HPA Axis Conditions PDF

DISORDERS OF THE HYPOTHALAMIC- PITUITARY-ADRENAL (HPA) AXIS Authors Anupreet Sandhu, BSc, PharmD Slides adapted from Scot Simpson, 2023 Lecture Objectives Explain management considerations for adrenocortical insufficiency e.g., Addison Disease Explain management considerations for adre...

DISORDERS OF THE HYPOTHALAMIC- PITUITARY-ADRENAL (HPA) AXIS Authors Anupreet Sandhu, BSc, PharmD Slides adapted from Scot Simpson, 2023 Lecture Objectives Explain management considerations for adrenocortical insufficiency e.g., Addison Disease Explain management considerations for adrenal excess e.g., Cushing Syndrome Explain management considerations for hyperprolactinemia Related Readings: Pharmacotherapy: A Pathophysiologic Approach (12th Edition) Chapter 97: Adrenal Gland Disorders Chapter 98: Pituitary Gland Disorders 2  Adrenal Glands Located at the top of each kidney Adrenal medulla (10% of the gland) Secretes catecholamines Primary stimulus for secretion is neural (sympathetic nervous system) Adrenal cortex (90% of the gland) Secretes 3 types of hormones Mineralcorticoids- aldosterone corticosteroids Glucocorticoids- cortisol Adrenal Androgens 3  Adrenal Cortex H3C Cortisol CH3 Regulates enzyme levels for CH3 metabolism CH3 CH3 May act to limit inflammation and immune responses Permissive role in blood pressure Cholesterol HO maintenance Stress stimulates secretion above basal levels O CH 2OH CH 2OH C O CHO C O HO OH HO Androstenedione O Cortisol Adrenal Androgen Aldosterone O O Mineralocorticoid Glucocorticoid  Recall: Endocrine and Cardiovascular Values lecture… Hypothalamic-Pituitary-Adrenal Axis Stress Hypothalamus Corticotropin Releasing Hormone(CRH) Anterior Pituitary Adrenocorticotropic Hormone (ACTH) Negative Feedback Adrenal Cortex Cortisol CH OH 2 C O HO OH Cortisol Target Cells in the Periphery O 5 Adrenal Disorders Can be categorized as either hyperfunction or hypofunction of the adrenal gland Hyperfunction: Cushing’s Syndrome(hypercortisolism), hyperaldosteronism Hypofunction: Addison’s disease (adrenal insufficiency), genetic abnormalities of steroidogenesis Over or under production of adrenal gland hormones can have significant clinical consequences These hormones help regulate blood pressure, metabolism, immune response, stress response, bodily functions 6 Adrenocortical Insufficiency Primary: Destruction or dysfunction of adrenal cortex (Addison Disease) Most cases (80-90%) are caused by an autoimmune dysfunction 30-60 cases per 1,000,000 More common in women Results in deficiencies in cortisol, aldosterone, and androgen levels Secondary: Deficient secretion of Adrenocorticotropic Hormone (ACTH) Glucocorticoid therapy (important implication if therapy is stopped or dose reduced) 7 Adrenocortical Insufficiency Hypothalamus Corticotropin Releasing Hormone Anterior Pituitary Primary Autoimmune destruction Adrenocorticotropic Hormone (Addison Disease) Infection (Tuberculosis) ✘ Negative Feedback Trauma Surgery Adrenal Cortex Cortisol CH OH 2 C O HO OH Cortisol Target Cells O 8 Adrenocortical Insufficiency Hypothalamus Secondary Deficient ACTH secretion Drugs Corticotropin Releasing Hormone Glucocorticoids Anterior Pituitary Prednisone e.g., >20 mg daily for ≥3 weeks Adrenocorticotropic Hormone Negative Feedback Adrenal Cortex Cortisol CH OH 2 C O HO OH Cortisol Target Cells O 9 Adrenocortical Insufficiency- Clinical Presentation Weakness, lethargy, fatigue Anorexia and weight loss Abdominal symptoms (nausea, vomiting, abdominal pain) Hypoglycemia Hyperpigmentation of skin (only in primary insufficiency from excessive ACTH levels) Mineralocorticoid deficiency Hypotension, dehydration, hyponatremia, hyperkalemia 10 Plasma ACTH and Glucocorticoid Levels at Different Timepoints During the Day 11 Debono M, et al. J Clin Endocrinol Metab 2009;94:1548-54 Plasma ACTH and Glucocorticoid Levels at Different Timepoints During the Day Morning plasma cortisol level (6 AM to 9 AM) 500 nmol/L rules out primary adrenal insufficiency Drug-test interactions: oral contraceptives increase cortisol-binding globulin (CBG) levels, resulting in elevated total cortisol levels† *Source: My Health Alberta – ACTH and Cortisol Tests (www.myhealth.alberta.ca) 12 †Klose M, et al. J Clin Endocrin & Metab 2007;92:1326-33 Primary Adrenocortical Insufficiency Management: Which Corticosteroid is best? Glucocorticoid Mineralocorticoid Equivalent Activity Activity Oral Dose Short-Acting (T1/2 8-12 hrs) (mg) Hydrocortisone 1 1 20 Cortisone 0.8 0.8 25 Intermediate-Acting (T1/2 12-36 hrs) Prednisone 4 0.3 5 Prednisolone 5 0.3 5 Methylprednisolone 5 0.25 4 Triamcinolone 5