Adrenal hypofunction Notes

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Primary adrenal insufficiency

Waterhouse-Friderichsen syndrome

NOTES NOTES ADRENAL HYPOFUNCTION GENERALLY, WHAT IS IT? PATHOLOGY & CAUSES ▪ Disorders of adrenal cortex resulting in loss of essential steroid hormones (corticosteroids, mineralocorticoids, androgens) CAUSES ▪ Addison’s disease ▫ Multiple causes; primarily autoimmune ▪ Waterhouse–Friderichsen syndrome (WFS) ▫ Primarily caused by meningococcal infection, sepsis COMPLICATIONS ▪ Adrenal crisis ▫ Addison’s, WFS ▪ Disseminated intravascular coagulation ▫ WFS SIGNS & SYMPTOMS ▪ Hypoglycemia, hypotension, electrolyte imbalance ▪ Adrenal crisis: dehydration, electrolyte imbalance, shock 76 OSMOSIS.ORG DIAGNOSIS DIAGNOSTIC IMAGING Ultrasound, CT scan ▪ Visualizes enlarged, calcified, solid/ hemorrhagic glands OTHER DIAGNOSTICS ▪ Rapid adrenocorticotropic hormone (ACTH) test confirms adrenal hypofunction TREATMENT MEDICATIONS ▪ Hormone replacement: hydrocortisone, fludrocortisone ▫ Dehydroepiandrosterone (DHEA) in some cases OTHER INTERVENTIONS ▪ Treat underlying cause
Chapter 13 Adrenal Hypofunction ADDISON'S DISEASE osms.it/addisons-disease PATHOLOGY & CAUSES ▪ Endocrine disorder characterized by primary adrenal insufficiency due to bilateral adrenal cortex destruction ▪ Adrenal cortex destruction → ↓ production of adrenocortical hormones → glucocorticoid, mineralocorticoid, androgen deficiency ▫ Adrenals only source of androgens in biologically-female individuals; testicles supply androgens in biologically-male individuals ▪ ↓ cortisol → ↓ adrenal medullary epinephrine synthesis → ↓ serum epinephrine, compensatory norepinephrine production CAUSES ▪ Autoimmune destruction (e.g. polyglandular autoimmune syndrome type 2) ▪ Infection (e.g. tuberculosis, fungal infections) ▪ Adrenal hemorrhage (e.g. WFS) ▪ Adrenal vein thrombotic infarction ▪ Metastatic infiltration ▪ Drugs that inhibit cortisol biosynthesis (e.g. ketoconazole, suramin) norepinephrine ▪ Hyponatremia ▫ Mineralocorticoid deficiency → sodium loss + ↓ volume due to ↑ vasopressin secretion secondary to ↓ cortisol ▪ Hyperkalemia, mild hyperchloremic acidosis due to mineralocorticoid deficiency ▪ Hypoglycemia due to ↓ gluconeogenesis ▪ Gastrointestinal ▫ Abdominal pain, anorexia, nausea, vomiting → weight loss ▪ Intolerance of temperature extremes ▪ Hyperpigmentation due to ACTH stimulation of melanocyte activity ▪ Vitiligo due to autoimmune destruction of melanocytes ▪ Salt cravings due to hyponatremia ▪ ↓ libido, ↓ pubic, axillary hair in biologicallyfemale individuals due to ↓ adrenal androgens ▪ Psychiatric symptoms (e.g. confusion, depression) ▪ Addisonian crisis triggered by stress ▫ Hypoglycemia ▫ Vasomotor/circulatory collapse; shock may be unresponsive to vasopressors due to ↓↓ cortisol, potentially fatal COMPLICATIONS ▪ Addisonian crisis precipitated by physiologically stressful events (e.g. surgical procedures, trauma, infection, dehydration) SIGNS & SYMPTOMS ▪ Fatigue, weakness are common initial symptoms ▪ Hypotension, postural hypotension, syncope ▫ ↓ glucocorticoids → ↓ vascular responsiveness to angiotensin II and Figure 13.1 An example of increased skin pigmentation in an individual with Addison’s disease (left) and resolution post-treatment (right). OSMOSIS.ORG 77
▪ ↑ serum ACTH ▪ Plasma renin activity ▫ ↑ renin, compensatory to ↓ aldosterone ▪ ↓ serum sodium, ↑ serum potassium, mild hyperchloremic acidosis OTHER DIAGNOSTICS Figure 13.2 Hyperpigmentation of the gums in an individual with Addison’s disease. DIAGNOSIS DIAGNOSTIC IMAGING Abdominal CT scan ▪ Enlarged adrenal glands with tuberculosis/ malignant mass; small if autoimmune adrenalitis/advanced tuberculosis; calcifications if infectious cause ▪ Visualizes adrenal gland hemorrhage/ thrombosis Abdominal X-ray ▪ Adrenal calcifications if infectious cause LAB RESULTS ▪ ↓ serum cortisol ▫ Blood draw in AM when cortisol levels should peak ▪ History, physical examination with characteristic findings ▪ Rapid ACTH test ▫ Administer 250µg synthetic ACTH (cosyntropin) intravenous (IV)/ intramuscular (IM) → insufficient/no cortisol produced in response TREATMENT MEDICATIONS ▪ Life-long glucocorticoid replacement; e.g. hydrocortisone, mineralocorticoid replacement ▫ E.g. fludrocortisone ▪ Biologically-female individuals may need low dose dehydroepiandrosterone (DHEA) ▪ Addisonian crisis ▫ Glucocorticoids, epinephrine, glucose, isotonic fluids ▪ Stress dose of glucocorticoid during any surgical intervention/significant trauma ▫ Premedication/induction-maintenancegradual titration to baseline dose WATERHOUSE–FRIDERICHSEN SYNDROME osms.it/waterhouse-friderichsen PATHOLOGY & CAUSES ▪ Uncommon, severe syndrome characterized by adrenal failure related to overwhelming infection, adrenal gland hemorrhage 78 OSMOSIS.ORG ▪ Bacterial infection → septicemia → release of bacterial endotoxins → endothelial dysfunction → seeding of bacterial emboli into adrenals → bleeding into one/both
Chapter 13 Adrenal Hypofunction adrenal glands → hemorrhagic necrosis → adrenocortical insufficiency → adrenal crisis CAUSES ▪ Associated with sepsis caused by organisms (e.g. Neisseria meningitidis (80% of cases), Streptococcus pneumoniae, Neisseria gonorrhoeae, Escherichia coli, Haemophilus influenzae, Staphylococcus aureus) COMPLICATIONS ▪ Disseminated intravascular coagulation (DIC) ▪ Profound shock ▪ Potentially life-threatening SIGNS & SYMPTOMS ▪ Initial presentation: malaise, fever, chills, headache, vomiting ▪ Signs of shock (e.g. hypotension, tachycardia, tachypnea) ▪ Widespread petechial lesions → purpura → plaques ▪ Cyanosis, AKA dusky gray color of skin DIAGNOSIS OTHER DIAGNOSTICS ▪ History, physical examination with characteristic findings ▪ Rapid ACTH test ▫ Insufficient/no cortisol produced indicates adrenal insufficiency TREATMENT MEDICATIONS ▪ Adrenal insufficiency ▫ IV glucocorticoids ▪ Infection ▫ Antibiotics (e.g. IV penicillin, cefotaxime/ ceftriaxone if meningococcal infection) ▪ Shock ▫ IV fluids, vasopressors, supplemental oxygen ▪ DIC ▫ Packed red blood cells (RBCs), cryoprecipitate, fresh frozen plasma, platelets OTHER INTERVENTIONS ▪ Prevention ▫ Routine vaccination against meningococcal disease DIAGNOSTIC IMAGING CT scan ▪ Identifies blood collection within adrenals Ultrasound ▪ Adrenal hemorrhage appears solid, diffusely echogenic LAB RESULTS ▪ Blood culture ▫ Identifies causative organism ▪ Adrenal insufficiency ▫ ↓ serum sodium, ↓ glucose, ↑ potassium, ↓ serum cortisol ▪ DIC ▫ ↑ fibrinogen degradation products, ↑ D-dimer levels, prolonged PT, aPTT OSMOSIS.ORG 79

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