Adrenal Pathophysiology: Gupta Flashcards
Epidemiology, pathophysiology, pathology and clinical features of adrenal hyperfunction including Cushing syndrome, adrenogenital syndrome, and Conn syndrome. And a pathophysiologic mechanism or implication for treatment or prognosis, given an image and/or clinical scenario.
Cushing syndrome:
::ACTH dependent
–Cushing Dz [pit. adenoma] 70%. Young adult women. Functional adenoma.
–ectopic corticotropic syndrome. Non-pit. tumors, SSC of lung.
Histology: bilateral diffuse or nodular hyperplasia of adrenal gland. Expanded zona reticularis.
Cushing syndrome most often due to exogenous glucocorticoids. Results in bilateral adrenal atrophy (adrenals take vacation bc someone else is doing the work).
::ACTH independent
–adrenal adenoma 10%
–adrenal carcinoma 5%
Cortisol is HIGH. ACTH is low.
Adrenogenital syndrome:
Cause congenital adrenal hyperplasia (CAH)
Most common cause: 21-hydroxylase deficiency (can’t make cortisol or aldosterone, make too much testosterone bc no ACTH feedback on Pit/Hypoth)
2nd most common: 11B-hydroxylase
Gross: HUGE adrenal glands!
Histology: diffuse cortical hyperplasia, particularly involving the zona reticularis (where androgens are made), and cortical cells are lipid depleted.
May also have corticotrophic hyperplasia in ant. pit. as well.
Conn syndrome: Primary hyperaldosteronism caused by adrenocortical adenoma. Renin-angiotensin system suppressed. Elevated BP. Hypokalemia. Seen in younger people. A characteristic feature of aldosterone-producing adenomas is the presence of eosinophilic, laminated cytoplasmic inclusions, known asspironolactone bodies (white halo inclusion within cell).
Tx for aldosterone producing adenomas: Spirinolactone.
Epidemiology, pathophysiology, pathology and clinical features of adrenal insufficiency including Waterhouse-Friderichsen syndrome and Addison disease. And a pathophysiologic mechanism or implication for treatment or prognosis, given an image and/or clinical scenario.
Acute causes of adrenal insufficiency:
::Adrenal crisis- rapid withdrawal of steroids of failure of body to increase endogenous steroids with stressor present.
::Acute hemorrhagic necrosis
::Waterhouse-Friderichsen syndrome:
Overwhelming sepsis, typically due to Neisseria meningitidis, leading to shock, hemorrhagic obliteration of adrenals, extreme acute adrenal insufficiency and disseminated intravascular coagulation.
Other causal bacteria include Staphylococcus aureus and Streptococcus pneumoniae.
Gross: “bag of blood” appearance of the hemorrhagic adrenals and extreme purpura/eccymoses on skin due to DIC.
Micro: so much hemorrhage, you can’t tell what you’re looking at anymore
Chronic causes of adrenal insufficiency:
90% are caused by autoimmune disease, AIDS, infections or cancer.
About 90% of tissue has to be destroyed for clinical manifestations.
Patients present with fatigue, weakness and GI disturbances.
Primary adrenocortical insufficiency also has high ACTH levels and skin pigmentation.
::Addison disease
Lots of causes:
Autoimmune adrenalitis (most common cause of 1’ adrenal insuff. in western world). Auto-Abs to APS1 and APS2.
Infection (TB, fungal). Look for granuloma.
Amyloid, sarcoid
Metastatic carcinoma (multiple adrenal nodules? –> met. carcinoma from lung, breast, kidney)
Gross: adrenal atrophy
Labs: Lack of cortisol –> HYPOglycemia/natremia, HYPERkalemia. Na+ wasting, K+ hoarding. Lack of insulin suppression and glycogenolytic/gluconeogenic stimulation.
Secondary causes of adrenal insufficiency:
-Decreased stimulation of the adrenals due to deficiency of ACTH
-Pituitary neoplasm, inflammation
-Long-term steroids
Findings: No hyperpigmentation b/c pit. not working either.
Prompt rise in cortisol levels with ACTH administration.
Epidemiology, pathophysiology, pathology and clinical features of adrenal and related neoplasms. And a pathophysiologic mechanism or implication for treatment or prognosis, or differentiate a malignant one from a benign one, given an image and/or clinical scenario.
Primary adrenocortical neoplasms:
More likely malignant in children (Li-Fraumeni [P53] and Beckwith-Wiedemann). Not morphologically distinct from non-functioning adrenal neoplasms. Carcinomas more likely to be functional.
Adrenocortical adenomas: solitary, circumscribed nature
Discuss ACTH-independent hyperplasia or primary cortical hyperplasia.
Very uncommon.
::Macronodular >3mmtypically sporadic but associated with McCune-Albright (GNAS mutations). Cortisol is regulated by non-ACTH hormones. Microscopic nodularity also seen.
::Micronodular
