endocrinology (primary hyperaldosteronism)

Question 1

what is the prevalence of primary hyperaldosteronism

Answer 1

primary hyperaldosteronism is probably the most common adrenocortical disorder in cats and it may be an important cause of arterial hypertension in this species

Question 2

what is the cause of primary hyperaldosteronism

Answer 2

primary hyperaldosteronism is an adrenocortical disorder (i.e., adenoma or less commoly carcinoma) characterised by excessive, autonomous secretion of mineralocorticoids, mainly aldosterone, leading to systemic arterial hypertension and/or hypokalemia

Question 3

what are the potential barriers to diagnosis

Answer 3

it is most likely underdiagnosed

this may in part be due to the frequent association of arterial hypertension and/or hypokalemia with chronic renal disease

BUT, CKD may itself be a consequence of primary hyperaldosteronism

Question 4

what are aldosterone actions

Answer 4

the epithelia of the kidneys, colon and salivary glands are the classic target tissues for circulating aldosterone

it readily passes through the plasma membrane of these epithelial cells and binds to the cytoplasmic mineralocorticoid receptor

in epithelial cells of the distal nephron, it activates sodium reabsorption from the urine and generates an electrochemical gradient that facilitates the passive transfer of potassium from the tubular cells into the urine

Question 5

how aldosterone may increase blood pressure

Answer 5

aldosterone may increase blood pressure through two main mechanisms:
- expansion of plasma and extracellular fluid volume
- increased total peripheral resistance

Question 6

could you explain the non-epithelial actions of aldosterone

Answer 6

long-term mineralocorticoid excess may lead to microangiopathies, with fibrosis and proliferation of endothelial and smooth muscle cells, in tissues such as heart and kidneys

Question 7

how is aldosterone metabolised

Answer 7

little is known about the metabolism of aldosterone in cats

the liver is generally considered to be the most important site for inactivation and conjugation of steroid hormones

in cats, steroid hormones are excreted mainly and almost exclusively via the bile into the feces

Question 8

explain the pathophysiological mechanisms that may lead to hhypersecretion of aldosterone

Answer 8

two pathophysiological mechanism may lead to hypersecretion of aldosterone:

- a reduction in the effective arterial blood volume (due, for example, to heart failure) activates the renin-angiotensin system, which in turn persistently stimulates aldosterone synthesis
    - this pathophysiological response to hypovolemia is called secondary hyperaldosteronism or high-renin hyperaldosteronism

- an autonomous aldosterone hypersecretion in primary hyperaldosteronism which is associated with suppressed plasma renin activity (= low-renin hyperaldosteronism)

Question 9

explain the pathophysiological consequences of excessive aldosterone secretion

Answer 9

they are related to increased sodium and water retention and increased renal potassium excretion which result in systemic arterial hypertension and potassium depletion

Question 10

what are the possible clinical implications of hyperaldosteronism

Answer 10

affected cats have episodic muscle weakness that results in a plantigrade stance in the hindlimbs, difficulty in jumping and/or a characteristic ventroflexion of the neck

in other cats, the presenting clinical signs are dominated by signs of arterial hypertension (i.e., loss of vision due to retinal detachment and/or intraocular hemorrhages)

it is important to note that not all cats with primary hyperaldosteronism present with signs of hypokalemia and with signs of arterial hypertension

Question 11

what is the signalment for primary hyperaldosteronism

Answer 11

median age of 13 years

no breed or sex predilection

Question 12

list possible clinical signs of primary hyperaldosteronism

Answer 12

elevated arterial blood pressure

hypertensive ocular signs (e.g., hyphema, retinal edema and detachment)

hypokalemic polymyopathy

Question 13

what are the typical laboratory abnormalities

Answer 13

hypokalemia
- hypernatremia combined with hypokalemia was found in only one of 17 cats in one study

elevation in plasma urea, creatine and creatinine kinase

increase in plasma aldosterone concentration

renin activity below or within the reference interval

Question 14

what could make you think about primary hyperaldosteronism in your differentials

Answer 14

primary hyperaldosteronism should be considered in any cat with elevated arterial blood pressure and/or hypokalemia, particularly if hypertension and/or hypokalemia are relatively refractory to treatment

Question 15

what are the screening tests for primary hyperaldosteronism

Answer 15

1/ plasma aldosterone/renin ratio
- in cats with unilateral or bilateral zona glomerulosa tumors, the PAC may be very high and the PRC is usually completely suppressed

- in cats with idiopathic bilateral nodular hyperplasia of the zona glomerulosa, the PAC may be only slightly elevated or within the upper limit of the reference interval
    - in the presence of hypokalemia, even a mildly elevated aldosterone level can be regarded as inappropriately high

2/ urine aldosterone/crreatinine ratio
- the reference interval did not facilitate differentiation between healthy cats and those with primary hyperaldosteronism

3/ suppression test with telmisartan

Question 16

what could be confirmatory tests

Answer 16

1/ diagnostic imaging
- a visible adrenal mass may not be a functional neoplasm that is causing the clinical signs

- conversely, functional neoplasms need not to be large in order to cause clinically relevant hyperaldosteronism and may therefore be well below the detection limit of US, CT or MRI
    - a human study concluded that CT/MRI results did not accurately identify the source of aldosterone excess in as many as 38% of patients
    - therefore, inaccurate adrenal diagnostic imaging results can happen

differentiation between unilateral and bilateral hyperaldosteronism and detection of any vascular extension or distant metastases are essential to determine the optimal therapeutic strategy

Question 17

what is the medical treatment of hyperaldosteronism

Answer 17

medical therapy with a mineralocorticoid receptor blocker is instituted together with potassium supplementation and antihypertensive drugs if needed

the aldosterone receptor blocker most often used in cats is spironolactone
- initial dose 2 mg/kg PO q 12h
- increased as needed to control hypokalemia but a dose in excess of 4 mg/kg may cause anorexia, diarrhea and vomiting

persistant arterial hypertension can be treated with the calcium channel blocker amlodipine at an initial oral dose of 0.1 mg/kg q 24h