HOSP #	165965617	WARD	Endocrine Ward
CONSULTANT	Dr Heleen Vreede	DOB/AGE	33 y female

Abnormal Result

Salivary Cortisol = 36 nmol/L

Presenting Complaint

Struggling with a right hand abscess – seen at the hand surgeons for the abscess. She ascribed this hand abscess due to “easy bruising”.

The patient is stable but feeling generally unwell with proximal muscle weakness.

Reported symptoms of depression.

History

In 2017 a pituitatry microadenoma was diagnosed after the patient presented with weight gain, moon facies, easy bruising and being weak proximally.

The Cushings disease is ACTH – dependent (determined with a DDAVP stimulation test – see below).

The patient was known to Endocrinology and Neurosurgery departments and unfortunately had lost two of her booked surgery dates for transsphenoidal petrosal sinus sampling due to the COVID pandemic. She was then

Hypertension on ACEi, HCTZ, Amlodipine

Examination

On this visit the patient was found to have proximal muscle weakness, and had signs and symptoms of a severe depressive episode.

Laboratory Investigations

25/02/2021	25/02/2021	26/02/2021
9:30	17:00	0:00
642	636	675

Midnight salivary cortisol 36.00 nmol/L

        Salivary cortisol reference intervals (when performed on a Roche Cobas
        analyzer):

        Reference Range:
         Morning   (06:00 - 10:00)  < 24.10 nmol/L
         Afternoon (16:00 - 20:00)  < 9.65  nmol/L
         Midnight +/- 30 minutes    < 11.30 nmol/L

        Ref: Cobas package insert

Other Investigations

CT Scan in 2017 confirmed a microadenoma of the pituitary gland (<1cm)

From figure 1, a 37.6% increase in cortisol is observed (722 to 994 nmol/L).

Final Diagnosis

ACTH- dependent Cushings Syndrome (Cushings Disease). The patient was initiated on Ketokonazole, an antifungal which has shown to decrease cortisol in some patients in a multicenter study where they mention it’s “worth a try” (J Clin Endocrinol Metab. 2014 May;99(5):1623-30. doi: 10.1210/jc.2013-3628). The liver enzymes in this patient didn’t increase significantly (not shown).

The patient does get intermittent hypokalemia (2.9mM the morning of presentation) but the clinicians are hesitant to start on spironolactone. Potassium was being replaced. One of the Endocrinologists (Dr Bill Toet) also advised stopping the HCTZ since it may worsen hypokalemia

Depression – likely related to the hypercortisolism – patient was initiated on fluoxetine.

Take Home Message

Thiazide diuretics increase the excretion of sodium, chloride, and water by inhibiting sodium ion transport across the renal tubular epithelium. Although thiazides may have more than one action, the major mechanism responsible for diuresis is to inhibit active chloride reabsorption at the distal portion of the ascending limb or, more likely, the early part of the distal tubule (i.e., the cortical diluting segment). Exactly how chloride transport is impaired is unknown. Thiazides also increase the excretion of potassium and bicarbonate, and they decrease the urinary excretion of calcium and uric acid. Hydrochlorothiazide may be used to reduce hypercalciuria and prevent the recurrence of calcium-containing renal calculi. By increasing the sodium load at the distal renal tubule, hydrochlorothiazide indirectly increases potassium excretion via the sodium-potassium exchange mechanism. Hypochloremia and hypokalemia can cause mild metabolic alkalosis.

Salivary Cortisol: The cortisol concentration in saliva is 10-fold lower than total serum cortisol and accurately reflects the serum concentration, both levels being lowest around midnight.  A meta-analysis for 11 studies analysed, found mean sensitivity and specificity of the salivary cortisol assay were both >90%. This analysis confirms the reliability of the saliva cortisol assay as pragmatic tool for the accurate diagnosis of Cushing syndrome. 

Close monitoring of liver enzymes is necessary when patients are initiated on ketokonazole, as it is prone to cause hepatitis.

HOSP #		WARD	Red Cross Hospital Oncology ward
CONSULTANT	Dr Amith Ramcharan / Dr Jody Rusch	DOB/AGE	11y Female

Abnormal Result

Persistent hyponatremia

2018 supracellar JPA (Astrocytoma)

Seizures – phenobarb.

Chemo @ 8 y of age.

Vincristin and Carboplatin administration

Craniospinal radiation – leptospinal

Presenting Complaint

Seizures – controlled with Phenobarbital

History

This is an 11 year old patient with a suprasellar JPA (Juvenile Pilocytic Astrocytoma). The tumour was diagnosed at 8y of age, upon which chemotherapy with Vincristine and Carboplatin was initiated. The pituitary was close to the area of radiation therapy as well.

Examination

The patient’s hydration status was normal and there was no cerebral edema.

Laboratory Investigations

The patient was found to have hypothyroidism and started on T4 replacement 50ug mane.

Other Investigations

Urine electrolytes on 23/02/2021:

• Na 54 mM
• K 31.3 mM
• Cl 110 mM
• Osmol 554 mOsmol
• Fractional reabsorption of phosphate: 85%

Final Diagnosis

Unknown – but likely indicates a tubular loss of sodium due to the chemotherapeutic agent(s).

Take Home Message

Chemotherapeutic agents does cause tubulopathy.

TMP/GFR is likely a better indicator of renal phosphate handling than only fractional reabsorption of phosphate. This can be calculated mathematically or read from a nomogram.

HOSP #		WARD	Antenatal Clinic
CONSULTANT	Dr Heleen Vreede	DOB/AGE	30y Female

Abnormal Result

Glucose of < 0.1 mmol/L in a healthy individual being compos mentis.

Presenting Complaint

The patient is following up for routine check-up concerning possible hyperglycemia.

History

The mother is a known diabetic on treatment.

Examination

N/A

Laboratory Investigations

Glucose at 11h00	<0.1 mmol/L
Glucose at 14h00	1.5 mmol/L
Glucose at 20h00	2.6 mmol/L
Glucose at 06h00 (next morning – the day on which bloods were sent to the laboratory)	6.2 mmol/L

Other Investigations

Glucose at 11h00	0.8 mmol/L
Glucose at 14h00	2.6 mmol/L
Glucose at 20h00	2.1 mmol/L
Glucose at 06h00 (next morning – the day on which bloods were sent to the laboratory)	5.7 mmol/L

The condition of the collection tubes were confirmed. All were taken in the correct collection tubes (Sodium Fluoride tubes) and appears to be correctly labelled.

Final Diagnosis

The conclusion from above findings are the following:

1. Not enough NaF was present in the sample to adequately inhibit glycolysis, enabling a falsely decreased glucose reading in the older samples (>12 hours old).
2. The patient wasn’t aware that the powder should stay in the tube when blood is collected, hence discarded the powder before taking her capillary blood samples.

Take Home Message

• Microtainer (R) specimen containers can be identified without the caps by the colour of the writing on the outside of the tube (in this case grey – the same colour as the cap).
• The presence of the correct collection tube does not equal the presence of the additive.
• Attention to detail is necessary to solve cause and effect in some cases.
• In this case the nursing staff in the Antenatal clinic was informed about the powder in the collection tubes which should not be discarded. The nurse whom I spoke to was completely unaware that the powder in the collection tube served any function.
• Glucose measurement from capillary blood samples, as in this case, can likely be inaccurate due to many possible pre-analytical (or analytical) reasons. It is however still likely a valid alternative to a resource-constrained setting, especially in South Africa, where patients cannot afford their own glucometers or where there are shortages of handheld glucometers, or more importantly, glucose measuring sticks (or cartridges).