Primary adrenal insufficiency (Addison's disease)

Autoimmune adrenalitis (often anti-21-hydroxylase)

• Isolated adrenal insufficiency
• Polyglandular autoimmune syndrome type I (autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, APECED syndrome)
• Polyglandular autoimmune syndrome type II

Infectious adrenalitis

• Tuberculosis
• Disseminated fungal infection: esp. Histoplasmosis and Paracoccidiodomycosis
• HIV infection and AIDS: more often due to opportunistic infections
• Others: syphilis, African trypanosomiasis

Hemorrhagic infarction/thrombosis (a/w meningococcemia (Waterhouse-Friderichsen syndrome); a/w PsA(?))

Metastatic disease (esp. lung, breast, stomach, colon ca, and lymphoma; often missed!)

Drugs (usually compensated by increased ACTH secretion)

• Inhibit cortisol biosynthesis: etomidate, ketoconazole, fluconazole, metyrapone, suramin
• Accelerate the metabolism of cortisol: phenytoin, barbiturates, rifampin
• Adrenocorticolytics: mitotane

Severe inflammatory disease

Secondary adrenal insufficiency

Panhypopituitarism

• Large tumors or craniopharyngiomas
• Infectious disease, e.g. tuberculosis or histoplasmosis
• Infiltrative disease or lymphocytic hypophysitis
• Head trauma
• Large intracranial artery aneurysms
• Hypotension, e.g. Sheehan syndrome
• Hemorrhage, e.g. pituitary apoplexy

Isolated ACTH deficiency (autoimmune or genetic causes * too rare!)

Familial cortisol-binding globulin deficiency

Traumatic brain injury

Drugs

• High-dose progestins, e.g. megestrol acetate
• Opiates
• Immune check-point inhibitor

Tertiary adrenal insufficiency

Abrupt cessation of high-dose glucocorticoid therapy

Correction of hypercortisolism (Cushing's syndrome)

Others: tumors, infiltrative diseases such as sarcoidosis, cranial radiation

Clinical manifestations - dependent on:

* rate * extent of loss * mineraocorticoid function * degree of stress

Adrenal crisis 11

Caused by either mineralocorticoid / glucocorticoid deficiency

Manifestated by shock, anorexia, N/V, abdominal pain, weakness, fatigue, lethergy, fever, confusion, coma, *abdominal/flank/back/lower chest pain*

Precipitated by infection, stress, insufficient replacement, acute gland destruction

Chronic primary adrenal insufficiency

Symptoms of mineralocorticoid / glucocorticoid / (women) androgen deficiency

• Secondary/tertiary: normal minerocorticoid function

Manifestated by fatigue, weight loss, GI upset, muscle and joint pain, pubic hair loss and amenorrhea in women

• More specific: skin hyperpigmentation, postural hypotension, salt craving
• Laboratory findings: hyponatremia, hyperkalemia, anemia

• 通常Proximal DVT / PE就要用藥，病情嚴重才考慮溶栓(PE)／取栓(DVT)，IVC filter目前證據等級低
• 分為Provoked / Unprovoked，決定用3-6個月或更久
• Distal DVT和Subsegmental PE是否用藥仍待討論
• 常見用法 

               (1) DOAC

               (2) 先UFH / LMWH再DOAC

               (3) 先UFH / LMWH再Wafarin

• 用藥前考慮

               (1) 癌症

               (2) 腎功能

               (3) 懷孕

               (4) 其他凝血異常

Unfractioned heparin (UFH)

• 較易產生HIT(heparin-induced thrombocytopenia)、頻繁監控血中濃度
• 使用時機：ESRD、需要隨時停藥或逆轉(protamine)

Low molecular weight heparin (LMWH)

• Cancer-related VTE 的第一線藥物，但要打針

Warfarin (Cofarin)

• 要和UFH/LMWH重疊至少五天，抽血監測 INR 2.0~3.0
• 效果和DOAC相仿，但出血機率更高，且作用慢、需監測濃度

Direct oral anticoagulants (DOACs)

• Edoxaban (Lixiana): higher risk of bleeding (esp. gastric cancer)
• Rivaroxaban (Xarelto): monotherapy
• Apixaban (Eliquis): monotherapy
• Dabigatran (Pradaxa): no evidence in cancer patients