Case study 002

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Question 1

Mrs. N.M. is a 69-year-old retired nurse, who had a history of bipolar disorder and had been on lithium for more than 9 years. She was admitted to the hospital because of delirium, excessive urination, muscle pain and vomiting.

On examination:

Height: 170 cm, Weight: 66 kg, BMI: 22.8
BP: 142/93 mmHg, Heart Rate: 86/min, Respiratory rate: 24/min, Temperature: 36.9⁰C, O₂SAT: 96%

What laboratory values need to be monitored if a patient is taking lithium? (select all that apply)

A	Serum potassium
B	Serum sodium
C	Renal function
D	Thyroid function
E	Serum calcium
F	Leucocytic count
G	Hemoglobin

Question 2

Mrs. N.M.’s laboratory values are as follows:

Blood analysis:
- CBC:
  - RBCs: 4.1 x 10¹²/L, Hemoglobin: 135.5 g/L, Hematocrit: 0.39
  - MCV: 88 fL, MCH: 32 pg, RDW: 12.2%, Reticulocytes 1%, ESR: 8 mm/hour
  - WBC: 12.5 x 10⁹/L, (Neutrophils: 8.1 x 10⁹/L, Lymphocytes: 3.5 x 10⁹/L, Basophils: 0.09 x 10⁹/L, Eosinophils: 0.32 x 10⁹/L, Monocytes: 0.5 x 10⁹/L)
  - Platelet counts: 287 x 10⁹/L
- Na: 152 mmol/L, K: 4.0 mmol/L, Cl: 112 mmol/L, Ca (total): 2.7 mmol/L, Ca (ionized): 1.3 mmol/L
- Glucose: 5.9 mmol/L, HbA1C: 6.0%, BUN: 8.0 mmol/L, Creatinine: 85.3 µmol/L, Uric acid: 312 mmol/L
- Triglycerides: 2.1 mmol/L, Cholesterol: 5.3 mmol/L, HDL: 0.95 mmol/L, LDL: 2.3 mmol/L
- Bilirubin: 14 mmol/L, Albumin: 38 g / L, ALP: 122 U/L
- Plasma Lithium level: 1.8 mmol/L
- TSH: 1.4 uU/mL, Total T₄: 83.2 nmol/L, Free T₄: 10 pmol/L, Total T₃: 2.0 nmol/L, Free T₃: 5.3 pmol/L
- Aldosterone (recumbent): 0.56 nmol/L
- Plasma parathyroid hormone level: 5.6 pmol/L
- Plasma Arginine Vasopressin: 3.72 pmol/L
- Plasma Osmolarity: 318 mOsmol/Kg
Urinalysis:
- Volume: 7.2 L/24 hours
- Color: clear watery, pH: 6.5, Specific gravity: 1001, Osmolarity : 102 mOsmol/kg; Glucose, Ketones, Albumin, Bilirubin: negative, WBCs and RBCs: 0 and 2/HPF, Squamous epithelial cells: 2/HPF, Casts, crystals: negative, Yeast: ++

How would you interpret the serum lithium level of 1.8 mmol/L for this patient?

A	Lower than the therapeutic range.
B	Normal, it is within the therapeutic range.
C	Higher than the therapeutic range.
D	Cannot be interpreted without knowing the daily dose of the medication.

Question 2 Explanation:

Serum lithium level should be monitored at the beginning of the treatment (to determine therapeutic range) and during treatment regularly. To see the therapeutic range of lithium please refer to the “Normal laboratory values” table. Value of 1.8 mmol/L is higher than the therapeutic drug level, which indicates lithium toxicity.

Question 3

What laboratory tests would you perform next for this patient? (select the top two)

A	Dexamethasone suppression test
B	Water deprivation test
C	Captiprol challenge test
D	Desmopressin injection test
E	Creatinine clearance
F	TRH stimulation test

Question 3 Explanation:

To learn more about each of these tests please, refer to the methodology section.

Question 4

Further laboratory investigation was requested:

The following are readings of body weight, plasma, and urine osmolarity prior to the start of water deprivation test and 6 hours after cessation of fluid intake:

	Baseline Time	6 hours
Weight (kg)	66	65
Plasma osmolarity (mOsmol/kg)	318	324
Urine osmolarity (mOsmol/kg)	102	104

After desmopressin (DDAVP) injection: Urine osmolarity (mOsmol/kg): 106 What does it indicate that the water deprivation test and desmopressin injection does not change the urine osmolarity?

A	Renal compensatory mechanisms maintain urine osmolarity even after water deprivation or desmopressin injection.
B	Since ADH is the main hormone to regulate water reabsorption, the ADH deficiency in Mrs. N.M. case caused water loss and low urine osmolarity.
C	Urine osmolarity did not increase after desmopressin injection because renal tubules cannot respond to ADH even in the presence of normal plasma ADH level

Question 4 Explanation:

After water deprivation and desmopressin injection the urine osmolarity should increase as ADH stimulates water reabsorption in the distal convoluted tubules and the collecting ducts. In this case, we can observe that even after giving desmopressin the urine osmolarity stays low, which indicates that the renal tubule cells cannot respond to ADH.

Question 5

What is definitive diagnosis of Mrs. N.M.’s case?

A	Drug induced cranial (central) diabetes insipidus
B	Type 2 diabetes mellitus
C	Drug induced nephrogenic diabetes insipidus
D	Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
E	Drug induced acute renal failure
F	Nephrogenic diabetes insipidus secondary to chronic renal failure

Question 5 Explanation:

Lithium induced nephrogenic diabetes mellitus occurs in 10-15% of patients who are on long-term lithium therapy. Lithium blocks the adenyl-cyclase enzyme in the renal tubular cells, and because ADH acts through the second messenger cAMP, it eventually prevents the response to ADH. Please make sure you complete Case Study 6.7 to learn more about ADH and other type of diabetes insipidus.

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