750 rose by 24% between 1966-70 and 1971-76 in our region whilst the AML rate rose by 70%. The increase in the CML registration rate for the North Wes...

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750 rose by 24% between 1966-70 and 1971-76 in our region whilst the AML rate rose by 70%. The increase in the CML registration rate for the North West is particularly noteworthy because, although less than the AML increase, it exceeded the corresponding national increase to a much more significant extent. If this difference between the regional and national trends for CML has been due merely to diagnosis and registration improving more in the North West than elsewhere, we should have expected it to be associated with a more marked difference for AML, which our clinical colleagues tell us was not diagnosed as completely as CML in the past. We conclude that CML incidence may genuinely have risen in this region, but not in other parts of the country. The reason for any such rise must remain a matter of speculation. A variety of different agents has been identified as capable of inducing leukaemia, and in a region with a complex and continually changing pattern of industrial activity it is wise to keep an open mind. We are engaged in developing new techniques for areal monitoring of reported incidence and plan a series of researches into areal and occupational patterns of cancer incidence.

Department of Community Medicine, University of Manchester,


Manchester M13 9PT

Department of Epidemiology and Social Research, University Hospital of South Manchester





Department of Medicine, Division of Endocrinology, VA Medical Center, Long Beach, California 90822, U.S.A.


SIR,—I have seen a 34-year-old scaffolder who was in the habit of dropping the scaffold bars rather sharply on his right shoulder. He presented with symptoms very similar to those described by Dr Williams and his colleagues (Sept. 20, p. 637) and he made an uneventful recovery. It is interesting there seem to be no reports of



King’s College Hospital,


London SE5 9RS



adrenal androgen-stimulating hormone does not exist", Aug. 30, p. 454), Dr Anderson speculates that an adrenocortical androgen (AA) stimulating hormone is "mythical" because (1) it has not yet been isolated, and (2) it need not be invoked to explain the often observed divergence between cortisol and AA secretion. With respect to (1), the same was said about human prolactin and other hormones a decade ago. Anderson supports his second reason with a novel explanation of the adrenarche. He theorises that, over the first five years of a child’s life, a high intra-adrenocortical inner zone cortisol level induces cells at the basal layer of the zone fasciculata to differentiate into zona reticularis cells. These cells would then presumably be the source of the AA that characterise the adrenarche. This is an interesting and provocative hypothesis, which could be tested directly-for example, by incubating human fasciculata cells in vitro in high and low cortisol environments, and monitoring possible transformation to reticularis cells by sampling AA in the media. Despite the ingenuity of this theory, however, there are several reasons why it does not eliminate the need to postulate an AAstimulating hormone 1,2 (AASH) or a cortical androgen stimulating hormone3,4 (CASH). First, it assumes that AA are produced mostly or solely by the zona reticularis, and published data supporting this concept are still limited. Second, after AA reach peak levels between ages 20 and 30, cortisol levels remain constant with age, but AA


SIR,—Golden et al. 11have reported that the skin breakdown in kwashiorkor heals more rapidly when zinc is applied topically. They also found low plasma zinc concentrations in malnourished children with skin sores. 12 These workers concluded that the skin lesions are caused by a zinc deficiency11, 12 but they did not explain how the children became zinc deficient. It seems unlikely that the zinc deficiency observed in kwashiorkor can be entirely accounted for by insufficient zinc These children have protein, not energy, malnutrition, usually because their food is largely of plant origin; however, foods of plant origin are not low in zinc. A contributing factor to the zinc deficiency in kwashiorkor may be poor absorption of zinc. Evans et al.15 have suggested that picolimc acid, a metabolite of tryptophan produced in the exocrine cells of the pancreas, is required for zinc absorption. 15 Thus a protein poor




NM, Richards GE, Conte FA, Kaplan SL Clinical disorders of adrenal function and puberty an assessment of the role of the adrenal cortex in normal and


puberty in man and evidence for an ACTH-like pituitary adrenal androgen stimulating hormone. In James VHT, Serio M, Guisti G, Martini L, eds.


1. Grumbach


The endocrine function of the human adrenal cortex: Serono symposium 18 London. Academic Press, 1978: 583. 2. Sklar CA, Kaplan SL, Grumbach MM. Evidence for dissociation between adrenarche and gonadarche: Studies in patients with idiopathic precocious puberty, gonadal dysgenesis, isolated gonadotropin deficiency, and constitutionally delayed growth and adolescence. J Clin Endocrinol Metab 1980; 53: 548. 3. Parker L, Odell W. Evidence for existence of cortical androgen-stimulating hormone

Am J Physiol 1979; E616. L, Kozbur X, Kawahara C, Geduld S, Odell W. In vitro evidence for cortical androgen-stimulating hormone (CASH). Sixth Int Congr Endocrinol 1980: abstr

11. 12. 13. 14.

4. Parker



C, Brown H, Simons E, Carter D, Kumagal L, Englert E. Adrenocortical function and cortisol metabolism in old age. J Clin Endocrinol Metab 1961, 21: 1197 Smith M, Rudd B, Shirley A, Rayner P, Williams J, Duignan N, Bertrand P. A radioimmunoassay for the estimation of serum dehydroepinadrosterone sulphate in normal and pathological sera. Clin Chim Acta 1975; 65: 5. Migeon C, Keller A, Lawrence B, Shephard T. DHA and androsterone levels in human plasma. J Clin Endocrinol Metab 1956; 17: 1051 Hendrikx A, Heyns W, de Moor P Influence ofa low-calorie diet and fasting on the metabolism of DHAS in adult obese subjects. J Clin Endocrinol 1968, 28: 1525 Moore F The metabolic care of the surgical patient Philadelphia. W B. Saunders 1959.74. Herrmann W, Hayes M, Goldenberg I, Schmidt I Urinary 17-Ks in surgical stress J Clin Endocrinol 1959, 19: 849. Golden MHN, Golden BE, Jackson AA. Skin breakdown in kwashiorkor responds to zinc. Lancet 1980, i: 1256 Golden EB, Golden MHN Plasma zinc and the clinical features of malnutrition Am J Clin Nutr 1979; 32: 2490-94. Hamilton EM, Whitley E. Nutrition: Concepts and controversies. St Paul, Minnesota West Publishing, 1979: 135, 235, 286. Latham MC, McGandy RB, McCann MB, Stare FJ. In: Thomas BA, ed Scope’ manual on nutrition Kalamazoo, Michigan: Upjohn 1972: 28, 65, 72-75. Evans GW. Normals and abnormal zinc absorption in man and animals The trytophan connection. Nutr Rev 1980; 38: 137/141.

5. West




hod carriers or meat market porters with subclavian vein thrombosis, and the explanation may be that both the hod and the carcass have to be lifted and balanced on the shoulder before any forward movement is made.


decrease dramatically. 5-7 How would Anderson’s theory account for a slow induction of AA-producing cells by high intra-adrenal cortisol concentrations until the third decade, and then the opposite effect thereafter? Third, in fasting8and stress, 9,10 cortisol and AA secretion can diverge over a time course of days, rather than years, as his theory requires. If Anderson’s concept of intra-adrenal control of AA in the adrenarche is accepted, the observed changes in AA secretion in aging, fasting, and stress remain unexplained. I feel, like Mark Twain on his own erroneously recorded obituary, that reports of the death of CASH (or AASH) have been greatly exaggerated.