Toxicology

In Victoria, from 2001 to 2011, 115 deaths were identified with codeine and ibuprofen co-detected in postmortem toxicological analysis or with codeine–ibuprofen analgesic misuse described in the coroners’ findings.

Jennifer L Pilgrim · Malcolm Dobbin · Olaf H Drummer

A young boy’s painful encounter with a moth playing possum.

John J van Bockxmeer · Jennifer Green

DMAA was recently banned in Australia and other countries owing to toxicity, lack of health benefits, and concerns about long-term safety and potential for misuse. A trawl of the NSW Poisons Information database confirms the wisdom of the ban and suggests an expanded role for the database in future.

Jared A Brown · Nick A Buckley

Accidental carbon monoxide poisoning as a result of burning charcoal briquettes has continued despite the introduction of mandatory warnings.

Jared A Brown · Nick A Buckley

To the Editor: On 5 June 2012, the forum “Eliminating childhood lead toxicity in Australia — a little is still too much” was held at Macquarie University to examine new evidence on the toxicity of lead and its implications for Australian children and communities. Presently, the National Health and Medical Research Council (NHMRC) recommends an increasingly obsolete intervention level that was established in 1993: blood lead levels ...

Mark P Taylor · Chris Winder · Bruce P Lanphear

Objectives: To describe the epidemiology and toxicity of caffeinated energy drink exposures in Australia.Design, setting and subjects: Retrospective observational study analysing data from calls regarding energy drink exposures recorded in the database of an Australian poisons information centre over 7 years to 2010.Main outcome measures: Type of exposure; co-ingestants; symptoms reported; and reported hospitalisations.Results: Callers reported 297 exposures to energy drinks, which showed an increasing annual trend from 12 in 2004 to 65 in 2010. Median age for the 217 subjects with recreational exposure was 17 years (interquartile ratio [IQR], 15–21; range, 11–60) and 57% were male. One hundred recreational users co-ingested other substances, predominantly alcohol (50) or other caffeinated products (44). The number of energy drinks consumed in one session varied greatly (median, 5 units; IQR, 3–8; range, 1–80). Most subjects who reported recreational use reported experiencing symptoms (87%). The most common symptoms were palpitations, agitation, tremor and gastrointestinal upset. Twenty-one subjects had signs of serious cardiac or neurological toxicity, including hallucinations, seizures, arrhythmias or cardiac ischaemia. At least 128 subjects (57 with no co-ingestants) required hospitalisation.Conclusions: Reports of caffeine toxicity from energy drink consumption are increasing, particularly among adolescents, warranting review and regulation of the labelling and sale of these drinks. Educating adolescents and increasing the community’s awareness of the hazards from energy drinks is of paramount importance.

Naren Gunja MB BS, FACEM · Jared A Brown BPharm(Hons), MPH

An inquisitive physician explores the effects of a poisonous mushroom first-hand Illness from eating mushrooms is a worldwide phenomenon.1 In Australia, poisoning appears rare but deaths have occurred in recent years,2,3 perhaps partly due to the changing ethnic mix of the country to include cultures more comfortable with eating wild mushrooms despite knowledge of the risks involved.1 The usual outcome of eating a poisonous mushroom is gastrointestinal disturbance. This may be severe and can lead to death via dehydration and electrolyte changes; children, cats and dogs are particularly vulnerable.4 Here, I present my personal case, which illustrates the typical symptoms of poisoning due to Chlorophyllum molybdites. Amanita muscaria, another mushroom present in Australia, known for its hallucinogenic properties. Image kindly provided by Michael Egan. Clinical recordI (a 53-year-old man of Anglo-Celtic-Saxon ancestry) observed a crop of mushrooms in a lawn in the Perth suburb of Wembley near dusk. Some were flat with a white top and underbelly (gills), with brown scales covering most of the top. I immediately recognised these as being inedible. However, nearby were several small button shaped mushrooms with pale cream tops, and pale white or pink under-surfaces. I picked some of these and examined them more closely indoors. As I became convinced that these were not related to the large inedible mushrooms nearby and believed they were typical button mushrooms, even though they did not have a brown underbelly, I tasted them. I had two small bites of about 5 g each from two mushrooms. The taste was sweet, nutty, typically mushroom-like, and indeed very pleasant. I went on with normal activities, ate a normal evening meal (that did not contain mushrooms) and settled down for the evening. About 2 hours after ingesting the mushrooms, I felt nauseated. I retired to bed and about 30 minutes later waves of nausea overtook me, and over the next 90 minutes, I vomited over 40 times in total. At this point, profuse watery diarrhoea also occurred and after the second bout of this I was overcome with intense sweating, and a feeling of impending syncope. Unable to move from the toilet for fear of blacking out, I lowered myself to the floor where I lay in a drenching sweat, feeling faint and with a self-measured pulse rate of 30 beats/min. After some minutes, I gathered some strength and crawled through the house to the room of one of my children. She described me as extremely pale, drenched in sweat, and confused. I was taken to the emergency department by ambulance. My heart rate was 56 beats/min and my blood pressure was 110/60 mmHg. An intravenous line was inserted (on the third attempt), and 4 L of fluid were given over 2 hours. A single dose of ondansetron was administered intravenously. I had one further episode of diarrhoea and no further vomiting. Blood testing showed an elevated white cell count (15.1 × 109/L; reference interval [RI], 4.0–11.0 × 109/L) and a raised neutrophil count (13.9 × 109/L; RI, 2.0–7.5 × 109/L). Haemoglobin, urea, creatinine and bicarbonate levels and liver function tests were normal. I recovered after fluid resuscitation and felt well enough to return home, although no urine was passed while in the emergency department. Subsequently, I noted no ill effects other than feeling a little tired the next day. The mushroomInitial attempts to identify the mushroom via the Western Australian Poisons Information Centre and various WA Government and university departments were unsuccessful due to lack of suitably qualified staff. Extensive internet searching revealed a website with useful pictures of many of the local mushrooms,5 but further exploration of the eight or so that might have matched did not seem to yield features consistent with the ingested mushroom — remnants of which were still held, and relatives of which continued to grow at the same site (Box). However, after several more days of observation it was clear that the small button mushrooms became the flat-topped cream, brown-scaled ones, and that later these grew quite large (up to 15 cm wide) and their gills became pale green (Box). This change allowed a definitive identification as C. molybdites, the green-gilled mushroom,5 with further confirmation coming from two experts (Neale Bougher, WA Department of Environment and Conservation, and Heino Lepp, Australian Government Department of Sustainability, Environment, Water, Population and Communities, personal communication). DiscussionThe green-gilled mushroom is the species responsible for most mushroom poisoning in the United States.6 It resembles an edible mushroom (Chlorophyllum brunneum — the common brown parasol), but the green gills are characteristic. The US has maintained a mushroom poisoning database for many years, but despite this epidemiological breakthrough, fewer than 2900 cases have been reported to it. Several syndromes are associated with mushroom poisoning.6 The most common is similar to that associated with the green-gilled mushroom with gastrointestinal side effects, often with marked cramping abdominal pain and muscarinic effects. Heart rate may be raised or slowed, presumably depending on the balance of toxin and dehydration. Occasional deaths have been reported from ingestion of the green-gilled mushroom and other species that cause this syndrome.7 One death has been reported in Australia due to a muscarinic syndrome caused by a Rubinoboletus species, a large pink-brown mushroom with a wavy surface and white gills.8 The most dangerous ingestion is that associated with mushrooms that produce amatoxins, in particular Amanita phalloides (deathcap mushroom). These often produce minimal initial effects, but after a window of 24–48 hours, acute liver failure occurs and is often fatal. Worldwide, around 50% of ingestions of these mushrooms result in death. In the US, the mortality rate has fallen to around 10% with supportive care and liver transplantation.1,6 Unfortunately, these mushrooms were imported into Australia and are now established around Canberra, in some suburbs of Melbourne, and have also been reported in Adelaide.3 A cluster of cases including one death in Canberra was reported in the Journal in 2006.2 Other mushroom ingestion syndromes include predominantly cholinergic, hallucinogenic, glutaminergic or disulfiram-like reactions.4,9 The take-home message here is the cornerstone of all advice from all experts regarding the eating of wild mushrooms — namely, never eat any mushrooms with white gills nor any wild mushrooms, and even more simply — do not eat any mushrooms that you do not positively know.10 Amanita muscaria, another mushroom present in Australia, known for its hallucinogenic properties. Image kindly provided by Michael Egan.

Lindsay C Mollison MB BS, MPH, FRACP

We report two Australian patients with possible cobalt toxicity related to metal-on-metal total hip replacements. Both patients were treated for osteoarthritis with a DePuy ASR (articular surface replacement) XL Acetabular Hip System prosthesis, which contains cobalt and chromium, and which has recently been recalled from the market. (MJA 2011; 194: 649-651) Clinical recordsPatient 1A 73-year-old woman presented to our orthopaedic clinic in February 2011 for follow-up of a right total hip replacement that had been performed 5 years previously because of osteoarthritis. At review, she had neurological symptoms, including cognitive decline, memory difficulties and depression, which had been present for 7 months since a cerebrovascular episode. She also had a continuous metal taste in her mouth and complained of severe headaches, anorexia and weight loss. She had mild groin pain but otherwise no symptoms related to her hip. X-rays showed a well fixed, well aligned implant, with mild osteopaenia around the acetabular component. Her serum cobalt level was 410 nmol/L (reference range, 0–20 nmol/L) and chromium level was 240 nmol/L (reference range, 0–100 nmol/L). The cerebrovascular episode had occurred in July 2010, when the patient experienced symptoms consistent with a stroke: dizziness, disorientation, nausea, vomiting and being “off balance on the left side”. She had particularly noted difficulty in remembering names and registering information (both written and aural), headaches and cerebellar signs (ataxia and dysdiadochokinesis). She had been admitted to the stroke unit and treated with ongoing clopidogrel. A computed tomography (CT) scan at this time showed a hypodensity in the right anterior commissure, although it could not be confirmed whether this represented a lacunar infarct or a perivascular space. CT angiogram, echocardiogram and thyroid function test results were all normal and she had no previous history of depression or dementia. The patient’s original hip replacement had been done in 2006 with an ASR (articular surface replacement) hip prosthesis (ASR XL Acetabular Hip System [DePuy Orthopaedics, Warsaw, Ind, USA]), comprising a large-diameter metal (cobalt and chromium) cup with a large modular metal head on a titanium Corail stem (Box). A revision total hip replacement was performed in March 2011, principally because of her systemic symptoms and elevated cobalt and chromium levels. The ASR metal cup and head were removed and the stem retained. Her acetabulum was revised with an all-polyethylene cemented cup and the head was changed to a ceramic one. At the time of surgery, 30 mL of turbid fluid was aspirated from the joint and debridement of metal stained tissue was undertaken. The concentration of cobalt in the joint fluid was 4218 nmol/L and chromium was 217 000 nmol/L. Cerebrospinal fluid (CSF) collected at surgery showed a cobalt level of 9 nmol/L and a chromium level of 13 nmol/L (no reference ranges for these in CSF), showing that the ions had crossed the blood–brain barrier. At 8-week follow-up after the revision surgery, the patient felt much improved. She had regained a normal appetite and gained weight, the metallic taste in her mouth had gone, and she had less fatigue and greater energy. The hip pain had completely resolved and she was walking up to 2 km a day. Her serum cobalt level had reduced to 60 nmol/L. Patient 2A 60-year-old male professor of engineering presented in January 2011 with systemic symptoms, for follow-up after a right total hip replacement with a DePuy ASR XL Acetabular Hip System prosthesis 4 years previously. He had no hip symptoms, but an x-ray showed quite marked bone loss around the acetabular component. Before his hip replacement surgery, the patient had been working full time and enjoyed excellent general health, apart from pain and stiffness in his right hip secondary to osteoarthritis. Three years after the surgery, he developed symptoms that steadily increased in severity: painful muscle fatigue in all limbs associated with cramps in the hands and feet, particularly at night; dyspnoea and feeling faint when performing simple tasks; inability to climb a flight of stairs without needing to rest; and a decline in cognitive function (although this was not quantified). He particularly noted problems with remembering names and poor concentration. His previously stable hypertension had become uncontrolled and required additional medication. The patient’s serum cobalt level had been measured in September 2010 and found to be 185 nmol/L, and subsequently remained consistently elevated at between 213 nmol/L and 258 nmol/L. His chromium level was never elevated. In February 2011, the patient had a revision total hip replacement performed because of his systemic symptoms, in spite of having no hip symptoms. At revision surgery, the titanium stem was retained, and the metal head and cup were changed to ceramic and polyethylene versions, respectively. There was no metal debris or localised tissue reaction. Immediately before the revision surgery, the patient’s serum cobalt level was 258 nmol/L, with a normal level of chromium (88 nmol/L). At 8-week follow-up after the revision surgery, the patient reported significant improvement in his energy levels and a decrease in muscle pains. He had significantly improved exercise tolerance and was able to walk without restriction. His serum cobalt level had fallen to 42 nmol/L. DiscussionTotal hip replacement is generally a successful operation, with a long clinical history of good outcomes. Conventional total hip prostheses consist of a metal head that fits into a polyethylene cup. Concerns have been raised, particularly in younger patients, that the plastic cup suffers wear and tear with time and may require revision. In an attempt to decrease wear at the interface of the articulation, metal-on-metal bearings (Box), composed of cobalt and chromium, have gained widespread popularity and have been used extensively, particularly in the United States. However, some of these metal-on-metal prostheses have not lived up to the promise of increased durability. The Australian National Joint Replacement Registry (NJRR) notes large differences in the performance of different types of metal-on-metal hip prostheses. An acceptable upper rate of failure of hip prostheses is considered to be below 1% per year, with the vast majority of implants studied by the NJRR falling well below this failure rate.1 The ASR prosthesis originally implanted in both patients reported here has recently been withdrawn from the market, after about 100 000 were implanted worldwide. Its revision rate reported on the NJRR in 2010 was 6.4% at 3 years when inserted with a Corail stem and 10.9% at 5 years when inserted as a resurfacing.1 Updated guidance from the British Hip Society’s 2011 conference noted a higher than anticipated early failure rate [in large-diameter metal-on-metal hip replacements]. These range from [a] 21% revision rate at 4 years (potentially rising to 35% if all currently known painful implants progress to revision) to 49% at 6 years for the ASR XL device. Other devices have a revision or impending revision rate of 12 – 15% at 5 years.2 An additional problem with metal-on-metal bearings is that they release a variety of metal ions into local tissue and the general circulation, with chromium being the most widely reported of these. Increased cobalt levels have been reported to be associated with neurological3,4 (hand tremor, incoordination, cognitive decline, depression, vertigo, hearing loss and visual changes), cardiac (arrhythmias and cardiomyopathy) and endocrine5,6 symptoms. Symptoms of cobaltism have been previously described when cobalt was used to treat refractory anaemia in patients 40 years ago.7 The term “arthroprosthetic cobaltism” has been coined to describe these manifestations in patients with joint replacements.3 The direct effect of cobalt on cells has recently been explored. Exposure to cobalt ions was found to significantly inhibit osteoblast function by reducing alkaline phosphatase activity and calcium deposition, and to rapidly induce the secretion of proteins IL-8 and MCP-1 in primary human osteoblasts.8 This may have implications for bone ingrowth onto implants and osteolysis around the hip replacement. Other reported effects of elevated cobalt levels on cells include abnormal lymphocyte function,9,10 chemokine secretion11 and ischaemic changes in rat brains.12 A relationship between symptoms and peak cobalt levels, or the length of exposure to cobalt, has not been established. We believe our patients’ symptoms were related to their elevated cobalt levels, resulting from cobalt leaching out of their hip prostheses. Both patients had metal-on-metal hip prostheses, and both patients’ cobalt levels were reduced after removal of the metal-on-metal prosthesis. We are concerned that cobalt toxicity may be under-recognised, particularly if patients consult doctors who may not be aware of the details of the patient’s hip replacement and the potential for release of cobalt into the circulation. The British Hip Society recommends regular follow-up of patients with metal-on-metal hip replacements for at least 5 years and probably for the life of the prosthesis.2 Clinical manifestations of cobalt toxicity may occur many years after implantation of the prosthesis and appear to stay elevated over extended periods of time.13 Long-term exposure to cobalt may also be associated with cancer.14 Patients should therefore be followed up carefully, with specific questioning about alterations in neurological, cardiac, respiratory and endocrine function. In the presence of persistently elevated metal ion levels and symptoms consistent with metal toxicity, once other causes have been excluded, revision hip replacement is the only method available to decrease the ion levels. X-ray of Patient 1’s right metal-on-metal articulation hip replacement, with well fixed cementless femoral and acetabular implant

Xinzhan Mao MD · Andrew A Wong MB BS, PhD, FRACP · Ross W Crawford MB BS, DPhil(Oxon), FRACS(Orth)

To the Editor: A 28-year-old man presented to his general practitioner with a history of epigastric pain and constipation over 1 month. In addition, he had a history of chronic low back pain. Findings on physical examination were unremarkable. Laboratory investigations showed normo-chromic, normocytic anaemia with basophilic stippling (Box 1). His whole-blood lead level was subsequently estimated to be 4.12 μmol/L (level recommended by the National Health and Medical Research Centre for all Australians, < 0.48 μmol/L). The patient was referred for toxicological review. Further questioning revealed he had used three Ayurvedic medicines (Vatyog [Arya Aushadhi Pharmaceutical Works, Indore, India], Sahacharadi [Arya Vaidya Nilayam, Madurai, India] and Gandharvahastadi [Arya Vaidya Nilayam, Madurai, India]) for back pain, dispensed to him 3 months earlier during a trip to India. He ceased taking the medications, and a 19-day course of oral chelation with succimer was administered. His blood lead concentration fell rapidly, with a moderate rebound 6 weeks after the completion of chelation therapy. A negative blood lead result for the patient’s pregnant partner excluded environmental exposure in the patient’s home. Vatyog and Sahacharadi were analysed for heavy metals (Gandharvahastadi was not available for analysis). Sahacharadi was lead-free, but the Vatyog tablet tested contained 448 μg of lead. The patient had potentially ingested 896 μg of lead daily for 3 months. World Health Organization guidelines recommend daily lead intake should not exceed 3.5 μg/kg/day.1 Dietary intake of lead in developed nations has been reported to be about 0.1–0.7 μg/kg/day.1 Ayurvedic medicine originated in India more than 2000 years ago and relies heavily on herbal products.2 Many people take Ayurvedic medicine without any problems. In some traditional remedies, salts of heavy metals are included as active ingredients.3 A study in the United States found that one-fifth of Ayurvedic herbal products manufactured in South India and sold in Boston contained potentially harmful concentrations of lead, mercury or arsenic, or combinations of these.2 In Australia, traditional Indian and Chinese medicines authorised for supply are regulated as complementary medicines and must meet manufacturing and quality standards that ensure the absence of contaminants.3 However, there is no quality control of medications imported for personal use or purchased over the internet. Importantly, this case involved tablets prepared by a registered pharmaceutical manufacturer and presented in sophisticated packaging (Box 2). Reports of lead contamination from traditional Indian and Chinese medicines have been intermittently publicised4,5 and include recent warnings from the New South Wales Health Department concerning Ayurvedic medicines. Patients with lead toxicity commonly present with non-specific clinical features, and lead poisoning might only be suspected when a blood film shows anaemia with basophilic stippling. While enquiring about a patient’s environmental, occupational and social history is important for determining possible sources of lead exposure, clinicians should also ask patients if they have used alternative and complementary medicines and whether these were obtained in Australia or from overseas. 1 Blood film from the patient showing coarse basophilic stippling 2 Packaging from the lead-containing Ayurvedic medicine

Nilika G Wijeratne · James C G Doery · Andis Graudins

To the Editor: About 5% of Australians of Asian, African, Middle Eastern or Mediterranean descent have glucose-6-phosphate dehydrogenase (G6PD) deficiency.1 Affected babies can develop massive haemolysis within hours of exposure to clothes stored with mothballs containing naphthalene. It has long been known that this results in severe jaundice, which may lead to kernicterus2 and profound brain damage, for which the cost is either a lifetime of dependency and very expensive care, or death. We are aware of three cases of kernicterus in babies with G6PD deficiency in Australia in the past 3 years, one of which was associated with exposure to naphthalene in mothballs. One baby died. The exact incidence of severe neonatal jaundice and kernicterus in Australia is unknown, but it is the subject of an ongoing study funded by the Cerebral Palsy Foundation and coordinated through the Australian Paediatric Surveillance Unit. In Australia, packages of naphthalene mothballs must carry a warning that the product is harmful to children. However, clinical directors of neonatal units that comprise the Australian and New Zealand Neonatal Network have unanimously agreed that warning labels give insufficient protection. They have called on the Australian Pesticides and Veterinary Medicines Authority (APVMA) to act in harmony with the European Union, which banned the sale of mothballs containing naphthalene in 2008,3 following a report by the European Chemicals Bureau.4 The adverse risk–benefit ratio for naphthalene provides strong justification for its withdrawal. A submission to this effect has been lodged with the APVMA. Some mothballs contain paradichlorobenzene, a chemical related to naphthalene and associated with haemolysis. Less toxic products that protect clothes against moths exist. Department stores in the United Kingdom have replaced moth repellents containing naphthalene with products containing natural substances, such as sandalwood and lavender. Between 2004 and 2010, the New South Wales Poisons Information Centre reported that it received about one call per week concerning children exposed to naphthalene in moth repellents (Box). The Victorian Poisons Information Centre reported 53 calls in 2008.5 While acknowledging the importance of raising awareness of the dangers of naphthalene, we believe that the safest course is prevention — that is, an Australia-wide ban of mothballs containing naphthalene. Readers who wish to report cases of naphthalene toxicity are encouraged to contact APVMA at aerp@apvma.gov.au. Number of calls to the New South Wales Poisons Information Centre reporting children exposed to napthalene in moth repellents, 2004–2010 Year Number of calls 2004 55 2005 59 2006 65 2007 67 2008 73 2009 45 2010 71 Total (average) 435 (62) Source of data: Judith Kirby, Department Head, NSW Poisons Information Centre, personal communication.

on behalf of the Advisory Committee of the Australian and New Zealand Neonatal Network

Objective: To describe the clinical features and laboratory findings in patients with definite red-bellied black snake (RBBS; Pseudechis porphyriacus) bites, including correlation with results of venom assays. Design, patients and setting: Prospective cohort study of patients with definite RBBS bites, recruited to the Australian Snakebite Project from January 2002 to June 2010. Main outcome measures: Clinical and laboratory features of envenoming; peak venom concentrations and antivenom treatment. Results: There were 81 definite RBBS bites; systemic envenoming occurred in 57 patients (70%) and local envenoming alone occurred in one patient. Systemic envenoming was characterised by local envenoming in 55 patients (96%), systemic symptoms in 54 patients (95%), anticoagulant coagulopathy with a raised activated partial thromboplastin time (aPTT) in 35 patients (61%) and myotoxicity in seven patients (12%). One patient required non-invasive ventilation for severe myotoxicity that resulted in muscle weakness. Three patients developed local ulceration. There were no deaths. Twenty-two envenomed patients (39%) received tiger snake or black snake antivenom, and administration within 6 hours of the bite was associated with normalisation of the aPTT. Eight patients (36%) had immediate hypersensitivity reactions to antivenom, including one case of anaphylaxis. The median peak venom concentration in 37 systemically envenomed patients with serum available was 19 ng/mL (interquartile range, 12–50 ng/mL; range, 3–360 ng/mL), which did not correlate with clinical severity. In 17 patients who received antivenom and had venom concentration measured, no venom was detected in serum after the first antivenom dose, including nine who were given one vial of tiger snake antivenom. Conclusion: RBBS envenoming caused local effects, systemic symptoms, anticoagulant coagulopathy and, uncommonly, myotoxicity. One vial of tiger snake or black snake antivenom appears to be sufficient to remove venom and neutralise reversible effects, but hypersensitivity reactions occurred in over a third of patients.

Andrew Churchman BM BS(Hons) · Margaret A O’Leary PhD · Nicholas A Buckley BMed, FRACP, MD · Colin B Page MB ChB, FACEM, MMedSci(Clin Epi) · Alan Tankel BSc, MB ChB, FACEM · Chris Gavaghan MB BS, FACEM · Anna Holdgate MB BS, FACEM, MMed · Simon G A Brown MB BS, FACEM, PhD · Geoffrey K Isbister BSc, FACEM, MD

To the Editor: Over-the-counter herbal supplements to promote weight loss have become increasingly popular. Several of these products contain potentially hepatotoxic substances. We present the first reported Australian case of acute hepatotoxicity associated with the weight-loss product Hydroxycut Hardcore (Iovate Health Sciences, Blasdell, NY, USA). Hydroxycut contains various ingredients, including extracts of the herbs Garcinia cambogia and Camelia sinesis (green tea root), and the chromium salt, chromium polynicotinate. A recent review cites these three ingredients as possible causes of Hydroxycut hepatotoxicity.1 A 23-year-old, previously well, construction worker presented to his doctor with a 2-month history of lethargy and jaundice. Test results confirmed serum liver enzyme derangement, and the patient was advised to stop taking the weight-loss supplement. Results of repeat testing a week later showed worsening liver enzyme levels and he was referred to our hospital. On arrival, the patient denied any symptoms except moderate lethargy and icteric sclera. He was usually well with no relevant medical or surgical history. He weighed 83 kg. He denied drinking alcohol, using prescription or non-prescription drugs, or receiving a blood transfusion. He had had unprotected sexual intercourse 2–3 months earlier. A previously obtained tattoo was being extended by a reputable tattoo parlour. He had been using Hydroxycut Hardcore daily for 10 weeks (obtained from his local outlet of a global nutritional products retailer) in an attempt to lose weight and tone muscle. He claimed to have taken the dosage recommended by the manufacturer (six capsules daily); he was taking no other supplements. Physical examination revealed mild jaundice without other features of chronic liver disease or portal hypertension. However, in addition to abnormal blood levels of liver enzymes, bilirubin and iron, results of the patient’s liver biopsy showed severe acute hepatitis (Box). The abnormal test results were consistent with acute drug toxicity. The patient improved without specific treatment and was discharged 8 days after presentation, with near-normal serum liver enzyme levels. He was well on follow-up at 4 weeks. Two reports from the United States link Hydroxycut Hardcore to acute liver injury in otherwise well young males.2,3 The American Food and Drug Administration in May 2009 advised consumers to stop using the product, based on 23 reports linking it to serious injury, including one case of liver failure leading to death.4 In May 2009, Australia’s Therapeutic Goods Administration (TGA) issued a warning to consumers about the product, although noting that no adverse events had so far been reported in Australia.5 In view of this first reported Australian case of Hydroxycut hepatotoxicity, we advise medical practitioners and consumers in this country to be wary of the product, and call on the TGA to re-examine its continued availability. Investigation results for a 23-year-old man with liver dysfunction after using Hydroxycut Hardcore Investigation Result (reference range) Blood tests Aspartate aminotransferase (U/L) 1182 (12–36) Alanine aminotransferase (U/L) 2950 (5–40) Alkaline phosphatase (U/L) 121 (50–140) Bilirubin (µmol/L) 113 (3–18) Prothrombin time (seconds) 13 (11–15) Iron (µmol/L) 68 (11–30) Ferritin (µg/L) 1897 (30–400) Iron saturation (%) 99 (16–50) Paracetamol Not detected Hepatitis A, B, C Negative HIV Negative Autoantibodies Not detected Epstein–Barr virus, cytomegalovirus, toxoplasma, leptospira, coxiella Negative Haemochromatosis genetic testing No abnormality Other tests Abdominal ultrasound No abnormality Percutaneous liver biopsy Severe acute lobular hepatitis with areas of bridging necrosis; no bridging fibrosis or cirrhosis were seen Hepatic iron index 1.1 (< 2.0)

N Nudrat Rashid · Jason Grant