Comments Prolactin Responses to Thyrotropin-Releasing Hormone in ProteinCalorie Malnutrition D. J. BECKER, A. I. VINIK, B. L. PIMSTONE, AND M. PAUL Isotope Laboratory and M.R.C. Endocrine and Diabetes Research Group, Departments of Medicine and Child Health, University of Cape Town, Cape Town, South Africa ABSTRACT. Basal plasma prolactin (hPRL) concentration is low, but the response to thyrotropinreleasing hormone (TRH) is within the normal range, in children with protein-calorie malnutrition (PCM) before treatment. Treatment results in increased basal hPRL concentration and an increased response
to TRH. The above findings contrast with normal or high basal TSH and the normal or exaggerated response to TRH provocation in untreated PCM. The reason for this divergence is obscure. (J Clin Endocrinol Metab 41: 782, 1975)
NTERIOR pituitary function is variable in V children with protein-calorie malnutrition (PCM). Serum growth hormone levels are elevated (1), presumably due to hypersecretion (2); cortisol (and thus corticotropin) secretion rate is normal or inappropriately raised (3), and plasma thyrotropin (TSH) is normal or increased (4). In contrast, basal serum gonadotropins are low, and the response to gonadotropin-releasing hormone subnormal (5). The abnormal hormone secretion is corrected with treatment of the malnutrition. Human prolactin (hPRL) can now be measured by radioimmunoassay (6) and serum hPRL has been shown to rise after thyrotropin-releasing hormone (TRH) administration (7,8,9). In this paper we present data on the hPRL responses to TRH before and after treatment for PCM.
monstrable sequelae and were euthyroid. After careful explanation of the nature and details of the studies to be carried out, written consent was obtained from a parent of each child.
Materials and Methods Patients Eight children with PCM 11-41 months old were studied. All were underweight for age and hypoalbuminemic, while most demonstrated classical dermatoses and all but 2 were edematous. Each child was treated with antibiotics, vitamins, hematinics, and potassium chloride from the time of admission. Protein was withheld from the diet until the initial test had been completed on the second hospital day. The control subjects comprised 8 ambulant children 7-24 months old whose weights were over the third Boston percentile. Three had recovered from pneumonia and 5 were being followed routinely at a neonatal jaundice follow-up clinic. None of the latter had any deReceived November 26, 1974.
Methods Tests on all children with PCM were performed after an 8 h fast on the morning after admission and again after 3-5 weeks of treatment in hospital. The control children were tested on one occasion only. A basal blood sample was withdrawn by venipuncture for serum albumin and hormone estimations. Thereafter 100 jug synthetic TRH was given as an intravenous bolus over 2 minutes and blood was sampled again 20, 40, and 60 minutes later. There were no obvious side effects from TRH. Blood was centrifuged and the serum frozen until assayed 4 - 8 weeks later. hPRL was assayed by the double antibody technique (6). hPRL (V-L-S 1) for labelling and standards, and antiserum (V-L-S 1) were provided by the National Pituitary Agency, U.S.A. The assay is sensitive to 0.5 ng/ml. Intra-assay variation of 3 samples of differing hormonal content was 2-5%. All patient and control samples were assayed simultaneously. Paired analysis using Student's t test for significance was carried out for patient data and unpaired Student's t test for the comparison of control and patient data.
Results Compared with those of the controls, mean fasting 40 and 60 min hPRL concentrations of patients with untreated protein-calorie malnutrition, were significantly lower than normal, but the peak response to TRH, although lower, did not achieve significance. Treatment resulted in a
782
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783
COMMENTS rise in the basal hPRL concentrations to normal levels and in the responses to TRH to higher than normal values, but the latter were not significant. Comparison of serum hPRL before and after treatment showed a significant increase in the basal and individual hPRL levels after treatment.
Discussion In PCM patients, the basal levels of hPRL and the responses to TRH were substantially lower in untreated PCM and rose on recovery. Although basal 40 and 60 min post-TRH hPRL values were significantly below normal, these observations might reflect only a small sample and their importance is uncertain. Clearly, however, 3 weeks of treatment of PCM patients resulted in significant enhancement of the hPRL response to TRH. This contrasts with the data for TSH on the same patients in which basal levels were normal or elevated and the response to TRH often exaggerated and usually sustained (4) in untreated PCM. While both hormones normally show a parallel rise after this provocative stimulus, discordant responses have been noted (7,8,9). Our finding of somewhat low hPRL responses to TRH in patients whose TSH responses were either normal or exaggerated, again argues in favor of separate release mechanisms. The low basal hPRL and slightly low responses to provocative stimulation a"re in accordance with data on LH release in a similar group of children (5) but contrast sharply with the raised levels of growth hormone (1) and probably of corticotropin (3). This variable effect of PCM on anterior pituitary function is puzzling and suggests either selective impairment of individual hypothalamic-pituitary releasing mechanisms for reasons which are at present not obvious, or that individual hormonal responses are more specifically related to the metabolic demands of these patients. It has been shown that fasting for 36 hours in adults depresses the basal hPRL level and the response to TRH (11). There are possible metabolic features in common between PCM and fasting, but any inferences on common factors regulating hPRL secretion would be speculative. Somewhat paradoxically, patients with anorexia nervosa who are less than 60% of their ideal weight have normal hPRL responses to TRH (12), but these patients do not have edema and/or water retention and show a completely different dietary pattern.
TABLE 1. Plasma prolactin (mean ± SE) responses to TRH before and after dietary treatment in proteincalorie malnutrition and in controls Plasma prolactin (ng/ml) Minutes
Before treatment
Patients (n = 8)
0 20 40 60
1.0: t 34.1 dt 18.6 it 12.2 it
0.2 9.0 13.4 5.2
Controls (n = 8)
0 20 40 60
15.4 it 55.4 it 56.6 dt 36.1:t
4.2 12.5 18.5 11.9
P
to TRH. The above findings contrast with normal or high basal TSH and the normal or exaggerated response to TRH provocation in untreated PCM. The reason for this divergence is obscure. (J Clin Endocrinol Metab 41: 782, 1975)
NTERIOR pituitary function is variable in V children with protein-calorie malnutrition (PCM). Serum growth hormone levels are elevated (1), presumably due to hypersecretion (2); cortisol (and thus corticotropin) secretion rate is normal or inappropriately raised (3), and plasma thyrotropin (TSH) is normal or increased (4). In contrast, basal serum gonadotropins are low, and the response to gonadotropin-releasing hormone subnormal (5). The abnormal hormone secretion is corrected with treatment of the malnutrition. Human prolactin (hPRL) can now be measured by radioimmunoassay (6) and serum hPRL has been shown to rise after thyrotropin-releasing hormone (TRH) administration (7,8,9). In this paper we present data on the hPRL responses to TRH before and after treatment for PCM.
monstrable sequelae and were euthyroid. After careful explanation of the nature and details of the studies to be carried out, written consent was obtained from a parent of each child.
Materials and Methods Patients Eight children with PCM 11-41 months old were studied. All were underweight for age and hypoalbuminemic, while most demonstrated classical dermatoses and all but 2 were edematous. Each child was treated with antibiotics, vitamins, hematinics, and potassium chloride from the time of admission. Protein was withheld from the diet until the initial test had been completed on the second hospital day. The control subjects comprised 8 ambulant children 7-24 months old whose weights were over the third Boston percentile. Three had recovered from pneumonia and 5 were being followed routinely at a neonatal jaundice follow-up clinic. None of the latter had any deReceived November 26, 1974.
Methods Tests on all children with PCM were performed after an 8 h fast on the morning after admission and again after 3-5 weeks of treatment in hospital. The control children were tested on one occasion only. A basal blood sample was withdrawn by venipuncture for serum albumin and hormone estimations. Thereafter 100 jug synthetic TRH was given as an intravenous bolus over 2 minutes and blood was sampled again 20, 40, and 60 minutes later. There were no obvious side effects from TRH. Blood was centrifuged and the serum frozen until assayed 4 - 8 weeks later. hPRL was assayed by the double antibody technique (6). hPRL (V-L-S 1) for labelling and standards, and antiserum (V-L-S 1) were provided by the National Pituitary Agency, U.S.A. The assay is sensitive to 0.5 ng/ml. Intra-assay variation of 3 samples of differing hormonal content was 2-5%. All patient and control samples were assayed simultaneously. Paired analysis using Student's t test for significance was carried out for patient data and unpaired Student's t test for the comparison of control and patient data.
Results Compared with those of the controls, mean fasting 40 and 60 min hPRL concentrations of patients with untreated protein-calorie malnutrition, were significantly lower than normal, but the peak response to TRH, although lower, did not achieve significance. Treatment resulted in a
782
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 14 November 2015. at 13:29 For personal use only. No other uses without permission. . All rights reserved.
783
COMMENTS rise in the basal hPRL concentrations to normal levels and in the responses to TRH to higher than normal values, but the latter were not significant. Comparison of serum hPRL before and after treatment showed a significant increase in the basal and individual hPRL levels after treatment.
Discussion In PCM patients, the basal levels of hPRL and the responses to TRH were substantially lower in untreated PCM and rose on recovery. Although basal 40 and 60 min post-TRH hPRL values were significantly below normal, these observations might reflect only a small sample and their importance is uncertain. Clearly, however, 3 weeks of treatment of PCM patients resulted in significant enhancement of the hPRL response to TRH. This contrasts with the data for TSH on the same patients in which basal levels were normal or elevated and the response to TRH often exaggerated and usually sustained (4) in untreated PCM. While both hormones normally show a parallel rise after this provocative stimulus, discordant responses have been noted (7,8,9). Our finding of somewhat low hPRL responses to TRH in patients whose TSH responses were either normal or exaggerated, again argues in favor of separate release mechanisms. The low basal hPRL and slightly low responses to provocative stimulation a"re in accordance with data on LH release in a similar group of children (5) but contrast sharply with the raised levels of growth hormone (1) and probably of corticotropin (3). This variable effect of PCM on anterior pituitary function is puzzling and suggests either selective impairment of individual hypothalamic-pituitary releasing mechanisms for reasons which are at present not obvious, or that individual hormonal responses are more specifically related to the metabolic demands of these patients. It has been shown that fasting for 36 hours in adults depresses the basal hPRL level and the response to TRH (11). There are possible metabolic features in common between PCM and fasting, but any inferences on common factors regulating hPRL secretion would be speculative. Somewhat paradoxically, patients with anorexia nervosa who are less than 60% of their ideal weight have normal hPRL responses to TRH (12), but these patients do not have edema and/or water retention and show a completely different dietary pattern.
TABLE 1. Plasma prolactin (mean ± SE) responses to TRH before and after dietary treatment in proteincalorie malnutrition and in controls Plasma prolactin (ng/ml) Minutes
Before treatment
Patients (n = 8)
0 20 40 60
1.0: t 34.1 dt 18.6 it 12.2 it
0.2 9.0 13.4 5.2
Controls (n = 8)
0 20 40 60
15.4 it 55.4 it 56.6 dt 36.1:t
4.2 12.5 18.5 11.9
P
