characteristics of cancer.With functioning tumors, both benign and malignant, the adjacent adrenal cortex and that of the contralateral adrenal gland are atrophic, as a result of suppression of endogenous ACTH by high cortisol levels. 16 Presentation - 12 January 2024

15. Complications : Muscle weakness : hypercortisolism causes selective atrophy of fast twitch type 2 Myofibers with resultant decreased muscle mass and proximal limb weakness. Secondary diabetes : glucocorticoids induce gluconeogenesis and inhibit the uptake of glucose by cells , resulting in secondary diabetes . Cutaneous haemorrhages ( striae) : the skin become thin and fragile and is easily bruised. Leading to cutaneous haemorrhages , particularly in abdominal area. Osteoporosis: cortisol increses resumption of bone and consequent osteoporosis. Increase risk for a variety of infections glucocorticoids suppress the immune response. Patients are at increasd history risk for a variety of infections .

16. THANK YOU 18 Presentation - 12 January 2024