Endocrinology

There is yet no convincing evidence that testosterone therapy is safe or effective in counteracting any effects of ageing One of the most challenging and time-consuming aspects of medical practice is discussing with patients what they have gleaned from the Internet or popular lay publications. One topic of such discussion is the use of testosterone in male ageing, with public interest fuelled by persuasive publications like Maximising manhood,1 The testosterone revolution2 and Male menopause.3 Much of the information gained from these books may seem to be very convincing, but is, at best, “ahead of the evidence”. It is often difficult for doctors not to appear old-fashioned, ignorant or downright contrary when showing scepticism or advising caution in the face of such conviction. . . . beware when entrepreneurial business ventures overtake evidence-based medicine. In this issue of the Journal, Handelsman (page 419) has documented temporal and regional trends in testosterone prescribing in Australia.4 He has shown increases in prescribing corresponding to popular promotion of androgen therapy in ageing. This rise has been particularly marked in Western Australia, coincident with the opening in that state of entrepreneurial clinics aimed at the ageing-male market. There is no doubt that testosterone therapy benefits patients with documented hypogonadism associated with conditions such as Klinefelter’s syndrome and hypopituitarism. Current prescribing guidelines allow for this, regardless of age. However, for the use of testosterone in men of middle age and older with borderline low serum levels of testosterone, the evidence for both efficacy and safety is yet to be established. The original description of the efficacy of testosterone therapy for the vicissitudes of age has been shown to be no more than a powerful placebo effect.5 Nevertheless, it would seem that those who espouse testosterone therapy in this setting have identified an expanding market. The Australian population is ageing: 28% of men are over the age of 50 and 12% over the age of 65 years. It is projected that by 2021, 4.0 million Australians will be over the age of 65, an increase of 1.7 million from today’s estimate.6 Together with a documented fall in testosterone level with age, where it is estimated that 20% of men over the age of 60 will have a testosterone level below the reference range, this predicts a large population of men as potential customers for androgen therapy.7,8 Although most studies have shown a gradual decline in testosterone level with age, the clinical consequences of this are not known. Conditions such as muscular frailty, loss of bone mass, cognitive decline and erectile dysfunction are also age related, but whether testosterone deficiency has a causal role is not clear. More importantly, it has not yet been established that testosterone therapy has any role in correcting these conditions. It has been a widely held belief that androgen deficiency is a common and correctable cause of erectile dysfunction. However, in a cohort of 1455 men presenting with erectile dysfunction, we found that testosterone deficiency constituted a correctable cause in only 3%.9 All of those who responded to testosterone therapy for erectile dysfunction had a testosterone level < 7 nmol/L, well below the reference range of 11–37 nmol/L. The use of testosterone therapy in patients with normal or slightly depressed androgen levels seems to be of little benefit.10 A similar finding has been documented in the response of bone density to testosterone therapy. The largest and longest-term study in this setting examined testosterone treatment in 108 men aged over 65 years with a baseline testosterone level more than 1 standard deviation below the young adult mean (ie, < 16.5 nmol/L).11 Lumbar spine bone density rose significantly only in those with a baseline testosterone level below the reference range (ie, below 10 nmol/L). Another, smaller study has shown a significant increase in lumbar spine density with androgen therapy in men with a baseline testosterone level < 12.1 nmol/L.12 Muscle mass and strength decrease with age, and it is tempting to link this with the decline of testosterone. In hypogonadal men, testosterone therapy improves muscle strength. In men aged over 65 years, testosterone treatment leads to a fall in fat mass and a rise in lean body mass, together with a perception of increased strength. However, although a perception of improved muscle function was reported, no objective change in measured physical function, such as walking or stair climbing, knee flexion or in muscle strength as measured by dynamometer, was demonstrated.13,14 The safety of sex hormone therapy in menopausal women, used widely for the last 60 years, has recently been scrutinised and reassessed.15 Knowledge about the safety of sex hormone replacement in men is, by contrast, in its infancy. No studies have been conducted for long enough to identify the long term risks of androgen therapy in ageing. Because of lack of statistical power in studies, it is not known whether testosterone use will increase the incidence of androgen-dependent disease such as prostate cancer, although a sustained rise in prostate-specific antigen level has been observed.13 Two other side-effects of testosterone treatment have been identified in short term studies, namely an increase in obstructive sleep apnoea and increased haematocrit and polycythaemia, both of which may have implications for cardiovascular risk.13,16 Handelsman has documented the effect on testosterone prescribing of entrepreneurial clinics aimed at the ageing-male market.4 Daily, we see advertisements for similar commercial enterprises which deal in unregistered and/or unproven prescribing, including DHEA (dehydroepiandrosterone) or testosterone to men and women, progesterone cream, and lozenges of variable mixes of oestrogens, progestins and androgens. We should beware when entrepreneurial business ventures overtake evidence-based medicine. What is needed now regarding testosterone therapy in ageing are large, long-term, prospective, randomised, placebo-controlled studies to establish if there is, indeed, benefit for specific symptoms and to identify potential risks.17

Bronwyn GA Stuckey BA, FRACP

Objectives: To analyse temporal trends and geographical variations in testosterone prescribing in Australia.Design and setting: An analysis of testosterone prescribing over the past 11 years according to products and region, determined by Pharmaceutical Benefits Scheme (PBS) expenditure in Australian states and territories.Main outcome measure: Patterns of monthly PBS expenditure on injectable, oral and implantable testosterone products from 1 January 1991 to 30 December 2001, classified by state or territory.Results: There were two periods (1993–1994 and 1998–1999) of striking upsurge followed by declines in national total prescribing of testosterone. These changes were more prominent for oral than injectable testosterone products, and patterns were similar in all regions, apart from a disproportionately higher peak in Western Australia in 1998. On a per-capita basis, Western Australia showed a dramatic increase in prescribing of oral and implantable, but not injectable, testosterone coinciding with the opening of a franchised men’s sexual health clinic in Perth.Conclusion: The two striking upsurges in testosterone prescribing despite no convincing new evidence to justify them appear to reflect promotional activity to prescribe testosterone for older men, rather than overcoming the underdiagnosis of androgen deficiency related to pituitary or testicular disease in younger men. The curtailments after the introduced restrictions to PBS prescribing for older men without overt androgen deficiency were partial and temporary, suggesting that such regulatory barriers are only partly successful in counteracting the commercial and populist pressure driving excessive testosterone prescribing. Professional and community education is needed for appropriate diagnosis of genuine androgen deficiency in younger men, while discouraging unproven testosterone treatment for ageing men.

David J Handelsman FRACP, PhD

Gordon R W Davies Psychiatrist, 33 Smith St, Wollongong, NSW 2500. alienistATihug.com.au To the Editor: The recent article on obesity by Proietto and Baur in the Journal1 coincided with another by Campos in New Scientist,2 in which he criticised the conventional view of the risks of obesity and the norms usually accepted. Campos quoted evidence suggesting that, in fact, the group in the overweight range (body mass index [BMI], 25–30 kg/m2) are healthier than those with a BMI below 25 kg/m2. He also noted that between 1990 and 2002, despite a further increase in the prevalence of obesity in the United States, the incidence of type 2 diabetes hardly changed, while cardiovascular death rates fell. According to Campos, similar claims about the risks of obesity have been repeated over the past 50 years and relate more to cultural and political factors than to reliable scientific evidence. Clearly, this view is inconsistent with that articulated by Proietto and Baur. While Campos’ view obviously does not apply to the grossly obese, there is a strong suggestion that the overall evidence base is inconsistent. This may be because the assumption of a linear relationship between excess weight and illness is false. It is further likely that there is confounding of variables, with weight a proxy for lack of exercise. As Campos points out, large-scale observational studies are inevitably poorly controlled. If this is so, then it may well be more useful for the medical profession to emphasise exercise and lifestyle rather than weight loss. It may be much easier to obtain and reinforce behavioural change in these areas, and avoid the common feeling of hopelessness (“why bother”) expressed by people who find it hard to diet and to lose weight.

Gordon R W Davies

Ray C McHenry,* Richard W Gilhome,* Chris Hensman* * General Surgeon, Eastern Surgical, Suite 7529, Police Road, Mulgrave, VIC 3170. To the Editor: We take issue with the recommendations on treatment of morbid obesity in the otherwise excellent article on obesity management by Proietto and Baur.1 Like most non-surgical clinicians involved in the management of obesity, they fail to differentiate between the treatment of obesity (body mass index [BMI], 30–35 kg/m2) and morbid obesity (BMI > 35 kg/m2). The literature is crystal clear — non-surgical treatments are unsuccessful in achieving and maintaining weight loss in morbid obesity.2,3 We are unaware of any branch of medicine, other than morbid obesity management, where respected clinicians routinely recommend treatments (drugs, diet and lifestyle modification) which have been proven not to be effective. We challenge all clinicians to accept what the evidence clearly shows, that: the only known effective treatment for morbid obesity is surgery;2,3 and laparoscopic adjustable gastric banding is much safer than bypass/diversion surgery4 and just as effective; it is the treatment of choice for morbid obesity.

Ray C McHenry · Richard W Gilhome · Chris Hensman

Huy A Tran Director of Clinical Chemistry, John Hunter Hospital, Hunter Region Mail Centre, Locked Bag No 1, New Lambton Heights, NSW 2310. huy.tranAThunter.health.nsw.gov.au To the Editor: I read with interest the recent article on obesity in Australia by Proietto and Baur1 and would like to comment on the issue of proteinuria and measurement of insulin level in obese patients. Proteinuria in obesity, commonly referred to as obesity-related glomerulopathy, is a clinical syndrome with an estimated incidence of about 2% in obese subjects.2 With a fifth of the population being obese,1 the sheer number suspected to have this condition will create an enormous management and cost burden. Furthermore, the incidence of this condition appears to have increased disproportionately to the incidence of obesity.2 The syndrome of obesity-related glomerulopathy comprises the triad of morbid obesity, marked proteinuria without oedema, and normal serum albumin concentration. It can occur in any degree of obesity but is more common in the morbidly obese group (body mass index > 40 kg/m2; Class III obesity). It often presents as proteinuria on urinary dipstick testing, with marked proteinuria seen on confirmatory testing (up to 32 g/day).2 Other features of the nephrotic syndrome do not occur, and the cholesterol level is often lower than that in patients with nephrotic syndrome. However, glomerular filtration rate is raised, and glomerulosclerosis is seen on biopsy. The pathogenesis is unknown. Obesity-related glomerulopathy is a diagnosis of exclusion: secondary causes of proteinuria should be fully eliminated, including hypertensive renal disease and undetected type 2 diabetic renal disease. More often than not, biopsy will be required to guide management, with cost implications. Although the condition is said to be benign, in a small proportion of patients it progresses to end-stage renal failure requiring replacement therapy, further adding to the cost of management. Fortunately, the condition is readily reversible with weight loss, which is an important emphasis in management. 3 My second comment relates to the case of the overweight adolescent described by Proietto and Baur. In this patient, measurement of insulin level is not indicated.4 There is no standardised insulin immunoassay, the sample has to be collected and processed correctly to produce a valid result, and the result would not add to or alter the management of the condition. It is doubtful if normative data exist for adolescents, but the clinical picture suggests the insulin resistance syndrome. As the primary goal would be to detect disordered glucose metabolism, appropriate testing of glucose level is all that is required.

Huy A Tran

Joseph Proietto,* Louise A Baur† * Endocrinologist, Department of Medicine, Repatriation Hospital, Heidelberg, VIC 3081; † Paediatrician, Children's Hospital at Westmead Clinical School, Sydney, NSW. j.proiettoATunimelb.edu.au In reply: We agree with McHenry and colleagues that, until very recently, surgery was the only effective treatment for morbid obesity. However, the development of effective pharmacotherapy that targets the underlying cause — increased hunger — may well change this situation, as evidenced by the effect of leptin treatment in leptin-deficient children.1 In the not-too-distant future, a medical alternative may be possible. The issue of the relative merits of surgery to insert a foreign body (gastric band) or permanently alter the anatomy of the gastrointestinal tract versus lifelong pharmacotherapy will need to be considered. However, economic as well as health issues may be important, and, as McHenry and colleagues suggest, may still favour surgery as the preferred therapy. We thank Davies for bringing to our attention Campos’ book The obesity myth, in which he claims that overweight individuals are in fact healthier than those of normal weight.2 While many of the book’s other claims can be challenged (such as the statements that the prevalence of type 2 diabetes is not rising in the United States, and that bald men have higher testosterone levels), the fact that there is no simple linear relationship between body mass index (BMI) and illness is correct. Sex, race and fat distribution can all influence the relationship. Moderately overweight women with gynoid (hip and thigh) fat are not at increased risk of illness.3 In contrast, South Asian people have an increased risk of developing diabetes at lower BMI values than people of European background. We agree with Davies that maintaining fitness through regular exercise is very important in minimising the health consequences of obesity. Tran raises the issue of whether it is useful to measure insulin levels in children. It is not unreasonable to assume that insulin levels are raised in most obese children, but this is not always the case. The National Health and Medical Research Council clinical practice guidelines for management of overweight and obesity in children and adolescents state that: “Fasting insulin and glucose should be considered in obese children or adolescents, particularly those with a family history of type 2 diabetes, those with acanthosis nigricans and those from certain ethnic backgrounds”.4 In the presence of insulin resistance, serum glucose level remains normal because of high insulin levels. Thus, glycaemia cannot be used to monitor improvement in insulin sensitivity.

Joseph Proietto · Louise A Baur

Forty-five years as a doctor with diabetes has given Alan Stocks personal insight into how to manage life and practice when living with a chronic illness. Diabetes has proved beneficial to his career, rather than a disadvantage. As a final-year medical student in 1959, over a 2-week period I experienced increasing thirst, polyuria and lassitude, and lost 5 kg in weight. Suspecting diabetes, I performed a urine test using Clinitest. The test was negative for glucose, and, believing my symptoms were caused by pre-examination stress, I took no action. Golden Jubilee meeting of Diabetes Australia – NSW, 1987 The meeting marked the 50th anniversary of the foundation of the first Diabetes Association in Australia. Shown in the photo are John Townend, Chairman of Diabetes Australia – NSW; Phyllis Lush, the first person to receive insulin in Australia; Kempson Maddox (her physician); and the author. Over the next 4 weeks my symptoms worsened rapidly, and I failed a pathology examination. I was so ill that, like all medical students at some time or other, I was convinced I had some sort of malignancy. Finally it dawned upon me that the first test might have been wrong. A repeat test showed high glucose and acetone levels — a random blood glucose level of 25 mmol/L established the diagnosis. Immediate admission to a diabetic ward was advised, but I asked if I could delay admission until the next morning, as I had a date that evening (diabetics often rebel against their condition, but not usually as quickly as that!). There followed a hurried discussion, and my request was granted, provided I first gave myself an injection of insulin. This accomplished, I had a most enjoyable evening, and can still remember being able to sit through the first act of an opera without having to visit the toilet. Already I had learned several valuable lessons about clinical medicine, and diabetes in particular: Urine-testing equipment has a limited shelf-life (in retrospect, that first test tablet must have deteriorated); Always trust your clinical judgement, rather than laboratory tests alone; People with insulin-dependent diabetes should take immediate responsibility for their condition, and should give their own first insulin injection; self-injection is easy, and not to be feared; The effect of insulin is dramatic; Wherever possible, diabetes management should be adapted to fit the patient’s lifestyle. Given my initial fears, to learn that I had a treatable condition came as a great relief, and since that first day I have never resented my diabetes, regarding it more as a constant companion than an illness. In fact, diabetes has proved beneficial to my career, rather than a disadvantage. I had originally hoped to become a surgeon, but was advised at the time that this path would be unwise, in view of the unpredictable hours and mealtimes it would entail. Therefore, I decided to specialise in diabetes. This has allowed me better to understand my own condition. Moreover, I believe that many patients derive comfort and confidence from knowing that their diabetes specialist, who also has diabetes, is apparently in good health! Now semi-retired, I walk 30–60 minutes daily, and am much fitter than when I worked 12-hour days. Apart from some symptomless vascular calcification, I am completely free of long-term complications. I look after the day-to-day management of my diabetes myself, but visit an endocrinologist once a year (for a full medical check-up and complications screen) and an ophthalmologist every 1–2 years. Speaking personally, my wonderful wife has been of inestimable support over the years, and we have two splendid children and two grandchildren. I play golf, which is an ideal sport for the diabetic, as the amount of exercise is moderate and predictable (unlike tennis or cricket) and safe (unlike football). I am also active in madrigal singing. Although I am interested in motor racing, my diabetes precluded me from holding a racing licence; I also had to surrender my glider pilot’s licence on diagnosis. However, I have been able to enjoy membership of a Beefsteak & Burgundy Club, learning to adjust my insulin doses to cope with some remarkable dining extravaganzas! I have found it easy to deal with most of the usual problems of living with diabetes. The need to eat regularly and diet carefully has lessened in more recent years with the advent of ultrashort-acting insulin and the basal-bolus insulin regimen. I am able to avoid jetlag on long trips by travelling business class and combining alcohol and temazepam to ensure 12 hours’ sleep (contrary to textbook advice!), plus aspirin to prevent deep venous thrombosis. My biggest problem is the ever-present risk of hypoglycaemia — in particular, the problem of hypoglycaemia unawareness, which remains the “Achilles’ heel” of type 1 diabetes. Perversely, the harder one tries to avoid hyperglycaemia and achieve an HbA1c level low enough to prevent vascular and neurological complications, the greater becomes the risk of hypoglycaemia unawareness. Now, after 45 years of living with diabetes, I have total unawareness of nocturnal hypoglycaemia, and limited ability to recognise daytime episodes. Regrettably, like most diabetics, I deny that I am hypoglycaemic, even when it is obvious to all around me, and I may become obstreperous when asked to consume carbohydrate! The reason for this denial response is obscure, but may relate to the strict warning given to all newly-diagnosed diabetics (and indelibly etched on their consiousness) to avoid sugar — a message that floats to the surface during hypoglycaemic confusion. The reason for the violent, uncooperative behaviour is equally obscure, but may simply represent release of the underlying personality from inhibition by the superego, much as occurs with alcohol intoxication. When acutely drunk, some people become aggressively antisocial, while others become quiet and morose. International Diabetes Federation meeting in New Delhi, 1976 The author (left) enjoys himself with colleague Brian Hirschfeld and elephant. My wife has rescued me from countless episodes of nocturnal hypoglycaemia, and has saved my life on several occasions. Fortunately, I have rarely become violent when hypoglycaemic, and have learned — admittedly slowly — that when my wife says “You’re hypo!” (a) she is always correct, and (b) it is easier to eat the jelly beans than to argue! Certainly, the frequency of daytime and nocturnal hypoglycaemia can be reduced by using newer long-acting insulin analogues such as insulin glargine or insulin detemir, and can be virtually abolished using a continuous subcutaneous insulin infusion (CSII) — but at a price! Insulin glargine, not yet available under the Pharmaceutical Benefits Scheme, costs $800–$1200 a year. CSII costs about $2500 a year for the consumables alone, but the Federal Government, in its May 2004 Budget, promised to subsidise these costs to the value of $20 per month from September 2004. I have tried CSII on three separate occasions and, while my glycaemic control was undoubtedly better, the inconvenience, high cost, and risk of skin infections were unacceptable. A basal-bolus insulin regimen using Novorapid three times a day via an Innovo pen injector suits me well, and the Innovo memory feature is of great assistance on the occasions when I can’t remember if and when I gave the last dose. Insulin glargine at bedtime allows me much smoother glycaemic control than isophane insulin. Of course, not all diabetics feel as positively as I do; many fear injections, fingerpricks, blindness and gangrene (but, interestingly, not heart attacks!). My view is that injections using 31-gauge needles really don’t hurt, that fingerpricks are a small price to pay for good health, and that long-term complications should be preventable without sacrificing an enjoyable lifestyle. However, diabetes is a constant companion, and one is reminded that one is diabetic every hour of every day. The ability to cope with that certainty goes a long way towards being able to live successfully with diabetes.

Alan E Stocks AM, FRCPE, FRACP

The National Diabetes in Pregnancy Advisory Committee (NDIPAC) is a multidisciplinary committee established in November 2000 by the Commonwealth Department of Health and Aged Care as part of the National Diabetes Strategy. On behalf of the NDIPAC, we present the first Australian consensus statement (endorsed by the Committee in February 2004) on diabetes control for women with type 1 or type 2 diabetes who are preparing for pregnancy: Women planning pregnancy should aim to achieve a target HbA1c value of < 7% (where the upper limit of the normal range for people without diabetes is < 6%) (If the normal range for people without diabetes is specified otherwise, the target HbA1c level should be < 1% above the upper limit of normal.) The following important qualifying statements apply: Women with diabetes should aim to achieve the best control of diabetes possible in preparation for pregnancy. This should include achieving blood glucose levels as close to the normal range as possible, while avoiding hypoglycaemia. Decisions about the precise glucose level targets to be achieved should be made on an individual basis, with collaboration between the woman and her healthcare team. Women who are able to achieve better control of their diabetes than the target value indicated above (eg, an HbA1c level of 6%) should be encouraged to maintain these levels in preparation for pregnancy. Other aspects of care are also important in preparation for pregnancy. These include healthy eating, taking folic acid supplements, and detection and treatment of other diabetes-related complications. It is recommended that tighter control of blood glucose levels (eg, HbA1c < 6% or within the upper limit of the normal range) be targeted once pregnancy is achieved to minimise the risk of pregnancy complications and long-term metabolic consequences for the child. These recommendations were made after reviewing and discussing the available data (the references listed here are a selection of the data sources considered the most relevant).1-15 The recommendations have now been endorsed by the Australasian Diabetes in Pregnancy Society, the Australian Diabetes Society, the National Diabetes Strategy Group and the Royal Australasian College of General Practitioners. The NDIPAC suggests that the recommendations be used to determine action strategies for improving outcomes in pregnancies complicated by diabetes. For example, they could be applied in: designing appropriate enhanced primary-care guidelines and target HbA1c levels for women in their child-bearing years; flagging pathology results (specifically, the HbA1c value in women of child-bearing potential) for action by treating clinicians; ongoing monitoring of pre-pregnancy glycaemic control using the framework of the National Diabetes in Pregnancy Audit Program (for more information, see the Australasian Diabetes in Pregnancy Society website, www.adips.org).

on behalf of the National Diabetes in Pregnancy Advisory Committee

Paget’s disease of bone is common, affecting up to 4% of Australians over the age of 55 years. The incidence of the disease and the severity of newly diagnosed cases appear to be falling, for unknown reasons. The cause of Paget’s disease is unknown, but there is a strong genetic influence. Recently, mutations in the sequestosome 1/p62 gene have been identified as a cause of familial Paget’s disease and of some apparently sporadic cases of the disease. The disease is often asymptomatic, but can cause bone pain, deformity, fracture and other complications. Paget’s disease is eminently treatable. Potent bisphosphonates such as pamidronate, alendronate and risedronate relieve symptoms and may reduce the risk of complications. The Pharmaceutical Benefits Scheme subsidises treatment only for patients with symptomatic disease. A strong case be made for also treating asymptomatic patients with involvement of long bones, vertebrae or base of skull, patients with significant osteolytic lesions, and perhaps all younger patients.

John P Walsh FRACP, PhD

Objective: To examine the trends in processes of diabetes care and in participant outcomes after an intervention in two remote regions of Australia.Design: Follow-up study over 3 years.Setting: Seven health centres in the Tiwi Islands and the Katherine West region of the Northern Territory.Participants: 137 Aboriginal people with type 2 diabetes.Intervention: Implementation of a multifaceted trial, including transfer of purchasing and planning responsibility to local health boards, the development and dissemination of clinical guidelines supported by electronic registers, recall and reminder systems and associated staff training, and audit and feedback.Main outcome measures: Trends in the proportion of Aboriginal people receiving services in accordance with clinical guidelines and in the proportion for whom specified levels of blood pressure and glycosylated haemoglobin (HbA1c) were achieved; health staff perceptions of barriers to effective service delivery.Results: An initial improvement in overall service levels from 40% to 49% was not fully sustained over the 3-year period. The overall proportion of services delivered varied from 22% to 64% between communities and over time. The proportion of participants whose most recent HbA1c level was less than 7% improved from 19% to 32%, but there was little change in blood pressure control. Perceived barriers to service delivery included discontinuities in staffing, lack of work-practice support and patients’ acceptance of services.Conclusions: Multifaceted interventions can improve quality of care in this environment, but achieving sustainable, high-quality care in a range of services and local conditions presents particular challenges. Developing and testing strategies for consistent and sustained improvement should be a priority for service providers and researchers.

Ross S Bailie MPhil(MCH), MD · Damin Si MMed · Samantha J Togni MA · Gary W Robinson PhD · Peter H N d’Abbs PhD

Chin-Pin Yeo,* Melissa J Gillett,† Samuel D Vasikaran‡ * Chemical Pathologist, † Biochemistry Registrar, ‡ Head, Core Clinical Pathology and Biochemistry, Royal Perth Hospital, GPO Box X2213, Perth, WA 6847. gptycpATsgh.com.sg To the Editor: In about 2% to 5% of patients with subclinical hypothyroidism, the condition progresses to overt hypothyroidism each year.1 It is currently recommended that thyroid function tests should be repeated at 6- to 12-month intervals to monitor improvement or worsening in level of thyroid-stimulating hormone (TSH).1 Testing for thyroid peroxidase antibody (TPOAb) is also common practice in subclinical hypothyroidism, as it has been shown that individuals with raised TSH and TPOAb levels have a 40-fold increased risk of developing overt hypothyroidism.2,3 We audited the management of patients who had a result indicating subclinical hypothyroidism from our hospital laboratory, focusing on follow-up thyroid function and TPOAb tests. In December 2003, we retrospectively inspected clinical case notes of patients who had been reported in November 2002 with a TSH level of 4.1–9.9 mIU/L (normal reference interval, 0.4–4.0 mIU/L) and a free thyroxine (FT4) level within the reference range of 10–23 pmol/L (subclinical hypothyroidism). We also contacted the patients’ general practitioners (GPs) for further information when necessary. There were 72 patients with results suggesting subclinical hypothyroidism. Of these, we excluded 29 from other hospitals and three whose GPs were not able to be contacted. Of the remaining 43 patients, 18 had no previous history of thyroid disease (8 men and 10 women; age range, 24–90 years). Six patients were seen in the emergency department, four in the outpatient clinics, and eight in the wards. All the laboratory reports of subclinical hypothyroid results were accompanied by a comment advising repeat thyroid studies at a later date and thyroid antibody tests. However, only three of the 18 patients (17%) had TPOAb tested. Only seven of the 18 patients (39%) were followed up with repeat thyroid function tests, at intervals ranging from 3 days to 7 months. One patient, with a TSH level of 9.8 mIU/L, was started on thyroid replacement therapy. The GPs of 10 of the 11 patients who did not have follow-up testing were not informed of the initial TSH results. The low rate of follow-up of hospital patients with a first-time diagnosis of subclinical hypothyroidism is of concern. While the increase in TSH level in some of these patients may have been related to sick euthyroidism, this can only be confirmed by normalisation of TSH level on repeat testing. TPOAb testing can be deferred until confirmation of persistently raised TSH level. Better strategies, such as a computerised system for selective copying of results to GPs whenever relevant, and inclusion of treatment advice dependent on TPOAb status in the reports,4 may be needed to improve follow-up.

Chin-Pin Yeo · Melissa J Gillett · Samuel D Vasikaran

Adam P Morton* * Endocrinologist, Mater Hospital, South Brisbane, QLD 4101. AmortonATmater.org.au To the Editor: I appreciated the recent comprehensive review of androgen deficiency and replacement therapy in men by Handelsman and Zajac.1 I ask their opinion of the importance of obstructive sleep apnoea as a cause of secondary hypogonadism, and also of the safety of androgen replacement in men with hypogonadism who have obstructive sleep apnoea but are intolerant of continuous positive airway pressure (CPAP) treatment. In my practice, obstructive sleep apnoea is one of the most common associations, if not indeed causes, of hypogonadotropic hypogonadism. Several studies have shown that obstructive sleep apnoea is associated with secondary hypogonadism, which is partly or completely reversed by both CPAP treatment and uvulopalatopharyngoplasty.2-4 Secondary hypogonadism is also a feature of several conditions in which there is a high prevalence of obstructive sleep apnoea, including chronic spinal cord injury and cardiac failure. Of concern, studies have shown that androgen replacement may precipitate or worsen obstructive sleep apnoea.5,6 Similarly, a study of women with endogenous androgen excess caused by polycystic ovary syndrome found they were 30 times more likely to suffer from sleep-disordered breathing than control women.7 A single case report describes resolution of obstructive sleep apnoea in a non-obese woman after removal of a benign testosterone-producing ovarian tumour.8 Thus, I would value Handelsman and Zajac’s comments as to whether they consider obstructive sleep apnoea to be an important cause of secondary hypogonadism, and whether symptoms of this condition should be sought before initiating androgen replacement therapy.

Adam P Morton

David J Handelsman,* Jeffrey D Zajac† * Director, ANZAC Research Institute, Concord Hospital, Hospital Road, Concord, NSW 2139; † Head, Department of Medicine, Austin Hospital, Melbourne, VIC. djhATanzac.edu.au In reply: We thank Morton for his thoughtful comment that, in addition to monitoring for obstructive sleep apnoea precipitated by testosterone therapy, it may be worthwhile screening for this condition before starting treatment. Symptoms to be sought include daytime sleepiness and partner reports of loud and irregular snoring, especially among overweight men with large collar size. Obstructive sleep apnoea rises steeply in prevalence with age and causes mild hypogonadotropic hypogonadism, which is rectified by effective continuous positive airway pressure (CPAP) treatment.1 Obesity, depression, cardiovascular disease and other conditions that become more common with age have similar effects. Together, they contribute to the lower blood testosterone levels found in unselected older men, in whom testosterone remains an unproven treatment.2 This condition differs from classical hypogonadotropic hypogonadism caused by hypothalamic or pituitary disorders, which routinely requires lifelong testosterone replacement, and (occurring in a younger population) is rarely associated with obstructive sleep apnoea. The prevalence of obstructive sleep apnoea precipitated by testosterone treatment remains unclear. A case precipitated by injectable testosterone has been reported,3 while testosterone has potential adverse effects on sleep in older men.4 Clinical experience suggests that, among younger hypogonadal men, obstructive sleep apnoea is a rare idiosyncratic reaction to testosterone, which, like polycythaemia, may be particularly related to supraphysiological blood testosterone levels. However, the prevalence may be higher among older men. Hence, we agree that pretreatment screening is wise (rather than proven) for older men starting testosterone treatment, but is not routinely necessary for young men with classical hypogonadism.

David J Handelsman · Jeffrey D Zajac

Sharon J Gardiner,* Evan J Begg,† Carl M J Kirkpatrick,‡ Robert B Buckham¶ * Drug Information Pharmacist, † Professor of Medicine, Christchurch School of Medicine and Health Sciences, Private Bag 4345, Christchurch, NZ; ‡ Lecturer, School of Pharmacy, University of Queensland, Brisbane; ¶ Drug Information Pharmacist, Christchurch Hospital, NZ sharon.gardinerATcdhb.govt.nz To the Editor: We wish to commend the Australasian Diabetes in Pregnancy Society (ADIPS) ad hoc working party for providing an update on the safety of metformin in pregnancy.1 However, we would like to comment on the information they provided on the safety of this drug in breastfeeding. Metformin can be regarded as a well studied drug with respect to its distribution into human breastmilk;2,3 most drugs are not as well served in this regard. As Simmons et al indicated,1 the infant “dose” in breastmilk is small at less than 0.4% of the maternal dose, corrected for body weight. This is substantially lower than the arbitrary cut-off of 10% used to guide drug use during lactation and thus implies safety.4 Further evidence for the safety of this drug in breastfeeding arises from failure to detect metformin in blood sampled from four of six infants exposed via breastmilk (limit of detection, 5–10 μg/L) and lack of adverse effects noted in nine exposed infants.2,3 Simmons et al stated that infant exposure to metformin could be reduced by breastfeeding immediately before maternal dose ingestion and then avoiding feeding for at least 2–3 hours after the dose. For drugs with a short elimination half-life, this recommendation — avoiding feeding at peak drug concentrations in the milk — may reduce infant exposure. However, this is not the case for metformin. Two studies investigating metformin in breastfeeding have shown that the metformin peak plasma concentration occurs about 2–4 hours after the dose, while milk concentrations are “flat” across the entire dosing interval. This is distinctly different from most drugs, in which the drug concentrations in milk mimic the rise and fall of plasma concentrations, consistent with passive diffusion.2,3 The flat profile observed with metformin raises the possibility that the distribution of metformin into or out of breastmilk may involve an active process such as organic cation transporter(s), in addition to passive diffusion Given this unusual concentration profile in breastmilk, infant exposure (albeit small) will not be reduced by the practice of avoiding breastfeeding for a few hours after maternal dose ingestion, as suggested by Simmons et al. In other words, mothers may feed their infants at any time during the dosing interval and this will not affect infant exposure to metformin. We believe that there is sufficient evidence for metformin to be considered a safe therapeutic option in the treatment of diabetes or polycystic ovary syndrome in breastfeeding mothers, with the usual caveat of weighing up the risk–benefit ratio in each case.

Sharon J Gardiner · Evan J Begg · Carl M J Kirkpatrick · Robert B Buckham

David Simmons,* Barry N J Walters,† Janet A Rowan,‡ H David McIntyre§ * Professor of Medicine, Waikato Clinical School, Waikato Hospital, Hamilton, NZ; † Clinical Associate Professor, Department of Women’s and Children’s Health, King Edward Memorial Hospital, Subiaco, WA; ‡ Physician, Department of Obstetrics, National Women's Hospital, Auckland, NZ; § Director of Endocrinology, Mater Hospital, Brisbane, QLD. simmonsdATwaikatodhb.govt.nz In reply: We thank Gardiner et al for their commendation and support for our update on the safety of metformin in pregnancy.1 We agree with their analysis regarding the timing of the use of metformin during lactation. Nevertheless, we would like to highlight that the safety of metformin can not be assumed from the studies they quote, as these included very few subjects. Such studies, helpful as they may be, provide no imprimatur for the long-term safety for the growing infant and subsequent adult. While no babies had side effects reported during these studies, this may not be the case for other babies. Should a woman decide against the use of insulin to control hyperglycaemia postnatally, then the risk of potential known and unanticipated side effects of metformin should be discussed while obtaining informed consent for metformin use. However, during this discussion, it would also be prudent to weigh-up metformin use against breastfeeding with continued hyperglycaemia, an activity associated with greater obesity and impaired glucose tolerance in the offspring.2

David Simmons · Barry N J Walters · Janet A Rowan · H David McIntyre

Winston Chong Chair, Interventional Radiology Reference Group, Level 9, 51 Druitt Street, Sydney, NSW 2000. ranzcrATranzcr.edu.au To the Editor: I refer to the recent editorial on “Metformin and serious adverse effects”.1 I would like to highlight the position of the Royal Australian and New Zealand College of Radiologists (RANZCR) on the use of metformin hydrochloride when administering intravascular contrast media. The RANZCR has adopted an evidence-based approach in formulating its guidelines. The College guidelines on metformin hydrochloride and intravascular contrast media are available at <www.ranzcr.edu.au/open/policies/diagnostic_imaging/pol1_2.htm>. The current guideline is that there is no need for patients to stop taking metformin hydrochloride for 24–48 hours before administration of an intravascular contrast medium. Stopping or continuing to take metformin depends on the patient’s renal status, and the likelihood of inducing renal dysfunction when intravascular contrast is administered. If discontinuation is required, then the drug only needs to be stopped for 48 hours, commencing on the day of administration of intravascular contrast.

Winston Chong

Janelle C Nisbet,* Joanna M Sturtevant,† Johannes B Prins‡ * Endocrinology Registrar, † Renal Specialist Pharmacist, ‡ Director of Diabetes and Endocrinology; and Professor of Endocrinology, University of Queensland, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, QLD 4102. jprinsATsoms.uq.edu.au In reply: Chong’s letter highlights some important issues, and his points are well made. As we imply in our editorial,1 the evidence base on which to base guidelines and decisions is poor, which is one of the reasons that the guidelines differ widely between countries and organisations. Specialty-specific guidelines must also take into account practicalities. We elected to follow the more conservative end of the guideline spectrum in our suggestions, accepting that, in many circumstances, these would be difficult or impossible to follow. From a radiological perspective, it would require a significant change in practice to implement guidelines such as those we suggested, and the evidence base supporting such a change does not exist. Metformin is a short-acting drug and stopping it at the time of a potentially hazardous procedure will almost always be effective in preventing drug-related complications. Overall, the aim of our article was to raise awareness of the potential hazards of metformin use, and to encourage practitioners to follow available and relevant guidelines.

Janelle C Nisbet · Joanna M Sturtevant · Johannes B Prins

Objectives: To determine the incidence rate of coronary heart disease (CHD) in Australian Aboriginal people with type 2 diabetes, and to compare the impact of diabetes on CHD risk in Aboriginal women and men.Design: Cohort study.Setting: A remote Aboriginal community in the Northern Territory.Participants: 889 Aboriginal people aged 20–74 years followed up to 31 May 2003 after baseline examination in 1992–1995.Main outcome measures: Incidence rates of CHD (estimated for 123 participants with diabetes at baseline and 701 “non-diabetes” participants); rate ratios for diabetes risk (95% CI), with “non-diabetes” participants as the reference group.Results: Participants with diabetes at baseline had a higher rate of CHD (37.5 per 1000 person-years) than those without diabetes (7.3 per 1000 person-years). Adjustment for multiple CHD risk factors, such as age, smoking, alcohol consumption, systolic blood pressure, body mass index, high-density lipoprotein cholesterol and total cholesterol levels, resulted in a CHD rate ratio for women of 3.7 (95% CI, 1.6–8.9) (comparing women with diabetes with those without) and a CHD rate ratio for men of 1.4 (95% CI, 0.4–4.1) (comparing men with diabetes with those without).Conclusions: Aboriginal women with diabetes experienced a significantly higher risk of CHD than women without diabetes. Although the difference was not statistically significant, women with diabetes had a higher CHD risk than men with diabetes.

Zhiqiang Wang PhD · Wendy E Hoy MB BS, BScMed, FRACP

Objective: To assess primary care processes and clinical characteristics of adults with diabetes in remote northern Australian Indigenous communities.Design: Clinical audit from diabetes registers in 21 remote primary healthcare centres in the Torres Strait Health Service District (n = 921), three in Cape York, Queensland (n = 252), and three in the Northern Territory (n = 194), between September 2002 and February 2003.Participants and setting: Aboriginal and Torres Strait Islander adults with diabetes who were receiving their routine diabetes care in these 27 centres.Main outcome measures: Provision of regular checks for weight, blood pressure, glycaemia (HbA1c), proteinuria, lipid levels, renal function, eyes and feet, influenza and pneumococcal vaccination. Weight, blood pressure and glycaemic control.Results: Most routine diabetes checks were delivered according to recommended schedules, except for eye and foot checks in the NT. There were uniformly high rates of appropriate treatment for hypertension and albuminuria, but low rates of insulin treatment and self-monitoring despite a high mean HbA1c level (8.9%). Vaccination rates were low in the NT. Torres Strait Islanders with diabetes were significantly heavier than Aboriginals, but had lower mean diastolic blood pressure (77.3 mmHg compared with 79.5 mmHg) and lower prevalence of albuminuria and smoking.Conclusion: A high proportion of Aboriginals and Torres Strait Islanders requiring treatment for high blood pressure and proteinuria are receiving it. However, there is dissonance between the relatively high rates of routine checks and apparent lack of therapeutic action on glycaemia. More intensive management of glycaemia, including improved nutrition, exercise and (probably) insulin, is required to reduce microvascular complications.

Robyn A McDermott FAFPHM, PhD · Fiona Tulip AssocDipMRA · Barbara Schmidt BSc, MBA

Androgen deficiency is a clinical diagnosis confirmed by hormone assays. Among younger men, androgen deficiency is usually due to underlying hypothalamopituitary or testicular disorders. Androgen replacement therapy should be started after proof of androgen deficiency and should continue lifelong with monitoring. Men presenting with erectile dysfunction should be evaluated for androgen deficiency, but it is an uncommon cause; if overt androgen deficiency is confirmed, an underlying disorder needs further specialist investigation. In the absence of characteristic underlying testicular or pituitary disorders, new diagnosis of androgen deficiency in older men is difficult because of the non-specific symptoms and the decline in blood testosterone levels seen in healthy ageing and chronic medical disorders. There remains no convincing evidence that androgen therapy is either effective treatment or safe for older men unless they have frank androgen deficiency.

David J Handelsman FRACP, PhD · Jeffrey D Zajac PhD, FRACP

Bronwyn A L Crawford,* Channa Perera† * Endocrinologist and Clinical Senior Lecturer, Royal Prince Alfred Hospital and the University of Sydney, Sydney, NSW 2050; † Endocrinologist, Orange Base Hospital, Orange. brcrawfoATmail.usyd.edu.au To the Editor: Prolonged hypoglycaemia in patients taking a sulfonylurea may be refractory to intravenous glucose treatment with fatal consequences, as described by Veitch and Clifton-Bligh.1 Although these authors briefly mention the use of octreotide, we believe that an additional point in the “Lessons from practice” should have been: Octreotide may be an effective therapy in refractory sulfonylurea-induced hypoglycaemia. We describe the first two patients in whom we used this therapy. A 76-year-old man with type 2 diabetes was admitted after an acute myocardial infarction and cardiac arrest. He was successfully resuscitated and underwent emergency bypass surgery. His diabetes was controlled with gliclazide 80 mg twice a day. After surgery, he developed cardiac failure, renal impairment (serum creatinine level, 0.22 mmol/L) and frequent hypoglycaemic episodes. The gliclazide was stopped but, despite good oral dietary intake, hypoglycaemia worsened and failed to respond to vigorous intravenous glucose therapy. He suffered a hypoglycaemic seizure (blood sugar level, 0.8 mmol/L). Over the next day, he received more than 300 g of glucose in the form of a 10% glucose intravenous infusion, but, despite this, went into hypoglycaemic coma. Blood results were: insulin, 472 pmol/L (reference range [RR], 15–60 pmol/L); C-peptide, 7616 pmol/L (RR, 300–800 pmol/L); and gliclazide, 9.4 mg/L (steady state average, 2.5 mg/L). He was given an intravenous infusion (30 ng/kg per minute) of octreotide.2 Within an hour, his blood sugar level rose to 7.9 mmol/L and continued to rise. Dextrose and octreotide infusions were ceased within 13 hours, with no further episodes of hypoglycaemia. He was discharged home 2 days later. A 75-year-old man with type 2 diabetes was taking glibenclamide 2.5 mg each morning. He was transferred from a rural hospital with acute on chronic renal failure (serum creatinine level, 0.4 mmol/L), as well as recurrent hypoglycaemia. The glibenclamide was stopped, but blood sugar levels remained low, and he became comatose despite boluses of 50% dextrose and a continuous infusion of 10% dextrose. The high volume of intravenous fluid precipitated cardiac failure and pulmonary oedema, requiring inotropic support. Blood results were: blood sugar, 1.5 mmol/L; insulin, 1250 pmol/L; C-peptide, 20 949 pmol/L. As an alternative to the high-dose, continuous infusion of octreotide used in our first patient, we administered a single subcutaneous injection of octreotide 50 μg. One hour later, the patient’s blood sugar level had risen to 9.0 mmol/L. He had no further episodes of hypoglycaemia. Eight hours later, insulin and C-peptide levels had fallen markedly (insulin, 153 pmol/L; C-peptide, 5654 pmol/L). He made a full recovery. Octreotide is a somatostatin analogue that inhibits the secretion of a number of neuropeptides, including insulin. It is a safe and effective therapy for sulfonylurea-induced hypoglycaemia when initial therapy with oral or intravenous glucose fails.2-5 It is particularly useful in elderly patients with renal or cardiac complications, in whom fluid overload may be a limiting factor in intravenous dextrose therapy. Octreotide may also break the vicious circle that can occur in sulfonylurea-induced hypoglycaemia in which repeated dextrose boluses further stimulate insulin release.

Bronwyn A L Crawford · Channa Perera

Peter C Veitch,* Rory J Clifton-Bligh† *Specialist in Geriatric Medicine, Department of Aged Care and Rehabilitation Medicine; † Registrar in Endocrinology, Department of Endocrinology, Royal North Shore Hospital, Clinic 1, Level 3, Pacific Highway, St Leonards, NSW 2065. rcliftonATmed.usyd.edu.au In reply: Crawford and Perera highlight a very important point with respect to hospital-based treatment of sulfonylurea-induced hypoglycaemia. Whereas, in our article,1 we wished to emphasise the importance of recognising and preventing this condition in primary care settings, we agree that octreotide is an effective therapy in treating this condition. Octreotide inhibits the specific effect of sulfonylureas (glucose-stimulated β-cell insulin release) and prevents rebound hypoglycaemia, which, in this situation, may occur with the use of glucose.2 Case reports, including those elegantly presented and referenced by Crawford and Perera, clearly illustrate the safety and efficacy of octreotide in treating sulfonylurea toxicity when initial therapy with glucose fails. Octreotide may be administered either intravenously or subcutaneously, and its effect is maintained after a short course of therapy. At our own institution, we have now adopted guidelines for the treatment of refractory sulfonylurea-induced hypoglycaemia, which include the administration of octreotide (50 μg subcutaneously) every 8 hours for up to three doses, although, as Crawford and Perera note, some patients will have a sustained response after a single dose.

Peter C Veitch · Rory J Clifton-Bligh

Malvinder S Parmar Medical Director (Internal Medicine), Timmins and District Hospital, Suite 108, 707 Ross Ave East, Timmins, ON P4N 8R1, Canada. atbeatATntl.sympatico.ca To the Editor: I wish to add another cause of exogenous hyperthyroidism to those mentioned in the comprehensive review on hyper- and hypothyroidism by Topliss and Eastman.1 Inadvertent ingestion of animal thyroid (“hamburger” thyrotoxicosis), although rare, is worth mentioning. Meat may be inadvertently contaminated with thyroid tissue through the process of “gullet trimming” during butchering. While this process has been prohibited in most countries since the recognition of outbreaks of hamburger thyrotoxicosis,2,3 it may still occur when farm animals or wild game are prepared for consumption by farmers, hunters or local butchers unaware of the prohibition. I recently reported a case of a woman living on a farm in Canada who had five episodes of transient hyperthyroidism over a decade.4 These were initially diagnosed as episodes of “silent thyroiditis”, but were later attributed to consumption of meat patties contaminated with thyroid tissue, as the local butcher was not aware of the prohibition on gullet trimming. A history of eating wild game or locally prepared meat should be considered before a diagnosis of silent thyroiditis is made. Thyroid uptake of radioiodine is low in both conditions, but serum thyroglobulin level is raised in thyroiditis and decreased during the hyperthyroid phase of exogenous hyperthyroidism.

Malvinder S Parmar

Ngaire T Jones Medical Practitioner, Beaconsfield, WA. ngairejATbigpond.com To the Editor: The recent article on thyroid disorders by Topliss and Eastman notes that “around the world, iodine deficiency still remains the predominant cause of hypothyroidism” and furthermore that “mild iodine deficiency is re-emerging in Australia”.1 Indeed, the Journal has recently published at least two articles suggesting that the iodine status of the Australian population needs to be further explored.2,3 My question therefore is: when treating a patient who has results indicating clinical or subclinical hypothyroidism, would it be relevant and important to test for iodine deficiency (by 24-hour urine collection)? This seems analogous to undertaking iron studies in a patient with a falling haemoglobin level. In the same way that iron deficiency can exist and produce symptoms, even in the absence of anaemia, may not iodine deficiency affect health and well-being? Without the elemental “building blocks” of iron and iodine, the relevant systems are put into overdrive to no avail. It seems simple to test routinely for this possibility, correct any deficiency and then recheck thyroid function. There may be more “clinically significant iodine deficiency” than we realise. As it will no doubt be some time until further studies in the Australian population shed more light on this, is it not relevant meanwhile to at least check for this possibility in individual patients?

Ngaire T Jones

Duncan J Topliss,* Creswell J Eastman† * Director, Endocrinology and Diabetes, Alfred Hospital, Commercial Road, Melbourne, VIC 3004; † Director, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Sydney, NSW. Duncan.toplissATmed.monash.edu.au In reply: Jones asks if iodine excretion should be measured routinely in all patients with hypothyroidism in Australia as part of the initial assessment. We do not advocate this for the following reasons. Urinary iodine estimations are unreliable for assessing individual patients, as urinary iodine levels can vary considerably from day to day with iodine intake. These measurements should be reserved for population studies to provide an overall assessment of iodine nutrition in that population. In Australia, it is probable that virtually all cases of primary hypothyroidism are caused by chronic autoimmune lymphocytic thyroiditis, ablative therapy for Graves’ disease, or inadequate thyroxine replacement therapy in these conditions, as is the case in the United States and the United Kingdom.1-3 This contention is supported by data from the Busselton (Western Australia) survey on thyroid peroxidase antibody levels,4 which suggest that these antibodies will be of great diagnostic assistance, in contrast to the dubious clinical value of individual measurement of iodine excretion. In support of this view, in a large survey of the US population, where iodine intake has probably fallen similarly but not to the same degree as in Australia, there was no association between low urinary iodine levels and increased serum levels of thyroid stimulating hormone (TSH).5 In that study, the significant association between raised TSH and female sex disappeared after controlling for the presence of thyroid peroxidase antibodies, while the prevalence of clinical hypothyroidism was strongly correlated with positive results for these antibodies. In Australia, current information indicates that iodine deficiency, where it exists, is mild. The prevalence and regional variation are currently the subject of the National Iodine Nutrition Survey, which is surveying iodine excretion and thyroid size in primary school children. There is no evidence that this mild deficiency is associated with an increased prevalence of hypothyroidism. Jones’s suggestion that iodine deficiency impairs health by a mechanism other than impairment of thyroid function is not supported by any scientific evidence. Any consideration of advocating routine assessment of iodine status should await the results of the ongoing national study. However, iodine nutrition would appear to be best addressed as a public health issue, by promoting use of iodised salt and ensuring adequate iodine nutrition in pregnant and breastfeeding women and their infants.

Duncan J Topliss · Creswell J Eastman