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Why is my relatively healthy elderly patient so prone to hyperkalemia?

FA Manian MD, MPH, , , , , , , , , , , , , , , , , , , , , , , Leave a comment

Hyporeninemic hypoaldosteronism (HH)—without impairment of cortisol synthesis— is associated with hyperkalemic (type IV) renal tubular acidosis (RTA) and is not uncommon among older patients despite glomerular filtration rates (GFRs) >20 ml/min, and absence of diabetes mellitus or chronic tubulointerstitial disease (1-7).  

Hyperkalemia due to HH in the elderly should come as no surprise because the renin-angiotensin-aldosterone system (RAAS) function declines with age, reaching its lowest level by age 60. 1-4   In fact, older people have comparatively lower mean levels of plasma renin and aldosterone at baseline and have an impaired ability to mount appropriate responses to RAAS stimuli, such as upright posture, volume depletion, catecholamines, or potassium administration (3-5).

The impaired RAAS capacity in the elderly often becomes more obvious when they are prescribed medications that further suppress RAAS (3). These include angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, calcium-channel blockers, nonsteroidal anti-inflammatory agents and heparin (3,7). 

Drugs that increase aldosterone resistance, including potassium-sparing diuretics (eg, spironolactone, amiloride, triamterene, eplerenone) and certain antibiotics (eg, trimethoprim, pentamidine) may also aggravate hyperkalemia associated with HH (7). 

A variety of mechanisms leading to HH with aging have been proposed. These include impaired conversion of prorenin to renin, prostaglandin deficiency, sympathetic nervous system dysfunction and increased plasma levels of atrial natriuretic factors as found in congestive heart failure (1,7). 

Bonus pearl: Did you know that the first case of “pure hypoaldosteronism” was described in 1957 in a 71 year old non-diabetic patient with hyperkalemia in the setting of congestive heart failure? (8)

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References

  1. Bauer JH. Age-related changes in the renin-aldosterone system. Physiological effects and clinical implications. Drugs & Aging 1993;3:238-45. https://www.ncbi.nlm.nih.gov/pubmed/8324299
  2. Musso CG, Jauregui JR. Renin-angiotensin-aldosterone system and the aging kidney. Expert Rev Endocrinol Metab 2014;9:543-46. https://www.tandfonline.com/doi/full/10.1586/17446651.2014.956723
  3. Yoon HE, Choi BS. The renin-angiotensin system and aging in the kidney. Korean J Intern Med 2014;29:291-95. https://www.researchgate.net/publication/262530577_The_renin-angiotensin_system_and_aging_in_the_kidney
  4. Nadler JL, Lee FO, Hsueh W, et al. Evidence of prostacyclin deficiency in the syndrome of hyporeninemic hypoaldosteronism. N Engl J Med 1986;314:1015-20. https://www.ncbi.nlm.nih.gov/pubmed/3515183
  5. Williams GH. Hyporeninemic hypoaldosteronism. N Engl J Med 1986;314:1041-42. https://www.ncbi.nlm.nih.gov/pubmed/3515186
  6.  Block BL, Bernard S, Schwartzstein RM. Hypo-hypo: a complex metabolic disorder. Ann Am Thorac Soc 2016;13:127-133. https://www.ncbi.nlm.nih.gov/pubmed/26730868
  7. Michelis MF. Hyperkalemia in the elderly. Am J Kid Dis 1990;16:296-99.https://www.ajkd.org/article/S0272-6386(12)80005-9/pdf
  8. Hudson JB, Chobanian AV, Relman AS. Hypoaldosteronism. A clinical study of a patient with an isolated adrenal mineralocorticoid deficiency, resulting in hyperkaliemia and Stokes-Adams attack. N Engl J Med 1957;257:529-36. https://www.ncbi.nlm.nih.gov/pubmed/13464977

 

Why is my relatively healthy elderly patient so prone to hyperkalemia?

Can hypothyroidism be associated with hypertension?

FA Manian MD, MPH, , , , , , , , , , , Leave a comment

Short answer: Yes! Just as hyperthyroidism, hypothyroidism is also associated with hypertension (1-5). Compared to normal subjects, patients with hypothyroidism have a 3-fold increased prevalence of hypertension, usually diastolic (2). In fact, hypothyroidism has been identified as a cause of hypertension in 3% of patients with high blood pressure and is the most common cause of secondary hypertension after renovascular hypertension (1-3).

 
High systemic vascular resistance and increased arterial stiffness are among the important mechanisms explaining hypothyroid-induced hypertension (1). High systemic vascular resistance is thought to be due to the absence of the vasodilator effects of T3 on vascular smooth muscle and decreased response to beta-adrenergic stimulation, which in turn leads to increased alpha-adrenergic responses. Increased arterial stiffness may also contribute due to the myxedema involvement of the arterial wall. Other potential factors include free water retention due to an inappropriate secretion of anti-diuretic hormone (ADH) and obesity in hypothyroid patients (1,4).

 
Similar to its prevalence in hypothyroidism, hypertension is about 3-fold higher in patients with overt hyperthyroidism compared to normal subjects (1). However, in contrast to hypothyroid patients, the hypertension in hyperthyroidism is primarily “cardiogenic”, where the increased blood pressure levels are mainly maintained by the increased cardiac output due to high stroke volume and heart rate (1).

 
Thus, both hypothyroidism and hyperthyroidism can be associated with hypertension!

 
Bonus pearl: Did you know that hypertension due to hypothyroidism is typically associated with a low-renin state, is particularly sensitive to salt intake, and may not respond as well to angiotensin -converting enzyme inhibitors (1)?

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References
1. Mazza A, Beltramello G, Armigliato M, et al. Arterial hypertension and thyroid disorders: what is important to know in clinical practice? Annales d’Endocrinologie 2011;72:296-303. https://www.sciencedirect.com/science/article/abs/pii/S0003426611000886
2. Dernellis J, Panaretou M. Effects of thyroid replacement therapy on arterial blood pressure in patients with hypertension and hypothyroidism 2002; Am Heart J 2002;143:718-24. https://www.ncbi.nlm.nih.gov/pubmed/11923811
3. Anderson GH, Blakeman N, Steeten DHP. The effect of age on prevalence of secondary forms of hypertension in 4429 consecutively referred patients. J Hypertension 1994;12:609-15. https://insights.ovid.com/hypertension/jhype/1994/05/000/effect-age-prevalence-secondary-forms-hypertension/15/00004872
4. Saito I, ITO K, Saruta T. Hypothyroidism as a cause of hypertension. Hypertension 1983;5:112-15. https://www.ahajournals.org/doi/10.1161/01.hyp.5.1.112
5. Chaker L, Bianco AC, Jonklaas J, et al. Hypothyroidism. Lancet 2017;390:1550-62. https://www.ncbi.nlm.nih.gov/pubmed/28336049

Can hypothyroidism be associated with hypertension?