Delayed diagnosis of T3 supplementation in a bodybuilder presenting with tachycardia and features of sepsis

Abstract

A 25-year-old man presented generally unwell to the emergency department. Initial assessment identified systemic inflammatory response syndrome markers with an insect bite as a potential source of infection and he was treated for presumed sepsis. Tachycardia persisted and baseline thyroid function testing showed undetectable free thyroxine and thyroid-stimulating hormone (TSH), prompting further endocrine investigation. Triiodothyronine (T3) was markedly raised with normal TSH receptor antibodies, and the patient later confessed to supplementary testosterone and T3 use as part of bodybuilding activities. Following counselling, thyroid function normalised and the patient returned to his usual health. This case describes the diagnostic work up in a case of persistent tachycardia caused by T3 supplementation, demonstrating the potential for endocrine supplementation by bodybuilders which may be poorly understood and recognised by clinicians. T3 supplementation should be considered and a thorough drug history obtained in bodybuilders presenting with symptoms of thyrotoxicosis and deranged thyroid function tests.

Background

Endocrine supplementation in bodybuilders can cause adverse side effects which may initially be misinterpreted. This case report describes the diagnostic work up and management of a young male with persistent tachycardia which was ultimately found to be caused by triiodothyronine (T3) supplementation.

Supplementation in bodybuilders with the aims of sport-related performance and improved appearance is common.¹ Anabolic steroids and their complications have been the subject of extensive discussion,^{2 3} with the result that medical professionals are likely to be cognisant of their use as a drug of choice by body builders. However, many medics will be unfamiliar with the full range of supplements taken by body builders or their potential endocrine side effects.

This report illustrates the importance of a thorough history and enquiring diagnostic work up for a case of tachycardia of unclear aetiology. Physicians must have an awareness of the potential for self-medication by body builders and understanding of how this may present in order to manage similarly challenging cases.

Case presentation

A 25-year-old man was referred to the emergency department by his general practitioner feeling generally unwell with headache and sweating. Vital signs were as follows: heart rate 123, blood pressure 148/73, respiratory rate 25, oxygen saturations 97% on room air and temperature 37.2°C. There were no further findings of note on examination apart from an insect bite on the arm. The patient was commenced on intravenous fluids and oral antibiotics via the ambulatory unit for presumed sepsis secondary to an infected insect bite. Given ongoing tachycardia and malaise he was referred to the acute medical team.

Investigations

ECG showed sinus tachycardia.

The initial biochemical screen was remarkable for low free thyroxine (T4) and thyroid-stimulating hormone (TSH). Urea was elevated with normal creatinine and estimated glomerular filtration rate. White cell count was raised with a neutrophilia. Haemoglobin, liver function, electrolytes and clotting screen were at or close to normal range. Relevant tests are shown in table 1A.

Table 1.

Showing relevant investigation results

A. initial investigation results
	Result	Local reference range	Comment
Laboratory blood test
Free T4, pmol/L	<5.2	9.0–19.0	Low
TSH, munit/L	<0.01	0.3–4.2	Low
Urea, mmol/L	8.5	3.2–7.4	High
Sodium, mmol/L	139	135–145	Normal
Potassium, mmol/L	4.4	3.5–5.0	Normal
Creatinine, μmol/L	97	64–104	Normal
eGFR, mL/min/1.73 m2	82		Normal
Total bilirubin umol/L	3	0–21	Normal
ALT, int unit/L	46	10–45	High
ALP, int unit/L	88	30–130	Normal
Albumin, g/L	30	32–50	Normal
Haemoglobin, g/L	140	130–170	Normal
White cell count, ×109/L	17.5	4.0–11.0	High
Platelet count, ×109/L	405	150–400	High
Haematocrit, L/L	0.418	0.4–0.5	Normal
Red cell count, ×1012/L	4.35	4.5–5.5	Low
Mean cell volume, fL	96.1	83–105	Normal
Mean cell haemoglobin, pg	32.2	27–32	High
Mean cell haemoglobin concentration, g/L	335	315–345	Normal
Neutrophil count, ×10/L	13.78	2.0–7.0	High
Lymphocyte count, ×10/L	1.73	1.0–3.0	Normal
Monocyte count, ×10/L	1.25	0.2–1.0	High
Eosinophil count, ×10/L	0.45	0.02–0.5	Normal
Basophil count, ×10/L	0.19	0.02–0.1	High
immature granulocyte count, ×10/L	1.00	0–0.1	High
Prothrombin time, s	10.4	9.0–12.0	Normal
APTT, s	19.1	20–30.0	Low
INR	1.0		Normal
Microbiology
EBV EBNA IgG, blood	Negative
Hepatitis A virus IgM, blood	Negative
Hepatitis A virus total Ab screen, blood	Negative
HIV antibody/antigen screen, blood	Negative
Legionella Ag, urine	Negative

B. Second line investigations
	Result	Local reference range	Comment
Laboratory blood test
Free T3, pmol/L	7.5	2.6–5.7	High
Testosterone, nmol/L	80.7	8.4–22.7	High
FSH, int unit/L	<0.1	1–12	Low
Prolactin, munit/L	568	70–410	High
Midday cortisol, nmol/L	368	>350	Normal
TSH receptor antibodies, unit/L	0.5	0–0.4	High
Urinary metadrenalines
3-Methoxytyramin, nmol/mmol C	30	0–170	Normal
Metadrenaline, nmol/mmol C	20	0–120	Normal
Normetadrenaline, nmol/mmol C	40	0–300	Normal

ALP, alkaline phosphatase; ALT, alanine aminotransferase; APTT, activated partial thromboplastin time; EBNA, Epstein-Barr nuclear antigen; EBV, Epstein-Barr virus; FSH, follicle stimulating hormone; INR, international normalised ratio; T3, triiodothyronine; T4, thyroxine; TSH, thyroid-stimulating hormone.

In view of the abnormal thyroid function test results, an endocrine opinion was sought. Subsequent endocrine investigations revealed markedly elevated free T3 and borderline positive TSH receptor antibody. Testosterone and prolactin were raised with low follicle stimulating hormone (table 1B). Metanephrines were normal.

Differential diagnosis

On first presentation in the emergency department with sweating and malaise, the main differential was sepsis. The patient demonstrated systemic inflammatory response syndrome (SIRS) criteria comprising tachycardia, tachypnoea and leucocytosis, and the insect bite was considered a potential source of infection. However, microbiology investigations were all negative and the initial thyroid function results prompted further investigation into endocrine causes. Cortisol levels were reassuring for normal pituitary function, excluding secondary hypothyroidism. Normal metanephrines excluded phaeochromocytoma as a differential for sweating and tachycardia. The patient was consequently started on propranolol and propylthiouracil for thyrotoxicosis. The subsequent endocrine investigations (table 1B) were completed after discharge and reviewed in outpatient clinic.

Treatment

See Differential diagnosis section.

Outcome and follow-up

The patient was discharged the same day from the medical ambulatory assessment unit and reviewed 2 weeks later in endocrinology outpatients. On examination, he was well virilised with increased muscle bulk. He had normal secondary sexual characteristics including normal external genitalia examination with no testicular atrophy. There was no thyroid goitre or evidence of thyroid eye disease.

He admitted, on closer questioning, to be taking testosterone injections 375 mg/week for 14 weeks in cycles as well as tablets containing T3 25 μg/ day for 4 weeks, as part of recreational bodybuilding activities.

The patient was advised of the potential harms of supplementation with testoterone and T3 and cessation recommended for all supplements containing exogenous hormone. Propylthiouracil was stopped as intrinsic thyroid disease had been clinically excluded.

Eight months later, the patient reported feeling well and his thyroid function had normalised.

Discussion

Thyroid supplementation by bodybuilders with the aim of increasing fat breakdown can cause unwanted health effects which may be poorly recognised by health professionals.

Androgen anabolic steroids (AAS) are taken to increase muscle mass but have a wide range of well-documented complications⁴ affecting the endocrine system including impaired lipid profile⁵ and reduced fertility with low sperm count and abnormal sperm morphology.⁶ AAS have been associated with cholestatic jaundice,⁷ focal segmental glomerulosclerosis⁸ and cardiomyopathy.⁹ Testosterone supplementation can also have an erythropoeitic effect¹⁰ although in our case the patient had normal haemoglobin and haematocrit (without a presupplementation baseline for comparison), possibly because the supplementation was recent and the peak effect occurs at around 9–12 months, or as a result of superimposed suppression by systemic inflammatory response. In an anonymised self-administered questionnaire of 500 AAS users, the most common side effects were acne, insomnia, oedema, mood alterations, gynaecomastia, testicular atrophy, striae, sexual dysfunction and injection-site pain.¹¹

By contrast, T3 supplementation by bodybuilders is infrequently mentioned in the literature. Weight loss supplements containing T3 have been reported to cause flushing and palpitations, symptoms consistent with thyrotoxicosis,¹² but also thyrotoxic periodic paralysis.¹³ In body builders, ‘thyrotoxicosis facticia’¹⁴ and acute myocarditis¹⁵ have been described.

The World Anti-Doping Agency prohibits anabolic agents including testosterone at all times.¹⁶ Prohibition of thyroid hormones has been the subject of discussion but is currently not in place as inappropriate use of thyroid hormones can cause adverse health effects but is not thought to be performance enhancing.¹⁷

The clinician encountering bodybuilders using thyroid dietary supplements faces a number of challenges. First the range of presentations is likely to be disparate and easily attributable to other causes; in this case the inclusion of thyroid function tests in the initial blood test screen for tachycardia, as recommended by the National Institute for Health and Care Excellence,¹⁸ proved invaluable in signposting towards the final diagnosis.

Second, it is necessary to be able to respond confidently to unexpected biochemical results such as undetectable TSH and free T4. Involvement of an endocrine specialist can facilitate appropriate second line tests, importantly T3 and thyroid receptor antibodies, and advise on causes of ‘T3 toxicosis’ such as early hyperthyroidism or an autonomously functioning nodule,¹⁹ so that underlying pathology can be safely excluded. Thyroglobulin levels can also be helpful to differentiate between exogenous and endogenous causes of hyperthyroidism but were not measured in this case as the patient’s supplementation practice had become apparent.

Third, lack of awareness of supplementation practices and their potential side effects may result in an insufficiently high index of suspicion during the diagnostic work up. Clinicians must be able to recognise where non-descript signs such as tachycardia are due to supplementation and have the knowledge to council the patient on both the immediate association and risk of long-term complications. For example, T3 is thought by some bodybuilders to increase catabolism and drive fat loss, but in fact they should be advised of consequences including osteoporosis, atrial fibrillation, embolic events and, in the case of thyroid storm, even cardiovascular collapse and death.¹⁹

Finally, there must be a good doctor–patient relationship in order to enable a thorough and open history taking including recreational drug use. It is possible that details of the supplementation may not emerge during the first clerking and this case demonstrates the value of revisiting the history where there is diagnostic uncertainty. Furthermore, patients may not welcome the news that their self-medication choices are causing harm and may resist cessation advice, leading to disengagement with services,⁴ so good rapport is essential in producing a successful and permanent cure.

This discussion summarises current issues surrounding diagnostic work up and management of thyroid endocrine supplementation by bodybuilders, which are of relevance for clinicians working in general practice, emergency medicine, endocrinology and general medicine.

Learning points.

• Thyroid function testing should always be included as part of the diagnostic work up in cases of unexplained tachycardia.

• Supplementation by bodybuilders can lead to a range harmful endocrine complications which may be poorly understood and recognised by clinicians.

• Triiodothyronine supplementation should be considered and a thorough drug history obtained in patients who practise bodybuilding or similar activities presenting with symptoms of thyrotoxicosis and deranged thyroid function tests.

• Recognising the potential for disengagement with healthcare in patients who self-medicate can increase the likelihood of concordance and cessation of harmful supplements.