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What is indicated by a plasma aldosterone concentration (PAC) greater than 10 ng/dL?
Intravascular volume expansion is not relevant to the diagnosis of Conn's syndrome.
False
What confirmatory test is performed after an intravascular volume expansion indicates positive results?
Saline Infusion Test
The CT scan of the abdomen is used to locate the affected __________ gland.
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Match the following possible conditions with their associated descriptions:
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What condition is caused by an inherited defect in 11 β OH Steroid Dehydrogenase Type 2?
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Cushing's disease is an inherited condition related to 11 β OH Steroid Dehydrogenase Type 2 defects.
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What are the clinical presentations commonly associated with both AME and acquired conditions like Cushing's disease?
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Excess cortisol leads to apparent mineralocorticoid excess causing __________ and __________.
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Match the following conditions to their related causes:
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What percentage of the adrenal gland is constituted by the adrenal cortex?
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The adrenal medulla makes up the majority of the adrenal gland.
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At what weeks of intra-uterine life does hormone synthesis begin in the adrenal gland?
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The ________ vein drains the right adrenal gland directly into the inferior vena cava.
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Match the following adrenal arterial supplies to their corresponding sources:
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Which of the following is the starting material for the synthesis of aldosterone?
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Aldosterone is produced from Corticosterone through the action of Aldosterone synthase.
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Name one enzyme involved in the synthesis of glucocorticoids.
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The final product of the mineralocorticoids pathway is __________.
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Match the following enzymes with their functions:
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What condition is associated with defects in the steroid hormone production pathway?
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Estrogens are synthesized directly from cholesterol.
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Identify the region of the adrenal cortex where aldosterone synthesis occurs.
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Which hormone is associated with the hypothalamus and utilizes cAMP as a second messenger?
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Somatostatin is a hormone that increases cAMP levels.
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What is the primary mechanism of action of insulin on glucose uptake?
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The most potent vasoconstrictor is __________.
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Match the hormones with their respective regions of action:
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What is the first step in the JAK-STAT pathway after ligand binding?
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Erythropoietin is a hormone that uses the JAK-STAT pathway.
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Name one disease associated with mutations in the JAK pathway.
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The hormone ________ binds to the receptor and phosphorylates SMAD proteins in the STKR pathway.
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Match the following hormones to their respective pathways:
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Which of the following conditions can be acquired and lead to metabolic alkalosis?
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The oldest method for assessing aldosterone levels does not involve the effects of various drugs.
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What does the Endocrine Society recommend screening for in every newly diagnosed case of hypertension?
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The plasma renin activity (PRA) should be less than or equal to ______ ng/ml/hr to confirm positive results.
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Match the conditions with their associated descriptions:
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What is the primary cause of Exogenous Cushing's Syndrome?
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Hypercortisolism can be caused by both endogenous and exogenous factors.
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What are the two major effects of cortisol on protein metabolism?
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Cushing's syndrome often leads to __________ obesity characterized by a buffalo hump.
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Match the following symptoms with their corresponding effects in Cushing's syndrome:
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Which hormone is primarily produced by the Zona Glomerulosa of the adrenal gland?
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The adrenal medulla primarily produces cortisol.
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What is the principal hormone produced during fetal life by the adrenal gland?
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The adrenal gland consists of large lipid rich clear cells located in the __________ region.
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Match the following zones of the adrenal cortex with their respective hormones produced:
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What is the most common cause of Conn's syndrome?
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Familial Type-1 of Conn's syndrome is characterized by an autosomal dominant inheritance pattern.
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What hormone is primarily elevated in Conn's syndrome?
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Aldosterone promotes the reabsorption of sodium ($Na^+$) from the ________ into the bloodstream.
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Match the following types of Conn's syndrome with their features:
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Which of the following is NOT a symptom or condition associated with Conn's syndrome?
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In Conn's syndrome, diastolic blood pressure is typically lower than systolic blood pressure.
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What is the primary treatment for apparent mineralocorticoid excess?
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Study Notes
Conn's Syndrome Diagnosis Flowchart
- Increased intravascular volume suggests Conn's Syndrome, initiating further testing.
- Plasma Aldosterone Concentration (PAC) greater than 10 ng/dL indicates a need for further investigation.
- Saline Infusion Test involves infusing 2 liters of Normal Saline (NS) over 4 hours.
- Repeat PAC after saline infusion helps confirm the diagnosis.
- CT Abdomen (10c) is performed to locate the affected adrenal gland.
- CT scan determines the location of the issue in the adrenal gland, identifying potential conditions like 8/1 Hyperplasia or a tumor (U/L Adenoma).
- Aldosterone values greater than 10 ng/dL suggest Conn's syndrome, with higher values (210 ng/dL) providing more definitive evidence.
Hormone Production
- The synthesis of hormones, particularly aldosterone, begins with Cholesterol (LDL).
- The enzyme STAR initiates the pathway leading to Pregnenolone.
- Pregnenolone is converted to 170H-pregnenolone by 17a-hydroxylase.
- 170H-pregnenolone is further converted to 17a-hydroxyprogesterone by 17, 20 lyase, which leads to Deoxycorticosterone and finally Cortisol.
- Corticosterone is converted to 180H-corticosterone by 18-Hydroxylase, ultimately forming Aldosterone.
- 3B-Hydroxysteroid dehydrogenase is crucial for converting 17ahydroxypregnenolone to Progesterone.
- 17B-Hydroxysteroid dehydrogenase (type 3) and Aromatase convert androgens into estrogens.
- Dehydroepiandrosterone (DHEA) and other Androgens and Estrogens are produced through branching pathways and further synthesized in the gonads.
- The zona glomerulosa region of the adrenal cortex is involved in the production of specific steroid hormones.
- Defects in the pathway can lead to Congenital Lipid Hyperplasia.
11 β OH Steroid Dehydrogenase Type 2 Defects
- Both inherited and acquired forms of 11 β OH Steroid Dehydrogenase Type 2 Defects exist.
- Inherited forms include Apparent mineralocorticoid excess (AME).
- In AME, Cortisol converts to Cortisone, and excess cortisol leads to Apparent Mineralocorticoid Excess (AME).
- Acquired forms include Cushing's disease and Licorice excess.
- Both inherited and acquired defects cause salt and H₂O retention, resulting in hypertension (HTN) and hypokalemia.
PHYSIOLOGY OF ADRENAL CORTEX
- The adrenal gland is comprised of the adrenal cortex (80%) and adrenal medulla (20%).
- It resides on the kidney.
Anatomy
- The adrenal gland starts developing in the urogenital ridge during the 6th week of intrauterine life.
- Hormone synthesis begins in the 9th week, and urine formation in the 10th week of intrauterine life.
- The adrenal gland development completes by 32 to 36 weeks.
- SF-1 and DAX-1 are orphan receptors crucial for adrenal development.
- Transcription factors involved in adrenal development include SF-1, DAXI, and WNT4.
- The fetal to adult adrenal ratio is 4:1.
Blood Supply
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The adrenal gland receives arterial supply from:
- Superior suprarenal (from Inferior phrenic A branch)
- Middle suprarenal (from the aorta directly)
- Inferior suprarenal (from the Renal A branch)
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The adrenal venous drainage system varies based on location:
- Right adrenal vein drains into the IVC (Inferior vena cava)
- Left adrenal vein drains into the Left renal vein and then the IVC.
JAK-STAT/Cytokine Receptor
- The JAK-STAT pathway is a critical signaling pathway in cells, involving ligand binding, receptor dimerization, and phosphorylation of STAT proteins.
- Phosphorylated STAT proteins move to the nucleus, regulating gene transcription.
- Hormones utilizing JAK receptors include growth hormone, prolactin, and erythropoietin (EPO).
- JAK mutations are linked to conditions like polycythemia rubra vera, primary myelofibrosis, and essential thrombocytosis.
- The STKR pathway involves phosphorylation of SMAD proteins.
- Hormones employing STKR include activin, inhibin, BMP (bone morphogenic protein), and TGF-β.
Hormones/Receptors using GPCR
- Different hormones and receptors utilize GPCRs and second messengers in various regions of the body.
- Examples include CRH in the hypothalamus, ACTH, FSH, LH, and TSH in the anterior pituitary, and α (Gi), β in the ANS and vasoconstrictors.
- Hormones like secretin, glucagon, and somatostatin utilize cAMP in the GIT.
- PTH and Calcitonin rely on cAMP in miscellaneous cases.
Overview of Hormones
- Somatostatin, Angiotensin II, and acetylcholine receptors reduce cAMP levels.
- The action of some hormones is mediated by IP/DAG.
- Nitric Oxide and Atrial Natriuretic Factor (ANF) utilize CGMP.
- Urotensin is the most potent vasoconstrictor.
TKR
- TKR receptors dimerize after ligand binding and undergo autophosphorylation.
Hormones using TKR
- Insulin utilizes the PI3K Akt 1/2 pathway to activate GLUT4.
- All growth factors except TGF β employ TKR.
Mechanism of Action of Insulin
- Insulin-dependent glucose uptake occurs in adipose tissue, skeletal muscle, and the heart via GLUT4.
Conn's Syndrome
- Conn's syndrome, or Primary Hyperaldosteronism (PHA), is a hormonal disorder characterized by excessive aldosterone levels in the blood.
- Acquired cases are more common (90%) and can be caused by bilateral adrenal (B/L) micronodular hyperplasia or unilateral (WI) adrenal adenoma.
- Familial cases (10%) include Type-1 (Glucocorticoid-remediable aldosteronism) and Type-2 (CICNA mutation).
- Excess aldosterone leads to Aldosterone-induced protein (AIP) production, influencing sodium (Na+Na^+Na+) and potassium (K+K^+K+) transport.
Apparent Mineralocorticoid Excess (AME)
- AME is a disorder characterized by a defect in 11-β hydroxysteroid dehydrogenase T-II (11-β HSD2).
- Glucocorticoid remediable aldosteronism (GRA) involves a chimeric effect where ACTH activates and increases aldosterone secretion.
- Differences in inheritance patterns and features distinguish AME and GRA.
Endocrinology - Presentation
- Hypertension (HTN) with proximal/distal muscle weakness and fatigue are common presentation signs.
- Hypokalemia is confirmed by urine K+/creatinine and urine Spot K² levels.
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Metabolic Acidosis/Alkalosis:
- Gittelman syndrome and Bartter syndrome are associated with normal blood pressure.
- Acquired causes include Cushing Syndrome and Renal Tubular Acidosis (RTA).
- Inherited causes include PHA, AME, GRA, and Liddle Syndrome.
- The Endocrine Society recommends PHA screening for all newly diagnosed HTN patients regardless of age.
- Secondary HTN should be considered unless proven otherwise, with indicators like LVH, fundus changes, microalbuminuria, and increased central systolic BP.
- Renal and endocrine causes of HTN should be investigated.
Investigation
- The Aldosterone Renin Ratio (ARR) is an obsolete method due to drug interference.
- Newer screening tests involve early morning samples and assessing Plasma Aldosterone Concentration (PAC) and Plasma Renin Activity (PRA).
- Patients should be shifted to alternative drugs like α-blockers, hydralazine, or non-dihydropyridine if specific drugs interfere with the results of the original test.
Cushing's Syndrome
- Cushing's syndrome is caused by excessive cortisol production in the adrenal cortex.
- Cortisol deficiency can be endogenous or exogenous.
- Exogenous steroids are the most common cause of exogenous Cushing's syndrome.
- Inherited defects like AME and acquired defects like increased cortisol can cause endogenous Cushing's syndrome.
- Chronic stress can also lead to pseudocushing.
Effects on Various Systems
- Protein: Increased protein catabolism, decreased amino acid uptake in extrahepatic tissues, and decreased muscle protein synthesis.
- Carbohydrate: Increased gluconeogenesis, increased alanine uptake by the liver, and conversion of alanine to free fatty acids (FFA).
- Fat: Centripetal obesity, buffalo hump, minimal lipolysis.
- Mineralocorticoid Action: Metabolic alkalosis and hypokalemia.
- Sex Steroid Action: Acne, hirsutism, amenorrhea/oligomenorrhea.
- CNS Effect: Steroid-induced psychosis, depression ranging from Frank to Hypomanic depression.
Adrenal Gland
- The right adrenal gland is anterior to the inferior vena cava and right lobe of the liver, and posterior to the right crus of the diaphragm.
- The left adrenal gland is anterior to the stomach and pancreas, and posterior to the left crus of the diaphragm.
Histology
- The adrenal gland consists of a fetal zone and a definitive zone.
- The fetal zone produces DHEAS (Dehydroepiandrosterone sulfate) and regresses after birth.
- The definitive zone includes zona glomerulosa, zona fasciculata, and zona reticularis.
- The zona glomerulosa contributes 15% and produces aldosterone.
- The zona fasciculata contributes 75% and produces cortisol.
- The zona reticularis contributes 10% and produces DHEAS.
- Adrenarche occurs between 6 and 8 years old, leading to pubic and axillary hair growth, and regresses post-reproductive age.
RAAS: Renin Angiotensin Aldosterone System
- The adrenal gland consists of lipid-rich clear cells.
- The zona glomerulosa is the primary site for aldosterone synthesis.
- The RAAS system regulates aldosterone production.
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Description
This quiz covers the diagnosis process for Conn's Syndrome, including key tests like Plasma Aldosterone Concentration and the Saline Infusion Test. It also discusses hormone production starting from cholesterol and the role of enzymes in synthesizing aldosterone. Prepare to test your understanding of this important endocrine condition.
