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Table 7. Anna’ s follow-up results Investigation and reference range

Anna’ s follow-up results

Table 8. Lucy’ s initial investigations Investigation and reference range

Lucy’ s initial results Potassium mmol / L( 3.5-5.2) 3.9 Plasma renin concentration mU / L( 4.4-46) 7.4 Aldosterone pmol / L( 70-1090) 420

Figure 10. Liquorice tea. ARR pmol / mU(< 70) 57 reveals that Anna has had regular menstrual cycles after menarche at the age of 13 and has had two uncomplicated pregnancies. Physical examination does not reveal any signs of hyperthyroidism or androgen or glucocorticoid excess except central adiposity. Repeat potassium and a screen for hormonal causes for hypertension and hypokalaemia appear in table 6.

A thorough dietary history reveals that Anna started drinking 3-4 cups of home-brewed liquorice tea( see figure 10) daily a few months ago after reading of its possible health benefits. She is advised to stop consuming the tea and is started on spironolactone 25mg daily. Her blood pressure improves to 138 / 90mmHg and she maintains normokalaemia.

Anna is reviewed by her GP eight weeks later. Her biochemistry appears in table 7. Her blood pressure

1. Which THREE statements regarding hypertension are correct? a It is the leading cause of premature death worldwide. b Two in three people with hypertension are not well controlled. c After URTIs, this is the most common medical condition managed in primary care. d Hypertension is better thought of as a multisystem syndrome with abnormalities in the vascular, renal and endocrine systems.

2. Which ONE statement regarding the function of renin is correct? a Renin regulates the absorption of potassium from the gut. b Renin regulates the thirst centre. c Renin regulates blood pressure via salt homeostasis and modulation of vascular resistance. d Renin regulates the sensitivity of baroreceptors in the carotid sinus.

3. Which ONE may increase renin concentration? a Renal artery stenosis. b Excess salt in the diet. and biochemistry have normalised, and spironolactone is stopped.

This case, presenting as LRH with hypokalaemia and low aldosterone, demonstrates an acquired

cause of apparent mineralocorticoid excess from excess liquorice consumption. Liquorice contains glycyrrhetinic acid that can inhibit the enzyme 11βHSD2. This enzyme regulates the metabolism of cortisol, a steroid hormone produced by the adrenal glands. Cortisol has multiple functions, including salt and water homeostasis, immunity and metabolism. Cortisol and

c Beta blockers. d NSAIDs.

4. Which ONE medication decreases renin concentration? a Perindopril. b Irbesartan. c Moxonidine. d Atenolol.

5. Which THREE groups are at high risk of PA? a Controlled hypertension requiring four or more antihypertensive agents. b Sustained blood pressure greater than 150 / 110mmHg. c A family history of stroke below the age of 40. d Hyperkalaemia.

6. Which ONE is the most common known cause of LRH? a Liddle syndrome. b PA. c Apparent mineralocorticoid excess. d Gordon syndrome. aldosterone, both steroid hormones, can bind to the MR and increase renal sodium resorption. However, aldosterone is the main MR activator as 11βHSD2 protects the MR in

Hypertension affects one in three adults in Australia and is most commonly managed by GPs.

the kidneys by converting cortisol to cortisone, its metabolically inactive form. In this case, the function of 11βHSD2 is likely impaired because of the glycyrrhetinic acid found in liquorice. Normal physiological concentrations of cortisol can cause excess MR stimulation and lead to hypertension with hypokalaemia, low renin and low aldosterone concentrations.

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7. Which TWO statements regarding LRH are correct? a LRH is a rare subtype of hypertension. b Monogenic causes of LRH make up most cases of LRH. c It is estimated that two out of three patients with LRH will have an unclear underlying cause. d Medications such as verapamil, prazosin, hydralazine and moxonidine have little or no effect on renin concentrations.

LOW RENIN HYPERTENSION

8. Which THREE statements regarding PA are correct? a Excess aldosterone causes MR activation, salt and water retention and vascular remodelling. b A recent Australian study found that 14 % of treatment naïve patients with hypertension screened by GPs had PA. c Clinical characteristics of patients with PA are often

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Case study four

Lucy, a 57-year-old mother of three adult children, is referred by her GP to an endocrinologist for investigation of LRH. Family history is significant for hypertension, with a 53-year-old second-degree relative of Lucy’ s having had a stroke.

Lucy’ s initial investigations appear in table 8.

Repeat testing of renin and aldosterone concentrations are similar. A detailed clinical assessment does not reveal any interfering medications, herbal supplements or any clinical signs of glucocorticoid or androgen excess. Mean clinic blood pressure is 158 / 88mmHg despite verapamil 240mg daily.

Further investigations including a 24-hour cortisol, sodium, potassium, and urine steroid profile are also normal.

indistinguishable from those of patients with essential hypertension. d The most reliable test to screen for PA is a direct renin concentration.

9. Which THREE conditions have low renin, low aldosterone and hypokalaemia? a Gordon syndrome. b Apparent mineralocorticoid excess. c Liddle syndrome. d Geller syndrome.

10. Which TWO statements regarding LREH are correct? a It is more common in those of African descent and older age. b Only a small proportion of patients with hypertension and low renin do not have a clear diagnosis. c MRA may be the treatment of choice to lower blood pressure in most patients with LREH. d It is likely that the underlying disease processes in LREH culminate in an excess of salt and an expanded volume state, leading to high renin.

This is a case of LRH with unknown aetiology. There are no clear guidelines on the best choice of antihypertensive agents for patients with this condition. However, some studies have shown that MRAs are more effective in lowering blood pressure in LREH compared with ACEIs and ARBs. 43, 44 A trial of an MRA can be considered, for example, spironolactone 25mg daily, and can be up-titrated to achieve normotension and normal renin concentration.

CONCLUSION

HYPERTENSION affects one in three adults in Australia and is most commonly managed by GPs. As such, GPs play a vital role in ensuring patients are adequately investigated and treated. Despite the increase in measurement of the ARR in the assessment of hypertension, the significance of renin concentrations per se is often overlooked. There are multiple causes of LRH, with PA the most common. Timely diagnosis of PA and targeted treatment can improve blood pressure control, decrease medication burden and reduce cardiovascular and renal morbidity. Further research is warranted to understand the optimal treatment of patients with low renin who do not have a currently recognised cause of LRH.

RESOURCES

• Endocrine Society of Australia: Screening for primary aldosteronism— a guide to switching medications bit. ly / 3R3eSyx

• Hormones Australia— Primary aldosteronism bit. ly / 3R2aFLx

• Hudson Institute of Medical Research— REMASTER Trial bit. ly / 47rUT1W

Conflict of interest declaration Jun Yang has received project funding from DiaSorin Australia Pty Ltd for the measurement of aldosterone and renin in research samples unrelated to the current article.

Sonali Shah, Jun Yang and Peter Fuller are investigators for the REMASTER trial, a randomised controlled clinical trial at Monash Health, Victoria.

References Available on request from howtotreat @ adg. com. au