HOSP #	MRN96038757	WARD	F17 Surgical ward
CONSULTANT	Dr. Jody Rusch	DOB/AGE	26 y male

Abnormal Result

Potassium more than 10 mmol/L on the ion-selective electrode.

Presenting Complaint

The patient was admitted in surgery after bowel surgery, on total parenteral nutrition.

History

Surgery was done due to bowel obstruction.

Examination

Not available.

Typically:

A hallmark of small bowel obstruction is dehydration, which manifests as tachycardia, orthostatic hypotension, and reduced urine output, and, if severe, dry mucus membranes.

●Abdominal inspection will identify a variable degree of abdominal distention.

●Abdominal auscultation – Acute mechanical bowel obstruction is characterized by high-pitched “tinkling” sounds associated with the pain. With significant bowel distention, bowel sounds may become muffled, and as the bowel progressively distends, bowel sounds can become hypoactive.

●Abdominal percussion – Distention of the bowel results in hyperresonance or tympany to percussion throughout the abdomen. However, fluid-filled loops will result in dullness. If percussion over the liver is tympanitic rather than dull, it may be indicative of free intra-abdominal air. Tenderness to light percussion suggests peritonitis.

●Abdominal palpation may identify any abdominal wall or groin hernias, or abnormal masses.

Laboratory Investigations

Date	16/03/2020	14/03/2020	13/03/2020	12/03/2020	12/03/2020	11/03/2020	10/03/2020	08/03/2020
Time	07:22	10:38	10:30	19:59	12:32	21:23	16:05	12:53
Na	144	141	141		δ-  138	143	δ+  145	140
K	>10	2.6	3.0 L	3.0 L	INVH	3,2 L	δ+  3,7	3.0 L
Cl
Urea	4.4	5,1	5.0		5,5	6,9	δ+  5,5	2,5
Creat	47	60 L	60 L		64	67	66	62 L
Ca	1.63	2,24	2,27		2,13 L	2,23	2.30	2,23
Mg	0.38	δ- 0.67	δ+ 0.90		0.77	0.82	0.75	0.74
Phos	1.1	1.50 H	1,31		1,28	1,38	1,23	1,17
Uric acid
Total prot	CEGK				CEGK
Alb	30				39			40
Total bili	<3				3 L			4 L
Conj bili	2				INVH			2
ALT	35				28			32
AST	33				INVH			28
ALP	118				137 H			158 H
GGT	99				96 H			113 H
LD	138				δ+  465 H			317 H
CRP	2				7			6

Other Investigations

Repeated results later in the afternoon:

Date	16/03/2020	16/03/2020
Time	13:04	07:22
Na	144	144
K	δ+  3,3 L	>10
Cl
Urea	4.6	4.4
Creat	55	47
Ca	2.2	1.63
Mg	0.56	0.38
Phos	1.06	1.1
Uric acid
Total prot	CEGK	CEGK
Alb	37	30
Total bili	3 L	<3
Conj bili	2	2
ALT	46	35
AST	40	33
ALP	151	118
GGT	121	99
LD	230	138
CRP	2	2

Final Diagnosis

Likely EDTA contamination causing a falsely elevated potassium, decreased Calcium, Magnesium and ALP. The clinician was contacted and it was indeed medical undergraduate students who had taken the bloods, probably not realizing the order of draw, or toppling up the serum blood with some of the blood taken in an EDTA tube. This is evidenced by the high potassium, low calcium, magnesium and ALP. It is however evident that most other analytes were also lower than the repeat bloods later that day, hence:

Another likely possibility of the results in question could have been drip line contamination due to a potassium-containing fluid. The patient was indeed on total par-enteral nutrition, which usually contain large doses of potassium. This could be explained by the dilution of most analytes (as opposed to the raised potassium and normal sodium).

Take Home Message

It does not require much potassium EDTA contamination to evoke spuriously abnormal results. Potassium EDTA works as an anticoagulant by inhibiting clotting by chelation of the divalent cations such as calcium and magnesium, essential for the divalent cation-dependent proteolytic enzymes involved in the clotting cascade.

Gross potassium EDTA contamination of blood samples can be recognized by unexpected marked pseudohyperkalaemia and pseudohypocalcaemia. Serum alkaline phosphatase (ALP) activity can also be reduced in the presence of potassium EDTA contamination. Additionally, aspartate transaminase, alanine transaminase, lactate dehydrogenase, creatine kinase, amylase, unsaturated iron-binding capacity and bicarbonate can all be detrimentally affected in the presence of potassium EDTA contamination. Notably, some papers report potassium EDTA contaminated samples were mainly from inpatients compared to outpatients and primary care and the authors speculated that this is because blood samples in outpatients and general practice are largely but not exclusively collected by trained phlebotomists. It is our job as laboratorians to educate the newly trained clinicians about order of draw.

It is unfortunate that I couldn’t locate the undergraduate student who had taken these bloods, but at least the attending clinician was made aware of EDTA contamination.

HOSP #		WARD	Endocrine Clinic (OPD)
CONSULTANT	Dr. Jody Rusch	DOB/AGE	32 Year female

Abnormal Result

The clinician, an endocrinologist, phoned about discrepant results: Suppressed TSH, Low Free T4 and Normal (upper end of reference interval) Free T3.

Date	09/12/2020
TSH (mIU/L)	0.05 L
Free T4 (pmol/L)	4,8 L
Free T3 (pmol/L)	6,4

Presenting Complaint

The patient was known with Graves Disease complicated by quite severe Graves Eye Disease (orbitopathy).

History

Known with Graves disease with positive antibodies to TSH-receptors.

Examination

The clinical examination for this patient is not available, but the following is important:

Interestingly, patients may have no ocular symptoms at all, but may sometimes be distressed by the appearance of their eyes. The major ocular symptoms include:

• A gritty or foreign object sensation
• Excessive tearing that is often made worse by exposure to cold air, wind, or bright lights
• Eye or retroocular discomfort or pain
• Blurring of vision
• Diplopia
• Color vision desaturation
• Loss of vision in severe cases

The characteristic signs of Graves’ orbitopathy are proptosis (exophthalmos), tearing, and periorbital edema. In more severe disease, there may be severe conjunctival inflammation and ulceration from over exposure.

Laboratory Investigations

Date	09/12/2020	11/05/2020	08/11/2019	24/05/2019	29/01/2019	10/12/2018
TSH (mIU/L)	0.05 L (Rerun 0.05)	0.02 L	<0.01 L		<.01 L	<.01 L
Free T4 (pmol/L)	4,8 L (Rerun 4.9)	65,7 H	δ+>100.0 H	48,4 H	42,7 H	44 H
Free T3 (pmol/L)	6,4  (Rerun 6.4)				19,6 H

As above, the history of Graves disease is clear, which includes a suppressed TSH and raised Free T4 and Free T3.

Other Investigations

The Free T4, Free T3 and TSH was re-run on 10/12/2020, QC checked on these three analytes (all was within normal range) and pre-analytical labeling errors excluded as far we could.

Final Diagnosis

Graves eye disease, now with hypothyroidism.

Take Home Message

In Graves’ disease, the main auto-antigen is the thyroid-stimulating hormone (TSH) receptor (TSHR), which is expressed primarily in the thyroid but is also expressed in adipocytes, fibroblasts, and a variety of additional sites and appears to be closely aligned with the insulin-like growth factor 1 (IGF-1) receptor. TSHR antibodies and activated T cells also play an important role in the pathogenesis of Graves’ orbitopathy by activating retro-ocular fibroblast and adipocyte TSHR and IGF-1 receptors and initiating a retro-orbital inflammatory environment.

The retro-orbital tissue (and ocular muscles) increase in volume due to this inflammatory milieu, fibroblast proliferation and the accumulation of hydrophilic glycosaminoglycans (GAG’s), most notably hyaluronic acid.

Sometimes orbitopathy occurs in patients with hypothyroidism (high TSH, low free T4) due to classical chronic autoimmune thyroiditis (Hashimoto’s disease), and these patients may have stimulating TSH receptor (TSHR) antibodies but inadequate thyroid reserve.

In summary, the most important factors for development of Graves Eye Disease (orbitopathy) seems to be:

• Graves Orbitopathy antigen (which is the TSH-receptor): these are expressed extra-thyroidally, especially retro-orbitally.
• Role of TSH receptor antibodies
• Role of T-cells: Retroocular fibroblasts secrete GAG in response to cytokines such as interferon gamma and tumor necrosis factor (TNF)-alpha secreted by helper (CD4+) T cells of the Th1 type.

In cases of hypothyroidism, the action of deiodinase is increased to protect against the effects of hypothyroidism, likely the explanation of the increased Free T3 in this patient (compared to the low Free T4).