• Infections, particularly tuberculosis and those produced by fungi, also may cause primary chronic adrenocortical insufficiency. Tuberculous adrenalitis, which once accounted for as many as 90% of cases of Addison disease, has become less common with improved anti-tuberculosis therapy. With the resurgence of tuberculosis mainly because of HIV infection and immunodeficiency, this cause of adrenal deficiency must be borne in mind. When present, tuberculous adrenalitis usually is associated with active infection in other sites, particularly the lungs and genitourinary tract. Among fungi, disseminated infections caused by Histoplasma capsulatum and Coccidioides immitis also may result in chronic adrenocortical insufficiency. Patients with AIDS are at risk for the development of adrenal insufficiency from several other infectious (cytomegalovirus, Mycobacterium avium-intracellulare) and noninfectious (Kaposi sarcoma) complications of their disease.
• Metastatic neoplasms involving the adrenals are another potential cause of adrenal insufficiency. The adrenals are a fairly common site for metastases in patients with disseminated carcinomas, which sometimes destroy sufficient adrenal cortex to produce a degree of adrenal insufficiency. Carcinomas of the lung and breast are the source of a majority of metastases in the adrenals.
Any disorder of the hypothalamus and pituitary that reduces the output of ACTH, such as metastatic cancer, infection, infarction, or irradiation, leads to a syndrome of hypoadrenalism having many similarities to Addison disease. ACTH deficiency may occur alone, but in some instances, it is only one part of panhypopituitarism, associated with multiple pituitary hormone deficiencies. In patients with primary disease, the destruction of the adrenal cortex prevents a response to exogenously administered ACTH in the form of increased plasma levels of cortisol. By contrast, secondary adrenocortical insufficiency is characterized by low serum ACTH and a prompt rise in plasma cortisol levels in response to ACTH administration.
MORPHOLOGYTheappearanceoftheadrenalglandsvarieswiththecauseoftheadrenocorticalinsufficiency.Insecondaryhypoadrenalism,theadrenalsarereducedtosmall,flattenedstructuresthatusuallyretaintheiryellowcolorbecauseofasmallamountofresiduallipid.Auniform,thinrimofatrophicyellowcortexsurroundsacentral,intactmedulla.Histologicevaluationrevealsatrophyofcorticalcellswithlossofcytoplasmiclipid,particularlyinthezonafasciculataandzonareticularis.Primaryautoimmuneadrenalitisischaracterizedbyirregularlyshrunkenglands,whichmaybeexceedinglydifficulttoidentifywithinthesuprarenaladiposetissue.Onhistologicexamination,thecortexcontainsonlyscatteredresidualcorticalcellsinacollapsednetworkofconnectivetissue.Avariablelymphoidinfiltrateispresentinthecortexandmayextendintothesubjacentmedulla(
Fig.20.41 ).Themedullaisotherwisepreserved.Intuberculosisorfungaldiseases,theadrenalarchitecturemaybeeffacedbyagranulomatousinflammatoryreactionidenticaltothatencounteredinothersitesofinfection.Whenhypoadrenalismiscausedbymetastaticcarcinoma,theadrenalsareenlarged,andtheirnormalarchitectureisobscuredbytheinfiltratingneoplasm.