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Primary hyperaldosteronism(Conn’s syndrome):
An underdiagnosed disorderin both humans and cats
Michiel Kerstens and Hans Kooistra
Zona Glomerulosa
Zona fasiculata
Zona Reticularis
Adrenal gland
Adrenals
• adrenal cortex
mineralocorticoids: aldosterone (salt)
glucocorticoids: cortisol (sugar)
androgens (sex)
• adrenal medulla
catecholamines (adrenaline or epinephrine)
Adrenocortical disorders
* Adrenocortical hyperfunction:- mineralocorticoid excess- glucocorticoid excess- androgen excess
* Adrenocortical hypofunction- primary (Addison’s disease)- secondary
* Non-functional adrenocortical tumors
Adrenocortical disorders
* Adrenocortical hyperfunction:- mineralocorticoid excess
= primary hyperALDOSTERONism- glucocorticoid excess- androgen excess
* Adrenocortical hypofunction- primary (Addison’s disease)- secondary
* Non-functional adrenocortical tumors
JGC
AngiotensinogenAngiotensin I
Angiotensin II
ReninConverting enzyme
Aldosterone
The Renin-Angiotensin-Aldosterone system
Potassium excretionNa+ reabsorption
Adrenocortical disorders
* Adrenocortical hyperfunction:- mineralocorticoid excess
= primary hyperaldosteronism= Conn’s syndrome
- glucocorticoid excess- androgen excess
* Adrenocortical hypofunction- primary (Addison’s disease)- secondary
* Non-functional adrenocortical tumors
Jerome W. Conn
Professor of Medicine at University of Michigan; research devoted to adaptations to tropical heat.
At the Annual Meeting of the Central Society for ClinicalResearch (1954):
“I have prepared no comprehensive review of my personal philosophy of clinical investigation.Instead, I plan to make a scientific report to youabout a clinical syndrome, the investigation of
which has been most exciting to me.”
Jerome W. Conn
34-year-old woman (in 1954)
Since 7 years attacks of muscle spasm and muscle weaknessSince 4 years: arterial hypertension (176/104 mmHg)
Severe hypokalemia (K: 1.6 – 2.5 mmol/l)Slight hypernatremia (Na: 146 – 151 mmol/l)
Intraperitoneal administration of urine of this women to adrenalectomized rats resulted in a 22 times greatermineralocorticoid effect than urine of healthy humans
Jerome W. Conn
34-year-old women
Laparotomy: Adrenal gland tumor (right side) aldosterone-producing aldosteronoma (APA)
After adrenalectomy: almost complete disappearance of signs
(Hyper)Aldosteronism
20% ?? 10% ?? < 0.1% !!??
Cause of essential hypertension?
Underdiagnosed disorder: It is there, but you have to look for it
Jerome W. Conn
34-year-old women
Laparotomy: Adrenal gland tumor (right side) aldosterone-producing aldosteronoma (APA)
After adrenalectomy: almost complete disappearance of signs
(Hyper)Aldosteronism
20% ?? 10% ?? < 0.1% ?? 5-11%
Cause of essential hypertension?
12-year-old castrated male shorthaired cat
Emergency
• Not able to jump
• Cervical ventroflexion
• Falls in lateral recumbency
muscle weakness
hypokalemia ???
• Mydriasis
Blindness due to ….
Membrane potentials in nerve fibers and skeletal muscle fibers
• Na/K-ATPase: • Membrane
potential of –90 mV
• Action potentials: – Depolarization– Repolarization
Feline primary hyperaldosteronismclinical manifestations
Plasma [K+] ≈ 2.5 mmol/l
Afbeelding: http://www.fabcats.org
12-year-old castrated male shorthaired cat
[K+] 1.6 (3.4 – 5.2) mmol/l
[K+ ] < 3.4 mmol/l[K+ ] < 3.4 mmol/l
K shift ECF ICFe.g. insulin therapy
and alkalosis
K shift ECF ICFe.g. insulin therapy
and alkalosis
Inadequate intake:Fasting
Inadequate intake:Fasting
Gastrointestinal losses:VomitingDiarrhea
Gastrointestinal losses:VomitingDiarrhea
Excessive renal lossesExcessive renal losses
Major causes of hypokalemia in catsMajor causes of hypokalemia in cats
JGC
AngiotensinogenAngiotensin I
Angiotensin II
ReninConverting enzyme
Aldosterone
The Renin-Angiotensin-Aldosterone system
Potassium excretionNa+ reabsorption
12-year-old castrated male shorthaired cat
• Not able to jump
• Cervical ventroflexion
• Falls in lateral recumbency
hypokalemia !!!
due to hyperaldosteronism???
• Mydriasis
Blindness due to ….
arterial hypertension ???
12-year-old castrated male shorthaired cat
• Not able to jump
• Cervical ventroflexion
• Falls in lateral recumbency
hypokalemia !!!
due to hyperaldosteronism???
• Mydriasis
Blindness due to hypertension!
due hyperaldosteronism???
JGC
AngiotensinogenAngiotensin I
Angiotensin II
ReninConverting enzyme
Aldosterone
The Renin-Angiotensin-Aldosterone system
Potassium excretionNa+ reabsorption
12-year-old castrated male shorthaired catwith arterial hypertension
[K+] 1.6 (3.4 – 5.2) mmol/l
Aldosterone 12450 (60 – 630) pmol/l
Renin < 20 (110 – 540) fmol/l/s
PAC/PRA 6225 (0.3 – 3.8)
Primary hyperaldosteronism:
renal Na+ retention arterial hypertension blindness
Increased renal K+ excretion hypokalemia muscle weakness
Metastasised malignant aldosteronoma
Malignant aldosteronoma
• Considered “rare” by many veterinarians• unfamiliar• no routine arterial blood pressure measurement • symptomatical treatment of systemic arterial
hypertension and hypokalemia • “the chronic renal disease causes the
hypertension / hypokalemia”
Feline primary hyperaldosteronismreasons for underdiagnosis:
Underdiagnosed disorder: It is there, but you have to look for it