HOSP #	MRN77113313	WARD	Endocrinology OPD
CONSULTANT	Dr. Jody Rusch / Dr. Khalid Aligail	DOB/AGE	21y Female

Abnormal Result

The TSH stayed elevated on our assay (Roche Cobas 6000) with a high-normal free T4.

Presenting Complaint

The patient was seen at the endocrinology OPD for follow-up of her thyroid function tests and review of medications. No acute complaints were noted, but some interesting thyroid function results became known.

History

Previous multinodular goiter with thyrotoxicosis.  Had a complete thyroidectomy March-May 2020.

History of asthma, exema and “other allergies”. 

Current dose of eltroxin = 1.6 ug/kg ~ 100ug/day PO.  The patient (and doctor) declares good compliance to Rx.

Examination

Patient did not have any signs or symptoms of hypo or hyperthyroidism according to the endocrinologist.

Laboratory Investigations

Date	03/05/2021	26/04/2021	23/02/2021	23/10/2020	27/08/2020	08/05/2020	09/03/2020
TSH (uIU/mL) (0.27 – 4.2)	•15,17 H	18,54 H	13.10 H	21,61 H	32,19 H	δ+>100.00 H	7,72 H
Free T4 (pM) (12.0-22.0)	17,8	17,7	18,3	δ+ 16.0	11,8 L	δ-  9,7 L	δ+ 13,8
Free T3 (pM) (3.1 – 6.8)	4,3		4,2

The TSH seems to have stayed elevated on our assay (Roche Cobas 6000) with a high-normal free T4.  The free T3 is normal (which I advised should be measured to assess conversion between the hormones). I also sent the sample to Green Point Laboratory where a Beckman DXi analyser is used with a different antibody set of reagents and a different reference range.

Date	03/05/2021
TSH (uIU/mL)	15.4 (0.38-5.33)
Free T4 (pM)	13.6 (7.86-14.41)
Free T3 (pM)	4.3 (3.8-6.0)

Other Investigations

Auto-immune markers have been requested, since the patient was having prolonged iron deficiency, becoming anaemic, and the clincian raised a suspician of likely celiac disease.

Final Diagnosis

The diagnosis is still unsure, but the likely differential diagnosis is:

1. Decrease in deiodinase activity due to some reason – there are many causes.
2. Decrease in absorbtion of Levothyroxine

Take Home Message

Interference in thyroid function tests are commonly enquired about, especially by endocrinologists. This represents a big portion of our non-routine work and often quite a portion of time is spent on education of clinicians who do not necessarily have a laboratory background. Often, esoteric tests are requested which may not be warranted by the clinical scenario.

This case demonstrates a query raised by a clinician about possible interference in the TFT’s which is warranted. It is important to rule out as best one can, interference in the laboratory assay.

Various ways of determining whether interference is the culprit are:

• Dilution of the sample (in assays where the sample may be diluted – unsuitable for free-T4 as dilution will affect the “free” portion of hormone)
• Running the test on another methodology
• Running the test on another analyzer of the same methodology, but with slight differences, such as a different manufacturer of detection antibodies (e.g. Roche vs. Abbott vs. Siemens vs. Beckman vs. Ortho)
• Precipitating the antibodies e.g. desalting, or PEG-precipitation.
• Binding the antibodies, e.g. protein G or Protein A
• Using of “blocking tubes” which is a proprietary blood collection tube to bind antibodies

HOSP #		WARD	Endocrine clinic
CONSULTANT	Jody Rusch / Khalid Aligail	DOB/AGE	21 y female

Abnormal Result

TSH: < 0.01 mIU/L (0.27 – 4.2)

Free-T4: 80.9 pmol/L (12 -22)

Free-T3: 10.8 pmol/L (3.1 – 6.8)

Presenting Complaint

Started to have frequent supra-ventricular arythmias – hence placed on amiodarone by the cardiologists

History

Mitral valve repair in 2018.

Started Warfarin, then later stopped.

Upon routine visit for follow-up 1 w before, the cardiologist requested TFT’s.

Examination

• Denies chest pain, shortness of breath and has no symptoms of dyspnoea
• No lower limb oedema
• No sweating
• No abdominal complaints
• Patient is comfortable, no distress
• CVS unremarkable
• Muffled systolic murmur, JVP normal, No lower limb oedema.
• Fine tremor, pulse rate 84
• No eye signs
• Gland diffusely enlarged, and no focal nodules detected
• Bruit was clearly audible

Laboratory Investigations

TSH receptor antibodies = 3.3 U/L (<1.8)

Other Investigations

Radio-active Iodine thyroid uptake scan showed no uptake in the thyroid gland – not indicative of Graves Thyrotoxicosis.

Final Diagnosis

Summary: 21 y female, 1 y after mitral valve replacement placed on amiodarone now presented with a diffusely enlarged thyroid gland with a bruit clearly audible and no signs or symptoms of hyperthyroidism, but with biochemical evidence of significant hyperthyroidism

DDx: No symptoms pointing towards overt thyroid problems before initiating, thus this is likely Amiodarone – induced thyrotoxicosis

2 types are known, differentiated by either a diffusely enlarged thyroid which is more likely type 2 than type 1 .

Take Home Message

Rx differs between type 1 and type 2:

High iodine uptake is usually type 1 : usual Rx of Hyperthyroidism is given, thus Lugol’s iodine, else if non-responsive: radio-active Iodine or surgery.

If not much uptake on the uptake scan: Type 2 : points towards destruction of the gland : Rx = steroids

Which is more common?

In a local study of ~250 patients in 10y period it was found the longer it is left, the higher the chance of thyrotoxicosis. “Type 2 is likely more common”- prof Ross.

How does lithium thyroid disease work?

Lithium increases the enterothyroidal iodine recirculation : characteristically causing a : goiter with hypo or hyperthyroidism (thyroiditis).

Lithium inhibits proteases which liberates T3 and T4, hence inhibiting Iodine recirculation.

Interestingly, despite having a free T4 of ~80pmol/L, the patient had no symptoms whatsoever.

Also, of note, amiodarone more often causes hyperthyroidism than hypothyroidism.