1. Bondoc.Borela.Buenaventura.Buhat.Calaoagan. Carilo.Casi.Castano.Celino.Francisco.Garcia

2. Identifying data M.I is 35 y/o Female Married Filipino Roman Catholic Admitted for the first time at UERMMMC

3. Chief Complaint Generalized body weakness of 12 hours duration

4. History of Present Illness

5. Past Medical History Hypertension- diagnosed 7 years ago  Rx: Amlodipine 10 mg/tab 1 tab OD, Losartan 50 mg/tab 1 tab OD Surgery: ▫1999: Right oophorectomy ▫2008: total abdominal hysterectomy with left oophorectomy 2 years PTA, admitted due to similar episode of weakness No history of DM, thyroid, kidney, lung, heart disorders

6. Family History Father- DM type 2 Mother- hypertension No family history of heart, lung, kidney and connective tissue disorders Personal and Social History Unremarkable

7. Physical Exam Awake, conscious, coherent, stretcher bound Vital signs: BP is 150/100, HR- 76 bpm, RR-18 cpm, Temperature is 37.1 ˚C Remarkable findings: grade 3/5 pulses, Muscle strenght: 3/5 both upper extremities 1/5 on both lower extremites Normotonic, normoreflexive, intact sensation, other neurological exams are normal.

8. <3.4 mmol/L >4.3 mmol/L >50,000 WBC count<50,000 WBC count Bilateral Weakness NeurologicNeuromuscular JunctionMyopathies Serum K+ CBC Recent insulin, B-adrenergic, theophyline use, or, more rarely, anabolic stimulus or family history suggestive of hypokalemic periodic paralysis Skin, GI or Renal K Loss No Yes ABG AcidosisAlkalosis Urine K+ <20 mEq K/24 hrs>20 mEq K/24 hrs Redistribution or hypokalemic periodic paralysis Pseudohypokalemia Recent diuretic use? YesNoProbable diuretic- induced hypokalemia CHF, hepatic insufficiency, nephrotic syndrome or renal artery stenosis Yes Probable secondary hyperaldosteronism No Hypomagnesemia? Yes Hypomagnesemia induced hypokalemia No Serum bicarbonate? Low RTA, DKA or ureterosigmoidostomy Normal or High Random Urine K/C ratio <1.5 Thyrotoxic PP >1.5 Blood Pressure Elevated PRA and PAC Both Low CAH Cushing Syndrome Liddle Syndrome Both High RVH, COA, RST High PAC Low PRA Primary Aldosteronism LowHigh TSH >4.25 uLU/mL FT4: >1.7 ng/L TSH <0.34 uLU/mL FT4 <0.8 ng/L

9. Bilateral Weakness Neurologic Altered mental status Signs of UMN/LMN Sensory deficit Autonomic involvemen t Neuromuscular Junction Bulbar signs Fatigability Myopathies All limbs involved No sensory involvement No autonomic involvement

10. <3.4 mmol/L >4.3 mmol/L Bilateral Weakness NeurologicNeuromuscular JunctionMyopathies Serum K+

11. >50,000 WBC count<50,000 WBC count CBC Recent insulin, B-adrenergic, theophyline use, or, more rarely, anabolic stimulus or family history suggestive of hypokalemic periodic paralysis Skin, GI or Renal K Loss No Yes ABG AcidosisAlkalosis Urine K+ <20 mEq K/24 hrs>20 mEq K/24 hrs Redistribution or hypokalemic periodic paralysis Pseudohypokalemia Recent diuretic use? YesNoProbable diuretic- induced hypokalemia CHF, hepatic insufficiency, nephrotic syndrome or renal artery stenosis Yes Probable secondary hyperaldosteronism No Hypomagnesemia? Yes Hypomagnesemia induced hypokalemia No Serum bicarbonate? Low RTA, DKA or ureterosigmoidostomy Normal or High Random Urine K/C ratio <1.5 Thyrotoxic PP >1.5 Blood Pressure Elevated PRA and PAC Both Low CAH Cushing Syndrome Liddle Syndrome Both High RVH, COA, RST High PAC Low PRA Primary Aldosteronism LowHigh TSH >4.25 uLU/mL FT4: >1.7 ng/L TSH <0.34 uLU/mL FT4 <0.8 ng/L

12. Differentials Diagnoses Rule InRule Out LIDDELL’S SYNDROME Presence of hypokalemia Presence of metabolic alkalosis Commonly presents with hypertension Possible family history of the disease On the basis of imaging which showed a hypodense nodule on left lateral limb, which supports primary hyperaldosteronism ↑ serum sodium ↓ serum Aldosterone & renin

13. Rule InRule Out THYROTOXIC HYPOKALEMIC PERIODIC PARALYSIS Presents with episodic generalized weakness Presence of normal thyroid hormone levels during the episode of weakness ↑ Thyroid function test Lack of findings suggestive to support

14. MYASTHENIA GRAVIS Presence of weakness in upper and lower limbs Failure to regain movement/muscle strength after rest Lack of any ocular findings on neurological exam Lab findings are not suggestive to support this differential Rule InRule Out

15. Rule inRule out DIABETES MELLITUS Weakness of lower extremities Family history of diabetes Presence of hypertension Inc FBS No improvement of symptoms even after potassium administration Lack of other DM indicators Lack of associated findings such as abrupt onset of pain, tenderness and edema There was also absent hardness and induration in the thighs

16. Primary Aldosteronism Bilateral Adrenal Hyperplasia Aldosterone Secreting Adenoma CT scan

17. Primary Impression Hypokalemia secondary to Primary Aldosteronism (Conn’s Syndrome)

18. Why rule in Hypokalemia? Acute Generalized weakness Absence of UMN and LMN signs, Sensory and Autonomic Involvement, Bulbar signs and Fatigability. Marked decrease in K+ level (1.5mmol/L)

19. Definition of Hypokalemia Plasma K+ concentration <3.5 mmol/L May be due to: ▫Decreased net intake ▫Shift of K+ into cells ▫Increased net loss

20. Clinical Manifestations of Hypokalemia Usually asymptomatic ▫Unless plasma K+ concentration <3 mmol/L Fatigue, myalgia, muscular weakness of the lower extremities Severe Hypokalemia → progressive weakness, hypoventilation and complete paralysis

21. Occurrence of Metabolic Alkalosis High pH (7.56) Low pCO2 (32) High HCO3 (28.7) Result of K+ redistribution + excessive renal K+ loss K+ depletion → intracellular acidification → increase HCO3 production

22. Primary Hyperaldosteronism (Conn’s Syndrome)

23. Why rule in Primary Hyperaldosteronism? Triad of Hypertension, Hypokalemia, and Metabolic Alkalosis Elevated BP upon admission Diagnosed with HTN 7 years ago Poor compliance to maintenance medications Hypokalemia and Metabolic Acidosis on lab tests

24. Primary Hyperaldosteronism Syndrome associated with hypersecretion of adrenal mineralocorticoid Aldosterone Accounts for 5-10% of hypertension cases Peak incidence → 30-60 years old

25. Pathophysiology Cellular uptake of K+ ▫Aldosterone → inc. Na + -K + ATPase] → inc. transport of K+ into intracellular space Regulation of Renal K+ transport ▫Aldosterone → inc. Apical Na conductance, basolateral Na + -K + ATPase activity, and electrogenic Na absorption in the collecting tubules → K+ movement from intracellular to luminal fluid

26. Excessive aldosterone ▫increased sodium retention ▫decreased plasma renin ▫Increased renal potassium excretion → hypokalemia

27. Clinical Manifestations Hypokalemia Muscular weakness ▫K+ depletion in the muscle cell membrane Paresthesias Headache Polyuria Polydipsia Moderate hypertension (diastolic) ▫Due to inc. Na reabsorption

28. Plasma Renin Activity (PRA) Plasma Aldosterone Concentration (PAC) Primary Hyperaldosteronism is consistent with: ▫ ↓ PRA (baseline-12.69 ng/dL; post-12.36 ng/dL) ▫ ↑ PAC (<0.1 ng/mL/hr),

29. Diagnostics CT Scan

30. Course in the Ward Day of Admission ▫BP: elevated at 150/100mmHg ▫Inability to move both lower extremities ▫CBC  ↓ WBC count (13,100/L) with neutrophil predominance in absolute count ▫Serum electrolytes  ↓ potassium (1.5mmol/L) ▫Albumin & BUN: normal

31. Course in the Ward Day of admission ▫Uric acid: ↑ (22 umol/L) ▫Creatinine: ↑ (100 umol/L) ▫Urine electrolytes   potassium (9.2 mmol/l) ▫ABG  ↑ pH (7.56) and HCO3 (28.7mmol/L)  ↓ pCO2 (32mmHg)

32. Course in the Ward Day of admission ▫FBS: normal ▫Lipid profile: normal ▫Urinalysis  Few bacterial and epithelial cells ▫CXR: clear ▫IV potassium chloride drip was started ▫Thyroid function test was requested

33. Course in the Ward Day 2-3 ▫BP : 160/100mmHg ▫Movement of both legs from side to side ▫Gradual ↑ of potassium to 2.4mmol/L (day 3) ▫Thyroid function test: normal TSH and fT4 ▫Plan: saline suppression test when potassium level becomes normal

34. Course in the Ward Day 4-5 ▫Able to walk around the room without assist ▫Serum potassium: 4.7mmol/L  IV potassium  oral ▫Saline suppression test  Baseline plasma renin activity and aldosterone  2L IV saline infused over 4 hours  plasma aldosterone

35. Course in the Ward Day 4-5 ▫BP : 200/100mmHg  spironolactone 25mg/tab, 1 tablet BID and felodipine10mg/tab, 1 tablet OD ▫Dicharged with plans for follow-up ▫Plasma renin and aldosterone results after 2 weeks

36. Follow-up BP maintained at 100-120/70-80mmHg No recurrent weakness Saline suppression test ▫ ↑ baseline aldosterone: 12.69ng/dL ▫ ↑ aldosterone post-infusion: 12.36ng/dL ▫ ↓ plasma renin activitiy: <0.1ng/mL/hr

37. Follow-up Abdominal CT scan requested ▫Hypodense enhancing nodule, measuring 9.9 x 7.6 x 11.7mm, at the lateral limb of the left adrenal gland ▫Right adrenal gland unremarkable ▫No other abnormalities in the pre-contrast, arterial, portal venous and wash-out phases ▫Liver, pancreas and gallbladder are unremarkable ▫Referral to surgery

38. Management Control of hypertension and aldosterone level Potassium supplementation Abdominal CT scan Adrenalectomy ▫Laparoscopic vs. open surgery Complications Prognosis

39. THANK YOU!