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:
a. 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.
a. 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:
1. ACTH producing pituitary microadenoma- most common cause
2. ACTH secreting macroadenoma
3. 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:
1. Small cell carcinoma of lung - most common cause
2. Carcinoids
3. Medullary carcinoma of thyroid
4. PanNETs
5. Neuroendocrine neoplasm - ectopic CRH -> ACTH secretion ->
hypercortisolism
10. 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.
11. CUSHING SYNDROME
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
12.
13. 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.
14. 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
15.
16. 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.
17. 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 .
