Department , Division of Nephrology, Rigshospitalet, 2100 Copenhagen 00 Department of Chemical Pathology and Obstetric and Gynaecology, St. Bartholomews Hospital, London EClA 7BE2) Medical



By K.




and A. S.



Measurements of

plasma prolactin (hPr), growth hormone (HGH), thyrotrophin (TSH), luteinizing (LH) \p=n-\and follicle stimulating hormone (FSH) were performed in 20 women with chronic renal failure on regular dialysis. There was no significant difference in any of the hormone levels before and after the dialysis and no significant influence of the type of dialysis (haemodialysis and peritoneal dialysis) or the time of dialysis. Higher levels of plasma prolactin was found in the women on peritoneal dialysis than in the haemodialyzed women presumably due to the medical treatment.

In the peritoneally dialyzed group four women had irregular menstruations and normal gonadotrophic levels, but elevated hPr and it is suggested that this finding is similar to that seen in the amenorrhoeagalactorrhoea syndrome, where hPr presumably in some way have anti\x=req-\ gonadotrophic actions at the gonadal level.

In patients with chronic renal failure, undergoing regular haemodialysis, a variety of hormone disturbances have been found (Schatz et al. 1969; Binde¬ balle et al. 1973; Gonzales-Bar cena et al. 1973; Nagel el al. 1973). 3) Present address: Hvidore





have not been studied been reported in these patients, which were not related to the type of renal disease or to medical treatment (Nagel et al. 1973). The same group found higher plasma growth hormone (HGH) before than after the dialysis, which was related to the changes in plasma glucose. However, recent reports on changes in serum thyroid stimulating hormone (TSH) levels have been conflicting. Hershman et al. (1972) demonstrated a significant fall in levels of TSH after haemo¬ dialysis related to the heparin induced thyroxine changes. By contrast Nagel et al. (1973) could not demonstrate any TSH changes. Whether these changes in the circulating levels of the pituitary hormones are directly related to treat¬ ment has not been clearly evaluated. To provide an overall picture of the changes in hormone levels we have compared the levels of the pituitary hor¬ mones hPr, HGH, TSH, luteinizing hormone (LH) and follicle stimulating hormone (FSH) in women undergoing either chronic intermittent haemo¬ dialysis or chronic intermittent peritoneal dialysis.

Although circulating levels of pituitary hormones extensively, elevated levels of prolactin (hPr) have


Patients The patients for this study were selected normal dialysis over a period of 2 months.



chronic intermittent




admitted for their


Blood samples were collected once a week before and after dialysis for a period of 4 weeks in 10 female patients (Table 1). The average age was 36 years ranging from 14 to 50 years. The average period of chronic intermittent haemodialysis before the investigation was 36 months ranging from 7 to 50 months. Seven of the 10 women

bilaterally nephrectomized. Regular menstruations were seen


in 4 women while 2 women had irregular men¬ struations. Three women had amenorrhoea for more than 24 months and one. a girl of 14 years, had never menstruated. None of the patients had severe hepatic disease but 4 patients were chronic Austra¬ lian antigen positive without other signs of hepatitis.



chronic intermittent

peritoneal dialysis

an average age of 40 years ranging from 19 studied. The average period of dialysis before the investigation was 2 months ranging from 14 days to 4 months. Regular menstruations were seen in 3 patients while 6 patients had irregular men¬ struations and 1 patient had amenorrhoea for more than 24 months. None of the patients were bilaterally nephrectomized and none had signs of liver disease.

Ten female

to 58 years

patients (Table 2)



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Dialysis procedure dialyzed with disposable parallel plate dialyzers Boe-Dawids) for an average period of 10 h (range 9-11 h) twice a week and received a diet containing on average 0.8 g of protein per kg body-weight, 50 mEq. sodium, 50 mEq. potassium and about 800 ml fluid daily. During dialysis the patients were haemodialyzed by single injections of heparin in the return line from the dialyzer under repeated control of clotting time, which varied from 15 to 60 min. The total dose of heparin per dialysis ranged from 15 000

Haemodialysis. (Gambro-Lundia






to 25 000 IU.

Peritoneal dialysis. The patients were dialyzed with either a disposable peritoneal dialysis catheter or with a permanent peritoneal dialysis catheter a. m. Tenckholff. They were dialyzed once a week for an average period of 36 h (range from 30 to 42 h). The patients received a diet containing on average 0.5 g of protein per kg -

body-weight. Blood samples. after the dialysis.

In all patients blood samples were collected before (9 a. m.) and The study was repeated with weekly intervals for a period of 4 weeks. Details of the methods for measuring plasma immunoreactive hPr, GH, TSH, LH and FSH have been given elsewhere (McNeilly 1973; Mortimer et al. 1973; McNeilly 8c Hagen 1974). In the assays used, the normal ranges for plasma hPr (standardized against human pituitary prolactin supplied by Dr. H. Friesen) was 5.0-20.0 ng/ml; for LH (M. R. C. standard 68/40, 77 IU/ampoule) in normal females in the follicular phase was 0.8-6.8 mU/ml; for FSH (M. R. C. standard 69/104, 10 IU/ampoule) in normal female sub¬ jects in the follicular phase was 1.6-7.4 mU/ml; for TSH (M. R. C. standard 68/38) the normal range was 0.4-3.5 jjtU/ml. -


Table 1 shows the clinical data and the peptide hormone concentration for the women on chronic intermittent haemodialysis. None of the patients showed any significant (P > 0.01) changes in hormone concentrations before and after the haemodialysis and no linear correlation between any of the hormones and the BUN or serum-creatinine was found. In 3 of the 10 haemodialyzed women plasma prolactin was persistently elevated (> 20 ng/ml), while 2 patients had plasma prolactin concentration within the normal range throughout the period of investigation and 5 patients had levels just outside or in the upper end of the normal range. Only one of the haemodialyzed patients studied (No. 9) showed levels of HGH outside the normal range (-< 10 ng/ml) and no linear correlation was found between the increase in plasma prolactin and the levels of HGH. Plasma TSH was within the normal range in all patients. The gonadotrophic hormones LH and FSH showed an inverse relationship com¬ pared to normal pre-menopausal women with higher FSH than LH levels. Two women (No. 8 + 10) with amenorrhoea (menostasis for more than 2 years)

showed high post-menopausal values, while bilateral oophorectomy performed in 1970 upper end of the normal range.

who had a showed LH values in the

(No. 7),

one woman


The clinical data and the peptide hormone concentrations for the 10 women chronic intermittent peritoneal dialysis are shown in Table 2. Neither in this group could any significant (P > 0.05) linear correlation between any of the hormone concentrations before and after the dialysis be demonstrated. Nine of the 10 peritoneally dialyzed women showed persistently elevated plasma prolactin levels and the mean prolactin concentration was in this group significantly (P < 0.01) higher than in the group of haemodialyzed women. The only patient (No. 13) with plasma prolactin concentration within normal range was a woman of the age of 30 years, who had been on peri¬ toneal dialysis for only 1 month. However, no significant (P > 0.05) correla¬ tion between the period of dialysis and the elevation of plasma prolactin was found. In 4 patients (No. 12, 14, 19, 20) the concentration of HGH was above the normal range and these patients showed marked day to day variation (Fig. 1), but no correlation (r 0.409, >°>0.1) to the elevated prolactin levels was found. TSH was persistently elevated in one (No. 11) and intermittent elevated in another 2, while 7 patients showed normal values. The gonado¬ trophic hormones LH and FSH showed the same inverse relationship with on



No 12

No 19


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No 20




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Fig- L Percentage changes in serum prolactin and growth hormone levels before (B) and after (A) dialysis during a 4 weeks periods in patients No. 12, 14, 19 and 20.

values of FSH than LH as found among the haemodialyzed women. Two women (No. 19 + 20) were clinically post-menopausal, but only one (No. 19) showed high post-menopausal values. Four women (No. 12, 17, 18, 20) had irregular menstruation with normal gonadotrophin levels, but very ele¬ vated plasma hPr (31.8-133 ng/ml). None of the groups showed significant (P > 0.05) linear correlation between any of the hormone concentration and the time of dialysis, and no difference in hormone concentrations between anephric patients and non-nephrectomized patients could be demonstrated.



The present levels of hPr

agrees with that of Nagel et al. (1973) in that elevated occur in a high percentage (40 °/o) of patients undergoing chronic haemodialysis. In addition we have found that the percentage of elevated levels in patients undergoing chronic peritoneal dialysis was even higher (90%). In contrast to Nagel et al. (1972) we found that the elevated hPr levels in the last group appear to be directly related to the medical treatment, metyldopa, cyproheptadin and levomepromazine. This is underlined by the facts that 5 of the 10 peritoneal-dialyzed patients treated with these groups (No. 11, 12, 17, 19, 20) showed the highest levels of hPr (44.0-133.0 ¿ig/ml); and that the significant difference between the concentration of hPr in the haemo- and peritoneal-dialyzed group disappeared when these patients were excluded. The difference in prolactin levels in the haemo- and peritonealdialyzed group could also be due to the different time in chronic dialysis, 1.8 month and 36.2 month respectively in the two groups or could be due to a different stress response to the dialyzing procedure. However, the prolactin levels were not related to the time of chronic dialysis and the presumably stress induced fluctuating HGH levels were not related to the prolactin levels


(Fig. 1). The elevated levels of hPr were not manifested by galactorrhoea in any of the patients, even though these levels appeared to be permanently elevated. Plasma HGH levels were in the upper normal range or elevated in 50 °/o of both haemo- and peritoneal-dialyzed patients. In 8 of the 10 haemodialyzed patients higher levels were found before than after dialysis. This is in agree¬ ment with other investigators (Spitz et al 1970; Bindeballe et al. 1973; Nagel et al 1973) who showed a rise in plasma glucose post-dialysis accompanied by the anticipated fall in HGH, and could not be explained from the known sleep related increase in HGH (Sassin et al 1972; Alford et al. 1973), as none of the patients were sleeping during the last two hours of the dialysis. How-

significant change in HGH was seen in the peritoneal-dialyzed group dialysis. did not induce significant changes in the TSH levels. This Haemodialysis corroborates the recent report (Nagel et al. 1973) but does not agree with the concept ol a) heparin used in haemodialysis induces a rise in "free" thyroxine (Schatz et al. 1969; Hershman et al. 1972) or b) a fall in TSH after haemo¬ dialysis (Hershman et al. 1972). ever,


before and after the


patients with severe chronic disease such as chronic renal failure, the gonadal function is usually impaired, but can return during sufficient treat¬ ment with intermittent haemodialysis (Thaysen et al. 1975, in press). The high FSH/LH ratio found in this study indicates impaired gonadal function in both the haemodialyzed- and peritoneally dialyzed group. In 4 patients with clinical hypogonadism, normal levels of gonadotrophins but high levels of hPr was found. This situation is analogous to that found in post-partum women in whom gonadotrophin secretion, while within normal limits, does not show cyclical release for some time and oestrogen secretion is low (Reyes et al. 1972), and to the situation found in amenorrhoea-galactorrhoea-syndrome with elevated prolactin levels (Thorner et al. 1974). It appears therefore that in some of the patients in the present study the raised hPr levels in some way have antigonadotrophic actions at the gonadal level (McNatty et al. 1974). In conclusion there seems to be no difference in the pituitary hormone levels with chronic renal failure due to the type of chronic intermittent There were significantly higher levels of prolactin in peritonealdialysis. than haemodialyzed patients presumably due to the medical treatment whereas no significant difference in any of the other pituitary hormones was found. in


ACKNOWLEDGMENTS We are grateful to Drs. W. R. Butt, H. Friesen and A. S. Hartree for reagents used in the radioimmunoassays. We thank Miss J. Hook for technical assistance. A. S. McNcilly is supported by the Wellcome Trus, C. Hagen by the Danish Medical Research Council.

REFERENCES F. P., Baker H. W. G., Burger H. G., Kretser de D. ili., Hudson B., Johns M. W., Masterton J. P., Patel Y. C. 8c Rennte G. C: J. clin. Endocr. 37 (1973) 841. Bindeballe W'., Schemmel K., Drenkhahn E., Scharper H., Lahrtz H., Leybold K. 8e Niedermayer W.: Acta endocr. (Kbh.) Suppl. 777 (1973) 108. González-Barcena D., Kastin A. J., Schalch D. S., Torres-Zamora M., Perez-Pästen E., Kato A. Se Schally A. V.: J. clin. Endocr. 36 (1973) 117. Hershman J. M., Jones C. M. Se Bailey A. L.: J. clin. Endocr. 34 (1972) 574.


McNatty . P., Sawers R. S. Sc McNeilly A. S.: Nature (Lond.) 250 (1974) 653. McNeilly A. S.: Proc. roy. Soc. Med. 66 (1973) 863. McNeilly A. S. Se Hagen C: Clin. Endocr. 3 (1974) 427. Mortimer C. H., Besser G. M., McNeilly A. S., Marshall J. G, Harsoulis P., Tunbridge W. M. G., Gomez-Pan A. 8- Hall R.: Brit. med. J. 3 (1973) 73. Nagel T. C, Freinkel N., Bell R. H., Priesen H., Wilber J. F. Se Metzger B. E.: J. clin. Endocr. 36 (1973) 428. Reyes F. L, Winter J. S. D. Se Faiwan G: Amer. J. Obstet. Gynec. 144 (1972) 589. Sassin J. F., Frantz A. G., Weitzman E. D. 8e Kapen S.: Science 777 (1972) 1205. Schatz D. L., Sheppard K. H., Steiner G., Chauderlapaty C. S. Se de Veber G. .: J. clin. Endocr. 29 (1969) 1015. Spitz I. M., Rubenstein A. H., Bersohn L, Abrahams C. 8e Eowy G: Quart. J. Med. 39 (1970) 201. Thorner M. O., McNeilly A. S., Hagen C. 8c Besser G. M.: Brit. med. J. 2 (1974) 419. Received


November 22nd, 1974.

Pituitary hormones in women with chronic renal failure: the effect of chronic intermittent haemo- and peritoneal dialysis.

Measurements of plasma prolactin (hPr), growth hormone (HGH), thyrotrophin (TSH), luteinizing (LH)--and follicle stimulating hormone (FSH) were perfor...
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