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