Endocrine Regulation Of Blood Pressure

Endocrine Regulation of BloodPressureGrace M. Kroner, Ph.D.Clinical Chemistry FellowJune 1, 2020

Learning Objectives1. List the hormones that regulate bloodpressure.2. Compare the presentation of endocrinediseases that may cause hypertension.3. Interpret laboratory testing results forprimary hyperaldosteronism and diabetesinsipidus.

Outline Blood pressure– Regulation Hypertension– Primary hyperaldosteronism– Laboratory testing– Rare causes of apparent mineralocorticoid excess Hypotension– Diabetes insipidus– Laboratory testing

Why is appropriate blood pressure important? Needed to ensurenutrient andoxygen delivery totissues Too high bloodpressure hypertension Too low bloodpressure hypotensionOxygen poor,CO2 richOxygen rich,CO2 poor“Overview of hypertension in adults,” Up to Date, 2019; Image adapted from iagrams.jpg.

Blood Pressure Components12080Systole: contractionSystolic blood pressure (SBP)Diastolic blood pressure (DBP)Diastole: gy/chapter/19-3-cardiac-cycle/; stole.html

What factors change blood pressure?1. Cardiac output Depends on blood volumeAverage adult has 5 liters of bloodLarger volume pressureSmaller volume pressure“Chapter 11,” Robbins and Cotran Pathological Basis of Disease, 2010; https://www.ncbi.nlm.nih.gov/books/NBK526077/; Images an Horseshoe Falls with city of Niagara Falls, Ontario in background.jpg; waterfall/

What factors change blood pressure?1. Cardiac output2. Vascular resistance Depends on the size of blood vesselsRange from 5-10 µm to 2-3 cm!VasoconstrictionSmaller size pressureVasodilationLarger size pressure“Chapter 11,” Robbins and Cotran Pathological Basis of Disease, 2010; /blood-vessels.shtml;Images from lyurethane/dp/B06XDJ2BNF; kingReusable/dp/B07CZW9V7W/ref sr 1 8?dchild 1&keywords reusable straws&qid 1586189250&s home-garden&sr 1-8

How is blood pressure controlled?Increase blood pressureIncrease blood volumeVasoconstrictorsDecrease blood pressureDecrease blood volumeVasodilators Sympathetic nervous system Endocrine system– Hormones affect blood volume and blood vessel size Kidney– Produce antihypertensive substances“Overview of hypertension in adults,” Up to Date, 2019; “Chapter 11,” Robbins and Cotran Pathological Basis of Disease, 2010.

Endocrine InterconnectionBrainPosteriorpituitaryAntidiuretic hormone (ADH)HeartAtrial natriuretic peptide (ANP)Brain natriuretic peptide (BNP)AdrenalglandsKidneysBloodstreamAngiotensin IICatecholaminesAldosteroneRenin“Chapter 66,” Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, 6th edition, 2018; Chopra, Baby & Jacob. “Neuro-endocrineregulation of blood pressure.” Indian J Endocrinol Metab. 2011;15:S281-8; Body outline from g

Outline Blood pressure– Regulation Hypertension– Primary hyperaldosteronism– Laboratory testing– Rare causes of apparent mineralocorticoid excess Hypotension– Diabetes insipidus– Laboratory testing

Hypertension (HTN) is a significantpublic health concern Estimated USprevalenceamong adults:46% Increases riskof heart attack,heart failure,kidney diseaseand stroke*Based on self-report2017 ACC/AHA Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults; “Chapter 11,” Robbins andCotran Pathological Basis of Disease, 2010; “Overview of hypertension in adults,” Up to Date, 2019; “Cardiovascular risks of hypertension,” Up toDate, 2020; https://www.cdc.gov/bloodpressure/facts.htm; ts-statistics-show

Stages of Hypertension Change in 2017 to lower cut-off age 1 HTN 120 mmHg120-129 mmHg130-139 mmHgandandor 80 mmHg 80 mmHg80-89 mmHgStage 2 HTN 140 mmHgor 90 mmHg No perfect cut-off to eliminate risk– Often asymptomatic until severe complicationsdevelop2017 ACC/AHA Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults; “Chapter 11,” Robbins andCotran Pathological Basis of Disease, 2010; Image from london/.

Classification of Hypertension Primary hypertension– Contributing factors: GeneticsStressObesitySmokingPhysical inactivityHigh-salt dietSecondary15%Primary85% Secondary hypertension– Renal or endocrinemalfunction“Chapter 11,” Robbins and Cotran Pathological Basis of Disease, 2010; “Chapter 16,” Williams Textbook of Endocrinology, 2016;“Overview of hypertension in adults,” Up to Date, 2019; “Genetic factors in the pathogenesis of hypertension,” Up to Date, 2020.

What endocrine disorders may causehypertension? HyperaldosteronismCongenital adrenal hyperplasiaCushing syndromeApparent mineralocorticoid excessIncreased ism8-20%Rare0.1%Rare0.1-0.6%Rare 1% 1%“Chapter 11,” Robbins and Cotran Pathological Basis of Disease, 2010; “Chapter 16,” Williams Textbook of Endocrinology, 2016; “Overview ofhypertension in adults,” Up to Date, 2019; “Evaluation of secondary hypertension,” Up to Date, 2019; 2017 ACC/AHA Guideline for thePrevention, Detection, Evaluation and Management of High Blood Pressure in Adults; Image adapted from /the-adrenal-gland.

What endocrine disorders may causehypertension? HyperaldosteronismCongenital adrenal hyperplasiaCushing syndromeApparent mineralocorticoid excessIncreased ism“Chapter 11,” Robbins and Cotran Pathological Basis of Disease, 2010; “Chapter 16,” Williams Textbook of Endocrinology, 2016; “Overview ofhypertension in adults,” Up to Date, 2019; “Evaluation of secondary hypertension,” Up to Date, 2019; 2017 ACC/AHA Guideline for thePrevention, Detection, Evaluation and Management of High Blood Pressure in Adults; Image adapted from /the-adrenal-gland.

What other symptoms might patients have?DiagnosisHyperaldosteronismCushing ns and SymptomsHTN, hypokalemia, muscle weaknessCentral obesity, facial changes, glucoseintolerance, purple striaeFacial changes, increasing size of hands/feetWeight loss, warm skin, heat intolerance,nervousness, diarrheaWeight gain, dry skin, cold intolerance,constipationSeventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure, National Heart,Lung and Blood Institute, 2004.

How do physicians know to considersecondary testing? Abrupt onset of HTNNew onset of HTN at early or late ageInitial presentation with stage 2 HTNClinical clue(s) suggesting specific causeDrug resistant HTN– Occurs when goal BP is not obtained with 3 differentclasses of medications, or is obtained with 4medications– Up to 14.8% of treated hypertensive patients“Overview of hypertension in adults,” Up to Date, 2019; Seventh Report of the Joint National Committee on Prevention, Detection, Evaluationand Treatment of High Blood Pressure, National Heart, Lung and Blood Institute, 2004; “Definition, risk factors, and evaluation of resistanthypertension,” Up to Date, 2020; https://www.nature.com/articles/jhh2013140.

Renin-Aldosterone SystemInto bodySodiumWaterOut of bodyPotassiumHydrogen ions“Chapter 66,” Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, 6th edition, 2018; Image from Chemistry Class Slides, HorbachevskyTernopil State Medical University, Ukraine.

Renin-Aldosterone SystemImage from Chemistry Class Slides, Horbachevsky Ternopil State Medical University, Ukraine.

What is primary hyperaldosteronism? High blood pressure due to uncontrolledexcretion of aldosterone– Most common: Aldosterone-producing adenoma Bilateral idiopathic hyperaldosteronismOne or bothadrenal glands?– Relatively rare: Familial hyperaldosteronismUnilateral adrenal hyperplasiaAdrenal carcinomaEctopic aldosterone-producing tumor Increased risk for cardiovascular complicationsDiagnosis of primary aldosteronism, Up To Date, July 2018; Young et al. “Role of AVS in primary hyperaldosteronism,” Surgery, 2004; Funder et al.Endocrine Society Guidelines, 2016; “Evaluation of secondary hypertension,” Up to Date, 2019.

What is primary hyperaldosteronism? One adrenal gland affected aldosteroneproducing adenoma ( 30% of cases)ALDOSTERONEImage from Diagnosis of primary aldosteronism, Up To Date, July 2018; “Chapter 16,” Williams Textbook of Endocrinology, 2016.

What is primary hyperaldosteronism? Both adrenal glands affected bilateral adrenalhyperplasia ( 60% of cases)ALDOSTERONEImage from Diagnosis of primary aldosteronism, Up To Date, July 2018.

Testing for primary hyperaldosteronism Screening hypertensive patients Confirming primary hyperaldosteronism Classifying disease as unilateral or bilateralDiagnosis of primary aldosteronism, Up To Date, July 2018.

Testing for primary hyperaldosteronism Screening hypertensive patients– Prevalence may be up to 5-10% of hypertensivepatients– Plasma aldosterone: renin ratio– Expect: high aldosterone, low renin elevatedratio Normal ratio is between 4 and 10 Abnormal ratio can be 30-50Diagnosis of primary aldosteronism, Up To Date, July 2018; 2017 ACC/AHA Guideline for the Prevention, Detection, Evaluation and Managementof High Blood Pressure in Adults.

Testing for primary hyperaldosteronism Screening hypertensive patients– Pre-analytical concerns: Unrestricted salt intake Normal potassium No mineralocorticoid antagonists within 4 weeksInto bodySodiumWaterOut of bodyPotassiumHydrogen ionsDiagnosis of primary aldosteronism, Up To Date, July 2018; 2017 ACC/AHA Guideline for the Prevention, Detection, Evaluation and Managementof High Blood Pressure in Adults.

Testing for primary hyperaldosteronism Screening hypertensive patients Confirming primary hyperaldosteronism– Sodium loading to testaldosterone suppression– Urine or plasmaaldosteroneDiagnosis of primary aldosteronism, Up To Date, July 2018; Hypertension Canada’s 2018 Guidelines for Diagnosis, Risk Assessment, Preventionand Treatment of Hypertensions in Adults and Children, Can. J. Cardiol. 2018.

Testing for primary hyperaldosteronism Screening hypertensive patients Confirming primary hyperaldosteronism Classifying disease as unilateral or bilateral– CT (computed tomography) imaging and/oradrenal venous sampling– Critical for making treatment decisionsDiagnosis of primary aldosteronism, Up To Date, July 2018; Hypertension Canada’s 2018 Guidelines for Diagnosis, Risk Assessment, Preventionand Treatment of Hypertensions in Adults and Children, Can. J. Cardiol. 2018.

Why is classification so important? Treatment depends on classification:– One adrenal affected surgery to remove it– Both adrenals affected treat with drugsImage from Diagnosis of primary aldosteronism, Up To Date, July 2018.

Why can’t we just look at it? CT imaging notalways accurate orsensitive enough Incidentalomasmore likely inindividuals 40years Adenoma 4cmsuggests carcinomaliverpancreasspleenkidneySpinal cordDiagnosis of primary aldosteronism, Up To Date, July 2018; Image from -clothing.html.

How does adrenal venous sampling (AVS) work? Is more aldosterone producedfrom one adrenal gland oranother? May use cosyntropinstimulation– Minimize stress-induced changes– Maximize aldosterone andcortisol production Use fluoroscopy to help imagecatheterRossi et al. “Expert Consensus Statement on Use of AVS for primary aldosteronism subtyping.” Hypertension 2014; Daunt, N. “AVS: How to Makeit Quick, Easy and Successful,” RadioGraphics, 2005; Nishikawa et al. Endocrine Journal, 2011.

AVS Procedure OverviewGoals1. Right adrenal vein2. Left adrenal vein3. Inferior vena cavaMeasure aldosteroneand cortisolImage from Diagnosis of primary aldosteronism, Up To Date, July 2018.

AVS Procedure OverviewGoals1. Right adrenal vein2. Left adrenal vein3. Inferior vena cavaMeasure aldosteroneand cortisolImage from Diagnosis of primary aldosteronism, Up To Date, July 2018; Daunt, N. “AVS: How to Make it Quick, Easy and Successful,”RadioGraphics, 2005.

AVS Procedure OverviewGoals1. Right adrenal vein2. Left adrenal vein3. Inferior vena cavaMeasure aldosteroneand cortisolImage from Diagnosis of primary aldosteronism, Up To Date, July 2018.