1. Primary hyperaldosteronism (Conn’s syndrome): An underdiagnosed disorder in both humans and cats Michiel Kerstens and Hans Kooistra

3. Zona Glomerulosa Zona fasiculata Zona Reticularis Adrenal gland

4. Adrenals adrenal cortex adrenal cortex mineralocorticoids: aldosterone (salt) mineralocorticoids: aldosterone (salt) glucocorticoids: cortisol (sugar) glucocorticoids: cortisol (sugar) androgens (sex) androgens (sex) adrenal medulla adrenal medulla catecholamines (adrenaline or epinephrine) catecholamines (adrenaline or epinephrine)

6. Adrenocortical disorders * Adrenocortical hyper function: - mineralocorticoid excess - glucocorticoid excess - androgen excess * Adrenocortical hypo function - primary (Addison’s disease) - secondary * Non-functional adrenocortical tumors

7. Adrenocortical disorders * Adrenocortical hyper function: - mineralocorticoid excess = primary hyperALDOSTERONism - glucocorticoid excess - androgen excess * Adrenocortical hypo function - primary (Addison’s disease) - secondary * Non-functional adrenocortical tumors

8. JGC Angiotensinogen Angiotensin I Angiotensin II Renin Converting enzyme Aldosterone The Renin-Angiotensin-Aldosterone system Potassium excretion Na+ reabsorption

9. Adrenocortical disorders * Adrenocortical hyper function: - mineralocorticoid excess = primary hyperaldosteronism = Conn’s syndrome - glucocorticoid excess - androgen excess * Adrenocortical hypo function - primary (Addison’s disease) - secondary * Non-functional adrenocortical tumors

10. 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 Clinical Research (1954): “I have prepared no comprehensive review of my personal philosophy of clinical investigation. Instead, I plan to make a scientific report to you about a clinical syndrome, the investigation of which has been most exciting to me.” which has been most exciting to me.”

11. Jerome W. Conn 34-year-old woman (in 1954) Since 7 years attacks of muscle spasm and muscle weakness Since 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 greater mineralocorticoid effect than urine of healthy humans

12. 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?

13. Underdiagnosed disorder: It is there, but you have to look for it

14. 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?

15. 12-year-old castrated male shorthaired cat Emergency Not able to jumpNot able to jump Cervical ventroflexionCervical ventroflexion Falls in lateral recumbencyFalls in lateral recumbency  muscle weakness  hypokalemia ??? MydriasisMydriasis  Blindness due to ….

16. Membrane potentials in nerve fibers and skeletal muscle fibers Na/K-ATPase:Na/K-ATPase: Membrane potential of –90 mVMembrane potential of –90 mV Action potentials:Action potentials: –Depolarization –Repolarization

17. Feline primary hyperaldosteronism clinical manifestations Plasma [K + ] ≈ 2.5 mmol/l

19. Afbeelding: http://www.fabcats.org

20. 12-year-old castrated male shorthaired cat [K + ]1.6(3.4 – 5.2)mmol/l

21. [K + ] < 3.4 mmol/l K shift ECF ICF e.g. insulin therapy and alkalosis K shift ECF ICF e.g. insulin therapy and alkalosis Inadequate intake: Fasting Inadequate intake: Fasting Gastrointestinal losses: Vomiting Diarrhea Gastrointestinal losses: Vomiting Diarrhea Excessive renal losses Major causes of hypokalemia in cats

22. JGC Angiotensinogen Angiotensin I Angiotensin II Renin Converting enzyme Aldosterone The Renin-Angiotensin-Aldosterone system Potassium excretion Na+ reabsorption

23. 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 ???

25. 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???

26. JGC Angiotensinogen Angiotensin I Angiotensin II Renin Converting enzyme Aldosterone The Renin-Angiotensin-Aldosterone system Potassium excretion Na+ reabsorption

27. 12-year-old castrated male shorthaired cat with arterial hypertension [K + ]1.6(3.4 – 5.2)mmol/l Aldosterone12450(60 – 630)pmol/l Renin< 20(110 – 540)fmol/l/s PAC/PRA6225(0.3 – 3.8) Primary hyperaldosteronism:  renal Na + retention  arterial hypertension  blindness  Increased renal K + excretion  hypokalemia  muscle weakness Metastasised malignant aldosteronoma

28. Malignant aldosteronoma

30. Underdiagnosed disorder: It is there, but you have to look for it