AS-Adrenal+gland+pathology+I (2).pdf

ENDOCRINE PATHOLOGY: ADRENAL GLAND DYSFUNCTION Amal Sahyoun, PhD Assistant Professor, College of Dental Medicine [email protected] LEARNING OBJECTIVES Understand the etiologies and pathophysiology of adrenal gland dysfunction Identify the clinical features and laboratory findings of adrenal gl...

ENDOCRINE PATHOLOGY: ADRENAL GLAND DYSFUNCTION Amal Sahyoun, PhD Assistant Professor, College of Dental Medicine [email protected] LEARNING OBJECTIVES Understand the etiologies and pathophysiology of adrenal gland dysfunction Identify the clinical features and laboratory findings of adrenal gland dysfunction Identify diagnostic approaches and treatment of adrenal gland dysfunction ADRENAL GLAND -Located in the retroperitoneal cavity above each kidney -Two separate glands: o Medulla o Cortex -Adrenal cortex has 3 layers: o Zona glomerulosa o Zona fasciculata o Zona reticularis ADRENAL GLAND: ZONA GLOMERULOSA ADRENAL GLAND: ZONA FASCICULATA ADRENAL GLAND: ZONA RETICULARIS ADRENAL GLAND: ADRENAL MEDULLA ADRENAL GLAND -Adrenal cortex has 3 layers: o Zona glomerulosa → mineralocorticoids → aldosterone (SALT) o Zona fasciculata → glucocorticoids → cortisol (STEROID) o Zona reticularis → androgens → dehydroepiandostendione (DHEA), DHEA-sulfate, androstendione (SEX) - Adrenal medulla: Chromaffin cells  epinephrine and norepinephrine (STRESS) and small amounts of dopamine ADRENAL GLAND PATHOLOGY Hyperfunction Hypofunction Neoplasms Hyper aldosteronism Primary: Conn syndrome Hypercortisolism Primary: Cushing syndrome Adrenocortical insufficiency Primary acute: Waterhouse-Friderichsen Primary chronic: Addison disease Adrenocortical adenoma Adrenocortical carcinoma Androgenital syndromes Virilization syndromes Chromaffin cells Pheochromocytoma Neuronal cells Neuroblastic tumors HYPERFUNCTION OF ADRENAL CORTEX HYPERALDOSTERONISM MINERALOCORTICOID EXCESS – HYPERALDOSTERONISM - Over production of aldosterone from zona glomerulosa - Mainly associated with hypertension due to high reabsorption of sodium and water - It can be primary and secondary - Autonomous overproduction of aldosterone leading to Aldosterone suppression of the renin-angiotensin system - Primary hyperaldosteronism is caused by hyperfunctioning of the adrenal gland due to: o Bilateral idiopathic hyperaldosteronism o Aldosterone-producing adrenal cortical adenoma o Familial hyperaldosteronism (uncommon) https://doi.org/10.1016/j.semnephrol.2014.04.009 - JG-cells Renin MINERALOCORTICOID EXCESS – HYPERALDOSTERONISM - Bilateral idiopathic hyperaldosteronism: (60%) o Most common one o Adrenal hyperplasia  more replication and growth of adrenal cortex o Bilateral enlargement and replication of adrenal cells - Aldosterone-producing adrenal cortical adenoma: (35%) o Unilateral mass o Mostly benign o Secretory - Familial hyperaldosteronism (uncommon): (5%) o Rare genetic condition o Different genetic causes https://doi.org/10.1016/j.semnephrol.2014.04.009 MINERALOCORTICOID EXCESS – HYPERALDOSTERONISM - Bilateral idiopathic hyperaldosteronism: (60%) o Overactive adrenal glands o Diffuse hyperplasia of aldosterone-producing cells within the adrenal cortex (Zona glomerulosa) o Pathogenesis is unclear  Could be due to mutations of KCNJ5 o Found in older and less hypertension compared to adrenal adenoma - Aldosterone-producing adrenal cortical adenoma: (35%) - Familial hyperaldosteronism (uncommon): (5%) Turcu, A.F., Yang, J. & Vaidya, A. Primary aldosteronism — a multidimensional syndrome. Nat Rev Endocrinol 18, 665–682 (2022). https://doi.org/10.1038/s41574-022-00730-2 https://www.urologyhealth.org/urology-a-z/c/conns-syndrome MINERALOCORTICOID EXCESS – HYPERALDOSTERONISM - Bilateral idiopathic hyperaldosteronism: (60%) - Aldosterone-producing adrenal cortical adenoma: (35%) o Mutations of KCNJ5 (38%), CACNA1D (9.3%) and ATP1A1 (5.3%) o Activation of aldosterone synthase  Autonomous aldosterone synthesis - Familial hyperaldosteronism (uncommon): (5%) https://www.urologyhealth.org/urology-a-z/c/conns-syndrome https://www.sciencedirect.com/topics/neuroscience/kcnj3 Itcho, K.; Oki, K.; Ohno, H.; Yoneda, M. Update on Genetics of Primary Aldosteronism. Biomedicines 2021, 9, 409. https://doi.org/10.3390/biomedicines9040409 MINERALOCORTICOID EXCESS – HYPERALDOSTERONISM Morphology: Aldosterone producing adenomas: o Solitary o Well circumscribed o Small range 1-32 mm in diameter Normal o No visible mass o Bright yellow on cut section o Cells are lipid rich (zona fasciculata-like cells) and compact (eosinophilic) tumor cells https://en.m.wikipedia.org/wiki/File:Zona_fasciculata_versus_adrenocortical_adenoma.jpg Tumor MINERALOCORTICOID EXCESS – HYPERALDOSTERONISM + JG-cells - Secondary hyperaldosteronism: o Due to extra-adrenal cause due to activation of the renin-angiotensin system with elevated plasma levels of renin o Hyperactive juxtaglomerular cells  Renin secreting tumor (reninoma) Renin  very rare  Poor renal perfusion (low cardiac output, vessel damage, etc.. )  more common Aldosterone HYPERALDOSTERONISM : COMPLICATIONS Aldosterone 1. Secondary hypertension 2. Hypernatremia + 3. Hypokalemia 4. Metabolic Alkalosis Na+ H2O BV BP HYPERALDOSTERONISM: COMPLICATIONS Aldosterone 1. Secondary hypertension 2. Hypernatremia + 3. Na+ Hypokalemia Na > 145 4. Metabolic Alkalosis HYPERALDOSTERONISM: COMPLICATIONS Aldosterone 1. Secondary hypertension + 2. Hypernatremia 3. Hypokalemia 4. Metabolic Alkalosis K+ HYPERALDOSTERONISM: COMPLICATIONS Aldosterone 1. Secondary hypertension + 2. Hypernatremia 3. Hypokalemia 4. Metabolic Alkalosis H+ pH HYPERALDOSTERONISM: DIAGNOSIS Renin and aldosterone measurements Aldosterone Renin Normal PAR ratio Aldosterone Renin PAR ratio Primary hyperaldosteronism Secondary hyperaldosteronism Measure Adrenal Saline suppression test Adrenal CT/MRI Adrenal adenoma Aldosterone unilateral Adrenal hyperplasia Aldosterone bilateral Adrenal venous sample Supportive Primary hyperaldosteronism Urine and serum Aldosterone HYPERALDOSTERONISM: TREATMENT Aldosterone In case of: - o Adenoma  Purpose: remove tumor  Treatment: Adrenalectomy Na+ HCO3- - K+ H+ o Hyperplasia  Purpose: supress hyperplasia  Medications: Spironolactone or Eplerenone NA+ K+ H+ Spironolactone Eplerenone HYPERCORTISOLISM CORTISOL HORMONE Cortisol functions: o Circadian rhythm o Gluconeogenesis, proteolysis and lipolysis o Glycogenolysis o Blood pressure o Immune system HYPERCORTISOLISM: CUSHING’S SYNDROME  Cushing syndrome is an endocrine disorder due to overproduction of cortisol  Etiology:  Exogenous o Corticosteroid medications to treat autoimmune and inflammatory disorders (asthma or rheumatoid arthritis) o Similar to cortisol  mimics action on tissue  mimic the effect HYPERCORTISOLISM: CUSHING’S SYNDROME  Cushing syndrome is an endocrine disorder due to overproduction of cortisol  Etiology:  Endogenous ~ made by the body o ACTH-Dependent  Pituitary microadenoma Excess ACTH overstimulates zona fasciculata and overproduce cortisol o ACTH-Independent  Primary adrenocortical neoplasms (begnin or malignant) Cells in zona fasciculata divide abnormally and secrete excess cortisol Suppress CRH and ACTH production Cells autonomously producing cortisol CUSHING’S SYNDROME : SYMPTOMS (1) Hyperglycemia Diabetes mellitus and obesity (2) Hypertension  Increase risk of CVD (3) Vulnerable to infections (4) Dysfunction of ovarian and testicular functions CUSHING’S SYNDROME: SYMPTOMS (1) Hyperglycemia Diabetes mellitus and obesity (2) Hypertension  Increase risk of CVD (3) Vulnerable to infections (4) Dysfunction of ovarian and testicular functions CUSHING’S SYNDROME: SYMPTOMS o Fatigue and muscle wasting o Easy bruising o Truncal obesity o Moon face o Buffalo hump o Abdominal Striae o Fractures Colao, Annamaria & Md, Marco & Ferone, Diego & Casanueva, Felipe. (2014). Managing Cushing's disease: The state of the art. Endocrine. 47. 10.1007/s12020-013-0129-2. CUSHING’S SYNDROME : DIAGNOSIS (1) Measure cortisol levels  24-hour urine sample  Blood or saliva test (2) Measure ACTH levels  If high with high cortisol  pituitary microadenoma and or adrenal neoplams  If normal or low with high cortisol  adrenal neoplasms (3) Dexamethasone suppression test  Give low dose of dexamethasone (exogenous steroid) that should supress ACTH production  If cortisol levels drop  Pituitary microadenoma  If cortisol levels remains high  adrenal neoplasms (4) Imaging : MRI of pituitary and CT for adrenals CUSHING’S SYNDROME: TREATMENT o Exogenous medications  Drug must be gradually decreased and eventually stopped if possible  Avoid sudden withdrawal, this can lead to adrenal crisis (life threatening) o Pituitary microadenoma  Surgical resection of the tumour o Adrenal adenoma or carcinoma  Ketoconazole and metyrapone ( adrenal steroid inhibitors) REFERENCES  Robbins and Cotran Pathologic Basis of Disease, 9th edition or 10th edition. V Kumar; Elsevier Gary D. Hammer and Stephen J. McPhee Pathophysiology of Disease: An Introduction to Clinical Medicine, 8th edition. McGraw Hill. Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 13e