Conn's

Question 1

primary hyperaldosteronism

Answer 1

excess production of aldosterone, independent of the RAAS system - causing increased sodium and water retention and decreased renin release

Question 2

when should primary hyperaldosteronism be considered

Answer 2

features of hypertension, hypokalaemia or alkalosis in someone not on a diuretic (losing H⁺ ions (with K⁺)?)

sodium tends to be mildly raised or normal

Question 3

what is the most common cause of secondary hypertension

Answer 3

primary hyperaldosteronism

Question 4

how does aldosterone change pH

Answer 4

metabolic alkalosis - Aldosterone increases Sodium reabsorption in exchange for Potassium and Hydrogen in the distal renal tubule, resulting in a hypernatramic hypokalaemic metabolic alkalosis

Question 5

clinical features of primary hyperaldosteronism

Answer 5

asymptomatic or signs of hypokalaemia

weakness

cramps

paraesthesiae

polyuria and polydipsia

hypertension

Question 6

causes

Answer 6

solitary aldosterone producing adenoma - Conn’s syndrome (2/3)

bilateral adrenocortical hyperplasia (1/3)

rarely: unilateral hyperplasia, adrenal carcinoma or GAD(genetic)

Question 7

describe the pathology of the adenoma in Conn’s

Answer 7

solitary small bright yellow lesions that is buried within the gland

there are spironolactone bodies

Question 8

what mutations can cause APA (and therefore primary hyperaldosteronism )and hereditary hypertension

Answer 8

somatic mutations of the KCNJ5 gene encoding Potassium channel Kir3.4 can cause APA and hereditary hypertension

the potassium channel is a rectifying selective channel which maintain membrane hyperpolarisation

mutations lead to loss of ion selectivity - sodium enters and depolarises the cell

Question 9

glucocorticoid remediable aldosteronism

Answer 9

• Normally, aldosterone production is regulated by RAAS, potassium balance and transiently ACTH. Glucocorticoid Remediable Aldosteronism is an uncommon genetic disorder where the ACTH regulatory element of a gene fuses to the aldosterone synthase gene, increasing aldosterone production and bringing it fully and solely under the control of ACTH. There is production of hybrid steroids, cortisol and aldosterone.
• This means that aldosterone is not sensitive to Sodium and potassium balance. Results in chronic mineralocorticoid excess state.
• Results in a circadian pattern of aldosterone that parallels that of cortisol.

Question 10

managment of GRA

Answer 10

Administration of exogenous glucocorticoids that suppress ACTH results in the suppression of aldosterone levels and reversal of mineralocorticoid excess state.

Question 11

when should GRA be suspected

Answer 11

when there is family history of early hypertension

Question 12

diagnosis

Answer 12

1: confirm aldosterone excess

• • measure plasma aldosterone and renin - ARR ratio
• • if raised further investigate wtih saline suppression test
• • if plasma aldosterone not suppressed by >50% with 2l normal saline, PA confirmed

2: confirm subtype

• • adrenal CT to demonstrate adenoma
• • adrenal vein sampling

Question 13

what is the purpose of adrenal vein sampling

Answer 13

confirm adenoma is the true source of aldosterone excess

• if one side reveals increased aldosterone compared to the other - adenoma is likely and surgical excision indicated
• if no nodules/bilateral nodules think about adrenal hyperplasia or GRA

Question 14

management of Conn’s

Answer 14

unilateral laparoscopic adrenalectomy - if excess aldosterone has been confirmed by adrenal vein sampling

usually cures hypokalaemia and hypertension - if not spironolactone is used

Question 15

management of adrenal hyperplasia causing primary hyperaldosteronism

Answer 15

medically: spironolactone or eplerenone (aldosterone receptor antagonists)

Question 16

what are the benefits of eplerenone

Answer 16

doesnt cause hormonal disturbances: gynaecomastia, impotence, menstrual irregularities