Screening for Thyroid Disease

Screening for Thyroid Disease

128 enzymesS,IO,12,J, produced by the organism under the control of genes located in plasmids. 7,12,13,18,19 Transfer to other strains may result f...

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enzymesS,IO,12,J, produced by the organism

under the

control of genes located in plasmids. 7,12,13,18,19 Transfer to other strains may result from transduction whereby bacteriophage from the donor strain carries the plasmid with the resistance factor to the recipient.8,12,20 LACEy21,22 has reported a further possible mechanism, phage-mediated conjugation, which would allow the transfer of resistance factors between strains of Staph. aureus at a much higher frequency than that normally associated with transduction. In the Dublin outbreak, as in some previous episodes, various different

bacteriophage types of Staph. aureus were identified and it has been suggested that heterogeneity of infecting strains indicates spread of plasmids coding for gentamicin resistance between different strains.14,18,19,23,24 Other outbreaks have been associated with single bacteriophage types of Staph. aureus,’o indicating that individual gentamicin-resistant strains of this species retain their capacity to spread and infect susceptible hosts. In some outbreaks, gentamicinresistant strains of Staph. aureus have spread to patients not previously treated with aminoglycosides,9 but there are several reports suggesting that exposure to antibiotics increases the risk.9,10,12,13 Such antibiotics include not only aminoglycosides but also unrelated agents such as ampicillin and methicillin, to which the strains concerned were also resistant. This is rather like the position which arose with methicillin-resistant Staph. aureus, when previous exposure to methicillin and related agents was thought to be less important than exposure to other &bgr;-lactam antibiotics, such as

ampicillin.5,25 Perhaps more obviously important in the development of resistant bacterial clones is the strong selective pressure exerted by actual exposure to gentamicin. There is compelling evidence-as with fusidic acid,6,26 neomycin,27,28 and the closely related kanamycin-to implicate topical gentamicin in the initial appearance of these gentamicin-resistant 17

18. 19

Dowding JE. Mechanisms of gentamicin resistance in Staphylococcus aureus. Antimicrob Agents Chemother 1977, 11: 47-50. Wood DO, Carter MJ, Best GK Plasmid-mediated resistance to gentamicin in Staphylococcus aureus. Antimicrob Agents Chemother 1977; 12: 513-17. Wyatt TD, Ferguson WP, Wilson TS, McCormick E Gentamicin resistant Staphylococcus aureus associated with the use of topical gentamicin. J Antimicrob

Chem 1977, 3: 213-17 20. de Saxe M, Porthouse A Gentamicin resistance in Staphylococcus aureus Lancet 1979; ii: 370-71. 21 Lacey RW. Evidence of two mechanisms of plasmid transfer to mixed cultures of Staphylococcus aureus J Gen Microbiol 1980, 119: 423-35 22. Lacey RW, Lord VL Transfer of gentamicin resistance between cultures of Staphylococcus aureus in nutrient broth, serum and urine J Med Microbiol 1980, 13: 411-21. 23. Greenhood GP Hill DL, Dixon RE, Carter MJ, Kanto WP Changing phage typing patterns of

epidemic gentamicin-resistant Staphylococcus aureus. Evidence for of gentamicin resistance. Lancet 1979, i: 289-91. 24 Schaefler S, Jones D, Perry W, Ruvinskaya L, Baradet T, Mayr E, Wilson ME. Emergence of gentamicin and methicillin-resistant Staphylococcus aureus strains in New York City hospitals. J Clin Microbiol 1981, 13: 754-59. 25. Ayliffe GAJ, Green W, Livingston R, Lowbury EJL. Antibiotic-resistant Staphylococcus aureus in dermatology and burns wards J Clin Pathol 1977; 30: transmission


Alder VG, Warin RP. Pyogenic cocci in infantile eczema throughout one year. Br Med J 1975: iii: 199-201. 27. Alder VG, Gillespie WA. Influence of neomycin sprays on the spread of resistant staphylococci. Lancet 1967; ii: 1062-63. 28. Lowbury EJL, Babb JR, Brown VI: Collins BJ. Neomycin-resistant Staphylococcus aureus in a burns unit J Hyg Camb 1964, 62: 221-28.

26. Smith


variants.8,11,12,19,29 Indeed, arguing from experience with neomycin-resistant strains of Staph. aureus LACY accurately forecast the advent of gentamicin resistance in this species-an eventuality which may have been brought forward by the inclusion of the agents in topical steroid preparations.30 Multipleantibiotic-resistant strains of Staph. aureus are very common in dermatological and burns units, where topical antibiotics tend to be used.25 Transfer of resistance to gentamicin from gentamicin-resistant strains to gentamicin-sensitive strains has been seen on the skin of volunteers31 and so has transfer of resistance from Staph. albus to Staph. aureus.32 If this happens in

patients, topical gentamicin probably

enhances the


Do these stories from Dublin’4 and the U.S.A.’6 herald the renaissance of epidemic staphylococcal infection in hospitals? SHANSON’ believes that things are likely to continue much as they are: most general hospitals will experience endemic staphylococcal infections, notably in surgical patients, with occasional outbreaks due to multiple-antibiotic-resistant strains of Staph. aureus. The Dublin epidemic, according to HONE and co-workers, 14 resulted from a multiplicity of factors including lack of isolation facilities and difficulties in operating a uniform, effective antibiotic policy throughout their group of hospitals. If these factors receive the attention they clearly merit, and if topical antibiotics are used judiciously, SHANSON’s optimistic forecast may prove to be correct.

Screening for Thyroid Disease testing of newborn babies for congenital hypothyroidism is now widely practised,as an extension to screening programmes for phenylketonuria ROUTINE

based on the Guthrie test. There is still room for debate as to whether blood thyroxine (T4) or thyroid-stimulating hormone (TSH), or both, should be measured in the initial screen, but questions relating to cost-benefit analysis have not presented difficulties. Indeed, the inclusion of screening for - hypothyroidism in the Guthrie test programme has enhanced the costeffectiveness of neonatal screening programmes. Congenital hypothyroidism is a medically important condition, frequently unsuspected clinically to begin with although having quite a high incidence, and for which an effective treatment exists-all factors that should be taken into account when any screening programme is under consideration.1 The case for screening of apparently healthy adults for unsuspected thyroid dysfunction has not been J, Noble WC. Acquisition of antibiotic resistance by Staphylococcus aureus in skin patients. J Clin Pathol 1978, 31: 1187-92 Lacy RW. Antibiotic resistance plasmids of Staphylococcus aureus and their clinical

29. Naidoo 30.

importance. Bact Rev 1975; 39: 1-32. 31. Naidoo J, Noble WC. Transfer of gentamicin resistance between strains of Staphylococcus aureus on skin. J Gen Microbiol 1978; 107: 391-93. 32. Naidoo J, Noble WC. Transfer of gentamicin resistance between coagulase-negative and coagulase-positive staphylococci on skin. J Hyg Camb 1981; 86: 183-87. 1. Wilson JMG, Jungner G Principles and practice of screening for disease. Geneva World Health Organisation, 1968


established. Although biochemical evidence, based on serum T4 or TSH measurements, may be obtained that clearly suggests the presence of minor degrees of hypothyroidism or hyperthyroidism, there is no good evidence that treatment is beneficial in either form of minor subclinical dysfunction. What is more, in the case of possible hyperthyroidism, all forms of treatment for the established condition (medical, surgical, or radioiodine) carry the risk of inducing hypothyroidism and possibly other more serious complications, so treatment cannot be justified for subclinical disease. In adults, therefore, well-population screening for thyroid dysfunction is contraindicated at present. Casefinding, however, is a different matter since this can involve the testing of patients, who have sought health care, for disorders which may be unrelated to their chief

complaints.2 discussed the place of "routine" thyroid-function tests for patients admitted to hospital. We concluded that many problems remained unresolved in relation to serum T4 measurements-nowadays the test most likely to be performed in any admission multiphasic screening (AMS) or case-finding programme that includes a search for possible thyroid dysfunction in adults. We drew attention 1.0 difficulties that are sometimes encountered in the interpretation of T4 results in patients, and we referred to the use of "follow-up" or "second-line" tests such as serum freethyroxine index (FTI), or triiodothyronine (T3), or TSH in helping to resolve these difficulties. There still remained problems due to the variable and sometimes unpredictable effects of non-thyroidal illness on the results, and therefore on the interpretation, of thyroidfunction tests.4,5 We concluded that routine screening of thyroid function (by AMS of hospital patients) had not yet been shown to be worthwhile. This conclusion now needs to be reviewed. On the technical side, the development of specific, reliable, and simple radioimmunoassay and EMIT methods for measuring serum T4 means that many laboratories can now do these assays in considerable numbers, often daily. On the other hand, neither T3 nor TSH assays have reached the same stage of development, so T4 is likely to remain the test of choice for several years in any AMS or case-finding programme Four years ago,3


involving thyroid-function assessment. Thyroid disease is common in elderly patients6 and, if the potentially misleading effects of drugs and intercurrent illness on the results of thyroid-function tests can be discounted, some geriatricians believe that AMS should always be performed, and that the chemical tests should always include T4 measurements. Doctors who hold this view may welcome the support of 2 Sacket DL. Holland WW Controversy in the detection of disease. Lancet 1975; ii: 357-59 3 Editorial Problems with serum-thyroxine. Lancet 1977, ii: 74-75. 4 Carter JN. Corcoran JM, Eastman CJ, Lazarus L. Effect of severe, chronic illness on thyroid function Lancet 1974, ii 971-74 5 Birkhauser M, Busset R, Burer T, Burger A. Diagnosis of hyperthyroidism when serum-thyroxine alone is raised. Lancet 1977; ii: 53-56. 6 Hodkinson HM Biochemical diagnosis of the elderly. London: Chapman and Hall, 1977

EPSTEIN and co-workers,7 from San Diego, who claim to have shown that "the inclusion of T4 in a screening panel and the pursuit of unexpected deviations appears to be both efficient and effective". EPSTEIN et al. reached this conclusion after examining the question, "Given that a biochemical screening pattern is to be done for other reasons, is the marginal or incremental cost of including a T4 test justified by the marginal or incremental increase in health output?" For patients admitted to geriatric assessment units, it is a widely held view that intensive and extensive investigation should be undertaken early in their stay. The high "hotel charges" of hospital stay, the

importance of identifying potentially remediable conditions quickly, and the ease of performing AMS profiles can all be offered as justifications for AMS. The view that all information is potentially valuable distracts attention from the low diagnostic yield of the Birmingham and Hammersmith AMS studies,8 and from the positively discouraging account of the "value" of AMS, as assessed in Adelaide.9 The method of costing adopted by EPSTEIN et al.meant that they excluded from consideration the costs-undoubtedly substantial-of the pre-existing AMS programme. conclude that the cost of diagnosing or ruling out each case of suspected thyroid disease (i.e., the cost of obtaining the initial abnormal T4 values plus the cost of any related follow-up tests) in the 3603 patients screened was as little as$11 136, or $3.09 per patient screened. They also assessed health effectiveness, measured in "discounted Well-Years". It is highly questionable whether EPSTEIN et al. were right to keep the costs of T4 tests separate from the costs of the pre-existing AMS programme, especially since the medical value of AMS is still open to question.10 The average gain of about 0-5 well-years (discounted at 5%) for the 4 hypothyroid and 2 hyperthyroid patients treated as a result of the San Diego study is likewise not very impressive. However, the benefits might have been more convincing if the physicians concerned had not overlooked or decided to ignore results on 29 of the 111 patients in whom abnormal serum T4 values were observed. Cost-benefit analysis of AMS, and indeed of all screening programmes, is difficult,2,11but this merely emphasises the need to conduct such studies critically. We conclude that serum T4 has gained a place in AMS programmes for elderly patients, but that the difficulties in interpretation remain. The main danger still lies in the uncritical use of AMS, whether or not the range of tests includes T4, since doctors are in danger of missing abnormal results when presented

This allowed them


KA, Schneiderman LJ, Bush JW, Zettner A. The ’abnormal’ screening serum thyroxine (T4): analysis of physician response, outcome, cost and health effectiveness. J Chron Dis 1981; 34: 175-90. 8. Whitehead TP, Wootton IDP Biochemical profiles for hospital patients Lancet 1974,

7. Epstein

ii 1439-43 9. Durbridge TC, Edwards F, Edwards RG, Atkinson M Evaluation of benefits of screening tests done immediately on admission to hospital Clin Chem 1976, 22: 968-71. 10 Editorial Admission multiphasic screening. Lancet 1976 ii: 1229-30. 11 Knox EG. Screening for disease Lancet 1974; ii: 1434-36


with masses of figures. Even if their attention is drawn to abnormalities, doctors still tend to discount many of the abnormal results provided by routinely performed AMS profiles. Although many laboratories find AMS administratively convenient and economical to perform, on a cost-per-test basis, there is still a lot to be said for discretionary and critical methods of requesting investigations. It is usually easier to interpret abnormalities when there has been a clinical reason for requesting a test in the first place, and this fact cannot be stressed too often in the teaching of medical students and in the continuing education of

geriatricians. POISONING WITH ENTERIC-COATED ASPIRIN ENTERIC-COATED aspirin tablets are so formulated principally to reduce gastric intolerance and occult blood loss. The aspirin is absorbed much more slow1yl than from conventional tablets, so they are unsuitable for treatment of acute painful conditions. Management of overdose can be very troublesome, especially if the preparation also contains

paracetamol (acetaminophen). After overdose with enteric-coated aspirin, plasma salicylate measurements are unreliable as a guide to prognosis. Indeed, in one recent case salicylate was not detected at all in a blood sample taken on admission, and since the patient seemed well, he was discharged home after gastric lavage only to die fifteen hours later. Thus, if it is suspected that an enteric-coated or other slow-release aspirin preparation has been taken, the patient must be kept under observation for at least twenty-four hours and the plasma salicylate concentration should then be measured again. Salicylate concentrations may not reach their highest value until sixty or seventy hours after the overdose.3,4 Otherwise, the treatment of salicylate poisoning due to enteric-coated preparations is the same as for conventional aspirin overdose-i.e., gastric aspiration and lavage; correction of dehydration, hypokalaemia, and acidosis; and institution of forced alkaline diuresis if the plasma salicylate exceeds 500 mg 1- and the patient is severely poisoned clinically. 5,6 ’Safapryn’ contains 300 mg of enteric-coated aspirin with an outer layer of 250 mg paracetamol. ’Safapryn-Co’ contains a small amount of codeine additionally. Patients who take an overdose of either of these drugs are therefore at risk from paracetamol-induced liver damage as well as from delayed salicylate intoxication. Since nausea, vomiting, and abdominal pain are early symptoms of both aspirin and paracetamol poisoning the correct diagnosis may be missed if it is not realised that safapryn contains both drugs. Prolongation of the prothrombin time, metabolic

disturbances, and renal failure may also arise in both types of

poisoning although once these more serious signs have developed other clinical features should suggest the correct diagnosis. Early diagnosis of paracetamol poisoning is 1 Nimmo WS, King IS, Prescott LF. Paracetamol and aspirin absorption from and Safapryn-Co. Br J Clin Pharmacol 1979: 7: 219-20


2 Guardian, April, 2, 1981. 3 Todd PJ. Sills JA. Harris F. Cowen JM Problems with overdoses of sustained-release aspirin Lancet 1981: i 777. 4 Data obtained from the National Poisons Information Service.

5 Vale JA. Meredith 1981 97-103

TJ Poisoning Diagnosis

6. Matthew H, Lawson AAH Treatment of Churchill Livingstone, 1979: 82-93

and treatment, London. common


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for liver damage can be prevented only if oral methionineor intravenous N-acetylcysteine8is given within


twelve hours of the overdose. Once the liver has been damaged it is possible that salicylate intoxication will be exacerbated by a reduction in the capacity to transform the drug into non-toxic metabolites. Salicylate also interferes with one of the more common laboratory assays for paracetamol in plasma,’, 10 and all samples which are positive for paracetamol must therefore be checked by a specific test for salicylates. The number of slow-release preparations is steadily increasing and it is important that toxicity testing of such drugs should include the time-course of adverse effects after a large single overdose. This information should be included in the data sheet, many of which at present contain inadequate information." Since there is little evidence that they are more effective than single drugs and they are often more expensive,







recommended. 12 REPTILIAN SALMONELLOSIS SALMONELLAE were isolated from turtles some 35 years ago, but the association with human salmonellosis was not reported until 1963.13 Less than a decade later, 14% of the estimated 2 million human salmonellosis cases reported in the United States were linked to pet turtles-most commonly the red-eared terrapin (Pseudemys scripta elegans). People becoming infected usually do so within a month of acquiring the reptile. Chiodini and Sundberg14 have exhaustively reviewed the human salmonelloses acquired from animals of the order Testudinata. Recorded experience in the United Kingdom began in 1967, when Newman15reported salmonellosis in a small girl whose pet tortoise proved to be a carrier of Salmonella canastel; then Gumsley16 described an investigation in the Doncaster area in which several salmonella serotypes were isolated from terrapin tanks after a case of gastroenteritis in a child. A terrapin-linked S. java infection in a child in a neighbouring borough led to a wholesaler in Haringey, which prompted that local health authority to mount a careful investigation. An excellent paper by Orton and Henderson17 describes that investigation, the subsequent preventive action, and a consideration of the inadequacy of existing legislation to control the threat of human infection from terrapins. An index to the paper, by Ball,18 is valuable in recommending standards for the care and management of terrapins. In 1975, Clegg and Heath,’9 veterinarians, drew Hamlyn AN, Lesna M, Record CO, Smith PA, Watson AJ, Meredith T, Volans GN, Crome P. Methiomne and cysteamine in paracetamol (acetaminophen) overdose, prospective controlled trial of early therapy. J Int Med Res 1981, 9: 226-31 8. Prescott LF, Illingworth RN, Critchley JAJH, Stewart MJ, Adam RD, Proudfoot AT Intravenous N-acetycysteine: the treatment of choice for paracetamol poisoning. Br Med J 1979; ii: 1097-1100. 9. Glynn JP, Kendal SE Paracetamol measurement. Lancet 1975; i: 1147-48. 10. Mace PFK, Walker G. Salicylate interference with plasma paracetamol method Lancet 7




Prescott LF. Inadequate information about drug overdosage in manufacturers’ data sheets. Br Med J 1980, 280: 1418. 12. British National Formulary. London: British Medical Association and the Pharmaceutical Society of Great Britain, 1981: 130-31. 13 Communicable Disease Center Salmonella Surveillance Rep. 1963, 10: 22-24. 14 Chiodini R, Sundberg JP. Salmonellosis in reptiles. A review. Am J Epidemiol 1981; 113: 494-99. 15 Newman LT. Salmonellosis in tortoises. Br Med J 1967; iv: 296-97. 16. Gumsley PA. Terrapins traced as the cause of acase of paratyphoid fever. Public Health Insp 1968; 76: 490. 17. Orton WT, Henderson WG. The infected terrapin Commun Med 1972; 127: 89-91. 18. Ball D. Varieties, importation and care of terrapins Commun Med 1972; 127: 91-92 19. Clegg FC, Heath PJ. Salmonella excretion by terrapins and the associated hazard of human health. Vet Record 1975; 96: 90-91


Illingworth RN,