Systemic hypertension associated with hypercortisolism is common in people, affecting 70%-85% of the patients. The pathophysiological mechanisms for hypertension in HAC are incompletely understood, but in people a multifactorial model has been proposed with many pathways involved: the renin-angiotensin system, an increased mineralocorticoid activity, the sympathetic nervous system, the vasoregulatory system, metabolic factors, vascular remodeling and sleep apnea. In human medicine, risk factors for hypertension associated with hypercortisolism are reported. In pediatric patients there is a positive correlation between SH and high circulating cortisol concentrations. In addition, SH is more frequent in pediatric patients with ACTH-independent Cushing's syndrome (CS). In adults, this tendency has also been observed in patients with ACTH-independent CS, but the prevalence of SH is similar for ACTH-dependent and independent hypercortisolism. Furthermore, in adults with CS, age, body mass index and duration of hypercortisolism have been associated with the development of SH, but no correlation is observed with circulating cortisol concentrations. Hypertensive human patients with hypercortisolism tend to have lower potassium blood concentrations than normotensive patients, especially those with ectopic CS in which hypokalemia is frequent and strongly associated with hypertension.
Systemic hypertension is also recognized in dogs with HAC with a prevalence between 31% and 86%. Some pathophysiological mechanisms have also been proposed, such as increased mineralocorticoid activity, decreased nitric oxide concentrations or increased renal vascular resistance. There are few studies assessing the risk factors for SH in dogs with HAC; in previous studies, no difference in the prevalence or severity of SH is observed between dogs with PDH or ADH and there is no correlation between systolic blood pressure (SBP) and age, sex, reproductive status or results of the ACTH-stimulation tests. Previous studies have inconsistently identified a relationship between SBP and urinary protein to creatinine ratio (UPC) or baseline cortisol concentrations. A correlation between SBP and UPC but not with baseline cortisol concentrations has been described; however, other authors have found a correlation between SBP and baseline cortisol concentrations but not with UPC.
The objectives of our study were to determine the prevalence and severity of SH in dogs with naturally occurring HAC and to identify potential risks factors for SH in these dogs.
Background: Systemic hypertension (SH) is common in dogs with hyperadrenocorticism (HAC) however there are not many studies assessing its prevalence and risk factors.
Objectives: To determine the prevalence and severity of SH in dogs with HAC and its association with clinical and laboratory findings to identify potential risk factors.
Animals: Sixty-six client owned dogs with spontaneous HAC.
Methods: Retrospective cross-sectional study. Medical records of dogs with HAC were reviewed. Systolic blood pressure (SBP) was measured using Doppler ultrasonography. Clinical signs, physical examination findings and clinicopathologic data (CBC, serum biochemistry and electrolytes, urinalysis and urinary culture, and adrenal function tests) were reviewed for analysis.
Results: Prevalence of SH (≥150 mm Hg) was 82% (54/66) and prevalence of severe SH (≥180 mm Hg) was 46% (30/66). All dogs with thrombocytosis had SH (P = .002), and a platelet count ≥438 x 103/μL was 100% specific and 61.1% sensitive to predict SH (AUC = .802, P = .001). Median potassium levels were lower in hypertensive dogs (4.1 mEq/L, range 3.1-5.4 mEq/L) than in normotensive ones (4.5 mEq/L, range 4.0- 5.0 mEq/L) (P = .007). Dogs with UPC ≥ 0.5 had higher median SBP than those without proteinuria (P = .03). Dogs with concurrent diabetes mellitus seemed to have a reduced risk of SH (OR = .118, 95%CI = .022-.626, P = .02).
Conclusions and Clinical Importance: In conclusion, SH, which is frequently severe, is common in dogs with HAC and blood pressure should be routinely assessed in dogs with a suspicion of HAC. In those cases in which blood pressure cannot be routinely evaluated, the presence of thrombocytosis, low potassium concentrations and proteinuria should raise concerns about possible SH and the risk of TOD and might incite the clinician to perform this procedure. The association between SH and potassium concentrations might suggest a role of MR in the development of hypertension in these dogs; however further studies are needed to investigate the relationship between SH, aldosterone and 11β-HSD activity in dogs with HAC.
These findings might suggest that mineralocorticoid receptors (MR) could be involved in the development of SH in dogs with HAC. The MR has the same affinity to aldosterone and cortisol, but not to cortisone. The enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD) converts cortisol into cortisone, and it is abundantly expressed in the classical mineralocorticoid target tissues (eg, renal cortex, vascular endothelium and smooth muscle cells), binding the selectivity of MR to aldosterone. Hypercortisolism saturates the 11β-HSD allowing cortisol to bind the MR and resulting in a cortisol induced apparent mineralocorticoid excess. In people with hypercortisolemia, this feature has been associated with sodium retention and potassium excretion, which could contribute to the development of SH.
Finally, dogs with concurrent DM and HAC seemed to have a reduced risk of development of SH; this finding should be further investigated.
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