Understanding adrenal disorders, whether endogenous or related to glucocorticoid use is important to the day-to-day care of patients with rheumatologic disease. This article addresses diagnosis and treatment of these disorders, with particular attention paid to Cushing syndrome.
Knowledge of both adrenal insufficiency and Cushing syndrome are important in the care of patients with rheumatologic disease due to clinical similarities in relation to glucocorticoid in rheumatologic diseases. Difficulties in differentiating between adrenal insufficiency and active or worsening disease often arise when glucocorticoids are tapered in patients with conditions such as vasculitis and polymyositis. In addition there are striking similarities with adrenal insufficiency and diseases such as fibromyalgia syndrome and polymyalgia rheumatica. Similarly, the proximal muscle symptoms of Cushing syndrome can be mistaken for several other disorders such as polymyositis. Osteoporosis is a major concern in patients with endogenous and glucocorticoid-induced Cushing syndrome.
Adrenal insufficiency is classified into three subtypes based on where the abnormality is based in the hypothalamic pituitary adrenal (HPA) axis. Primary insufficiency is caused by adrenal gland damage. The secondary form is related to insufficient corticotrophin (ACTH) from the pituitary gland. The tertiary form is related to insufficient corticotrophin-releasing hormone (CRH) from the hypothalamus.
Acute adrenal insufficiency, or adrenal crisis, is severe and characterized by shock. This is often related to mineralocorticoid deficiency, but not always in severe cases related to exogenous glucocorticoid withdrawal. Chronic primary adrenal insufficiency is related to deficiency of glucocorticoid, mineralocorticoid, and even androgen deficiency in women.
Causes and Associations with Rheumatologic Disease
Primary adrenal insufficiency, or Addison disease, initially was most commonly related to tuberculosis, but now is typically caused by autoimmune adrenalitis in the Western world (69% to 91.2%). Additionally, in one retrospective study, a concomitant autoimmune disorder was seen in nearly 50% of patients with autoimmune adrenalitis, including most commonly autoimmune thyroid disease and vitiligo, but less commonly Sjogren syndrome. Although concomitant connective tissue disease is only occasionally reported in literature (in addition to Sjogren syndrome), there are also reports of systemic lupus erythematosis, rheumatoid arthritis, systemic sclerosis, Takayasu arteritis, and ankylosing spondylitis. More frequently thrombosis of the adrenal gland, caused by antiphospholipid antibody syndrome, is seen. Polyglandular autoimmune syndrome type II (APSII) has some reported association with rheumatoid arthritis and Sjogren syndrome. The reported association with rheumatologic disease is infrequent and may be coincidence; association with polyglandular autoimmune syndrome type I is not reported. This may be because of differences in HLA type.
Secondary adrenal insufficiency can be related to the destruction of the pituitary gland or deficiency of ACTH. Classically, this is associated with hemorrhage of the pituitary gland, or thrombosis such as seen when sarcoidosis affects the pituitary gland. There have been a few reports of opiate induced secondary adrenal insufficiency. Glucocorticoid use can cause secondary or tertiary adrenal insufficiency.
Tertiary adrenal insufficiency is most commonly related to withdrawal of glucocorticoids. Glucocorticoid-induced adrenal insufficiency can be caused by several mechanisms, including decreased hypothalamic synthesis of CRH, blockade of the actions of CRH on the anterior pituitary, and, after prolonged or profound deficiency of ACTH, adrenal atrophy.
Adrenal crisis can occur in patients with all forms of adrenal insufficiency, but more often is associated with primary adrenal insufficiency. The trigger can be infection or other major stress with no or insufficient glucocorticoid intake. Certainly, bilateral adrenal hemorrhage or infarction and pituitary infarction can cause this also. Abrupt discontinuation of corticosteroids and inadequate supplementation in stress are other causes of adrenal crisis.
Signs and Symptoms
The symptoms of adrenal crisis are more severe than chronic adrenal insufficiency. The distinguishing feature of adrenal crisis is shock, and other signs and symptoms depend on whether the patient has underlying primary or secondary adrenal insufficiency. Table 1 displays the signs and symptoms of adrenal insufficiency.
|Gastrointestinal symptoms a||xx||x||x|
|Flexion contracture||x c||xx c|