Work in progress
contamination of the glassware and inherent errors of this contamination are avoided. The patient is saved from the inconvenience of venepuncture for collection of blood. Lastly, this technique avoids the necessity of having additional instrument like a well type scintillation counter. On the other hand, this technique has its own pitfalls. It gives an extra parameter for diagnosis of hyperthyroidism but fails to discriminate euthyroidism from hypothyroidism. However, PB13rI estimation also suffers from a similar drawback. The new technique may not be valid in cases of liver damage and kidney disorders. Since radioactivity in the liver is expressed in terms of countslmin, it is necessary that for the sake of comparison same amount of radioactivity is administered to each patient and the efficiency of the counting equipment does not change. External scintillation counting of liver is a new test added to the armamentarium of many other tests for the evaluation of thyroid status. Although it does not offer a precise value of hormonal concentration, because of the accuracy by which it could differentiate euthyroid goiters from toxic goiters, it could certainly be used as a rapid screening procedure in a busy thyroid clinic. The high uptake of lslI by thyroid gland is always not suggestive of hyperthyroidism and some additional test like estimation of PB1311, stable PBI or Hemolsky’s test of uptake of labelled triiodothyronine by R.B.C. is required. In comparison to all these techniques liver counts are much simpler, rapid and involves no extra expenditure, and could be a great help to those laboratories which are newly started especially in developing countries. K. B. DESAI M.C. PATEL M. N. MEHTA S. M. SHARMA R. D. GANATRA F. P. ANTIA Radiation Medicine Centre, Bhabha Atomic Research Centre, c/o Tata Memorial Hospital, Pare& Bombay 400 012, India
dcknowledgement-Authors wish to thank Shri Balvinder Singh for doing the statistical analysis of the data on the Fortran digital computer. References
1. POCHINE. E. In Dynamic Clinical Studies with Radioisotopes (Edited by KWSELEY R. M. and TAUXE W. E.) AEC-TID 7678, Oakridge, TN (1964). 2. SHARMAS. M., DESAI K. B., MEHAN K. P., GANATRAR. D., MEHTA, M. N., SUNDARAM K. and ANTIAF. P. J. Nucl. Med. 6, 598 (1965).
73
3. International Atomic Energy Agency Consultant’s
Meeting on Calibration and standardization of thyroid radioiodine uptake measurements. Br. J. Radiol. 35, 205 (1962). 4. HAMOLSKY M. W. and FRREDBERG,A. S. New Engl. J. Med. 262, 70 (1960).
International Journal of Nudcar Medicine and Biology, 1976,Vol.3, pp. 73-76. Pcrgamon Press.Printedin Northern Ireland
Trace
Elements
in Human
PitUital=y*
(Received 16, October 1975) IXWOdUCtiO2J
THE LITERATURE on the concentration of the various chemical elements in the whole human brain as well as in its various segments is fairly extensive. Specimens from “healthy” subjects and subjects who died from a variety of diseases have been studied. Reports of these researches have been compiled and referenced by ANSPAUGH,ROBINSON,MAFUIN and LOWE(~). Information is available for the following elements: B, Mg, P, S, Ca, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ca, Se, Ru, Al, St, Zr, Nb, MO, Ag, Cd, Sn, Te, Ba, Au, Hg, Pb, and Bi. In contrast, very little has been reported on the elemental content of human pituitary. Only three reports were found in the literature.(2-4) ZONDEK and BIER(~) reported bromine levels in the pituitary. RIGGS et a1.f3) studied lead content in pituitaries of 99 subjects. AHLMARK(*)reported on mercury levels, in pituitaries from subjects who died of Hg poisoning. Since the pituitary is such a vital organ, one wonders about the role of its trace elements. How many metals make up its matrix? Are any of these essential to its normal function? Do the number of elements and quantities change with age and/or disease? Are any of the elements related to neurological symptoms or disease? The purpose of this report is to present data for several trace elements observed in human pituitaries obtained from adult subjects who died of ischemic heart disease, carcinoma and cirrhosis of the liver. None of these subjects suffered from mental diseases. Material
and Methods
Entire pituitary specimens were obtained from 14 adult male subjects ranging from 42 to 83 years. The * This work was supported in part by WHO Research Grant C3/181/52 from the Division of Cardiovascular Diseases, World Health Organization, Geneva, Switzerland
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Work in progress
chief histopathological diagnosis of each subject was as follows: Subject* 1
Age
Postmortem findings
42
ferred into a clear, small pre-weighed beaker. The sample was weighed, frozen and lyophilized for about 120 hr. Following this, the specimen was weighed again and the percentage of the remaining dry solid was calculated. The entire residue was placed into a 1.5 ml polyethylene vial, sealed and irradiated.
Acute myocardial infarct; moderate right coronary arteriosclerosis, severe left coronary arterioStandards sclerosis; pulmonary edema Aqueous solutions were prepared from analytical 54 Adenocarcinoma of rectum; pul2 grade salts of the elements measured: Fe(NO,)s. monary emphysema; chronic pas6HsO; ZnSOl; RbCl; SeO,; NH&r; Cr(C&HsO,),; sive congestion 54 3 Bronchogenic carcinoma; acute Hg(CsH,O,),; %SG,; Co(CsHaO&4HsG; HAuC&.3H,O and SbsO,. The water was distilled multiple duodenal ulcers; acute and was prepared by passing through anion-cation hemorrhagic cystitis resin. (Amberlite, Mb-l, Rohm and Hass Co., 4 54 Laennec’s cirrhosis; upper gastroPhiladelphia, PA). The conductivity was measured intestinal bleeding; multipleacute frequently, the observed resistance varying between gastric ulcers 2,000,OOO and 2,400,OOOn cm. 100 ,ul quantities of 5 55 Myocardial infarct; severe atheroeach standard were placed a on 3-ems piece of clean sclerosis of left coronary artery cellulose acetate paper and air dried. Each dried 6 57 Bronchogenic adenocarcinoma; standard was placed into a 1.5 ml polyethylene vial thyroid adenoma and sealed. 7 58 Adenocarcinoma of rectceigmoid colon with massive generalized metastases and extensive periNeutroniwadiationand y-ray counting toneal adhesion Blanks, standards and samples were neutron 8 63 Advanced liver cirrhosis; as&is activated in the CP-5 Reactor at Argonne National and pulmonary congestion Laboratory. The neutron flux in the isotope tray 9 64 Bronchogenic squamous cell carused was approximatly 2.4 x 101sn/cma/sec. and cinoma of the right main stem the irradiation period was 24 hr. Specimens were bronchus removed from the reactor, allowed to cool for a 67 Massive subarachnoid hemorrhage 10 period of 3 to 5 days to allow sodium-24 and other in left cerebral hemisphere and short lived isotopes to decay and then transferred to cerebellum; intracerebral hemnon-irradiated polyethylene vial of the same dimenorrhage 11 Squamous carcinoma with bone . sions to maintain uniform sample geometry. 71 Samples were counted for 2000 and 6000 second metastases. General severe arterperiods using a 36 ml Ge(Li) Scintillation Detector in iosclerosis conjunction with a 4096 channel pulse-height anaThrombosis of basillary artery; 12 72 lyzer. No chemical separation were performed. The cerebral and coronary arteriotape recorded data was transferred onto IBM cards sclerosis; arterial hypertension and processed through an IBM-360 Computer. Squamous cell carcinoma; coro13 73 Analyses consisted of the integration of the most nary atherosclerosis prominent y-ray peaks for each isotope with approPulmonary edema with conges14 83 priate corrections for decay, size of sample, blanks, \ tion; megaloblastic anemia strength of standards and flux variations.(6*7) The y ray energies selected for each radionuclide are presented in Table 1. After removal of the brain, the entire pituitary gland was carefully removed and immediately transResults andDiscllssion + Postmortem examinations were performed between 12 and 16 hr after death. Proper precautionary measures against contamination of the samples were rigidly employed and followed guidelines described previously.(s)
Trace elements concentrations found in thii study are presented in Table 2. This information extends somewhat the meager information currently available in the literature. Of the 14 elements presently observed, two have been previously studied: Bromine
75
Work in ~ogress TABLE 1. Physical properties of radionuclides observed after 24HR irradiation of human pituitaries by thermal neutrons
Isotope @‘+Br l=Cd lgeAu 12sSb *sRb srcr 5sFe 2osHg ‘Yje 65Zn is4cs ssco
Principal y-ray energies, MeV
Half-life 35.8 hr 2.3 days 2.7 days 2.75 days 18.7 days 27.8 days 45.1 days 46.9 days 120.0 days 245.0 days 2.07 yr 5.2 yr
0.554 0.492 0.411 0.564 1.076 0.320 1.098 0.246 0.246 1.115 0.604 1.173
0.776 0.527
1.291 0.279
0.796 1.333
was reported to be 15-30 times greater in the pituitary than in any other organ;(s) Mercury was reported in pituitaries to two male adults who died of mercury poisoning.(4) The Hg content in the pituitary of a 23-yr-old male was between 25 and 35 yg/g. This young man was employed packing seed-dressing containing methyl mercury for a period of one month before he became ill and died two months later. The other subject was a 57-yr-old male who for five years had on repeated occasions impregnated wood with TABLE
methyl mercury preparation. The mercury content in the pituitary was less than 5.7 pg/g. Lead was the only additional element that was previously reported.@) The lead study, based on analysis of kidneys and pituitary from 110 human subjects, claimed an association of elevated Pb levels to disease and related them directly to neurological symptoms in a high percentage of cases. Pituitaries from healthy subjects contained an average 16.3 fig Pb/g dry tisse, while those from non healthy (variety of diseases) contained 39.6. The bromine levels in this report are in the range of 0.3-4.2 ,ug/g dry tissue (ppm). This is considerably less than that reported by ZONDEK and BIER(~). Furthermore the bromine levels in other organs (liver, myocardium, lung, spleen) do not vary more than four fold from the levels observed in the pituitaries.* In the present study the Hg level ranged from 0.1 to 1.4 ppm on a dry weight basis except for subject 13. The Hg level in the pituitary of this man was 23.9 ppm, while Se was 9.4 ppm. Both these levels were much greater than those from the remainder of subjects (Table 2). This subject, a 73 year old male, had a diagnosis of metastatic carcinoma and coronary insufficiency. As study of his hospital chart revealed 13’Cs-needle implantation on three different occasions: 800, 3700 and 500 gamma, and several X-ray * Unpublished data
2. Trace elements in human pituitary-mg
1.0 g dry tissue (ppm)
Wt of Subject
1 2 3 4 5 6 7 8 9 10 11 12 13 14 Mean S.D.
Age 42 54 54 54 55 57 58 63 64 67 71 72 73 83 61
organ
Solid
gm
%
0.50 0.30 0.63 0.65 0.72 0.51 0.55 0.40 0.47 0.39 0.51 0.62 0.74 0.54 0.54 f0.13
nc = not counted nd = not detected
18.24 17.47 18.26 20.44 17.84 21.62 17.93 19.33 20.38 18.56 18.04 19.70 19.48 17.02 18.88 f1.31
Fe 219 299 165 258 290 240 219 302 213 231 155 255 195 277 237 146.6
Zn 28.4 28.7 18.5 24.7 29.1 29.7 28.4 33.1 23.5 29.4 26.5 30.2 24.8 32.1 27.7 53.7
Rb 11.5 nc nc 10.1 13.1 nc 8.4 nc 19.8 10.5 6.3 10.9 14.1 nc
Se 3.55 1.01 0.55 0.99 1.11 1.66 0.85 0.96 0.73 0.83 1.32 2.11 1.02 1.19 50.95
Br
Cr
Hg
CS
Co
0.27 nc nc 0.55 0.81 nc 4.2 nc nc 1.84 0.82 0.33 1.09 nc
nd 0.53 nd nd nd nd 0.67 0.33 nd nd nd 0.83 nd nd
1.39 0.36 0.09 0.16 0.62 0.29 0.32 0.66 0.12 0.05 0.27 0.77
0.040 0.095 0.026 0.043 0.073 0.066 0.045 0.016 0.051 0.015 0.016 0.025 0.039 0.081 0.045 60.023
0.026 0.042 0.034 0.039 0.070 0.029 0.036 o.oi3 0.011 0.098 0.030 0.033 0.035 0.033 0.041 5.0.02!
0.07 0.37 10.38
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Work in progress
therapies. There was no record of any Hg containing medications or drugs or radioisotopic scans. In regard to the remaining elements in Table 2, no direct comparison can be made since no other information was found in the literature. Present information reveals that the total pituitary, contains the following amounts of elements studied : Iron, 90-209 ,ug; Zn, 8-21; Rb, 3-10; Se, 0.3-1.3; Br, 0.1-2.1; Cr, 0.1-0.5; Hg, 0.02-0.70; Cs, 0.005-0.043; Co, 0.005-0.05. It is interesting to note that Cr was found in only 4 of 14 pituitaries. Cadmium, gold and antimony were observed but not quantitated in 4, 3 and 2 subjects respectively. It is possible that these four elements are measurable in all pituitaries but were not detected in all of our samples because of long decay times for some samples. Although no values are given for sodium and potassium, their presence was noted in all samples. Closer study of presented data reveals no apparent correlation between the levels of elements observed and age of disease. No correlation was observed with respect to age of the subjects and the weight of the gland. The average weight of pituitaries collected was 0.54 g which is in accord with the 0.5-0.6 range given by GRAY(*I. This lack of correlation with these diseases may imply that as far as these elements are concerned the subjects studied may be representative of the general population and that these elements play a very fundamental role in the pituitary function. Since none of the subjects in the present study suffered from neurological disorders, a similar study of pituitaries from subjects with such disorders could prove very informative. Equally significant would be a study of subjects with various endocrine disorders, since these are effectively influenced by this vital gland. Patients who have undergone hemodialysis and have developed neurological sequelae should be compared with the subjects reported. Analysis for manganese for example in a control group would be of specific interest when compared with clinically similar chronic manganese toxicity@) and the syndrome of dyspraxia and multifocal seizure associated with chronic hemodialysis.(lO)
E. L. KANABROCKI* J. GRECO L. A. GRAHAM E. KAPLAN M. E. RUBNITZ Y. T. OESTER * Present address: U.S. Customs Laboratories, 610 Canal Street Chicago, Illinois 60607
Nuclear Medicine Service, Veterans Administration Hospital, Hines, Illinois, 60439
s. BRARt P. S. GUSTAFSON
D. M. NELSON Argonne National Laboratory, 9700 South Cass Avenue, Argonne, Illinois, 60439
F. ~OLINARI C. E. MOORE Loyola University North Campus, Chicago, Illinois 60626
J. A. KA~AEXOCKI Notre Dame University, Notre Dame, Indiana 46556
References L. R., ROBINSON W. L., MARTINW. H. 1. ANSPAUGH et al. Compilation of published information on elemental concentrations in human organs in both normal and diseased states. UCRL 51013 (1) Rev August 1971, UCRL 51013 (2) August 1971, UCRL 51013 (3) December 1971, UCRL 51013 (4) July 1973. H. and BIER A. Klin Woschchr 11, 759 2. ZONDEK (1932). Ibid. 11, 760 (1932). T. V. and REINHOLD J. C. 3. RIGGSH. E., LETONOFF Am. J. Clin. Path. 14, 175 (1944). 4. AHLMARKA. Br. J. Ind. Med. 5, 117 (1948). E. L. 5. MARKSG. E., MOORE C. E., KANABRoCKI et al. Ap~l. S’ectr. 26, 532 (1972). R., LEVY H. B. and NIDAY J. B. 6. GUNNINK Identification and determination of y-ray emitters by computer analysis of Ge(Li) spectra. LICID 15140, 1967. 7. U.S. Department of Health Education and Welfare Public Health Service. National Center for Radiologic Health, Rockville, Maryland. Radioassay procedures for environmental samples. pp. l-5 1 (1967). 8. GRAY H. Anatomy of the Human Body. Lea & Febiger, Philadelphia. 9. COOKEDAVID G. and BRAIT KENNETHA. Arch. Neuro. 30,59 (1974). 10. ALFREYA. C., MQXHELL J. M., BROOKSW. et al. Trans. Am. Sot. Artif. Int. Organs 13, 257 (1972). t Present address: Wcstmont, Ill. 60559
347 W.
Naperville
Road,